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Safety and pharmacodynamic mechanism of ropivacaine lumbar anesthesia in Cesarean section.
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Lumbar anesthesia is the preferred anesthetic approach for puerperae undergoing cesarean section in China. To observe the safety of administering different doses of ropivacaine for cesarean section and its pharmacodynamic mechanism, we randomly divided 180 pregnant women undergoing cesarean section into three groups: group A, 10 mg ropivacaine (0.50%); group B, 12 mg ropivacaine (0.50%); and group C, 14 mg ropivacaine (0.50%). Pharmacodynamic index, anesthesia quality and incidence of untoward reactions of each group were observed. Group A performed the poorest and group C the best in evaluation of sensory and motory block (P less than 0.05). With regard to evaluation of hemodynamic index, hemodynamic parameters of the three groups had significant differences after medication; mean arterial pressure (MAP) of patients in group B decreased at time points T1, T2 and T3 and heart rate (HR) became much higher at T1 (P less than 0.05); MAP of the patients in group C decreased at T1, T2, T3 and T4, but HR became higher at T1 and T2 (P less than 0.05); HR of group B was higher than that of group A at T1 (P less than 0.05); MAP of the patients in group C had a significant decrease at T1, T2, T3 and T4, but HR became higher at T2 (P less than 0.05); MAP of patients in group C significantly decreased compared to group B at T1 and T2, but HR became higher at T2 (P less than 0.05). Fluctuation of oxyhemoglobin saturation (SpO2) of all patients was between 95% and 99%. There was no occurrence of myocardial ischemia or arrhythmia. 1-min Apgar score of neonates of the three groups had no significant difference (P0.05). The incidence of adverse reactions of the patients in group C was much higher than that of the patients in the other groups (P less than 0.05). Twelve mg ropivacaine (5%) is the most suitable dose for pregnant women undergoing cesarean section as it can achieve a sound anesthetic effect and high safety and, moreover, has little influence on respiratory and circulatory functions.
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2,335,301 |
The cancer paradigms of mammalian regeneration: can mammals regenerate as amphibians?
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Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells. Interestingly, regenerating amphibian cells are highly resistant to oncogenic transformation. Therapeutic approaches to improve mammalian regeneration mainly include stem-cell transplantations; but, these have proved unsuccessful in non-regenerating organs such as the heart. A recently developed approach is to induce de-differentiation of mature cardiomyocytes using factors that trigger their re-entry into the cell cycle. This novel approach raises numerous questions regarding the balance between transformation and regeneration induced by de-differentiation of mature mammalian somatic cells. Can this balance be controlled artificially? Do de-differentiated cells acquire the protection mechanisms seen in regenerating cells of lower organisms? Is this model unique to the cardiac tissue, which rarely develops tumors? This review describes regeneration processes in both mammals and lower organisms and, particularly, the ability of regenerating cells to avoid transformation. By comparing the characteristics of mammalian embryonic and somatic cells, we discuss therapeutic strategies of using various cell populations for regeneration. Finally, we describe a novel cardiac regeneration approach and its implications for regenerative medicine.
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2,335,302 |
Management of systemic lupus erythematosus during pregnancy: challenges and solutions.
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Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease predominantly affecting women, particularly those of childbearing age. SLE provides challenges in the prepregnancy, antenatal, intrapartum, and postpartum periods for these women, and for the medical, obstetric, and midwifery teams who provide their care. As with many medical conditions in pregnancy, the best maternal and fetal-neonatal outcomes are obtained with a planned pregnancy and a cohesive multidisciplinary approach. Effective prepregnancy risk assessment and counseling includes exploration of factors for poor pregnancy outcome, discussion of risks, and appropriate planning for pregnancy, with consideration of discussion of relative contraindications to pregnancy. In pregnancy, early referral for hospital-coordinated care, involvement of obstetricians and rheumatologists (and other specialists as required), an individual management plan, regular reviews, and early recognition of flares and complications are all important. Women are at risk of lupus flares, worsening renal impairment, onset of or worsening hypertension, preeclampsia, and/or venous thromboembolism, and miscarriage, intrauterine growth restriction, preterm delivery, and/or neonatal lupus syndrome (congenital heart block or neonatal lupus erythematosus). A cesarean section may be required in certain obstetric contexts (such as urgent preterm delivery for maternal and/or fetal well-being), but vaginal birth should be the aim for the majority of women. Postnatally, an ongoing individual management plan remains important, with neonatal management where necessary and rheumatology followup. This article explores the challenges at each stage of pregnancy, discusses the effect of SLE on pregnancy and vice versa, and reviews antirheumatic medications with the latest guidance about their use and safety in pregnancy. Such information is required to effectively and safely manage each stage of pregnancy in women with SLE.
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2,335,303 |
Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.
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Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.
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2,335,304 |
Digoxin reduces the mutagenic effects of Mitomycin C in human and rodent cell lines.
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Digoxin is a drug widely used to treat heart failure and studies have demonstrated its potential as anticancer agent. In addition, digoxin presents the potential to interact with a series of other compounds used in medicine. The aim of the present study was to evaluate in vitro the cytotoxicity, genotoxicity and mutagenicity of digoxin and its potential to interact with the mutagen Mitomycin C (MMC). The cytotoxicity of digoxin was assessed by employing the MTT method and the comet assay was performed to assess the genotoxicity of this medicine in CHO-K1 and HeLa cell lines. Besides, the cytokinesis-block micronucleus assay was performed to assess the mutagenicity and the antimutagenicity of this drug. The Ames assay was also performed with TA98 and TA100 strains of S. typhimurium. Results showed that digoxin was cytotoxic, genotoxic and mutagenic for HeLa and CHO-K1 cell lines at concentrations many times higher than those observed in human therapeutic conditions. Nevertheless, an antimutagenic effect against the mutagen MMC was observed on both cell lines in concentrations near those used therapeutically in humans. This chemoprotective effect observed is an interesting finding that should be better explored regarding its impact in anticancer chemotherapy.
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2,335,305 |
Resonance Frequency Breathing Biofeedback to Reduce Symptoms of Subthreshold PTSD with an Air Force Special Tactics Operator: A Case Study.
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The prevalence rates of post-traumatic stress disorder (PTSD) have been estimated to be several times higher in military populations compared to the national average. Special Tactics operators are a group that is more likely to avoid seeking psychological care due to the stigma and other consequences the diagnosis may have on their military careers. There is a need for more effective and less stigmatizing interventions to treat this population. Psychophysiological methods have been proven to be efficacious in treating PTSD, yet have received less attention as an adjunctive intervention. Resonance frequency (RF) biofeedback is a form of cardiorespiratory intervention that has shown promise as an effective treatment. The current case study examined the use of RF biofeedback in combination with other physiological and evidence-based methods as part of a comprehensive treatment approach. The client showed a significant drop from his initial scores on a screening assessment by the end of treatment, and demonstrated continued progress despite a 3-month break from the therapy. This author proposed that the synergistic effects of the multi-phased treatment approach contributed to the client's progress. Furthermore, a case was made for using multiple techniques when treating subthreshold PTSD and related symptoms within a treatment resistant population.
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2,335,306 |
The Effect of Intravenous Dexmedetomidine Compared to Propofol on Patients Hemodynamics as a Sedative in Brachial Plexus Block: A Comparative Study.
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The quest for an ideal sedative during regional anesthesia is on. Although propofol has been accepted as a sedative intraoperatively, it can be associated with troublesome hemodynamic changes. Dexmedetomidine is a new alpha 2 agonist used widely for sedation.</AbstractText>In this study, we tried to compare equivalent doses of dexmedetomidine infusion with propofol with emphasis on their effect on the hemodynamics.</AbstractText>Prospective, single-blinded randomized controlled trial.</AbstractText>In a single blinded study, 60 American Society of Anesthesiologists (ASA) I and II patients scheduled for forearm surgeries under brachial plexus block were randomized to receive either propofol (Group I) or dexmedetomidine (Group II) infusion. Ultrasound-guided supraclavicular brachial plexus block was given in all the patients. After confirming adequate motor and sensory blockade, they were administered an initial loading dose of the drug over 10 min followed by a maintenance dose till the end of the surgery. The rate of infusion was titrated to maintain Ramsay sedation score of 2-4. Intraoperative hemodynamic and respiratory effects were documented along with surgeon and patient satisfaction. Any adverse effect such as hypotension, bradycardia, nausea, and vomiting was also noted.</AbstractText>The data collected were evaluated using Stata version 10. P</i> < 0.05 was considered statistically significant.</AbstractText>Heart rate decreased significantly in Group II (dexmedetomidine) while mean arterial pressure decreased significantly in Group I (propofol). There was no increase in the incidence of bradycardia or hypotension in either groups. Patient satisfaction score was significantly greater in Group II (dexmedetomidine) while surgeon satisfaction score was similar in both the groups.</AbstractText>Dexmedetomidine at equivalent doses of propofol has a similar hemodynamic and respiratory effect, similar surgeon's satisfaction score, higher patient's satisfaction score, and no significant side effects in ASA I/II patients. Thus, dexmedetomidine may prove to be a valuable alternative to propofol for sedation in patients undergoing upper limb surgeries in brachial plexus block.</AbstractText>
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Analgesic Efficacy of Transverse Abdominal Plane Block after Elective Cesarean Delivery - Bupivacaine with Fentanyl versus Bupivacaine Alone: A Randomized, Double-blind Controlled Clinical Trial.
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The analgesic benefit of transversus abdominis plane (TAP) blocks for cesarean delivery remains controversial. In our study, we compared the analgesic efficacy of TAP block using local anesthetic bupivacaine and adjunct fentanyl with bupivacaine alone in patients undergoing elective cesarean section.</AbstractText>Our study was a randomized, double-blind, controlled clinical trial where sixty patients undergoing elective cesarean delivery under subarachanoid block (2 ml of 0.5% bupivacaine) were randomized into two groups, A and B. At the end of the surgical procedure, bilateral TAP block was performed guided by the ultrasound. Group A received 38 ml of 0.25% bupivacaine and 2 ml of 50 μg of fentanyl, whereas Group B received 38 ml of 0.25% bupivacaine + 2 ml of normal saline. The total volume was divided equally and administered bilaterally. Each patient was assessed for 24 h after TAP block, for time to rescue analgesia, pain using visual analog scale (VAS) score at rest and on movement, hemodynamic parameters (heart rate and blood pressure), nausea, vomiting, and sedation. Diclofenac 75 mg was given as rescue analgesia when the patient complained of pain or when VAS score >4.</AbstractText>Prolonged postoperative analgesia was noticed with both the groups, with a mean time to rescue analgesia of approximately 6.5 h. There was no significant difference in time to rescue analgesia (6.49 ± 0.477 vs. 6.5 ± 0.480) when both the groups were compared among themselves. The pain scores among the two groups when compared did not show any added benefit. Incidence of nausea, vomiting, and sedation when compared between both the groups showed no difference.</AbstractText>The TAP block as a part of a multimodal analgesic regimen definitely has a role in providing superior analgesia in the postoperative period. However, adjunct fentanyl to local anesthetic bupivacaine was found to have no added advantage when quality and duration of analgesia was compared.</AbstractText>
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2,335,308 |
Attenuation of Hemodynamic Response to Skull Pin Head Holder Insertion: Intravenous Clonidine versus Intravenous Lignocaine Infusion.
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Insertion of skull pin induces a significant increase in heart rate (HR), blood pressure (BP) and intracranial pressure. Alpha 2 agonist clonidine and intravenous (i.v.) lignocaine are effective in attenuating stress response. Local infiltration of pin site and scalp block with lignocaine are commonly used techniques for prevention of hemodynamic response to skull pin insertion. We compared the effectiveness of i.v. clonidine infusion and i.v. lignocaine infusion in suppressing the hemodynamic response to skull pin head holder insertion.</AbstractText>Randomized double blind study conducted with sample size - sixty patients, divided into two groups: Group C (n</i> = 30) - clonidine i.v. dose 2 μg/kg; Group L (n</i> = 30) - lignocaine i.v. dose 1.5 mg/kg.</AbstractText>All patients posted for elective craniotomy belonging to American Society of Anesthesiologists (ASA) 1 and 2, age group 18-70 were included in the study. ASA 3, 4; difficult airway; hypertensives; allergy to study drugs; ischemic heart disease; and arteriovenous malformations were excluded. Study drugs were administered 10 min prior to induction in 10 ml syringes with infusion pump over 10 min. Standard anesthesia protocol followed. HR, noninvasive BP, mean arterial pressure (MAP), and IBP were recorded at baseline (BL), after study drug (AD), 1 min after intubation (AI), 1 min prior to pin insertion -pre pin (PP), and 5 min after pin insertion (AP).</AbstractText>Descriptive and inferential statistical analysis - Student's t</i>- and Chi-square/Fisher exact test were used (SAS 9.2, SPSS 15.0) P</i> value described as *moderately significant (P</i> value: 0.01 < P</i> ≤ 0.05) **strongly significant (P</i> value: P</i> ≤ 0.01).</AbstractText>Groups were matched with respect to age (P</i> = 0.7), gender distribution (P</i> = 0.6), and weight (P</i> = 0.67) There was no difference in BL HR in two groups. Significant difference in HR was noted after intubation P</i> < 0.031 and pin insertion P</i> < 0.001 stages with lower HR in Group C (76.03 ± 9.88) versus Group L (98 ± 60.89) MAP recordings showed no statistically significant difference in two groups at BL and after drug administration stages. A significant difference was seen in intubation (P</i> < 0.014), very significant difference (P</i> < 0.001) was noted in pre- and post-pin insertion stages with MAP was lower in Group C (76.03 ± 9.88) versus Group L (87.17 ± 8.90).</AbstractText>i.v. clonidine at dose of 2 μg/kg is a better drug in attenuating hemodynamic response to skull pin head holder insertion than i.v. lignocaine.</AbstractText>
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Comparison of Analgesic Efficacy of Dexmedetomidine and Midazolam as Adjuncts to Lignocaine for Intravenous Regional Anesthesia.
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Intravenous regional anesthesia (IVRA) is safe, technically simple, and cost-effective technique compared to general anesthesia with success rates of 94-98% for upper and lower limb surgeries. The main disadvantage of this procedure is its limited duration for surgery, lack of postoperative analgesia, and tourniquet pain. To overcome this disadvantage, various adjuvants to lignocaine have been studied from time to time.</AbstractText>To compare the analgesic efficacy of dexmedetomidine and midazolam as adjuncts to lignocaine for IVRA for forearm and hand surgeries.</AbstractText>The study was conducted by the Department of Anaesthesia of Medical College and patients posted for elective as well as the emergency forearm and hand surgeries were included in the study. It was a prospective comparative study.</AbstractText>Sixty patients of either sex belonging to the American Society of Anesthesiologists Class I and II, in the age range of 18-65 years, scheduled for upper limb orthopedic surgery, either elective or emergency, were included in the study. All patients were administered IVRA in this prospective, double-blind, randomized study. Patients enrolled in the study were randomly divided into two groups of thirty each. Group M-received 40 ml of 0.5% lignocaine with midazolam 50 μg/kg and Group D-received 40 ml of 0.5% lignocaine with dexmedetomidine 1 μg/kg. Time of onset of sensory block, duration of analgesia, total dose of fentanyl given, intraoperative blood pressure, oxygen saturation, heart rate, postoperative analgesia, and adverse effects were recorded and compared between the groups.</AbstractText>The statistical evaluation was performed using SPSS version 17.0 software. All values were calculated with a 95% confidence interval. The parameters were expressed as mean ± standard deviation and t</i>-test was used for comparing demographic and clinical data. For comparisons, P</i> < 0.05 was considered statistically significant.</AbstractText>Mean duration of analgesia was 93 ± 28 min in dexmedetomidine group and 84 ± 28 min in midazolam group, and onset of sensory block was comparable in both groups.</AbstractText>Dexmedetomidine and midazolam, when used as adjuvants to lignocaine for IVRA, significantly improve the intraoperative conditions by providing superior quality of block. The superiority of one over the other could not be established as midazolam produced the early onset of block and less requirement of fentanyl, whereas dexmedetomidine when added to IVRA provided longer duration of analgesia (93 ± 28 min) in comparison to midazolam (84 ± 28 min).</AbstractText>
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2,335,310 |
[Hemodynamic and respiratory conditions of patients with obstetric fistulae operated under spinal anesthesia at the Regional Reference Hospital in Manakara, Madagascar].
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The objective was to evaluate the hemodynamic and respiratory conditions of patients who had undergone obstetric fistula surgery and to report our experience in the management of these patients. We conducted a descriptive cross-sectional study in the Operating Room and Intensive Care Unit of the Regional Reference Hospital in Manakara from 20 to 30 August 2013. All patients who had undergone obstetric fistula surgery under spinal anesthesia were included in the study. We excluded patients classified as ASA> 2 and those with cardiovascular or respiratory disorders. After pre-anesthetic consultation and preoperative assessments, patients received bupivacaine 12.5 mg with adrenaline 0,5% isobar intrathecal. They were placed in the Trendelenburg position for 5 minutes after the injection of anesthesia and during surgery. Intraoperative sensory level, blood pressure, heart rate, respiratory rate and peripheral capillary oxygen saturation (SpO2) were recorded. 57 patients were retained. The sensory and motor block were excellent in all patients. A metameric level higher than T6 was achieved in 56.36% of patients. Despite a few episodes of hypertension and tachycardia, no patient had respiratory or cardiovascular problems associated with Trendelenburg position. Only sensory level and respiratory rate showed a correlation with Trendelenburg position (p=0,01). This study suggests that Trendelenburg position can be used during spinal anesthesia if an appropriate anesthetic is administered, paying particular attention to changes in position and taking into account the pre-anesthetic examination.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Martinetti</LastName><ForeName>Andrianimaro Florelia</ForeName><Initials>AF</Initials><AffiliationInfo><Affiliation>Service Bloc opératoire- Réanimation, CHRD Moramanga, Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Franklin</LastName><ForeName>Rabenjarison</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Accueil-Triage-Urgences-Réanimation Médicale, Hôpital Joseph Raseta de Befelatanana, CHU Antananarivo Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lalao</LastName><ForeName>Randriamboavonjy Rado</ForeName><Initials>RR</Initials><AffiliationInfo><Affiliation>Faculté de Médecine d'Antananarivo Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Judicael</LastName><ForeName>Harioly Nirina Marie Osé</ForeName><Initials>HN</Initials><AffiliationInfo><Affiliation>Service Bloc opératoire-Réanimation, CHU Toamasina Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yvonne</LastName><ForeName>Rasolonjatovo Tsiorintsoa</ForeName><Initials>RT</Initials><AffiliationInfo><Affiliation>Service Bloc opératoire-Réanimation, Chirurgie maxillo-faciale Befelatanana, CHU, Antananarivo, Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Andriambelo</LastName><ForeName>Rajaonera Tovohery</ForeName><Initials>RT</Initials><AffiliationInfo><Affiliation>Service Réanimation Chirurgicale, Hôpital Joseph Ravoahangy Andrianavalona, CHU Antananarivo, Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nicole</LastName><ForeName>Rakotoarison Ratsaraharimanana Catherine</ForeName><Initials>RR</Initials><AffiliationInfo><Affiliation>Accueil-Triage-Urgences-Réanimation, Hôpital Joseph Ravoahangy Andrianavalona, CHU Antananarivo, Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Enintsoa</LastName><ForeName>Raveloson Nasolotsiry</ForeName><Initials>RN</Initials><AffiliationInfo><Affiliation>Accueil-Triage-Urgences-Réanimation Médicale, Hôpital Joseph Raseta de Befelatanana, CHU Antananarivo Madagascar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Edwige</LastName><ForeName>Ravaomanana</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>UNFPA - Madagascar.</Affiliation></AffiliationInfo></Author></AuthorList><Language>fre</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Etats hémodynamiques et respiratoires des opérées de fistules obstétricales sous rachianesthésie au CHRR Manakara, Madagascar.</VernacularTitle><ArticleDate DateType="Electronic"><Year>2016</Year><Month>11</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>Uganda</Country><MedlineTA>Pan Afr Med J</MedlineTA><NlmUniqueID>101517926</NlmUniqueID></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>S88TT14065</RegistryNumber><NameOfSubstance UI="D010100">Oxygen</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000775" MajorTopicYN="Y">Anesthesia, Spinal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003906" MajorTopicYN="Y">Developing Countries</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018475" MajorTopicYN="N">Head-Down Tilt</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="Y">Hemodynamics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008270" MajorTopicYN="N">Madagascar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007744" MajorTopicYN="N">Obstetric Labor Complications</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010100" MajorTopicYN="N">Oxygen</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056888" MajorTopicYN="N">Patient Positioning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012006" MajorTopicYN="N">Rectovaginal Fistula</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056152" MajorTopicYN="Y">Respiratory Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014719" MajorTopicYN="N">Vesicovaginal Fistula</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="fre">L'objectif était d'évaluer les états hémodynamiques et respiratoires des opérées de fistules obstétricales et rapporter nos expériences sur la prise en charge de ces malades. Il s'agit d'une étude transversale descriptive effectuée au Bloc opératoire et Réanimation du CHRR Manakara allant du 20 au 30 aout 2013. Etaient incluses les patientes opérées de fistules obstétricales sous rachianesthésie. Nous avons exclu les patientes classées ASA >2 et celles ayant des tares cardio-vasculaires ou respiratoires. Après consultations préanesthésiques, et bilans préopératoires, nous avons administré chez les patientes 12,5mg de bupivacaïne adrénalinée 0,5% isobare en intrathécal. Elles étaient mises en position de Trendelenburg 5 minutes après l'injection du produit anesthésique et durant toute l'intervention. Le niveau sensitif, la pression artérielle, la fréquence cardiaque, la fréquence respiratoire et la saturation pulsée en oxygène (SpO2) étaient enregistrés pendant l'intervention. Nous avons retenues 57 malades. Le bloc sensitivomoteur était excellent pour toutes les malades. Un niveau métamérique supérieur à T6 était atteint chez 56,36% des malades. A part quelques épisodes d'hypertension artérielle et tachycardie, nous n'avons trouvé aucune difficulté respiratoire ni cardiovasculaire en rapport avec la position. Seuls, le niveau sensitif et la fréquence respiratoire présentaient une corrélation (p=0,01). Cette étude suggère que la position de Trendelenburg est réalisable au cours de la rachianesthésie en utilisant un produit anesthésique approprié, en faisant attention, notamment aux changements de position et en tenant compte de l'examen préanesthésique.
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Interleukin 6 Inhibition and Coronary Artery Disease in a High-Risk Population: A Prospective Community-Based Clinical Study.
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Atherosclerosis is a chronic inflammatory disease, with interleukin 6 (IL-6) as a major player in inflammation cascade. IL-6 blockade may reduce cardiovascular risk, but current treatments to block IL-6 also induce dyslipidemia, a finding with an uncertain prognosis.</AbstractText>We aimed to determine the endothelial function responses to the IL-6-blocking agent tocilizumab, anti-tumor necrosis factor α, and synthetic disease-modifying antirheumatic drug therapies in patients with rheumatoid arthritis in a 16-week prospective study. Sixty consecutive patients with rheumatoid arthritis were enrolled. Tocilizumab and anti-tumor necrosis factor α therapy were started in 18 patients each while 24 patients were treated with synthetic disease-modifying antirheumatic drugs. Forty patients completed the 16-week follow-up period. The main outcome was flow-mediated dilation percentage variation before and after therapy. In the tocilizumab group, flow-mediated dilation percentage variation increased statistically significantly from a pre-treatment mean of (3.43% [95% CI, 1.28-5.58] to 5.96% [95% CI, 3.95-7.97]; P</i>=0.03). Corresponding changes were 4.78% (95% CI, 2.13-7.42) to 6.75% (95% CI, 4.10-9.39) (P</i>=0.09) and 2.87% (95% CI, -2.17 to 7.91) to 4.84% (95% CI, 2.61-7.07) (P</i>=0.21) in the anti-tumor necrosis factor α and the synthetic disease-modifying antirheumatic drug groups, respectively (both not statistically significant). Total cholesterol increased significantly in the tocilizumab group from 197.5 (95% CI, 177.59-217.36) to 232.3 (201.62-263.09) (P</i>=0.003) and in the synthetic disease-modifying antirheumatic drug group from 185.8 (95% CI, 169.76-201.81) to 202.8 (95% CI, 176.81-228.76) (P</i>=0.04), but not in the anti-tumor necrosis factor α group. High-density lipoprotein did not change significantly in any group.</AbstractText>Endothelial function is improved by tocilizumab in a high-risk population, even as it increases total cholesterol and low-density lipoprotein levels.</AbstractText>© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.</CopyrightInformation>
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Effects on QTc Interval of 2 Different Doses of Spinal Anesthesia in Inguinal Hernia Operations.
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BACKGROUND Cardiac arrhythmia is a significant cause of morbidity and mortality. In this study, through examination of the effects on the QTc interval of different doses of hyperbaric bupivacaine, we investigated the relationship with arrhythmia. MATERIAL AND METHODS A total of 60 patients were separated into 2 groups: spinal block was applied with 10 mg bupivacaine to Group S1 and with 15 mg to Group S2. The mean arterial pressure (MAP) and heart rate (HR) values were recorded before the spinal block and at 5 and 30 min after the block and at 60 min postoperatively. By recording the time of the spinal sensory block to reach T10 dermatome (Anaesth T) and the duration of the surgical procedure (Surg T.), the QTc intervals were calculated. RESULTS The demographic data were similar in both groups. A statistically significant difference was determined between the S1 and S2 groups between the baseline and the 30 mins after spinal block QTc intervals (p=0.001). No statistically significant difference in HR values was determined between the groups at baseline, 5 min after spinal block, and 1 h after surgery (all p>0.05), but at 30 min after spinal block value there was a statistically significant difference (p=0.010). No statistically significant difference was determined in MAP values between the groups at baseline and 1 h after surgery (p>0.05). CONCLUSIONS The QTc interval lengthened in a dose-dependent manner after spinal anesthesia was applied with different doses of bupivacaine, but the doses used did not cause any severe arrhythmia.
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2,335,313 |
[Deep versus moderate neuromuscular block during one-lung ventilation in lung resection surgery].
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Neuromuscular relaxants are essential during general anesthesia for several procedures. Classical anesthesiology literature indicates that the use of neuromuscular blockade in thoracic surgery may be deleterious in patients in lateral decubitus position in one-lung ventilation. The primary objective of our study was to compare respiratory function according to the degree of patient neuromuscular relaxation. Secondary, we wanted to check that neuromuscular blockade during one-lung ventilation is not deleterious.</AbstractText>A prospective, longitudinal observational study was made in which each patient served as both treated subject and control. 76 consecutive patients programmed for lung resection surgery in Gregorio Marañon Hospital along the year of 2013 who required one-lung ventilation in lateral decubitus were included. Ventilator data, hemodynamic parameters were registered in different moments according to train-of-four response (intense, deep and moderate blockade) during one-lung ventilation.</AbstractText>Peak, plateau and mean pressures were significantly lower during the intense and deep blockade. Besides, compliance and peripheral oxygen saturation were significantly higher in those moments. Heart rate was significantly higher during deep blockade. No mechanical ventilation parameters were modified during measurements.</AbstractText>Deep neuromuscular blockade attenuates the poor lung mechanics observed during one-lung ventilation.</AbstractText>Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.</CopyrightInformation>
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Dexmedetomidine sedation combined with caudal anesthesia for lower abdominal and extremity surgery in ex-preterm and full-term infants.
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Awake caudal anesthesia is a potentially attractive option, because the administration of general anesthesia is associated with a high rate of respiratory complications and hemodynamic disturbances and potential neurotoxic effects. To facilitate the caudal puncture and subsequent surgical intervention, additional sedatives are commonly administered.</AbstractText>We aimed to establish a new, safe, and effective anesthetic procedure for very young children with comorbidities.</AbstractText>We retrospectively analyzed 23 children who underwent lower abdominal or lower extremity surgery with dexmedetomidine sedation and caudal anesthesia from January 2015 to August 2015. Dexmedetomidine was initiated with a total bolus infusion of 0.7-1.1 μg·kg-1</sup> followed by a continuous infusion of 1 μg·kg-1</sup> ·h-1</sup> . Bupivacaine (2.5 mg·kg-1</sup> ) was supplemented with 5-10 μg·kg-1</sup> epinephrine to strengthen and prolong motor block. According to maturity at birth, two groups were defined: ex-preterm and full-term infants.</AbstractText>There were 12 ex-preterm and 10 full-term infants available for analysis. The median postmenstrual age was 44 (38-52) weeks in ex-preterm and 46.5 (40-72) weeks in full-term infants. Without any additional intervention, surgery was successfully accomplished in 82% of all cases. While respiratory complications were not a problem, hemodynamic disturbances commonly occurred. Maximum decreases in heart rate (HR) of 30% were accompanied by maximum decreases in mean arterial pressure (MAP) of 38%. No infant had a heart rate below 100 bpm. MAP declined in one ex-preterm infant to a minimum value of 32 mmHg.</AbstractText>Caudal anesthesia combined with dexmedetomidine sedation is an effective anesthetic technique for lower abdominal and extremity surgery in ex-preterm and full-term infants with severe comorbidities.</AbstractText>© 2017 John Wiley & Sons Ltd.</CopyrightInformation>
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The Effect of Unilateral Spinal Anaesthesia and Psoas Compartment with Sciatic Block on the Postoperative Pain Management in Total Knee Artroplastic Surgery.
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<i>Purpose</i>. This study was designed to investigate the effects of peripheral nerve block methods, applied through unilateral spinal anaesthesia on elderly patients to undergo total knee arthroplasty, on perioperative hemodynamic parameters and postoperative analgesia period. <i>Materials and Method</i>. 60 patients were randomly divided into two groups in the study. In group USA spinal anaesthesia was performed. In group PCS it was applied on psoas compartment block and sciatic nerve block. <i>Results</i>. Significantly higher intraoperative 60th and 90th minute mean arterial pressure values were ascertained in the PCS group compared to the USA group. The decrease observed in the 5th, 10th, and 20th minute MAP values in the USA group was statistically significant according to the control MAP value. Concerning within group comparisons, the decrease in 5th, 10th, and 20th minute heart rate values in the USA group was statistically significant compared with the control measurement value. The mean beginning time of sensory and motor blocks in the PCS group was found to be at a significantly advanced level compared with that in the USA group. <i>Conclusions</i>. The PCS block technique using bupivacaine hydrochloride ensured a higher haemodynamic efficiency in the perioperative period in high-risk elderly patients undergoing total knee arthroplasty. This trial is registered with ClinicalTrials.gov Identifier: NCT03021421.
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2,335,316 |
Promoting Recruitment using Information Management Efficiently (PRIME): statistical analysis plan for a stepped wedge cluster randomised trial within the REstart or STop Antithrombotics Randomised Trial (RESTART).
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Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped wedge, cluster randomised trial-within-a-trial of a complex intervention to help sites in the United Kingdom to attain their own target number of participants to recruit to the REstart or STop Antithrombotics Randomised Trial (RESTART, ISRCTN71907627).</AbstractText>Seventy-two hospital sites had opted into PRIME and were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location) to one of 12 months in which a complex intervention would be delivered. All sites began in the control state. The primary outcome is the total number of patients randomised into RESTART per month per site, which will be analysed in a negative binomial generalised linear mixed model. Secondary outcomes include the proportion of sites using stroke databases to identify potentially eligible patients before PRIME, frequency of using bespoke stroke audit data exports during PRIME, barriers to recruitment in PRIME, barriers to using the bespoke stroke audit data exports, and disadvantages of the bespoke stroke audit exports identified by PRIME sites. PRIME began in September 2015. The last intervention will be delivered in August 2016. Six-month follow-up will be complete in February 2017. This statistical analysis plan was written and submitted for publication before all sites received the PRIME intervention and before outcome data were known.</AbstractText>Final results of PRIME will be analysed and disseminated in 2017.</AbstractText>Northern Ireland Hub for Trials Methodology Research SWAT repository (SWAT22).</AbstractText>
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2,335,317 |
Combined use of dexmedetomidine and propofol in monitored anesthesia care: a randomized controlled study.
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Although propofol and dexmedetomidine have been widely used for monitored anesthesia care, their adverse effects necessitate the search for better methods. Therefore, we performed this randomized controlled trial to evaluate the combined use of propofol and dexmedetomidine.</AbstractText>Eighty-seven adult patients undergoing hand surgery under brachial plexus block were randomly allocated to receive 1.6 μg/ml of the target effect site concentration of propofol (P group) and infusion of 0.4 μg/kg/h dexmedetomidine following a loading dose of 1.0 μg/kg for 10 min (D group). The M group received a half-dose of both drugs simultaneously. The maintenance dose was adjusted to maintain an Observer Assessment of Alertness/Sedation score of 3. Cardiorespiratory variables, adverse effects, and drug efficacy were observed.</AbstractText>The significantly higher mean arterial pressure (mmHg) in the D group [P group 86.9 (12.6), D group 96.0 (12.2), M group 85.6 (10.6), p = 0.004)] and a significantly higher heart rate (beat/min) in the P group were observed [P group 67.3 (9.0), D group 57.8 (6.9), M group 59.2 (7.4), p < 0.001)]. The M group had a significant lower incidence of airway obstruction (p < 0.001) and the D group had a higher incidence of bradycardia requiring atropine (p = 0.001). The P group had higher incidences of hypoxia (p = 0.001), spontaneous movement (p < 0.001) and agitation (p = 0.001). The satisfaction scores of the patients (p = 0.007) and surgeon (p < 0.001) were higher in the M group. Onset time was significantly longer in the D group (p < 0.001).</AbstractText>The combined use of propofol and dexmedetomidine provided cardiovascular stability with decreased adverse effects. Additionally, it led to a similar onset time of propofol and achieved higher satisfaction scores.</AbstractText>KCT0001284 . Retrospectively registered 25 November 2014.</AbstractText>
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2,335,318 |
Promoting Recruitment using Information Management Efficiently (PRIME): study protocol for a stepped-wedge cluster randomised controlled trial within the REstart or STop Antithrombotics Randomised Trial (RESTART).
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Research into methods to boost recruitment has been identified as the highest priority for randomised controlled trial (RCT) methodological research in the United Kingdom. Slow recruitment delays the delivery of research and inflates costs. Using electronic patient records has been shown to boost recruitment to ongoing RCTs in primary care by identifying potentially eligible participants, but this approach remains relatively unexplored in secondary care, and for stroke in particular.</AbstractText><AbstractText Label="METHODS/DESIGN">The REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) is an ongoing RCT of secondary prevention after stroke due to intracerebral haemorrhage. Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped-wedge cluster randomised trial of a complex intervention to help RESTART sites increase their recruitment and attain their own target numbers of participants. Seventy-two hospital sites that were located in England, Wales or Scotland and were active in RESTART in June 2015 opted into PRIME. Sites were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location in Scotland vs. England/Wales) to one of 12 months in which the intervention would be delivered. All sites began in the control state. The intervention was delivered by a recruitment co-ordinator via a teleconference with each site. The intervention involved discussing recruitment strategies, providing software for each site to extract from their own stroke audit data lists of patients who were potentially eligible for RESTART, and a second teleconference to review progress 6 months later. The recruitment co-ordinator was blinded to the timing of the intervention until 2 months before it was due at a site. Staff at RESTART sites were blinded to the nature and timing of the intervention. The primary outcome is the total number of patients randomised into RESTART per month per site and will be analysed in a negative binomial generalised linear mixed model. PRIME began in September 2015. The last intervention was delivered in August 2016. Six-month follow-up will be complete in February 2017.</AbstractText>The final results of PRIME will be analysed and disseminated in 2017.</AbstractText>The PRIME study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial (SWAT) repository (SWAT22) on 23 December 2015.</AbstractText>
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Effects of three methadone doses combined with acepromazine on sedation and some cardiopulmonary variables in dogs.
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To evaluate the sedative and cardiopulmonary effects of three methadone doses, combined with acepromazine, in dogs.</AbstractText>Prospective, randomized, complete block study.</AbstractText>Six healthy, adult, cross-bred dogs weighing 17.2±4.4 kg (mean±standard deviation).</AbstractText>Each dog was administered four treatments: acepromazine (0.05 mg kg-1</sup>) alone or acepromazine (same dose) in combination with methadone (0.25, 0.50 or 0.75 mg kg-1</sup>). All drugs were administered intramuscularly. Sedation was scored by a numeric descriptive scale (NDS, range 0-3) and a simple numerical scale (SNS, range 0-10). Heart rate, invasive blood pressure, arterial blood gases and rectal temperature were measured at 15 to 30 minute intervals for 120 minutes.</AbstractText>According to NDS scores, mild to moderate sedation (NDS=1-2) was observed in most dogs in the acepromazine treatment, with only one out of six dogs scored as exhibiting intense sedation (NDS=3). All treatments with methadone resulted in significantly higher SNS scores compared with acepromazine alone. In these treatments, most dogs exhibited intense sedation (NDS=3). Increasing the dose of methadone from 0.25 to 0.50 or 0.75 mg kg-1</sup> prolonged sedation in a dose-related manner, but did not influence the degree of sedation. The main adverse effects following administration of acepromazine-methadone treatments were decreased blood pressure, mild respiratory acidosis and decreased rectal temperature. These effects were well tolerated and resolved without treatment.</AbstractText>In this study in six dogs, acepromazine-methadone administration resulted in intense sedation in most dogs. The results are interpreted to indicate that a low dose of methadone (0.25 mg kg-1</sup>) administered in combination with acepromazine (0.05 mg kg-1</sup>) will induce short-term sedation in dogs, whereas higher doses of methadone should be administered when prolonged sedation is desired.</AbstractText>Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,320 |
Prevalence of resting-ECG abnormalities in systemic lupus erythematosus: a single-center experience.
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Cardiovascular complications are a major cause of morbidity and even mortality among systemic lupus erythematosus (SLE) patients. Whether cardiac arrhythmias contribute to this burden among SLE patients, however, is not currently known. The goal of this study was to determine the prevalence of cardiac conduction abnormalities among SLE patients from a single center. We retrospectively reviewed the medical records of SLE patients who had 12-lead electrocardiograms (ECGs) available from various settings at a single academic center over the period of 10 years. In addition, ICD-9 codes for arrhythmias were obtained for the SLE patients whose ECGs were reviewed. The hospital setting (in-patient, out-patient, emergency department) and the indication for obtaining the ECG were evaluated. Two hundred thirty-five SLE patients had available ECGs. Sinus tachycardia was most common (18%). With direct ECG review, tachyarrhythmias were found in 6% of SLE patients, with the most common being atrial fibrillation (3%). Atrial fibrillation was seen even more frequently (9%) when ICD-9 codes were reviewed. No patients had brady-arrhythmias. QT prolongation was present in 17% of patients upon direct ECG review. More ECGs with tachyarrhythmias and QT prolongation were found among inpatients, with preoperative evaluation and gastrointestinal symptoms being the most common indications. Sinus tachycardia was the most common finding seen among our SLE patients with ECGs. Further study into the possible mechanisms behind this is warranted, including the possibility of autonomic nervous system involvement in SLE.
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2,335,321 |
Dexmedetomidine decreases the required amount of bupivacaine for ultrasound-guided transversus abdominis plane block in pediatrics patients: a randomized study.
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The effect of dexmedetomidine on the potency of bupivacaine for transversus abdominis plane (TAP) block in pediatric patients has not been investigated.</AbstractText>The primary objective of this study was to assess the effectiveness of dexmedetomidine to decrease the concentration of bupivacaine needed for analgesia for ultrasound-guided TAP block in a pediatric patient undergoing hernia repair or hydrocelectomy.</AbstractText>This is a randomized, double-blind, up-down, dose-finding study.</AbstractText>Operating room.</AbstractText>Sixty American Society of Anesthesiologists I and II patients aged 1-4 years scheduled for elective unilateral herniorrhaphy or hydrocelectomy.</AbstractText>Patients were randomly assigned to 1 of the 2 groups: group B (0.125% bupivacaine, 1mL/kg) TAP block or group BD (0.125% bupivacaine plus 2μg/kg dexmedetomidine, 1mL/kg) TAP block.</AbstractText>The response of each child was observed for 60 seconds after skin incision and evaluated as 'unsuccessful' when skin incision caused a change in hemodynamic parameters (heart rate and mean blood pressure) 20% more than the preincision values. If the response was determined to be unsuccessful, the concentration of bupivacaine administrated to the next patient was increased by 0.02%. If it was successful, the concentration of bupivacaine administrated to the next patient was decreased by 0.02%.</AbstractText>The minimum local anesthetic concentration of bupivacaine was 0.0839% (0.0137) in the B group and 0.0550% (0.0169) in the BD group. The difference was statistically significant (t=7.165, P=.0001). The total postoperative analgesic dosage of morphine was significantly higher in the B group (0.17±0.04 mg/kg) than the BD group (0.11±0.02 mg/kg, P=.001).</AbstractText>The addition of 2μg/kg of dexmedetomidine reduced the minimum local anesthetic concentration of bupivacaine used for a TAP block and improved postoperative analgesia in children undergoing surgery for inguinal hernia repair or hydrocelectomy.</AbstractText>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,322 |
Use of test dose allows early detection of subdural local anesthetic injection with lumbar plexus block.
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A 56year-old woman underwent a lumbar plexus block for a revision of a left total hip arthroplasty. During the block procedure, the needle was advanced over the transverse process and isolated quadriceps twitches were elicited. After administering a test dose of 3ml of 1.5% lidocaine, the patient developed loss of sensation in the L3-4 dermatomal distribution that progressed caudally to involve both legs followed by inability to move the left leg. The patient shortly thereafter became hypotensive and sensory block spread cephalad and peaked at C7 bilaterally suggesting possible subdural spread of local anesthetic. The patient was resuscitated with normalization of blood pressure and eventually had full resolution of motor and sensory block. Subdural spread of local anesthetic is a potential complication of lumbar plexus block related perhaps to injection of local anesthetic near dural sleeves of nerve roots. The use of a test dose allows early recognition of subdural injection and may limit consequences of inadvertent subdural spread of local anesthetic.
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2,335,323 |
Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication.
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Picornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi membrane vesicular and lipid transport, we hypothesized that PKD played a role in viral replication. We present multiple lines of evidence in support of this hypothesis. First, infection of HeLa cells with human rhinovirus (HRV) induced the phosphorylation of PKD. Second, PKD inhibitors reduced HRV genome replication, protein expression, and titers in a concentration-dependent fashion and also blocked the replication of poliovirus (PV) and foot-and-mouth disease virus (FMDV) in a variety of cells. Third, HRV replication was significantly reduced in HeLa cells overexpressing wild-type and mutant forms of PKD1. Fourth, HRV genome replication was reduced in HAP1 cells in which the PKD1 gene was knocked out by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Although we have not identified the molecular mechanism through which PKD regulates viral replication, our data suggest that this is not due to enhanced interferon signaling or an inhibition of clathrin-mediated endocytosis, and PKD inhibitors do not need to be present during viral uptake. Our data show for the first time that targeting PKD with small molecules can inhibit the replication of HRV, PV, and FMDV, and therefore, PKD may represent a novel antiviral target for drug discovery.<b>IMPORTANCE</b> Picornaviruses remain an important family of human and animal pathogens for which we have a very limited arsenal of antiviral agents. HRV is the causative agent of the common cold, which in itself is a relatively trivial infection; however, in asthma and chronic obstructive pulmonary disease (COPD) patients, this virus is a major cause of exacerbations resulting in an increased use of medication, worsening symptoms, and, frequently, hospital admission. Thus, HRV represents a substantial health care and economic burden for which there are no approved therapies. We sought to identify a novel host target as a potential anti-HRV therapy. HRV infection induces the phosphorylation of PKD, and inhibitors of this kinase effectively block HRV replication at an early stage of the viral life cycle. Moreover, PKD inhibitors also block PV and FMDV replication. This is the first description that PKD may represent a target for antiviral drug discovery.
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2,335,324 |
Cardiorenal syndrome type 4: A study of cardiovascular diseases in chronic kidney disease.
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The heart and the kidneys are tightly interlinked with each other. So, primary disorder of one of these organs often results in the secondary dysfunction of other. Such interactions play a vital role in the pathogenesis of a clinical entity called cardio-renal syndrome (CRS). CRS type 4 refers to the development of cardiac failure in the patients with CKD.</AbstractText>To study the prevalence of various cardiac diseases in the patients with CKD and risk factors for it.</AbstractText>Eighty patients with CKD who were being treated at KIMS, Hubli, from 1st January 2015 to 30th June 2015 were selected. Clinical evaluation and relevant investigations including echocardiography were done.</AbstractText>Mean age of study population was 43.50±14.53 years. Heart failure with reduced ejection fraction (HFrEF) and Heart Failure with preserved ejection fraction (HFpEF) were present in 21 (26.25%) and 59 (73.75%) respectively. Left ventricular (LV) hypertrophy was present in 55(68.75%). Thus, the prevalence of CRS type 4 was 61 (76.25%). Pericardial effusion was present in 12 (15%). Complete heart block was present in 2 (2.5%). Pulmonary hypertension (PH) was present in 35 (43.75%). Mean central venous pressure (CVP) and interdialysis fluid retention were significantly greater among those with LV failure, compared to those without LV failure (p=0.0002, p=0.025 respectively). Mean hemoglobin was significantly lower among patients with LV failure, compared to those without LV failure (p=0.032).</AbstractText>The prevalence of cardiorenal syndrome type 4 is substantially high in patients with CKD and carries adverse outcome in relation to patient management.</AbstractText>Copyright © 2016. Published by Elsevier B.V.</CopyrightInformation>
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2,335,325 |
Evaluation of the effect of an offset implant configuration in the posterior maxilla with external hexagon implant platform: A 3-dimensional finite element analysis.
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Slight offset of the central implant in 3-unit implant-supported prostheses has been reported to improve biomechanical behavior. However, studies that assessed the effects of an offset implant configuration in the posterior maxilla are scarce.</AbstractText>The purpose of this 3-dimensional (3D) finite element analysis was to assess the effects of splinting in 3-unit implant-supported prostheses with varying implant positions (straight-line or offset configuration) in terms of the stress/strain distribution on bone tissue and the stress distribution on abutment screws.</AbstractText>Three 3D models were used to simulate a posterior maxilla bone block (type IV): straight-line implants supporting single crowns (model M1), straight-line implants supporting 3-unit splinted fixed dental prosthesis (model M2), and an offset implant configuration supporting 3-unit splinted fixed dental prosthesis (model M3). The applied forces were 400 N axially and 200 N obliquely. The type of implant platform simulated was an external hexagon. von Mises stress on the abutment screws was measured, and the maximum principal stress and microstrain values were used to perform cortical bone tissue analysis. Analysis of variance (ANOVA) and the Tukey honest significant differences post hoc test were used to determine the significance of the results and interactions among the main variables (α=.05).</AbstractText>In all models, oblique load increased the stress on abutment screws and bone tissue and the microstrain on bone tissue. Model M3 decreased the stress concentration on the abutment screws and bone tissue. With regard to microstrain distribution, model M3 had the smallest values, and M1 and M2 had similar values.</AbstractText>Splinting associated with an offset implant configuration was effective for decreasing the stress on abutment screws and bone tissue and the microstrain on bone tissue.</AbstractText>Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,326 |
Bioelectronic neuromodulation of the paravertebral cardiac efferent sympathetic outflow and its effect on ventricular electrical indices.
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Neuromodulation of the paravertebral ganglia by using symmetric voltage controlled kilohertz frequency alternating current (KHFAC) has the potential to be a reversible alternative to surgical intervention in patients with refractory ventricular arrhythmias. KHFAC creates scalable focal inhibition of action potential conduction.</AbstractText>The purpose of this article was to evaluate the efficacy of KHFAC when applied to the T1-T2 paravertebral chain to mitigate sympathetic outflow to the heart.</AbstractText>In anesthetized, vagotomized, porcine subjects, the heart was exposed via a midline sternotomy along with paravertebral chain ganglia. The T3 paravertebral ganglion was electrically stimulated, and activation recovery intervals (ARIs) were obtained from a 56-electrode sock placed over both ventricles. A bipolar Ag electrode was wrapped around the paravertebral chain between T1 and T2 and connected to a symmetric voltage controlled KHFAC generator. A comparison of cardiac indices during T3 stimulation conditions, with and without KHFAC, provided a measure of block efficacy.</AbstractText>Right-sided T3 stimulation (at 4 Hz) was titrated to produce reproducible ARI changes from baseline (52 ± 30 ms). KHFAC resulted in a 67% mitigation of T3 electrical stimulation effects on ARI (18.5 ± 22 ms; P < .005). T3 stimulation repeated after KHFAC produced equivalent ARI changes as control. KHFAC evoked a transient functional sympathoexcitation at onset that was inversely related to frequency and directly related to intensity. The optimum block threshold was 15 kHz and 15 V.</AbstractText>KHFAC applied to nexus (convergence) points of the cardiac nervous system produces a graded and reversible block of underlying axons. As such, KHFAC has the therapeutic potential for on-demand and reversible mitigation of sympathoexcitation.</AbstractText>Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,327 |
Effects of Rapid Vaccine Injection Without Aspiration and Applying Manual Pressure Before Vaccination on Pain and Crying Time in Infants.
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To compare effects of rapid injection without aspiration and 10-second manual pressure before injection on pain severity and crying time in 4- to 6-month-old infants given the vaccine DTaP/IPV/Hib.</AbstractText>This is a randomized double-blind controlled study. The study population included all the infants presenting for DTaP/IPV/Hib to two family health centers between April and August in 2015. The study sample included 128 infants based on confidence interval of 95% and statistical power of 80%. The sample was divided into four groups: manual pressure, rapid injection without aspiration, manual pressure combined with rapid injection without aspiration, and control groups. There were 32 infants in each group. Gender was adjusted in all groups. Stratified and block randomizations were used.</AbstractText>Pain severity scores and crying time during and after the injections were significantly lower in the three intervention groups than in the control group (p = .001). The lowest increase in the mean heart rate during and after the injections occurred in the rapid injection without aspiration group (p < .05). In addition, the mean oxygen saturation before, during and after the injections was significantly lower in this group than in the other groups (p < .05). However, two infants in the rapid injection without aspiration group had low oxygen saturation levels starting before the injections. In fact, mean oxygen saturations did not change across time. This suggests that lower oxygen saturation in the rapid injection without aspiration group cannot be due to vaccines or the techniques used.</AbstractText>Manual pressure and rapid injection without aspiration are effective and useful in relief of pain and reduction of crying time due to vaccine injections in 4- to 6-month-old infants.</AbstractText>© 2017 Sigma Theta Tau International.</CopyrightInformation>
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2,335,328 |
Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates.
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Nonalcoholic steatohepatitis (NASH) is a progressive disease that is often accompanied by metabolic syndrome and poses a high risk of severe liver damage. However, no effective pharmacological treatment is currently available for NASH. Here we report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. We provide mechanistic evidence that CFLAR directly targets the kinase MAP3K5 (also known as ASK1) and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8 (also known as JNK1). Furthermore, we identified a small peptide segment in CFLAR that effectively attenuates the progression of steatohepatitis and metabolic disorders in both mice and monkeys by disrupting the N-terminus-mediated dimerization of ASK1 when the peptide is expressed from an injected adenovirus-associated virus 8-based vector. Taken together, these findings establish CFLAR as a key suppressor of steatohepatitis and indicate that the development of CFLAR-peptide-mimicking drugs and the screening of small-molecular inhibitors that specifically block ASK1 dimerization are new and feasible approaches for NASH treatment.
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2,335,329 |
Effects of avoiding neuromuscular blocking agents during maintenance of anaesthesia on recovery characteristics in patients undergoing craniotomy for supratentorial lesions: A randomised controlled study.
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Neuromuscular blocking agents have been one of the cornerstones of anaesthesia. With the advent of newer surgical, anaesthetic and neurological monitoring techniques, their utility in neuroanaesthesia practice seems dispensable. The aim of this prospective, comparative, randomised study was to determine whether neuromuscular blocking agents are required in patients undergoing supratentorial surgery when balanced anaesthesia with desflurane, dexmedetomidine and scalp block is used.</AbstractText>Sixty patients with the American Society of Anesthesiologists physical status I or II, aged between 18 and 60 years were included in the study. All patients received anaesthesia including desflurane, dexmedetomidine and scalp block. The patients were randomly allocated to receive no neuromuscular blocking agent (Group A) or atracurium infusion to keep train-of-four count 2 (Group B). The two groups were compared with respect to haemodynamic stability, brain relaxation scores and recovery characteristics. Haemodynamic parameters and time taken to achieve Aldrete score >9 and other secondary outcomes were analysed using Student's t</i>-test. Non-parametric data were analysed using the Mann-Whitney test.</AbstractText>The mean arterial pressure was comparable between the groups. The intraoperative heart rate was comparable; however, in the post-operative period, it remained higher in Group B for 30 min after extubation (P</i> = 0.02). The brain relaxation scores were comparable among the two groups (P</i> = 0.27). Tracheal extubation time, time taken for orientation and time required to reach Aldrete score ≥9 were comparable among the two groups.</AbstractText>The present study suggests that balanced anaesthesia using desflurane, dexmedetomidine and scalp block can preclude the use of neuromuscular blocking agents in patients undergoing supratentorial surgery under intense haemodynamic monitoring.</AbstractText>
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2,335,330 |
Neonatal lupus: Follow-up in infants with anti-SSA/Ro antibodies and review of the literature.
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Neonatal Lupus Syndrome (NLS) is a distinct clinical entity caused by transplacental passage of maternal anti-SSA/Ro antibodies (Ab). Mothers may have systemic lupus erythematosus, Sjögren syndrome, or other connective tissue disease, or may be completely healthy at the time of giving birth. NLS includes several clinical manifestations: complete congenital heart block (CCHB) and cutaneous lupus are the most common, while hepatobiliary disease, hematological manifestations and central nervous system involvement may occur. Data from literature on the incidence of the different clinical manifestations of NLS are difficult to compare because they come mostly from retrospective studies or prospective studies, but up to date no systematic follow-up was carried out. We performed a large prospective single-center study with a systematic clinical and instrumental follow-up until 9months of life, in order to evaluate the incidence and the clinical impact of NLS features. From 2004 to 2014 all infants born in our center to mothers with anti-SSA/Ro Ab were enrolled in a specific diagnostic and follow-up (FU) program. At birth, 50 infants born to mothers with anti-SSA/Ro Ab were found positive for anti-SSA/Ro Ab. Infants were tested for anti SSA/Ro Ab at 3months of life, if positive they were re-tested at 6 and 9months. At 9months anti-SSA/Ro Ab were positive in 10% of children. In two cases (4%) a CCHB was identified during pregnancy and required pacemaker implantation at birth. In 10% of cases a transient ECG alterations was found during follow-up. Hematological NLS features (anemia, neutropenia, thrombocytopenia) were found at birth and during FU in several patients, in all cases without clinical manifestations and in most cases with complete normalization at 9months. Mild and transient elevation of aminotransferases between 3 and 6months of life were found in 56% and 40% of patient, respectively; non-specific ultrasound cerebral anomalies in absence of clinical neurological signs were found at birth in 9 patients (18%), subsequently normalized. Prenatal maternal screening is of primary importance in order to early detect CCHB, which requires maternal treatment and pacemaker implantation at birth. Infants born to mothers with anti-SSA/Ro Ab should be monitored for all NLS features at birth. However, during the first months of life, these infants seem to develop only mild, transient and self-limited clinical manifestations, which in most cases are completely solved at 9months of life. This consideration, together with the evidence that only 10% of infants had anti-SSA/Ro Ab persistent in blood at 9months, suggests that follow-up of these children can be performed until 6-9months of life with good clinical safety. Moreover, a clinical and laboratory monitoring at 3months of life, when the highest incidence of hematological features and liver tests alterations are observed, is strongly recommended. In the future, it would be clarified if a follow-up until adulthood would be indicated in cases with persistent anti SSA/Ro or in all infants born to mother with anti SSA/Ro.
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2,335,331 |
A Randomized Controlled Study of 0.5% Bupivacaine, 0.5% Ropivacaine and 0.75% Ropivacaine for Supraclavicular Brachial Plexus Block.
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For any surgery in the upper extremity that does not involve the shoulder, a supraclavicular block is preferred, as it is a safe procedure associated with rapid onset and reliable anaesthesia. Although ropivacaine has been extensively studied for epidural anaesthesia, very few reports exist on its use in supraclavicular brachial plexus block.</AbstractText>This study was conducted to investigate and compare the effectiveness of supraclavicular brachial plexus anaesthesia with two different concentrations of ropivacaine (0.5% and 0.75%) and to compare them with the standard 0.5% bupivacaine.</AbstractText>Ninety patients of age 18 to 60 years belonging to American Society of Anaesthesiologists (ASA) status 1 or 2, admitted to Pondicherry Institute of Medical Sciences were chosen for the study and were divided into three groups. Group A received 30 ml of 0.5% bupivacaine, group B received 30 ml of 0.5% ropivacaine and group C received 30 ml of 0.75% ropivacaine into the supraclavicular region, by a nerve-stimulator technique. Onset time of each of the drug was recorded both for the sensory and motor block. Duration of sensory and motor block was recorded along with peri-operative haemodynamic monitoring.</AbstractText>The onset of complete sensory and motor block observed with both ropivacaine groups and bupivacaine was similar (16.85±6.67 min in group A, 17.79±5.03 min in group B and 18.48±6.14 in group C, p>0.05); onset of motor block (21.45±4.45 min in group A, 22.23±4.05 min in group B and 22.33±5.17 in group C, p < 0.05). The duration of sensory block with 0.5% bupivacaine was 11.58 hours, with 0.5% ropivacaine was 9.02 hours with 0.75% ropivacaine was 8.87 hours (p<0.001). The duration of motor block with 0.5% bupivacaine was 12.94 hours, with 0.5% ropivacaine was 8.29 hours with 0.75% ropivacaine was 7.89 hours (p<0.001). Multiple comparison test with Bonferroni correction showed there was statistically significant difference in mean duration of sensory block between Group A (0.5% bupivacaine) and Group B (0.5% ropivacaine) and also between Group A (0.5% bupivacaine) and Group C (0.75% ropivacaine). However, there were no statistically significant difference in mean duration of sensory block between Group B (0.5% ropivacaine) and Group C (0.75% ropivacaine). The preoperative, intra operative and postoperative heart rate, systolic & diastolic blood pressure and oxygen saturation were comparable among the three study groups (p>0.05). No side effects were recorded in the study.</AbstractText>The onset of sensory and motor block was similar in all the three groups. However, when compared to bupivacaine group, recovery of motor functions was faster in both the ropivacaine groups. Patients in all the 3 groups did not experience any adverse effects.</AbstractText>
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Acute Presentation of Juvenile Dermatomyositis with Subclinical Cardiac Involvement: A Rare Case.
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Cardiac involvements are common in patients with Dermatomyositis, most of which are not severe enough to present definite or readily observable symptoms. However, Cardiovascular (CVS) manifestations constitute a major cause of death in these patients. The most frequently reported clinically evident of CVS manifestations in-patient of dermatomyositis are Congestive Heart Failure (CHF), conduction aberrations, that may predispose to complete heart block and coronary artery disease. The principal pathophysiological mechanisms that may produce these cardiac manifestations involve coronary artery disease as well as small vessels vasculitis of the myocardium. Our case of a seven-year-old boy represent a unique manifestation of prolong PR interval with no overt clinical manifestation and who responded well to immunosuppressive treatment. His clinical, laboratory and investigative features of Juvenile Dermatomyositis (JDM) is presented here. It is hoped that this case will heighten the index of suspicion of cardiac condition in patients with JDM among medical practitioners.
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Cervical plexus anesthesia versus general anesthesia for anterior cervical discectomy and fusion surgery: A randomized clinical trial.
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Both general anesthesia (GA) and cervical plexus anesthesia (CPA) can be used for anterior cervical discectomy and fusion (ACDF) surgery. The aim of this study was to evaluate the influence of anesthetic techniques on perioperative mortality and morbidity in patients undergoing cervical surgery.From January 2008 to December 2015, 356 patients who underwent 1-level ACDF for cervical spinal myelopathy were prospectively reviewed. They were assigned to receive GA (group A) and CPA (group B). The analgesic efficacy of the block was assessed by anesthesia preparation time, the maximum heart rate, and mean arterial blood pressure changes compared with the baseline, time of postoperative revival, and duration of recovery stay. Duration of surgery, blood loss, and anesthesia medical cost were also recorded. Numerical rating scale (NRS) was used to evaluate pain at different time points. Postoperative nausea and vomiting (PONV) was assessed, and postoperative average administered dosages of meperidine and metoclopramide were also recorded. The spinal surgeon satisfaction, anesthetist satisfaction, and patient satisfaction were assessed.Both the anesthesia induction time and postoperative revival time were longer in group A than that in group B; both the duration of surgery and recovery stay were also longer in group A than that in group B, whereas there was no difference in blood loss between the 2 groups. The average dosage of both meperidine and metoclopramide was more in group A than that in group B, and the anesthesia medical cost was greater in group A than that in group B. There were no significant differences in baseline data of systolic blood pressure, diastolic blood pressure, and heart rate between the 2 groups. But the intraoperative data of systolic blood pressure, diastolic blood pressure, and heart rate were higher/larger in group B than that in group A. In group A, there was no complaint of pain in the surgery procedure, but the pain increased after GA, with highest degree at 8 hours postoperation; then the pain degree decreased, and the NRS was 1 at 24 hours postoperation. In group B, intraoperative pain was NRS 4, and pain degree decreased from 4 hours postoperation; the NRS was 2 at 24 hours postoperation. The incidence of severe PONV was higher in group A than that in group B. There was no significant difference in the spinal surgeon satisfaction and anesthetist satisfaction for the anesthetic techniques. There was significant difference in patient satisfaction between the 2 groups, with high satisfaction for GA.General anesthesia is superior to CPA in maintaining better intraoperative hemodynamic stability and providing high patient satisfaction with no intraoperative pain for patients receiving ACDF, but it entails longer surgery and anesthesia time, and requires more postoperative analgesic and anesthesia cost.
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Low titer, isolated anti Ro/SSA 60 kd antibodies is correlated with positive pregnancy outcomes in women at risk of congenital heart block.
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Congenital heart block (CHB) is an autoantibody mediated disorder presumably caused by placental transmission of maternal autoantibodies to Ro/SSA 52 kd, p200, Ro/SSA 60 kd, La/SSB ribonucleoproteins. This study investigated the clinical significance of isolated anti-Ro/SSA 52 kd, anti-p200, anti-Ro/SSA 60 kd, and anti-La/SSB antibodies in positive pregnant patients. One hundred sixty-three pregnant women positive to anti-Ro/SSA 52 kd and/or anti-Ro/SSA 60 kd and/or anti-La/SSB antibodies were prospectively enrolled in the study. Anti-Ro52, anti-Ro60, anti-p200, and anti-La antibodies were assayed using home-made ELISA assays. Isolated antibody positivity was found in 25 women (15.3%), while multiple antibody positivity in 138 (84.7%). Twenty-four developed CHB, and the 139 had a favorable pregnancy outcome. The prevalence of isolated anti-Ro/SSA 60 kd antibodies was significantly higher (p < 0.046) as the prevalence of lower mean antibody titers (p < 0.0001) in the later group. Confirmation of these results by large-scale studies could lead clinicians to recommend less stringent fetal echocardiography monitoring in women with isolated anti-Ro/SSA 60 kd antibodies.
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Effect of transversus abdominis plane block in combination with general anesthesia on perioperative opioid consumption, hemodynamics, and recovery in living liver donors: The prospective, double-blinded, randomized study.
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Transversus abdominis plane (TAP) block provides effective postoperative analgesia after abdominal surgeries. It can be also a useful strategy to reduce perioperative opioid consumption, support intraoperative hemodynamic stability, and promote early recovery from anesthesia. The aim of this prospective randomized double-blind study was to assess the effect of subcostal TAP blocks on perioperative opioid consumption, hemodynamic, and recovery time in living liver donors.</AbstractText>The prospective, double-blinded, randomized controlled study was conducted with 49 living liver donors, aged 18-65 years, who were scheduled to undergo right hepatectomy. Patients who received subcostal TAP block in combination with general anesthesia were allocated into Group 1, and patients who received general anesthesia alone were allocated into Group 2. The TAP blocks were performed bilaterally by obtaining an image with real-time ultrasound guidance using 0.5% bupivacaine diluted with saline to reach a total volume of 40 mL. The primary outcome measure in our study was perioperative remifentanil consumption. Secondary outcomes were mean blood pressure (MBP), heart rate (HR), mean desflurane requirement, anesthesia recovery time, frequency of emergency vasopressor use, total morphine use, and length of hospital stay.</AbstractText>Total remifentanil consumption and the anesthesia recovery time were significantly lower in Group 1 compared with Group 2. Postoperative total morphine use and length of hospital stay were also reduced. Changes in the MAP and HR were similar in the both groups. There were no significant differences in HR and MBP between groups at any time.</AbstractText>Combining subcostal TAP blocks with general anesthesia significantly reduced perioperative and postoperative opioid consumption, provided shorter anesthesia recovery time, and length of hospital stay in living liver donors.</AbstractText>© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</CopyrightInformation>
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Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells.
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Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased somatic hypermutation and chromosomal translocation frequency to the Igh locus and to several AID off-target sites. Both of these effects were completely abrogated in AID-deficient B cells. PI3Kδ inhibitors or ibrutinib increased the formation of AID-dependent tumours in pristane-treated mice. Consistently, PI3Kδ inhibitors enhanced AID expression and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukaemia and mantle cell lymphoma cell lines, and patients treated with idelalisib, but not ibrutinib, showed increased somatic hypermutation in AID off-targets. In summary, we show that PI3Kδ or Bruton's tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. This effect should be carefully considered, as such inhibitors can be administered to patients for years.
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Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.
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Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.
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Dual Mechanism for Inhibition of Inwardly Rectifying Kir2.x Channels by Quinidine Involving Direct Pore Block and PIP<sub>2</sub>-interference.
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Class IA antiarrhythmic drug quinidine was one of the first clinically used compounds to terminate atrial fibrillation and acts as multichannel inhibitor with well-documented inhibitory effects on several cardiac potassium channels. In the mammalian heart, heteromeric assembly of Kir2.1-2.3 channels underlies I<sub>K1</sub> current. Although a low-affinity block of quinidine on Kir2.1 has already been described, a comparative analysis of effects on other Kir2.x channels has not been performed to date. Therefore, we analyzed the effects of quinidine on wild-type and mutant Kir2.x channels in the <i>Xenopus</i> oocyte expression system. Quinidine exerted differential inhibitory effects on Kir2.x channels with the highest affinity toward Kir2.3 subunits. Onset of block was slow and solely reversible in Kir2.2 subunits. Quinidine inhibited Kir2.x currents in a voltage-independent manner. By means of comparative Ala-scanning mutagenesis, we further found that residues E224, F254, D259, and E299 are essential for quinidine block in Kir2.1 subunits. Analogously, quinidine mediated Kir2.3 inhibition by binding corresponding residues E216, D247, D251, and E291. In contrast, Kir2.2 current block merely involved corresponding residue D260. Using channel mutants with altered (phosphatidylinositol 4,5-bisphosphate PIP<sub>2</sub>) affinities, we were able to demonstrate that high PIP<sub>2</sub> affinities (i.e., Kir2.3 I214L) correlate with low quinidine sensitivity. Inversely, mutant channels interacting only weakly with PIP<sub>2</sub> (i.e., Kir2.1 K182Q, and L221I) are prone to a higher inhibitory effect. Thus, we conclude that inhibition of Kir2.x channels by quinidine is mediated by joint modes of action involving direct cytoplasmic pore block and an impaired channel stabilization via interference with PIP<sub>2</sub>.
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Evaluation of antihypertensive potential of Ficus carica fruit.
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Ficus carica L. (Moraceae) fruit is said to possess cardiovascular activity and has been used empirically in traditional phytotherapies for the treatment of hypertension and various other cardiovascular diseases.</AbstractText>This study investigated the antihypertensive and cardioinhibitory activity of the aqueous-methanol extract of F. carica fruit in rats.</AbstractText>Extract in 250, 500 and 1000 mg/kg doses (p.o.) were administered to normotensive Sprague Dawley rats and blood pressure was measured using non-invasive technique. Hypertension was induced in rats by oral administration of 10% glucose for 3 weeks. Hypotensive effect of extract (1000 mg/kg p.o) was studied in normotensive and glucose-treated hypertensive rats. Langendorff's isolated heart technique was used to assess the effect of crude extract on force of contraction and heart rate. In addition, antioxidant potential, TPC, TFC were also assessed by DPPH free radical scavenging activity, Folin-Ciocalteu reagent and AlCl3</sub> assay, respectively. Furthermore, phenolic compounds were analyzed using HPLC-DAD technique.</AbstractText>The 1000 mg/kg dose decreased blood pressure significantly in normotensive and glucose-treated hypertensive rats. The isolated heart study showed that the extract produced negative inotropic and chronotropic effects but it failed to block the stimulatory effect of both adrenaline and CaCl2</sub>. HPLC studies on the F. carica extract indicated the presence of quercetin, gallic acid, caffeic acid, vanillic acid, syringic acid, coumaric acid and chromotropic acid.</AbstractText>This study demonstrated that aqueous methanol extract of F. carica fruit exerted hypotensive and antihypertensive effects in glucose-induced hypertensive rats.</AbstractText>
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Comparison of caudal ropivacaine-morphine and paravertebral catheter for major upper abdominal surgery in infants.
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The caudal epidural block is one of the most commonly used regional anesthetic techniques in children. Administration of morphine via caudal injection enables analgesia, even for upper abdominal surgery. The thoracic paravertebral block has also been successfully used to treat perioperative pain during upper abdominal procedures in pediatric patients.</AbstractText>In the current study, we compared the two regional techniques for upper abdominal surgery in infants to determine whether one of them was preferable to the other.</AbstractText>Consecutive patients under 12 months of age who underwent upper abdominal surgery were retrospectively divided according to the chosen postoperative analgesia: Group C, caudal ropivacaine-morphine; Group P, paravertebral catheter. We analyzed the following outcomes: requirement for additional analgesics, pain scores, need for mechanical ventilation and oxygen dosage, postoperative blood pressure and heart rate, time to pass first stool, time until first full meal, and complications.</AbstractText>Twenty-one consecutive patients were included: 10 in Group C and 11 in Group P. Median age at surgery was 80 (47.5-270.0) and 84.5 (34.3-287.5) days, respectively. No difference was found between the two groups in requirement for additional analgesics at 24 h after surgery (median 1 in Group C vs 1 in Group P, P = 0.288, 95% CI: -2 to 1). BOPS pain scores were only lower in Group P when compared to Group C at 24 h after surgery (median 1 vs 2, P = 0.041, 95% CI: -2 to 0). None of the patients had perioperative complications.</AbstractText>In this small series, there was no significant difference between caudal ropivacaine-morphine and paravertebral catheter for postoperative care in infants undergoing upper abdominal surgery. Further prospective studies are needed to compare the efficacy and incidence of complications of caudal block and paravertebral catheter for postoperative analgesia.</AbstractText>© 2017 John Wiley & Sons Ltd.</CopyrightInformation>
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Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells.
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Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.
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A complicated multisystem flare of systemic lupus erythematosus during pregnancy.
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We report a case of systemic lupus erythematosus (SLE) in a young woman who became pregnant amid a severe flare. She continued to have active disease in the face of aggressive treatments complicated by several side effects of immunosuppressive drugs including recurrent sepsis and gestational diabetes. Her fetus was at risk for congenital heart block during the second and third trimesters. Despite an extremely guarded prognosis, she delivered a healthy baby girl. This case highlights the complexities of SLE management during pregnancy. We discuss the therapeutic options available in pregnancy, and highlight the importance of cross-specialty multidisciplinary care in these women.
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The effects of block training on pacing during 20-km cycling time trial.
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The aim of this study was to determine the effects of block training (BL) on pacing during a 20-km hilly cycling time trial (TT) in trained cyclists. Twenty male cyclists were separated into 2 groups: control and BL. The training of each cyclist was monitored during a period of 3 weeks. In the first week cyclists performed an overload period of 7 consecutive days of high-intensity interval training followed by 2 weeks of normal training. Cyclists performed 1 TT before intervention and 2 TT after 7 and 14 days at the end of training. Each training session consisted of 10 sets of 3 repeated maximal-effort sprints (15, 30, and 45 s) with an effort/recovery duration ratio of 1:5. The main finding of this study was that the power output displayed a significantly higher start from the start until the halfway point of the TT (p < 0.05). Additionally, power output was characterized by a significant higher end spurt in the final 2 km in the BL after 2 weeks at the end of training (p < 0.05). In addition, after 2 weeks at the end of the overload period the distribution of cadence was significantly lower throughout the TT (p < 0.01). Therefore, a short period of consecutive days of intense training enhances cycling performance and changes the power output in the beginning and final part of the TT in trained cyclists.
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Serial echocardiography for immune-mediated heart disease in the fetus: results of a risk-based prospective surveillance strategy.
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Mothers carrying anti-Ro antibodies are frequently referred for weekly echocardiograms to early detect and treat antibody-mediated fetal heart disease. We tested a surveillance strategy based on anti-Ro antibody titers.</AbstractText>From 2009 to 2014, 232 pregnancies were referred for maternal anti-Ro antibodies. At the baseline echocardiogram, anti-Ro titers were measured by enzyme-linked immunosorbent essay and results categorized as negative (<8 U/mL; n = 43; excluded), low-moderate positive (8-49 U/mL; n = 62; group 1) or high positive (50 - >100 U/mL; n = 127; group 2). Serial echocardiograms to ≥24 weeks were only recommended for group 2 mothers.</AbstractText>Group 1 patients underwent significantly less fetal echocardiograms when compared with group 2 mothers (median 2 vs. 4; p < 0.001). Isolated endocardial fibroelastosis (n = 1) and incomplete (n = 4) or complete (n = 4) heart block were diagnosed in 9 (8%) pregnancies with anti-Ro titers >100 U/mL but none with lower titers (odds ratio 17.78; p = 0.004). Incomplete block and endocardial fibroelastosis regressed with transplacental corticosteroid and immune globulin therapy.</AbstractText>Limiting serial fetal echocardiograms to women with high anti-Ro antibody levels is safe and more cost effective. While numbers of echocardiograms were significantly reduced in referrals with anti-Ro titers <50 U/mL, reversible abnormalities with prenatal treatment were detected by serial echocardiography in group 2 patients. © 2017 John Wiley & Sons, Ltd.</AbstractText>© 2017 John Wiley & Sons, Ltd.</CopyrightInformation>
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Free energy landscape remodeling of the cardiac pacemaker channel explains the molecular basis of familial sinus bradycardia.
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The hyperpolarization-activated and cyclic nucleotide-modulated ion channel (HCN) drives the pacemaker activity in the heart, and its malfunction can result in heart disorders. One such disorder, familial sinus bradycardia, is caused by the S672R mutation in HCN, whose electrophysiological phenotypes include a negative shift in the channel activation voltage and an accelerated HCN deactivation. The outcomes of these changes are abnormally low resting heart rates. However, the molecular mechanism underlying these electrophysiological changes is currently not fully understood. Crystallographic investigations indicate that the S672R mutation causes limited changes in the structure of the HCN intracellular gating tetramer, but its effects on protein dynamics are unknown. Here, we utilize comparative S672R <i>versus</i> WT NMR analyses to show that the S672R mutation results in extensive perturbations of the dynamics in both apo- and holo-forms of the HCN4 isoform, reflecting how S672R remodels the free energy landscape for the modulation of HCN4 by cAMP, <i>i.e.</i> the primary cyclic nucleotide modulator of HCN channels. We show that the S672R mutation results in a constitutive shift of the dynamic auto-inhibitory equilibrium toward inactive states of HCN4 and broadens the free-energy well of the apo-form, enhancing the millisecond to microsecond dynamics of the holo-form at sites critical for gating cAMP binding. These S672R-induced variations in dynamics provide a molecular basis for the electrophysiological phenotypes of this mutation and demonstrate that the pathogenic effects of the S672R mutation can be rationalized primarily in terms of modulations of protein dynamics.
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Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts.
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Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly affect cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II, and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiologic and pathophysiological processes. For example, the benzamide class I HDAC-selective inhibitor, MGCD0103 [<i>N</i>-(2-aminophenyl)-4-[[(4-pyridin-3-ylpyrimidin-2-yl)amino]methyl] benzamide], was shown to block cardiac fibrosis, a process involving excess extracellular matrix deposition, which often results in heart dysfunction. Here, we compare the mechanisms of action of structurally distinct HDAC inhibitors in isolated primary cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart. TSA, MGCD0103, and the cyclic peptide class I HDAC inhibitor, apicidin, exhibited a common ability to enhance histone acetylation, and all potently blocked cardiac fibroblast cell cycle progression. In contrast, MGCD0103, but not TSA or apicidin, paradoxically increased expression of a subset of fibrosis-associated genes. Using the cellular thermal shift assay, we provide evidence that the divergent effects of HDAC inhibitors on cardiac fibroblast gene expression relate to differential engagement of HDAC1- and HDAC2-containing complexes. These findings illustrate the importance of employing multiple compounds when pharmacologically assessing HDAC function in a cellular context and during HDAC inhibitor drug development.
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NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice.
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<AbstractText Label="BACKGROUND & AIMS">NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in Non-alcoholic fatty liver disease (NAFLD). We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis.</AbstractText>We fed foz/foz and wild-type mice an atherogenic diet for 16weeks, gavaged MCC950 or vehicle until 24weeks, then determined NAFLD phenotype. In mice fed an methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle for 6weeks and determined the effects on liver fibrosis.</AbstractText>In vehicle-treated foz/foz mice, hepatic expression of NLRP3, pro-IL-1β, active caspase-1 and IL-1β increased at 24weeks, in association with cholesterol crystal formation and NASH pathology; plasma IL-1β, IL-6, MCP-1, ALT/AST all increased. MCC950 treatment normalized hepatic caspase 1 and IL-1β expression, plasma IL-1β, MCP-1 and IL-6, lowered ALT/AST, and reduced the severity of liver inflammation including designation as NASH pathology, and liver fibrosis. In vitro, cholesterol crystals activated Kupffer cells and macrophages to release IL-1β; MCC950 abolished this, and the associated neutrophil migration. MCD diet-fed mice developed fibrotic steatohepatitis; MCC950 suppressed the increase in hepatic caspase 1 and IL-1β, lowered numbers of macrophages and neutrophils in the liver, and improved liver fibrosis.</AbstractText>MCC950, an NLRP3 selective inhibitor, improved NAFLD pathology and fibrosis in obese diabetic mice. This is potentially attributable to the blockade of cholesterol crystal-mediated NLRP3 activation in myeloid cells. MCC950 reduced liver fibrosis in MCD-fed mice. Targeting NLRP3 is a logical direction in pharmacotherapy of NASH.</AbstractText>Fatty liver disease caused by being overweight with diabetes and a high risk of heart attack, termed non-alcoholic steatohepatitis (NASH), is the most common serious liver disease with no current treatment. There could be several causes of inflammation in NASH, but activation of a protein scaffold within cells termed the inflammasome (NLRP3) has been suggested to play a role. Here we show that cholesterol crystals could be one pathway to activate the inflammasome in NASH. We used a drug called MCC950, which has already been shown to block NLRP3 activation, in an attempt to reduce liver injury in NASH. This drug partly reversed liver inflammation, particularly in obese diabetic mice that most closely resembles the human context of NASH. In addition, such dampening of liver inflammation in NASH achieved with MCC950 partly reversed liver scarring, the process that links NASH to the development of cirrhosis.</AbstractText>Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
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Intraocular pressure is sensitive to cumulative and instantaneous mental workload.
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We used a repeated-measures design to assess the impact of mental-task complexity on intraocular pressure (IOP). Fourteen participants performed three continuous 11-min blocks of a mental-workload task (3-back) and an oddball version of this task. Also, heart-rate variability (HRV), cognitive-performance scores, and subjective measure of mental load (NASA-TLX) were determined. IOP was taken before each block and afterwards as well as after recovery from mental tasks. We found that IOP increased during heavy mental workloads (p < 0.01). Consistent with this finding, the autonomic control (HRV) and the cognitive performance were significantly lower (p < 0.045, and p < 0.01, respectively), and the NASA-TLX scores were higher during the 3-back task (p < 0.01). We conclude that IOP is sensitive to mental workload, and it could provide a novel neuroergonomic tool to assess mental workload. Our study highlights a potential association between IOP and the nervous system's state of activation.
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2,335,349 |
[Application of ultrasound guidance for fascia iliaca compartment block in pediatric femoral surgery].
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<b>Objective:</b> To evaluate the efficacy of ultrasound guidance for fascia iliaca compartment block in pediatric femoral surgery. <b>Methods:</b> This study was a prospective study, thirty children who were American Society of Anesthesiologists (ASA) statusⅠ with 5-10 years old scheduled for femoral surgery were selected in orthopedics department in Second Affiliated Hospital of Wenzhou Medical University from May to December in 2014. After induction of general anesthesia, all the children were inserted the laryngeal mask. Then they were received fascia iliaca compartment block using ultrasound guidance under sevoflurane inhalation anesthesia. The indicators including heart rate(HR), mean arterial pressure(MAP), oxygen saturation(SpO(2)) and exhaled sevoflurane concentration were recorded before skin incision(T(1)), at 1, 5, 10 min after incision(T(2)-T(4))and at the end of the surgery(T(5)). Postoperative pain were assessed using the pain behavior assessment scale at awake time, 2 h and 4 h after surgery. The efficacy of postoperative analgesia and the satisfaction of parents at 2 h and 4 h after surgery were recorded. <b>Results:</b> The differences between HR、MAP and SpO(2) in children at T(1)-T(5) were no statistical significance (all <i>P</i>>0.05). Exhaled sevoflurane concentration at T(1)-T(5) were(2.50±0.51)%, (2.51±0.42)%, (2.50±0.41)%, (2.54±0.31)% and(0.61±0.20)%, respectively, the differences were statistically significant(<i>F</i>=13.503, <i>P</i><0.05), among them that at T(5) was significantly lower than at T(1)-T(4)(all <i>P</i><0.05). The pain score at awake time, 2 h and 4 h after surgery were (1.6±0.7), (3.3±1.4) and (3.9±1.3) scores, respectively. The parents satisfaction were 87% and 73% at 2 h and 4 h afer surgery respectively. <b>Conclusion:</b> The way of ultrasound guidance for fascia iliaca compartment block combined with general anesthesia can be safely and effectively used in pediatric femoral surgery. Using the technique of ultrasonic imaging, the fascia iliaca compartment can be directly observed and then the local anesthetics is injected, therefore the efficacy of block is improved.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nan</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Anesthesiology, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Q Q</ForeName><Initials>QQ</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>X W</ForeName><Initials>XW</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>J</ForeName><Initials>J</Initials></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Zhonghua Yi Xue Za Zhi</MedlineTA><NlmUniqueID>7511141</NlmUniqueID><ISSNLinking>0376-2491</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005205" MajorTopicYN="Y">Fascia</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005269" MajorTopicYN="N">Femur</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D035002" MajorTopicYN="N">Lower Extremity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="Y">Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059408" MajorTopicYN="N">Pain Management</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010149" MajorTopicYN="Y">Pain, Postoperative</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014463" MajorTopicYN="N">Ultrasonography</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="chi"><b>目的：</b> 评价超声引导下髂筋膜间隙阻滞在小儿股骨手术中的应用效果。 <b>方法：</b> 本研究为前瞻性研究，选择2014年5至12月温州医科大学附属第二医院骨科行股骨手术的患儿30例，美国麻醉医师协会(ASA)Ⅰ级，年龄5～10岁。全麻诱导后所有患儿置入喉罩，并在七氟烷吸入麻醉下行超声引导髂筋膜间隙阻滞。记录患儿切皮前(T(1))、切皮后1 min(T(2))、5 min(T(3))、10 min (T(4))和手术结束时(T(5))的心率、平均动脉压、脉氧饱和度及七氟烷呼出浓度等指标，采用疼痛行为评估量表对患儿苏醒时、术后2 h及4 h行疼痛评估，记录患儿的术后镇痛效果、术后2 h及4 h患儿家长的满意情况。 <b>结果：</b> 患儿在T(1) ～T(5)各时点心率、平均动脉压、脉氧饱和度比较差异均无统计学意义(均<i>P</i>>0.05)，T(1) ～T(5)各时点七氟烷呼气末浓度分别为(2.50±0.51)%、(2.51±0.42)%、(2.50±0.41)%、(2.54±0.31)%及(0.61±0.20)%，差异有统计学意义(<i>F</i>＝13.503，<i>P</i><0.05)，其中T(5)时点七氟烷呼气末浓度明显低于T(1)～T(4)时点(均<i>P</i><0.05)。苏醒时、术后2 h及4 h镇痛评分分别为(1.6±0.7)分、(3.3±1.4)分和(3.9±1.3)分。术后2 h及4 h的家长满意率分别为87%及73%。 <b>结论：</b> 超声引导髂筋膜间隙阻滞联合全身麻醉的方法可安全有效地应用于小儿股骨部位手术，利用超声成像技术可直接观察到髂筋膜间隙并把局麻药注入，因而提高阻滞效果。.
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[Coronary Artery Spasm during Anesthesia: Discussion of Cases Leading to Circulatory Collapse through 51 Reports of the Published Literature].
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Perioperative coronary artery spasm (GAS) is one of the serious complications leading to circulatory collapse. Here we retrospectively examined the impact of CAS and discussed its prevention strate- gies.</AbstractText>Reports of intraoperative CAS were iden- tified by using the PubMed and by manually searching the Journal of Japan Society for Clinical Anesthesia (2001-2015). Analyses were performed on 51 patients who developed CAS and had had no history of isch- emic heart disease.</AbstractText>Of the 51 analyzed patients, 19 developed circulatory collapse. In these patients, the rate of early administration of a sufficient dose of a coronary vasodi- lator was low, and they tended to have prolonged and/ or recurrent attacks. Among them, two patients may have had a problem due to the dosage and/or admin- istration method for coronary vasodilator, despite early administration. In addition, we found that a combina- tion of general anesthesia and epidural block may have contributed to the collapse. In three cases, it was diffi- cult to identify the predictors of circulatory collapse.</AbstractText>Awareness of CAS and vigilant moni- toring are crucial for preventing circulatory collapse. When a transient ST-segment change indicates possi- ble CAS, adequate dosages of a coronary vasodilator should be promptly administered.</AbstractText>
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2,335,351 |
A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant.
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The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.
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2,335,352 |
Lessons on dietary biomarkers from twin studies.
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Metabolomic and microbiome profiling are promising tools to identify biomarkers of food intake and health status. The individual's genetic makeup plays a significant role on health, metabolism, gut microbes and diet and twin studies provide unique opportunities to untangle gene-environment effects on complex phenotypes. This brief review discusses the value of twin studies in nutrition research with a particular focus on metabolomics and the gut microbiome. Although, the twin model is a powerful tool to segregate the genetic component, to date, very few studies combine the twin design and metabolomics/microbiome in nutritional sciences. Moreover, since the individual's diet has a strong influence on the microbiome composition and the gut microbiome is modifiable (60 % of microbiome diversity is due to the environment), future studies should target the microbiome via dietary interventions.
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2,335,353 |
Targeting the tight junction protein, zonula occludens-1, with the connexin43 mimetic peptide, αCT1, reduces VEGF-dependent RPE pathophysiology.
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A critical target tissue in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from attenuation/disruption of intercellular tight junctions. Zonula occludens-1 (ZO-1) is a major structural protein of intercellular junctions. A connexin43-based peptide mimetic, αCT1, was developed to competitively block interactions at the PDZ2 domain of ZO-1, thereby inhibiting ligands that selectively bind to this domain. We hypothesized that targeting ZO-1 signaling using αCT1 would maintain BRB integrity and reduce RPE pathophysiology by stabilizing gap- and/or tight-junctions. RPE-cell barrier dysfunction was generated in mice using laser photocoagulation triggering choroidal neovascularization (CNV) or bright light exposure leading to morphological damage. αCT1 was delivered via eye drops. αCT1 treatment reduced CNV development and fluid leakage as determined by optical coherence tomography, and damage was correlated with disruption in cellular integrity of surrounding RPE cells. Light damage significantly disrupted RPE cell morphology as determined by ZO-1 and occludin staining and tiling pattern analysis, which was prevented by αCT1 pre-treatment. In vitro experiments using RPE and MDCK monolayers indicated that αCT1 stabilizes tight junctions, independent of its effects on Cx43. Taken together, stabilization of intercellular junctions by αCT1 was effective in ameliorating RPE dysfunction in models of AMD-like pathology.</AbstractText>The connexin43 mimetic αCT1 accumulates in the mouse retinal pigment epithelium following topical delivery via eye drops. αCT1 eye drops prevented RPE-cell barrier dysfunction in two mouse models. αCT1 stabilizes intercellular tight junctions. Stabilization of cellular junctions via αCT1 may serve as a novel therapeutic approach for both wet and dry age-related macular degeneration.</AbstractText>
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2,335,354 |
Ten-year progression of coronary artery, carotid artery, and aortic calcification in patients with rheumatoid arthritis.
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Rheumatoid arthritis (RA) is associated with increased vascular calcification, although the rate of progress of calcification is uncertain. The aim of the study was to evaluate the progression of and the predictors for calcification in different vascular beds over 10 years. The 10-year actual coronary calcium score (CS) and 10-year predicted coronary CS, based on the pattern of the general population, were compared. Calcification of the coronary and carotid artery and the aorta was assessed by multi-detector computed tomography. Significant CS progression was determined by the difference between the square root of baseline and square root of follow-up calcium score (i.e., SQRT method). The 10-year predicted coronary CS was based on the mathematical formula derived by the Heinz Nixdorf Recall Study. A total of 49 patients (54 ± 11 years, 90% female) had a follow-up scan after 10.0 ± 0.2 years. The CS in all vascular beds was significantly increased; 55% of the patients had a significant progression of CS in the coronary, 29% in the carotid, and 80% in the aorta. Age and systolic blood pressure (SBP) were independently associated with calcification progression in all vascular beds. Importantly, the absolute increase in 10-year actual coronary CS was significantly higher than that predicted. In patients with RA, calcification in all vascular beds significantly increased over 10 years and was independently associated with age and SBP. Importantly, the absolute increase in 10-year actual coronary CS progression was significantly higher than that predicted.
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2,335,355 |
Sinus bradycardia after intravenous pulse methylprednisolone therapy in patients with systemic lupus erythematosus.
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Sinus bradycardia is reported as an adverse effect of high-dose glucocorticoid therapy. We report three cases of systemic lupus erythematosus, wherein intravenous pulse methylprednisolone was administered. The patients' average baseline heart rate was 72 beats/min, which decreased 30% from baseline at 61 h after beginning the therapy. The average minimum heart rate was 38 beats/min, and this rate continued for 169 h on average. No other causes for bradycardia were found, suggesting that the administration of glucocorticoid pulse therapy resulted in decreased heart rate.
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2,335,356 |
Heart Rate Changes in Response to Mechanical Pressure Stimulation of Skeletal Muscles Are Mediated by Cardiac Sympathetic Nerve Activity.
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Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm<sup>2</sup>) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: -56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (<i>r</i> = -0.65, <i>p</i> = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: -9 to +3 bpm, <i>p</i> < 0.0001) but not the vagus nerve (range: -75 to +30 bpm, <i>p</i> = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (<i>r</i> = 0.77, <i>p</i> = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (<i>r</i> = -0.62, <i>p</i> = 0.0066). These results suggest that cardiac sympathetic nerve activity regulates HR responses to muscle mechanical pressure stimulation and the direction of HR responses depends on the tonic level of the nerve activity, i.e., bradycardia occurs when the tonic activity is high and tachycardia occurs when the activity is low.
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2,335,357 |
Efficacy of Stellate Ganglion Blockade Applied with Light Irradiation: A Systemic Review and Meta-analysis.
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Stellate ganglion block has mostly been used to relieve symptoms of neuropathic pain; several potential complications have been reported. Noninvasive stellate ganglion block application using light irradiation (SG-LI) can be used as an alternative to conventional injection blockades. Based on the variety of application protocols among previous studies, it was needed to further identify the clinical efficacy of SG-LI in managing neuropathic pain or other disorders associated with sympathetic hyperactivity.</AbstractText>A comprehensive search of online databases was performed to identify experimental or observational studies reporting the efficacy of SG-LI in treating patients with disorders requiring sympatholytic management. The included studies were subjected to a meta-analysis and risk-of-bias assessment.</AbstractText>Twenty-one experimental studies with a Physiotherapy Evidence Database score of 6/10 and 5 observational studies with a Newcastle-Ottawa scale score of 7/9 were included in the analysis. A significant effect on pain relief favoring SG-LI was identified at a standard mean difference (SMD) of -2.05 [95% confidence interval (CI), -2.49 to -1.61; P < 0.00001]. Similar effects favoring SG-LI were found in peripheral blood flow (SMD, 1.26; 95% CI, 0.26-2.25; P = 0.01) and skin temperature (SMD, 1.31; 95% CI, 0.55, 2.08; P = 0.0007).</AbstractText>Stellate ganglion block application using light irradiation effectively relieves pain of various etiologies and successfully induces a sympatholytic response. Stellate ganglion block application using light irradiation may be a valuable addition to the contemporary pain management armamentarium.</AbstractText>
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2,335,358 |
Omega-3 Fatty Acid Could Increase One of Myokines in Male Patients with Coronary Artery Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.
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Omega-3 fatty acids have a protective role against cardiovascular disease and these protective properties are attributed to its anti-inflammatory effects. Myokines have anti-inflammatory properties and thereby reduce low-grade inflammation. Irisin, as a myokine, is considered to be therapeutic for human metabolic diseases. This study was conducted to determine the effects of Omega-3 fatty acids supplementation on serum irisin in men with coronary artery disease (CAD).</AbstractText>This study was an 8-week randomized, double-blind, placebo-controlled trial. Forty-eight CAD male patients (Omega-3, n = 24; control, n = 24) were randomly assigned to either Omega-3 or control groups by permuted block randomization method. Only the participants with more than 50% stenosis in at least one major coronary vessel were included.  A total of 3 participants in the control group were excluded from the study. Forty-five participants (Omega-3, n = 24; control, n = 21) completed the study. Participants took Omega-3 fatty acids supplement (720 mg eicosapentaenoic acid plus 480 mg docosahexaenoic acid) or placebo (edible paraffin) for 8 weeks. Serum irisin, high-sensitivity C-reactive protein (hs-CRP), lipid profile and anthropometric indices, body composition, and food intake were assessed before and after intervention. Statistical analyses were performed using SPSS software. Paired t-test was used for evaluating within-group effects from baseline. Variables with normal distribution were compared by independent t-test between 2 groups.</AbstractText>Compared to placebo, Omega-3 fatty acids increased serum irisin (P = 0.044) and decreased serum hs-CRP (P = 0.018) and LDL cholesterol (P = 0.031). Omega-3 fatty acids supplementation did not result in any significant changes in anthropometric measurements, blood pressure, serum lipids except for serum LDL, fasting blood glucose, body composition or serum insulin levels (all P > 0.05).</AbstractText>Omega-3 fatty acids supplementation could elevate serum irisin in male patients with CAD. Also, these fatty acids may able to decrease serum hs-CRP and LDL cholesterol.</AbstractText>
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2,335,359 |
Palliative care and Parkinson's disease: Meeting summary and recommendations for clinical research.
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Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson's disease (PD) and outpatient palliative care services are now offered by several movement disorders centers.</AbstractText>An International Working Group Meeting on PD and Palliative Care supported by the Parkinson's Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice.</AbstractText>Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research.</AbstractText>Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers.</AbstractText>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,360 |
Lethal mechanisms in gastric volvulus.
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A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.
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2,335,361 |
[Down syndrome and heart block secondary to neonatal lupus].
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In Down syndrome, so far, has not been reported it's association with congenital heart block, this entity is rare and occurred in only 1% of mothers who have systemic lupus erythematosus, the presence of anti-Ro antibodies cross the placenta presenting neonatal lupus with skin lesions and congenital heart block, bradycardia, which is why we describe the following case. This is a new male end product of asymptomatic young mother, but serological birth with stigmata of Down syndrome, birth presents congenital bradycardia rare manifestation abnormalities, but common in children of mothers with lupus are initiated study protocol, realizing you including laboratory tests and immunological studies cabinet as electrocardiogram and echocardiogram, which gave tone to take the mother immunological studies, being positive antiRo. We concluded that the risk of heart block in a patient with Down syndrome is the same as for the general population.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Illana-Bravo</LastName><ForeName>Carla Lucila</ForeName><Initials>CL</Initials><AffiliationInfo><Affiliation>Departamento de Cardiología Pediátrica, Hospital General Regional 36, Instituto Mexicano del Seguro Social, Puebla, Puebla, México. [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Méndez-Martínez</LastName><ForeName>Socorro</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Juan-Martínez</LastName><ForeName>María Enriqueta</ForeName><Initials>ME</Initials></Author></AuthorList><Language>spa</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Síndrome de Down y bloqueo cardiaco secundario a lupus neonatal.</VernacularTitle></Article><MedlineJournalInfo><Country>Mexico</Country><MedlineTA>Rev Med Inst Mex Seguro Soc</MedlineTA><NlmUniqueID>101243727</NlmUniqueID><ISSNLinking>0443-5117</ISSNLinking></MedlineJournalInfo><SupplMeshList><SupplMeshName Type="Disease" UI="C535758">Congenital heart block</SupplMeshName><SupplMeshName Type="Disease" UI="C536397">Neonatal Systemic lupus erythematosus</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004314" MajorTopicYN="N">Down Syndrome</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000151" MajorTopicYN="Y">congenital</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007231" MajorTopicYN="N">Infant, Newborn</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008180" MajorTopicYN="N">Lupus Erythematosus, Systemic</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000151" MajorTopicYN="Y">congenital</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="spa">En el síndrome de Down, hasta ahora, no se ha reportado su asociación a bloqueo cardiaco congénito, entidad poco frecuente, presentándose únicamente en el 1% de las madres que presentan lupus eritematoso sistémico. La presencia de anticuerpos anti-Ro atraviesan la barrera placentaria presentando lupus neonatal con lesiones dérmicas y bradicardia por bloqueo cardiaco congénito, motivo por el cual describimos el siguiente caso. Se trata de un recién masculino de término, producto de madre joven asintomática, pero con anormalidades serológicas, al nacimiento con estigmas de síndrome de Down y bradicardia congénita, manifestación poco frecuente pero común en hijos de madres con lupus, se inició protocolo de estudio, realizándole exámenes de laboratorio e incluyendo estudios inmunológicos y de gabinete como electrocardiograma y ecocardiograma, lo que dio pauta a tomar estudios inmunológicos a la madre, siendo positivos antiRo. Concluimos que el riesgo de presentar bloqueo cardiaco en un paciente con síndrome de Down es el mismo que para la población general.
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2,335,362 |
[Thoracic paravertebral block in the PACU for immediate postoperative pain relief after video-assisted thoracoscopic surgery].
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<b>Objective:</b> To investigate the effectiveness and safety of the thoracic paravertebral block(TPVB) in the post postanesthesia care unit(PACU) for patients suffered moderate to severe pain after Video-Assisted Thoracoscopic Surgery(VATS). <b>Methods:</b> 78 atients who complained moderate to severe pain on arrival to PACU after VATS were randomly assigned into two groups: thoracic paravertebral block treatment group(P group) and sufentanil treatment group(S group). The VAS Pain score at rest and movement, heart rate, blood pressure, and pulse oximetry 1 hour after treatment and duration of patients staying in the PACU after treatment were recorded. VAS Pain score at rest and on coughing at 8, 24 and 48 hours after treatment were closely monitored. Sufentanil comsumption, patient satisfaction and related complications were also recorded. <b>Results:</b> A successful TPVB was achieved in all patients in P group without puncture related complications. The VAS pain scores at rest and on coughing 1 hour, 8 hours, 24 hours and 48 hours after treatment in P group were significantly lower than the patients in S group. Systolic blood pressure 1 hour after treatment in P group was also lower than the patients in S group(118mmHg±14mmHg vs 128 mmHg±14 mmHg, <i>P</i>=0.021). SPO2 1 hour after treatment in P group was much higher than the patients in S group(95%±3% vs 92%±4%, <i>P</i>=0.015). The duration of patients staying in the PACU after treatment in both groups were similar. Sufentanil comsumption, rate of vomiting and nausea was significantly less and satisfaction was better in P group than thoses in S group. <b>Conclusion:</b> In the postanesthesia care unit, TPVB could provide effective and safe analgesia therapy for patients suffered from moderate to severe pain after VATS.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>West China Hospital of Sichuan University, Chengdu 610041, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>H K</ForeName><Initials>HK</Initials></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Y Q</ForeName><Initials>YQ</Initials></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Zuo</LastName><ForeName>Y X</ForeName><Initials>YX</Initials></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Zhonghua Yi Xue Za Zhi</MedlineTA><NlmUniqueID>7511141</NlmUniqueID><ISSNLinking>0376-2491</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>AFE2YW0IIZ</RegistryNumber><NameOfSubstance UI="D017409">Sufentanil</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D003371" MajorTopicYN="N">Cough</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010149" MajorTopicYN="Y">Pain, Postoperative</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017409" MajorTopicYN="N">Sufentanil</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020775" MajorTopicYN="Y">Thoracic Surgery, Video-Assisted</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="chi"><b>目的</b> 比较超声引导胸椎旁阻滞与阿片类药物治疗麻醉苏醒室胸腔镜手术后患者中重度疼痛的有效性和安全性。 <b>方法</b> 纳入疼痛剧烈的胸腔镜手术患者78例，数字随机分为超声引导胸椎旁阻滞组(P组)和舒芬太尼治疗组(S组)，记录两组患者治疗后1 h血压、心率、氧饱和度和静息/活动疼痛视觉模拟评分(VAS评分)，治疗后麻醉苏醒室停留时间，治疗8、24 h和48 h静息/活动疼痛VAS评分，术后48 h自控静脉镇痛泵舒芬太尼总量，恶心呕吐发生率和患者镇痛满意度。 <b>结果</b> P组患者治疗后1、8、24、48 h静息和活动疼痛VAS评分明显低于S组患者(<i>P</i><0.05)。治疗后1 h，P组患者氧饱和度明显高于S组(95%±3%与92%±4%，<i>P</i>＝0.015)，收缩压明显低于S组[(118±14) mmHg比(128±14) mmHg(1mmHg＝0.133 kPa)，<i>P</i>＝0.021]，舒张压和心率差异无统计学意义，两组患者治疗后PACU停留时间无显著差异。治疗后48 h P组患者自控静脉镇痛泵舒芬太尼总量明显低于S组，P组患者恶心呕吐发生率明显低于S组。术后镇痛满意度P组患者明显高于S组。 <b>结论</b> 麻醉苏醒室进行胸椎旁阻滞能够有效迅速缓解胸腔镜手术患者术后中重度急性疼痛，是一种安全有效的补救镇痛方式。.
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Performance Aspects and Physiological Responses in Male Amateur Boxing Competitions: A Brief Review.
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Slimani, M, Chaabène, H, Davis, P, Franchini, E, Cheour, F, and Chamari, K. Performance aspects and physiological responses in male amateur boxing competitions: a brief review. J Strength Cond Res 31(4): 1132-1141, 2017-Boxing is one of the most popular striking combat sports in the world. The aim of this review was to present data concerning performance analysis (time-motion and technical-tactical analysis) and physiological responses (i.e., blood lactate concentration [BLC], heart rate, and oxygen consumption) during novice and elite male simulated and official amateur boxing competitions in any age category. The present review shows that boxing competition is a high-intensity intermittent striking combat sport. Typically, the activity-to-rest ratio was higher in elite (18:1) than in novice (9:1) boxers and significant differences were observed between rounds (first round = 16:1, second round = 8:1, and third round = 6:1) in novice boxers. Thus, total stop-time and total stop-frequency increased over subsequent rounds in novice boxers. The technical-tactical aspects in elite and novice boxing bouts were different between rounds and dependent on the match outcome (i.e., winners vs. losers). Particularly, the current review highlights that triple-punch combinations, total combinations, block- and counter-punch combinations, total punches to the head, technical performance effectiveness, and defensive- and offensive-skills effectiveness may have contributed to win in novice and elite boxing competitions. Higher frequencies of technical movements were also observed in elite compared with novice boxers. From a physiological point of view, BLC increased significantly from postround 1 compared with postround 3 in novice boxing match. BLC was also higher in official than in simulated elite boxing matches in senior compared with junior boxers and in medium heavy-weight category compared with light- and medium-weight categories in junior boxing competition. A higher percentage of maximal heart rate (%HRmax) and maximal oxygen uptake (V[Combining Dot Above]O2max) were reported in round 3 compared with rounds 2 and 1 in elite boxing competition. In conclusion, these data are useful for both technical-tactical and physical conditioning sessions. Coaches and fitness trainers are encouraged to adjust their training according to these particular characteristics, specifically in terms of age, participants' level, weight categories, and combat contest type.
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2,335,364 |
Sjögren Syndrome and Pregnancy: A Literature Review.
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Autoimmune diseases do not impair fertility, and women with autoimmune diseases who become pregnant are likely to experience more complicated pregnancies than are women without the disease. Pregnancies complicated by these disorders have a high clinical impact on both the pregnancy and the disease. The effect of autoimmune disease on pregnancy differs according to the type of maternal disease, disease activity, severity of organ damage, antibody profile, and drug treatment. Sjögren syndrome is an autoimmune disease with a high prevalence of anti-SS-A (anti-Ro) and anti-SS-B (anti-La) antibodies. Anti-SS-A antibodies are associated with congenital heart block. Data on pregnancy outcomes in primary Sjögren syndrome are scarce.</AbstractText>We performed a review of the literature regarding pregnancy outcomes in women with Sjögren syndrome.</AbstractText>Women with Sjögren syndrome are likely to experience more complications during pregnancy than women without an autoimmune disease. Studies show a high incidence of poor fetal outcomes for these patients.</AbstractText>Women with Sjögren syndrome require prenatal counseling explaining the risks involved and the need to control the disease well before conception. High-risk pregnancies can be optimally managed by a multidisciplinary team.</AbstractText>
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[Development and Effects of a Heart Health Diary for Self-Care Enhancement of Patients with Heart Failure].
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The purpose of this study was to develop a heart health diary to promote self-care ability among patients with heart failure (HF), and to identify the diary's effect on self-care adherence, self-efficacy, and physical activity.</AbstractText>A randomized control-group pretestposttest design was adopted using block randomization. A calender-typed health diary was developed and it included a self-care checklist and education information on HF management. The experimental group were given guided counseling and education for 8 weeks and wrote a daily health diary during that period. Data were collected from the outpatient department of a tertiary medical center from February to April 2016. To verify the hypotheses, data for the experimental group (n=28) and control group (n=33) were analysed using the independent t-test with SPSS/WIN 21.0.</AbstractText>At the end of 8 weeks the experimental group had significantly higher scores for self-care adherence (t=-2.48, p=.016) and exercise related self-efficacy (t=-3.44, p=.001) compared to the control group.</AbstractText>The findings show that the application of a patient-directed heart health diary is an effective nursing intervention for improving HF patients' self-care adherence and exercise self-efficacy. Strategies to promote dietary self-efficacy are necessary along with further studies including repeated research with an increasing intervention period. Healthcare providers need to encourage the utilization of a health diary for HF patients as a tool for evaluation and for implementation that leads to self-care.</AbstractText>
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2,335,366 |
Dural Puncture Epidural Technique Improves Labor Analgesia Quality With Fewer Side Effects Compared With Epidural and Combined Spinal Epidural Techniques: A Randomized Clinical Trial.
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The dural puncture epidural (DPE) technique is a modification of the combined spinal epidural (CSE) technique, where a dural perforation is created from a spinal needle but intrathecal medication administration is withheld. The DPE technique has been shown to improve caudal spread of analgesia compared with epidural (EPL) technique without the side effects observed with the CSE technique. We hypothesized that the onset of labor analgesia would follow this order: CSE > DPE > EPL techniques.</AbstractText>A total of 120 parturients in early labor were randomly assigned to EPL, DPE, or CSE groups. Initial dosing for EPL and DPE consisted of epidural 20 mL of 0.125% bupivacaine plus fentanyl 2 μg/mL over 5 minutes, and for CSE, intrathecal 0.25% bupivacaine 1.7 mg and fentanyl 17 μg. Upon block completion, a blinded coinvestigator assessed the outcomes. Two blinded obstetricians retrospectively interpreted uterine contractions and fetal heart rate tracings 1 hour before and after the neuraxial technique. The primary outcome was time to numeric pain rating scale (NPRS) ≤ 1 analyzed by using Kaplan-Meier curves and Cox proportional hazard model. Secondary outcomes included block quality, maternal adverse effects, uterine contraction patterns, and fetal outcomes analyzed by using the χ test with Yates continuity correction.</AbstractText>There was no significant difference in the time to NPRS ≤ 1 between DPE and EPL (hazard ratio 1.4; 95% confidence interval [CI] 0.83-2.4, P = .21). DPE achieved NPRS ≤ 1 significantly slower than CSE (hazard ratio 0.36; 95% CI 0.22-0.59, P = .0001). The median times (interquartile range) to NPRS ≤ 1 were 2 (0.5-6) minutes for CSE, 11 (4-120) minutes for DPE, and 18 (10-120) minutes for EPL. Compared with EPL, DPE had significantly greater incidence of bilateral S2 blockade at 10 minutes (risk ratio [RR] 2.13; 95% CI 1.39-3.28; P < .001), 20 minutes (RR 1.60; 95% CI 1.26-2.03; P < .001), and 30 minutes (RR 1.18; 95% CI 1.01-1.30; P < .034), a lower incidence of asymmetric block after 30 minutes (RR 0.19; 95% CI 0.07-0.51; P < .001) and physician top-up intervention (RR 0.45; 95% CI 0.23-0.86; P = .011). Compared with CSE, DPE had a significantly lower incidence of pruritus (RR 0.15; 95% CI 0.06-0.38; P < .001), hypotension (RR 0.38; 95% CI 0.15-0.98; P = .032), combined uterine tachysystole and hypertonus (RR 0.22; 95% CI 0.08-0.60; P < .001), and physician top-up intervention (RR 0.45; 95% CI 0.23-0.86; p = .011).</AbstractText>Analgesia onset was most rapid with CSE with no difference between DPE and EPL techniques. The DPE technique has improved block quality over the EPL technique with fewer maternal and fetal side effects than the CSE technique for parturients requesting early labor analgesia.</AbstractText>
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2,335,367 |
Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation.
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Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation. Unexpectedly, activated STAT5 overrode Hippo-mediated inhibition and drove YAP1 to the nucleus. Consequent aberrant cardiomyocyte proliferation resulted in ventricular noncompaction that was markedly rescued by heterozygous loss of function of either ERBB2 or YAP1. Further investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to transition ERBB2 from early to late endosome for degradation. Our studies provide insight into mechanisms by which NUMB and NUMBL promote cardiomyocyte cell cycle withdrawal and highlight previously unsuspected connections between pathways that are important for cardiomyocyte cell cycle reentry, with relevance to ventricular noncompaction cardiomyopathy and regenerative medicine.
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2,335,368 |
The association of heart failure-related microRNAs with neurohormonal signaling.
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Heart failure (HF) is a widely prevalent syndrome imposing a significant burden of morbidity and mortality world-wide. Differential circulating microRNA profiles observed in HF cohorts suggest the diagnostic utility of microRNAs as biomarkers. Given their function in fine tuning gene expression, alternations in microRNA landscape could reflecting the underlying mechanisms of disease and present potential therapeutic targets. Using multiple computational target predicting algorithms together with the luciferase-based reporting platform, the interactions between HF-related microRNAs and the 3' untranslated regions (3'UTRs) of neurohormone associated genes were examined and compared. Our results indicate that although in silico prediction provides an overview of possible microRNA-mRNA target pairs, less than half of the predicted interactions were experimentally confirmed by reporter assays in HeLa cells. Thus, the establishment of microRNA/3'UTR reporters is essential to systemically evaluate the roles of microRNAs for signaling cascades of interest, including cardiovascular neurohormonal signaling. The physiological relevance of HF-related microRNAs on the expression of putative gene targets was further established by using gain-of-function assays in two human cardiac-derived cells. Our findings, for the first time, provide direct evidence of the regulatory effects of HF-related microRNAs on the neurohormonal signaling in cardiac cells. More importantly, our study presents a rational approach to further exploring microRNA profiling data in deciphering the role of microRNA in complex syndromes such as HF. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.
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2,335,369 |
Lipid emulsion injection-induced reversal of cardiac toxicity and acceleration of emergence from general anesthesia after scalp infiltration of a local anesthetic: a case report.
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A scalp block or wound infiltration of local anesthetic is thought to effectively control post-craniotomy pain. However, it can result in local anesthetic toxicity (LAST), which is difficult to distinguish from brain damage due to the surgical procedure when emergence from general anesthesia is delayed. Lipid rescue (infusion of a lipid emulsion) is a widely accepted treatment for LAST.</AbstractText>A 64-year-old man underwent surgical resection of a glioma in the brainstem. While still under general anesthesia, and before suturing of the wound, he received a 20-mL scalp infusion of ropivacaine 0.75%. His emergence from anesthesia was delayed, his respiration was suppressed, and premature ventricular contractions occurred; all of which are symptoms of LAST. Injection of a 20% lipid emulsion rapidly alleviated these symptoms. Interestingly, the blood concentration of ropivacaine increased after lipid rescue.</AbstractText>The increase in ropivacaine concentration in the blood after lipid rescue suggests that the intravenously administered lipid emulsion absorbed the ropivacaine from the intoxicated brain and heart tissue. This finding is consistent with the lipid sink theory as a mechanistic explanation of lipid rescue.</AbstractText>
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2,335,370 |
Reflex arc of the teeth clenching-induced pressor response in rats.
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Although "teeth clenching" induces pressor response, the reflex tracts of the response are unknown. In this study, dantrolene administration inhibited teeth clenching generated by electrical stimulation of the masseter muscles and completely abolished the pressor response. In addition, trigeminal ganglion block or hexamethonium administration completely abolished the pressor response. Local anesthesia of molar regions significantly reduced the pressor response to 27 ± 10%. Gadolinium (mechanoreceptor blocker of group III muscle afferents) entrapment in masticatory muscles also significantly reduced the pressor response to 62 ± 7%. Although atropine methyl nitrate administration did not change the pressor response, a significant dose-dependent augmentation of heart rate was observed. These results indicate that both periodontal membrane and mechanoreceptors in masticatory muscles are the receptors for the pressor response, and that the afferent and efferent pathways of the pressor response pass through the trigeminal afferent nerves and sympathetic nerves, respectively.
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2,335,371 |
Serious Illness Conversations in ESRD.
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Dialysis-dependent ESRD is a serious illness with high disease burden, morbidity, and mortality. Mortality in the first year on dialysis for individuals over age 75 years old approaches 40%, and even those with better prognoses face multiple hospitalizations and declining functional status. In the last month of life, patients on dialysis over age 65 years old experience higher rates of hospitalization, intensive care unit admission, procedures, and death in hospital than patients with cancer or heart failure, while using hospice services less. This high intensity of care is often inconsistent with the wishes of patients on dialysis but persists due to failure to explore or discuss patient goals, values, and preferences in the context of their serious illness. Fewer than 10% of patients on dialysis report having had a conversation about goals, values, and preferences with their nephrologist, although nearly 90% report wanting this conversation. Many nephrologists shy away from these conversations, because they do not wish to upset their patients, feel that there is too much uncertainty in their ability to predict prognosis, are insecure in their skills at broaching the topic, or have difficulty incorporating the conversations into their clinical workflow. In multiple studies, timely discussions about serious illness care goals, however, have been associated with enhanced goal-consistent care, improved quality of life, and positive family outcomes without an increase in patient distress or anxiety. In this special feature article, we will (<i>1</i>) identify the barriers to serious illness conversations in the dialysis population, (<i>2</i>) review best practices in and specific approaches to conducting serious illness conversations, and (<i>3</i>) offer solutions to overcome barriers as well as practical advice, including specific language and tools, to implement serious illness conversations in the dialysis population.
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2,335,372 |
Tropoelastin inhibits intimal hyperplasia of mouse bioresorbable arterial vascular grafts.
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Neointimal hyperplasia, which results from the activation, proliferation and migration of vascular smooth muscle cells (SMCs), is a detrimental condition for vascular stents or vascular grafts that leads to stenosis. Preventing neointimal hyperplasia of vascular grafts is critically important for the success of arterial vascular grafts. We hypothesized that tropoelastin seeding onto the luminal surface of the graft would prevent neointimal hyperplasia through suppressing neointimal smooth muscle cell proliferation. In this study, we investigated the efficacy of tropoelastin seeding in preventing neointimal hyperplasia of bioresorbable arterial vascular grafts. Poly (glycolic acid) (PGA) fiber mesh coated with poly (l-lactic-co-ε-caprolactone) (PLCL) scaffolds reinforced by poly (l-lactic acid) (PLA) nano-fibers were prepared as bioresorbable arterial grafts. Tropoelastin was then seeded onto the luminal surface of the grafts. Tropoelastin significantly reduced the thickness of the intimal layer. This effect was mainly due to a substantial reduction the number of cells that stained positive for SMC (α-SMA) and PCNA in the vessel walls. Mature elastin and collagen type I and III were unchanged with tropoelastin treatment. This study demonstrates that tropoelastin seeding is beneficial in preventing SMC proliferation and neointimal hyperplasia in bioresorbable arterial vascular grafts.</AbstractText>Small resorbable vascular grafts can block due to the over-proliferation of smooth muscle cells in neointimal hyperplasia. We show here that the proliferation of these cells is restricted in this type of graft. This is achieved with a simple dip, non-covalent coating of tropoelastin. It is in principle amendable to other grafts and is therefore an attractive process. This study is particularly significant because: (1) it shows that smooth muscle cell proliferation can be reduced while still accommodating the growth of endothelial cells, (2) small vascular grafts with an internal diameter of less than 1mm are amenable to this process, and (3) this process works for resorbable grafts.</AbstractText>Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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The cardioprotective effect of sildenafil is mediated by the activation of malate dehydrogenase and an increase in the malate-aspartate shuttle in cardiomyocytes.
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Recent evidence has shown the cardioprotective effect of PDE5 inhibition in myocardial ischemia/reperfusion injury, heart failure and cardiac hypertrophy. To investigate the biochemical changes that occur during PDE5 inhibition in cardiac cells, this study assessed the metabolic profile of the HL1 cell line, a murine atrial cell line with adult cardiomyocyte properties. After one hour of treatment with sildenafil, glycolysis was moderately but selectively stimulated, unlike the pentose phosphate pathway and the Krebs cycle. Moreover, malate and a-Ketoglutarate accumulated, paralleled by a decrease in aspartate and glutamate. Interestingly, increased activity of malate dehydrogenase (MDH) was also detected in these cells after sildenafil treatment. Thus, we hypothesized that sildenafil stimulates the malate-aspartate shuttle (MAS) with the final effect of transferring electrons and protons from glycolysis-derived cytosolic NADH into the matrix for use by the electron transport chain, using malate as an electron carrier. Through this metabolic modification, sildenafil may counteract what is often observed in ischemia, i.e. reduced MAS flux as well as a dramatic acceleration of glycolysis, which switches to lactate production. Additionally, the results observed in HL1 cells were also found in isolated mouse hearts. The documented metabolic alteration in cardiomyocytes upon treatment with sildenafil occurred by stimulating cGMP production, which did not activate PKG (cGMP-PKG signaling), since the addition of DT-2, a PKG inhibitor, did not block malate accumulation and increased MDH activity. Conversely, the addition of chelerythrine, a PKC inhibitor, counteracted both malate accumulation and MAS activation, supporting previous evidence that, upon the addition of sildenafil, some PKC isoforms may be implicated in cardioprotection (cGMP-PKC signaling). Interestingly, an increase in cGMP, driven by sildenafil, another cGMP stimulator such as nitroprusside (SNP), or a C-type natriuretic peptide (CNP) which does not inhibit PDE5, led to MAS stimulation and increased MDH activity.
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2,335,374 |
Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.
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Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.
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2,335,375 |
Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro.
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Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro.
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2,335,376 |
Human ventricular activation sequence and the simulation of the electrocardiographic QRS complex and its variability in healthy and intraventricular block conditions.
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To investigate how variability in activation sequence and passive conduction properties translates into clinical variability in QRS biomarkers, and gain novel physiological knowledge on the information contained in the human QRS complex.</AbstractText>Multiscale bidomain simulations using a detailed heart-torso human anatomical model are performed to investigate the impact of activation sequence characteristics on clinical QRS biomarkers. Activation sequences are built and validated against experimentally-derived ex vivo and in vivo human activation data. R-peak amplitude exhibits the largest variability in terms of QRS morphology, due to its simultaneous modulation by activation sequence speed, myocardial intracellular and extracellular conductivities, and propagation through the human torso. QRS width, however, is regulated by endocardial activation speed and intracellular myocardial conductivities, whereas QR intervals are only affected by the endocardial activation profile. Variability in the apico-basal location of activation sites on the anterior and posterior left ventricular wall is associated with S-wave progression in limb and precordial leads, respectively, and occasional notched QRS complexes in precordial derivations. Variability in the number of early activation sites successfully reproduces pathological abnormalities of the human conduction system in the QRS complex.</AbstractText>Variability in activation sequence and passive conduction properties captures and explains a large part of the clinical variability observed in the human QRS complex. Our physiological insights allow for a deeper interpretation of human QRS biomarkers in terms of QRS morphology and location of early endocardial activation sites. This might be used to attain a better patient-specific knowledge of activation sequence from routine body-surface electrocardiograms.</AbstractText>© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.</CopyrightInformation>
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2,335,377 |
Isoflurane versus sevoflurane with interscalene block for shoulder arthroscopic procedures: Value of process capability indices as an additional tool for data analysis.
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Hypotensive anaesthesia reduces intra-articular bleed and promotes visualisation during arthroscopy. The haemodynamic effects of inhalational agents isoflurane and sevoflurane were studied extensively, and both were found to reduce mean arterial pressures (MBP) to an equivalent magnitude. We investigated the relative ability of isoflurane vis-a-vis sevoflurane to maintain the target systolic blood pressure (SBP) in patients undergoing shoulder arthroscopic procedures.</AbstractText>In a prospective randomised study, 59 patients in two groups of 30 and 29 patients each received concomitant general anaesthesia (1.2-1.5 MAC of isoflurane and sevoflurane) and interscalene brachial plexus block. Nitrous oxide was used in both groups. Intraoperatively, serial blood pressure recordings of SBP, diastolic blood pressure (DBP), MBP and heart rates were done at every 3rd</sup> min intervals. The manipulations needed to achieve target SBP (T</i> = 90 mmHg) for optimal arthroscopic visualisation and treat unacceptable hypotensive episodes were noted. Conventional statistical tests and process capability index (PCI) evaluation were both deployed for data analysis.</AbstractText>Lower mean SBP and DBPs were recorded for isoflurane patients as compared to sevoflurane (P</i> < 0.05, for mean, maximum and minimum recordings). Higher mean heart rates were recorded for isoflurane (P</i> < 0.05). PCIs indicated that isoflurane was superior to sevoflurane in the ease of achieving target SBP of 90 mmHg as well as maintaining blood pressures in the range of 80-100 mmHg.</AbstractText>Isoflurane provides better intraoperative haemodynamic status vis-a-vis sevoflurane in patients undergoing shoulder arthroscopic surgery with preliminary interscalene blockade. The PCI can be a useful additional medical data analysis tool.</AbstractText>
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2,335,378 |
Techniques for Learning Descemet Membrane Endothelial Keratoplasty for Eyes of Asian Patients With Shallow Anterior Chamber.
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To describe several essential surgical techniques that overcome difficulties in performing Descemet membrane endothelial keratoplasty (DMEK) for inexperienced surgeons, especially those who perform DMEK on eyes of Asian patients.</AbstractText>Nine eyes of 9 Asian patients with bullous keratopathy who underwent DMEK were analyzed retrospectively. All patients were given a diuretic such as D-mannitol or acetazolamide shortly before surgery, with retrobulbar anesthesia and a Nadbath facial nerve block. Core vitrectomy before DMEK was performed in several cases in which a high vitreous pressure during surgery was predicted. The donor graft was stained with trypan blue, and a 25-G anterior chamber maintenance cannula was used to maintain the anterior chamber depth during graft insertion in all eyes.</AbstractText>The cornea became clear in all eyes. The best spectacle-corrected visual acuity had improved significantly 6 months after the surgery compared with preoperative values (P = 0.026). The corneal endothelial cell density was 1371 cells per square millimeter at postoperative 6 months.</AbstractText>Although DMEK is technically difficult, especially for inexperienced surgeons who operate on eyes of Asian patients, controlling anterior chamber pressure using various manipulations may help to prevent iatrogenic primary graft failure and lead to successful DMEK.</AbstractText>
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2,335,379 |
Reproducibility in measuring physical activity in children and adolescents with an acquired brain injury.
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To examine the reproducibility in measurement of physical activity performance using the ActiGraph®</sup> GT3X+ accelerometer in children aged 8-16 years with Acquired Brain Injury (ABI).</AbstractText>Reproducibility of standardized tasks: Thirty-two children with ABI (12 years 1 month, SD = 2 years 4 months; 20 males; Gross Motor Function Classification System I = 17, II = 15) performed the following activities on 2 consecutive days while wearing an accelerometer and a heart rate monitor: quiet sitting, slow walking (SW), moderate walking (MW), fast walking (FW) and rapid stepping on/off a block (STEP). Intra-class correlation coefficients (ICC) were calculated. Performance variability: Fifty-one participants (12 years 1 month, SD = 2 years 5 months; 27 males; GMFCS I = 26, II = 25) wore an accelerometer for 4 days in the community and reliability coefficients were calculated using standardized 12-hour time spent in moderate-to-vigorous physical activity (MVPA).</AbstractText>Test-re-test reproducibility was excellent for all activities (SW, ICC = 0.90; MW, ICC = 0.83; FW, ICC = 0.91; STEP, ICC = 0.89). Three days of monitoring produced excellent variability estimates of MVPA (R = 0.78).</AbstractText>Therapists can confidently use accelerometry as a reproducible measure of physical activity under standardized walking and stepping conditions, as well as in the community for children with ABI.</AbstractText>
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2,335,380 |
Effects of a Single-Dose Interscalene Block on Pain and Stress Biomarkers in Patients Undergoing Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.
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To compare the effects of a single-dose interscalene block and general anesthesia (SISB/GA) with the effects of GA only in the early postoperative period after arthroscopic rotator cuff repair by evaluating subjective pain visual analog scale scores and objective pain-related stress biomarkers.</AbstractText>Patients refractory to conservative treatment of the affected shoulder were enrolled in this prospective, randomized endpoint study. Patients diagnosed with a rotator cuff tear (1-4 cm) based on magnetic resonance imaging were included. Exclusion criteria were small (<1 cm) and massive (>4 cm) rotator cuff tears. Thirty-one patients each were randomized into the SISB/GA and GA treatment groups. Preoperative pain scores were measured at 6:00 AM on the day of surgery, measured again at 1 and 6 hours postoperatively, and then every 6 hours until 3 days postoperatively. Blood sampling was performed to evaluate the stress biomarkers insulin, dehydroepiandrosterone sulfate, and fibrinogen preoperatively at 6:00 AM on the day of surgery and postoperatively at 18, 42, and 66 hours (6:00 AM on postoperative days 1-3).</AbstractText>Pain scores were significantly decreased in the SISB/GA group (2.50 ± 0.94) versus the GA group (3.82 ± 1.31) on the day of surgery (P < .001), and especially at 6 hours postoperatively (SISB/GA: 2.42 ± 1.43; GA: 4.23 ± 2.17; P < .001). Insulin was decreased significantly in the SISB/GA group (10.55 ± 7.92 μU/mL) versus the GA group (20.39 ± 25.60 μU/mL) at 42 hours postoperatively (P = .048). There was no significant change in dehydroepiandrosterone sulfate or fibrinogen over time (P > .05).</AbstractText>After arthroscopic rotator cuff repair, an SISB effectively relieved pain on the day of surgery without any complications. In addition, insulin levels were significantly reduced at 42 hours postoperatively.</AbstractText>Level I, prospective randomized controlled trial.</AbstractText>Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,381 |
[Analgesic effects of ionotropic glutamate receptor antagonists MK-801 and NBQX on collagen-induced arthritis rats].
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The ionotropic glutamate receptorantagonists include two types: MK-801, antagonist of N-methyl-D-asparticacid (NMDA) receptor, and NBQX, antagonist of non-NMDA receptor.The above-mentioned ionotropic antagonists can block the glutamate and its corresponding receptor binding to produce analgesic effect. The objective of this research was to study two antagonists in analgesic effect on rat behavior,as well as to investigate the down-regulation and up-regulation of cyclooxygenase-2 (COX-2) and Janus-activated kinase (Jak3) in collagen-induced arthritis (CIA) rat serum and tissue fluid after the application of these antagonists, that is, the effect on molecular biology.</AbstractText>This study used the ionotropic glutamate receptors as the target and established CIA rat model. Vivo studies were used to observe changes in behavior and molecular biology of the CIA rat.Behavioral assessment includedmechanical allodynia and joint swelling in the CIA rat,where themechanical allodynia was measured using the paw-withdrawal threshold (PWT) with VonFrey filaments according to the "Up-Down" method,and the drainage volume was used to assess joint swelling. Then the blood samples taken from the heart of the rat and the tissue homogenate were collected to detect the down-regulation and up-regulation of COX-2 and Jak3 in the serum and tissue fluid after the antagonists wereused.</AbstractText>Using MK-801, NBQX alone or using the combination of these two antagonists,these three methods all could alleviate pain(P<0.01).The analgesic effect lasted more than 24 h.Both antagonists reached the peak of analgesia at the end of 4 hours post-injection. NBQX had stronger analgesic effect than MK-801 (P<0.05).Whether alone or combined use of these two antagonists,could not change the CIA rats' swelling of the joint (P>0.05). MK-801 could decrease the expression of COX-2 (P<0.01).At the same time, NBQX did not have this effect (P>0.05). Using MK-801, NBQX alone or combination of these two antagonists could not affect the increased expression of Jak3 caused by the CIA (P>0.05).</AbstractText>MK-801 and NBQX could both alleviate pain, NBQX was much better than MK-801. Neither MK-801 nor NBQX had the effect on the swelling of the joint. NMDA receptor and COX-2 inflammatory pathways had certain interactions. For Jak3, it could not be found to have cross-function with ionotropic glutamate signaling pathways by this experiment.</AbstractText>
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2,335,382 |
Substance P Inhibits the Collagen Synthesis of Rat Myocardial Fibroblasts Induced by Ang II.
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BACKGROUND The aim of this study was to explore the regulating effects of Substance P (SP) on the collagen synthesis of rat myocardial fibroblasts (CFBs) induced by angiotensin II (Ang II) and its potential mechanism. MATERIAL AND METHODS The CFBs of a neonatal SD rat were separately cultured and divided into the control group, Ang II treatment group, and treatment groups with different concentrations of SP, Ang II +; each group was given corresponding treatment respectively. RESULTS Ang II successfully induced the collagen synthesis of CFBs. Compared with the control group, the phosphorylation levels of TGF-β, erk, and smad2/3 were higher (p<0.05). Different concentrations of SP had an effect on Ang II-induced CFBs, reduced the collagen synthesis of CFBs, and increased the expressions of SP receptors, accompanied by lowering TGF-β protein, erk protein phosphorylation level, and smad2/3 protein phosphorylation level (p<0.05). Moreover, the higher the concentrations of SP, the more obvious of an effect it exerted. Treating the Ang II + SP group with aprepitant reduced the inhibiting effects of SP on collagen synthesis. The expression changes of collagen I and collagen III detected by immunocytochemistry were exactly in accordance with the results of qPCR and Western blotting. CONCLUSIONS SP can inhibit collagen synthesis of CFBs after Ang II inducing which may adjust the downstream signaling pathways associated protein including TGF-β, erk and smad2/3. SP can block the progress of myocardial fibrosis and is dose dependent, which is expected to be a promising target for the treatment of myocardial fibrosis.
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2,335,383 |
Velocity, Oxygen Uptake, and Metabolic Cost of Pull, Kick, and Whole-Body Swimming.
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The contributions of the limbs to velocity and metabolic parameters in front-crawl swimming at different intensities have not been identified considering both stroke and kick rate. Consequently, velocity, oxygen uptake (V̇O2</sub>), and metabolic cost of swimming with the whole body (swim), the upper limbs only (pull), and lower limbs only (kick) were compared with stroke and kick rate controlled.</AbstractText>Twenty elite swimmers completed six 200-m trials: 2 swim, 2 pull, and 2 kick. Swim trials were guided by underwater lights at paces equivalent to 65% ± 3% and 78% ± 3% of participants' 200-m-freestyle personal-best pace; paces were described as low and moderate, respectively. In the pull and kick trials, swimmers aimed to match the stroke and kick rates, respectively, recorded during the swim trials. V̇O2</sub> was measured continuously, with velocity and metabolic cost calculated for each 200-m effort.</AbstractText>The velocity contribution of the upper limbs (mean ± SD; low 63.9% ± 6.2%, moderate 59.6% ± 4.2%) was greater than that of the lower limbs to a large extent at both intensities (low ES = 4.40, moderate ES = 4.60). The V̇O2</sub> used by the upper limbs differed between the intensities (low 55.5% ± 6.9%, moderate 51.4% ± 4.0%; ES = 0.74). The lower limbs were responsible for a greater percentage of the metabolic cost than the upper limbs at both intensities (low 56.1% ± 9.5%, ES = 1.30; moderate 55.1% ± 6.6%, ES = 1.55).</AbstractText>Implementation of this testing protocol before and after a pull- or kick-training block will enable sport scientists to determine how the velocity contributions and/or metabolic cost of the upper- and lower-limb actions have responded to the training program.</AbstractText>
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2,335,384 |
The Effect of Zinc Supplementationon the Symptoms of Gastroesophageal Reflux Disease; a Randomized Clinical Trial.
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BACKGROUND Currently, it has been demonstrated that gastroesophageal reflux disease (GERD) is one of the most important disorders of the digestive system and the commixture of regular diet has a significant influence on its incidence, symptoms, and prognosis. The purpose of this study was to evaluate the effect of zinc supplementation, in combination with PPIs(Proton pump inhibitors), on the improvement of GERD symptoms. METHODS In a randomized double blind clinical trial, patients with reflux symptoms, who had obtained Reflux Disease Questionnaire (RDQ) score more than 8, were included and all the demographic features were recorded. Then, using upper gastrointestinal (GI) endoscopy, all the patients were divided into two groups as having non-erosive reflux disorder (NERD),or erosive reflux disorder (ERD). At the next step, based on random block statistical method, we divided the two groups into two subgroups; the drug subgroup [treated with PPIs (40 mg pantoprazole/daily), changing life style, and 220 mgzinc capsules daily] and the placebo subgroup [treated with PPIs, changing life style, and placebo]. After 3 months, we analyzed all data and the RDQ questionnaire was filled out for each patient. This project has been registered in Iranian Registry of Clinical Trials (IRCT) and all data were analyzed using SPSS software version 2. RESULTS A total of 140 patients (81 women and 59 men) with mean age of 42.78±11.5 years were included with 70 patients in each group. The most frequent presentations were heart burn (45.7%), and acid regurgitation (39.3%). The RDQ scores decreased after intervention in both drug (p<0.001) and placebo groups (p<0.001), which were statistically significant. But the difference of RDQ scores between the drug group and placebo group was not statistically significant (p=0.086). CONCLUSION Zinc supplementation cannot improve the severity of GERD.
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2,335,385 |
Clinico-anesthetic changes following administration of propofol alone and in combination of meperidine and pentazocine lactate in dogs.
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The aim of this study is to find out the effect of propofol and its combination with meperidine and pentazocine lactate on certain clinico-anesthetic profiles in dogs.</AbstractText>15 apparently healthy mongrel dogs of either sex of about 1 year of age were randomly divided into three groups of five dogs each. The animals of Group I were administered propofol intravenously alone "to effect," whereas meperidine at 2 mg/kgb.wt. and pentazocine lactate at 2 mg/kg b.wt. were injected intramuscularly 15 min before propofol "to effect" in Groups II and III, respectively. Atropine sulfate at 0.04 mg/kgb.wt. was injected intramuscularly 20 min before each treatment. Rectal temperature, heart rate, respiration rate, and anesthetic indices were recorded before and at 5, 10, 20, 30, and 60 min of induction.</AbstractText>As compared to Group I, the animals of Groups II and III exhibited a significant decrease (p<0.05) in the level of rectal temperature, respiration rate, and heart rate. Duration of recumbency, time of standing, time of recovery as well as the duration of analgesia were longer in pentazocine lactate (Group III) followed by meperidine (Group II) as compared to propofol alone (Group I). Meperidine treated dogs showed defecation and muscle twitching during anesthesia.</AbstractText>Meperidine and pentazocine are suitable opioids used in combination with propofol for achieving surgical anesthesia and helpful in reduction of propofol dose.</AbstractText>
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2,335,386 |
Congenital Complete Heart Block Presenting in Pregnancy: A Case Report.
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Congenital complete heart block presenting for the first time in pregnancy is a rare occurrence posing a therapeutic challenge. We present a case of unpaced preexisting congenital complete heart block in pregnancy diagnosed for the first time during routine prenatal care at her early weeks of gestation. Our patient was asymptomatic and haemodynamically stable and was managed conservatively with a multidisciplinary term approach. Intrauterine growth retardation (IUGR) was present and she was delivered by ceasarean section at term for foetal distress with IUGR. Prophylactic temporary pacing was done before surgery and was weaned off in the early postpartum period. When a multidisciplinary approach is used both maternal and neonatal outcome are favorable. We review the literature in an attempt to discuss the therapeutic policy for such patients.
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2,335,387 |
Regulation of oxidative phosphorylation through each-step activation (ESA): Evidences from computer modeling.
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The mechanisms responsible for matching of the highly varying ATP demand by ATP supply in muscle are of primary importance for pure science, sport science and medicine. According to the traditional opinion ATP supply is activated by elevated ADP and P<sub>i</sub> resulting from ATP hydrolysis during intensive work. Theoretical studies using the computer model of oxidative phosphorylation (OXPHOS) and the entire cell bioenergetic system developed by the author and co-workers lead to the each-step-activation (ESA) mechanism of the regulation of the system in skeletal muscle, heart and other tissues during work transitions. According to ESA not only ATP usage, but also all OXPHOS complexes (complex I, complex III, complex IV, ATP synthase, ATP/ADP carrier, P<sub>i</sub> carrier), NADH supply block and (anaerobic) glycolysis are directly activated by some cytosolic factor/mechanism during rest- or low-to-high work transitions. ESA conception results from large increase in oxygen consumption (V˙O<sub>2</sub>) and ATP turnover flux accompanied by only moderate or no changes in metabolite (ADP, P<sub>i</sub>, PCr, NADH) concentrations during work transitions in skeletal muscle and heart and from the uniform distribution among OXPHOS complexes of the metabolic control over V˙O<sub>2</sub>, as defined within Metabolic Control Analysis. Several theoretical studies carried out using the discussed computer model of the cell bioenergetic system are overviewed. It is demonstrated that this model, involving the ESA mechanism, is able to explain numerous, apparently unrelated to each other, properties of the system.
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2,335,388 |
Ultrasound-Guided Serratus Anterior Plane Block Versus Thoracic Epidural Analgesia for Thoracotomy Pain.
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Thoracotomy is one of the most painful surgical procedures. The aim of this study was to assess the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) compared with thoracic epidural analgesia (TEA) for controlling acute thoracotomy pain.</AbstractText>A prospective, randomized, observer-blinded, controlled study.</AbstractText>The study was performed as a single-institution study in the National Cancer Institute, Cairo University, Egypt.</AbstractText>All participants were cancer patients scheduled for thoracotomy.</AbstractText>This study was conducted from February to December 2015. Forty patients scheduled for thoracotomy under general anesthesia were allocated randomly into 1 of 2 groups with 20 patients each. SAPB was performed before extubation with an injection of 30 mL of 0.25% levobupivacaine followed by 5 mL/hour of 0.125% levobupivacaine. In the TEA group, thoracic epidural catheters were inserted preoperatively to be activated before extubation using a lower dose regimen to the SAPB group. Heart rate, mean arterial pressure, and the visual analog pain score (VAS) measurements were recorded for 24 hours. Rescue analgesia using intravenous morphine, 0.1 mL/kg, was administered if the VAS was >3.</AbstractText>Compared with preoperative values, the mean arterial pressure in the SAPB group did not change significantly (p = 0.181), whereas it decreased significantly (p = 0.006) in the TEA group. VAS scores and the total dose of morphine consumed were comparable in the 2 groups.</AbstractText>SAPB appeared to be a safe and effective alternative for postoperative analgesia after thoracotomy.</AbstractText>Copyright © 2017 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,389 |
Tailoring Nanostructure Morphology for Enhanced Targeting of Dendritic Cells in Atherosclerosis.
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Atherosclerosis, a leading cause of heart disease, results from chronic vascular inflammation that is driven by diverse immune cell populations. Nanomaterials may function as powerful platforms for diagnostic imaging and controlled delivery of therapeutics to inflammatory cells in atherosclerosis, but efficacy is limited by nonspecific uptake by cells of the mononuclear phagocytes system (MPS). MPS cells located in the liver, spleen, blood, lymph nodes, and kidney remove from circulation the vast majority of intravenously administered nanomaterials regardless of surface functionalization or conjugation of targeting ligands. Here, we report that nanostructure morphology alone can be engineered for selective uptake by dendritic cells (DCs), which are critical mediators of atherosclerotic inflammation. Employing near-infrared fluorescence imaging and flow cytometry as a multimodal approach, we compared organ and cellular level biodistributions of micelles, vesicles (i.e., polymersomes), and filomicelles, all assembled from poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) block copolymers with identical surface chemistries. While micelles and filomicelles were respectively found to associate with liver macrophages and blood-resident phagocytes, polymersomes were exceptionally efficient at targeting splenic DCs (up to 85% of plasmacytoid DCs) and demonstrated significantly lower uptake by other cells of the MPS. In a mouse model of atherosclerosis, polymersomes demonstrated superior specificity for DCs (p < 0.005) in atherosclerotic lesions. Furthermore, significant differences in polymersome cellular biodistributions were observed in atherosclerotic compared to naïve mice, including impaired targeting of phagocytes in lymph nodes. These results present avenues for immunotherapies in cardiovascular disease and demonstrate that nanostructure morphology can be tailored to enhance targeting specificity.
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2,335,390 |
Aspects of Quantitation in Mass Spectrometry Imaging Investigated on Cryo-Sections of Spiked Tissue Homogenates.
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Internal standards have been introduced in quantitative mass spectrometry imaging in order to compensate for differences in intensities throughout an image caused by, for example, difference in ion suppression or analyte extraction efficiency. To test how well the internal standards compensate for differences in tissue types in, for example, whole-body imaging, a set of tissue homogenates of different tissue types (lung, liver, kidney, heart, and brain) from rabbit was spiked to the same concentration with the drug amitriptyline and imaged in the same experiment using isotope labeled amitriptyline as internal standard. The results showed, even after correction with internal standard, significantly lower intensities from brain and to some extent also lung tissue, differences which may be ascribed to binding of the drug to proteins or lipids as known from traditional bioanalysis. The differences, which for these results range approximately within a factor of 3 (but for other compounds in other tissues could be higher), underscore the importance of preparing the standard curve in the same matrix as the unknown sample whenever possible. In, for example, whole-body imaging where a diversity of tissue types are present, this variation across tissue types will therefore add to the overall uncertainty in quantitation. The tissue homogenates were also used in a characterization of various phenomena in quantitative MSI, such as to study how the signal depends of the thickness of the cryo-section, and to assess the accuracy of calibration by droplet deposition. For experiments on liver tissue, calibration by spiked tissue homogenates and droplet deposition was found to provide highly similar results and in both cases linearity with R<sup>2</sup> values of 0.99. In the process, a new method was developed for preparation of standard curves of spiked tissue homogenates, based on the drilling of holes in a block of frozen liver homogenate, providing easy cryo-slicing and good quantitative performance.
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2,335,391 |
Low-dose Spinal Block With Continuous Epidural Infusion for Renal Transplantation in a Patient With Alport Syndrome: A Case Report.
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We aim to describe management of a patient receiving renal transplantation for chronic renal failure due to Alport syndrome with low dose of intrathecal bupivacaine and continuous epidural infusion of local anesthetic.</AbstractText>A 38-years-old man with chronic renal failure secondary to Alport syndrome underwent kidney transplantation. Because of a high risk of respiratory and cardiovascular complications related to the patient's baseline lung disease and abnormalities in heart conduction, we selected combined spinal-epidural anesthesia. The block was ultrasound-guided and performed at the T12-L1 interspace with 4.5 mg of 0.5% intrathecal hyperbaric bupivacaine followed by a continuous epidural infusion of 0.5% levobupivacaine mixed with 25 μg of Fentanyl at the initial rate of 8 mL/h. Sensory block to T5-T6 was obtained within 10 minutes. The patient then received mild sedation with Propofol and Remifentanil. Methylprednisolone and diuretics were administered before vascular unclamping according to our internal protocol. Surgery lasted 3 hours with no clinical or procedural complication.</AbstractText>Although renal transplantation is usually performed under general anesthesia, in a particularly complex patient with chronic renal failure, chronic obstructive pulmonary disease and a worsened respiratory mechanics, we applied a combined approach with a low dose of intrathecal bupivacaine and continuous epidural infusion of local anesthetic. The technique did not affect hemodynamics while having a positive impact on recovery of function of the transplanted organ with rapid improvement of urine output, serum creatinine, and blood urea nitrogen levels.</AbstractText>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,392 |
Individual differences in the reinforcing and subjective effects of d-amphetamine: Dimensions of impulsivity.
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Previous research has shown a relationship between impulsive personality and the subjective and reinforcing effects of d-amphetamine. Impulsive personality, however, is comprised of multiple dimensions. The association between different dimensions of impulsive personality and the subjective and reinforcing effects of d-amphetamine is unknown. The objective of this study was to assess the independent contributions of the "sensation-seeking" and "impulsivity" dimensions of the impulsive sensation-seeking subscale of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) to the subjective and reinforcing effects of d-amphetamine. Forty healthy emerging adults varying in scores on the sensation-seeking and impulsivity dimensions of the ZKPQ participated in a double-blind, placebo-controlled, randomized study comprised of 4 2-day blocks. Each 2-day block consisted of a sample day and self-administration day. Subjective effects and physiological measurements were taken prior to, and hourly for 3 hr following, dose administration. On sample days participants were given 8 capsules containing 0, 1, or 2 mg d-amphetamine. On self-administration days participants were able to earn capsules containing the same dose of d-amphetamine that was administered on the previous sample day by responding on a Modified Progressive Ratio Task. The "sensation-seeking" dimension was positively associated with drug taking on the Modified Progressive Ratio Task, subjective effects (e.g., "good effect"), and heart rate. However, no clear relationship between the "impulsivity" dimension and outcome measures was observed. In conclusion, these data suggest that the narrow sensation-seeking dimension of impulsive sensation-seeking is associated with initial drug liking and drug taking behavior and may be a key predictor of drug use initiation. (PsycINFO Database Record
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2,335,393 |
A Dynamical Threshold for Cardiac Delayed Afterdepolarization-Mediated Triggered Activity.
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Ventricular myocytes are excitable cells whose voltage threshold for action potential (AP) excitation is ∼-60 mV at which I<sub>Na</sub> is activated to give rise to a fast upstroke. Therefore, for a short stimulus pulse to elicit an AP, a stronger stimulus is needed if the resting potential lies further away from the I<sub>Na</sub> threshold, such as in hypokalemia. However, for an AP elicited by a long duration stimulus or a diastolic spontaneous calcium release, we observed that the stimulus needed was lower in hypokalemia than in normokalemia in both computer simulations and experiments of rabbit ventricular myocytes. This observation provides insight into why hypokalemia promotes calcium-mediated triggered activity, despite the resting potential lying further away from the I<sub>Na</sub> threshold. To understand the underlying mechanisms, we performed bifurcation analyses and demonstrated that there is a dynamical threshold, resulting from a saddle-node bifurcation mainly determined by I<sub>K1</sub> and I<sub>NCX</sub>. This threshold is close to the voltage at which I<sub>K1</sub> is maximum, and lower than the I<sub>Na</sub> threshold. After exceeding this dynamical threshold, the membrane voltage will automatically depolarize above the I<sub>Na</sub> threshold due to the large negative slope of the I<sub>K1</sub>-V curve. This dynamical threshold becomes much lower in hypokalemia, especially with respect to calcium, as predicted by our theory. Because of the saddle-node bifurcation, the system can automatically depolarize even in the absence of I<sub>Na</sub> to voltages higher than the I<sub>Ca,L</sub> threshold, allowing for triggered APs in single myocytes with complete I<sub>Na</sub> block. However, because I<sub>Na</sub> is important for AP propagation in tissue, blocking I<sub>Na</sub> can still suppress premature ventricular excitations in cardiac tissue caused by calcium-mediated triggered activity. This suppression is more effective in normokalemia than in hypokalemia due to the difference in dynamical thresholds.
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2,335,394 |
Neonatal lupus erythematosus: Report of a case with cutaneous, hematological and hepatobiliary findings.
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Neonatal lupus erythematosus is an autoimmune disorder mainly affecting the heart and skin. It is the most common cause of congenital heart block. In addition, hematological, hepatobiliary and neurological involvement may occur. Herein, we report a 23-day-old infant presented with annular, erythematous, and scaly and atrophic lesions on the face and trunk. Based on the clinical, laboratory and histopathological findings, she was diagnosed as neonatal lupus erythematosus. Neonatal lupus eryhtematosus should be considered in infants presenting with annular skin lesions, and we present this case to highlight the value of high index of clinical suspicion in diagnosis.
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2,335,395 |
Does Short-Duration Heat Exposure at a Matched Cardiovascular Intensity Improve Intermittent-Running Performance in a Cool Environment?
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To investigate whether a 5-d cycling training block in the heat (35°C) in Australian Rules footballers was superior to exercising at the same relative intensity in cool conditions (15°C) for improving intermittent-running performance in a cool environment (<18°C).</AbstractText>Using a parallel-group design, 12 semiprofessional football players performed 5 d of cycling exercise (70% heart-rate reserve [HRR] for 45 min [5 × 50-min sessions in total]) in a hot (HEAT, 35°C ± 1°C, 56% ± 9% RH) or cool environment (COOL, 15°C ± 3°C, 81% ± 10% RH). A 30-15 Intermittent Fitness Test to assess intermittent running performance (VIFT</sub>) was conducted in a cool environment (17°C ± 2°C, 58 ± 5% RH) before and twice after (1 and 3 d) the intervention.</AbstractText>There was a likely small increase in VIFT</sub> in each group (HEAT, 0.5 ± 0.3 km/h, 1.5 ± 0.8 × smallest worthwhile change [SWC]; COOL, 0.4 ± 0.4 km/h, 1.6 ± 1.2 × SWC) 3 d postintervention, with no difference in change between the groups (0.5% ± 1.9%, 0.4 ± 1.4 × SWC). Cycle power output during the intervention was almost certainly lower in the HEAT group (HEAT 1.8 ± 0.2 W/kg vs COOL 2.5 ± 0.3 W/kg, -21.7 ± 3.2 × SWC, 100/0/0).</AbstractText>When cardiovascularexercise intensity is matched (ie, 70% HRR) between environmental conditions, there is no additional performance benefit from short-duration moderate-intensity heat exposure (5 × 50 min) for semiprofessional footballers exercising in cool conditions. However, the similar positive adaptations may occur in HEAT with 30% lower mechanical load, which may be of interest for load management during intense training or rehabilitation phases.</AbstractText>
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2,335,396 |
Conditions of endotracheal intubation with and without muscle relaxant in children.
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Aim To compare intubation conditions and hemodynamic response of two induction regimens, with or without muscle relaxant using a combination of either fentanyl and propofol or propofol and suxamethonium. Methods A total of 80 children aged 4-12 years were enrolled in a prospective randomized double-blinded study. Children were randomly allocated in two equal groups. In group F induction was done with fentanyl and propofol, while propofol and suxamethonium were used in group S. Intubation conditions were assessed using Copenhagen Consensus Score (CCS), based on ease of laryngoscopy, position of vocal cords, degree of coughing, jaw relaxation and limb movements. Systolic blood pressure (SBP),diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were observed at preinduction, postinduction and postintubation at 1, 3 and 5 minute. Results Clinically acceptable CCS was found in 95% of patients in group F versus 100% in group S. Intubation conditions wereexcellent in 85%, good in 10% and poor in 5% of patients in group F. In the group F, signifficantly lower SBP and MAP postinduction and postintubation at 1 and 3 minute, and lower DBP postinduction and postintubation at 1 minute (p<0.05) was found comparing to group S. In group S, significantly higher postinduction and postintubation HR at 1 minute was found comparing to group F (p<0.05). Conclusion Induction combination fentanyl-propofol provide acceptable intubation conditions comparable with suxamethonium in children. This induction regimen ensures better hemodynamic stability associated with endotracheal intubation. It could be recommended for intubation when muscle relaxants are not indicated.
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2,335,397 |
Congenital heart block and immune mediated sensorineural hearing loss: possible cross reactivity of immune response.
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Immune-mediated sensorineural hearing loss may complicate systemic autoimmune diseases. We have previously reported the presence of antibodies directed against inner ear antigens in patients with Cogan syndrome, a disease characterized by sudden hearing loss and interstitial keratitis. Such autoantibodies cross-react with an epitope of SSA/Ro60 protein. Anti-Ro/SSA antibodies in pregnant women cross the placenta and reach the fetal tissues inducing an immune-mediated damage of the cardiac conduction system. We wanted to evaluate whether mothers with anti-Ro/SSA antibodies who gave birth to children with congenital heart block have antibodies directed against inner ear antigens and whether these antibodies are connected with the presence of immune-mediated sensorineural hearing loss. We did not find anti-inner ear antibodies in the majority of the mothers. On the contrary a 13-year-old boy with congenital heart block and sensorineural hearing loss was positive for the presence of anti-inner ear antigens antibodies. Moreover his serum was positive for the presence of anti-Ro60 peptide antibodies but did not recognize the entire protein Ro60 (TROVE2), a behaviour similar to that of sera from patients with Cogan syndrome. In conclusion the data obtained so far show that anti-inner ear antibodies do not recognize the entire protein TROVE2 and do not support the hypothesis that such antibodies may be involved in the pathogenesis of congenital heart block.
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2,335,398 |
The Yersinia pestis Effector YopM Inhibits Pyrin Inflammasome Activation.
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Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, innate immune responses can also sense some T3SS components to initiate anti-bacterial mechanisms. The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1β and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation. Some effectors, like Y. pestis YopM, may block inflammasome activation. Here we show that YopM prevents Y. pestis induced activation of the Pyrin inflammasome induced by the RhoA-inhibiting effector YopE, which is a GTPase activating protein. YopM blocks YopE-induced Pyrin-mediated caspase-1 dependent IL-1β/IL-18 production and cell death. We also detected YopM in a complex with Pyrin and kinases RSK1 and PKN1, putative negative regulators of Pyrin. In contrast to wild-type mice, Pyrin deficient mice were also highly susceptible to an attenuated Y. pestis strain lacking YopM, emphasizing the importance of inhibition of Pyrin in vivo. A complex interplay between the Y. pestis T3SS and IL-1β/IL-18 production is evident, involving at least four inflammasome pathways. The secreted effector YopJ triggers caspase-8- dependent IL-1β activation, even when YopM is present. Additionally, the presence of the T3SS needle/translocon activates NLRP3 and NLRC4-dependent IL-1β generation, which is blocked by YopK, but not by YopM. Taken together, the data suggest YopM specificity for obstructing the Pyrin pathway, as the effector does not appear to block Y. pestis-induced NLRP3, NLRC4 or caspase-8 dependent caspase-1 processing. Thus, we identify Y. pestis YopM as a microbial inhibitor of the Pyrin inflammasome. The fact that so many of the Y. pestis T3SS components are participating in regulation of IL-1β/IL-18 release suggests that these effects are essential for maximal control of innate immunity during plague.
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2,335,399 |
Cervical Interlaminar Epidural Injections at High Doses Do Not Increase Optic Nerve Sheath Diameter on a Long-Term Basis.
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Cervical epidural injection (CEI) is widely performed on patients with pain originating from the cervical spine. Studies have shown a good relationship between the optic nerve sheath diameter (ONSD) and the intracranial pressure (ICP).</AbstractText>The aim of this study was to evaluate the changes in the ONSD as a non-invasive surrogate marker of ICP after CEI.</AbstractText>Prospective observational study.</AbstractText>Hospital and ambulatory pain clinic.</AbstractText>Twenty patients undergoing CEI at the C5-6 level were enrolled in this observational study. The CEIs were performed using a total of 14 mL of mixture volume via the interlaminar approach in the right lateral decubitus position. The ONSD through ultrasonography was measured in the initial supine position (T0, baseline), 30 seconds after the completion of CEI (T0.5), at 30-second intervals for 5 minutes (T0.5~T5), and at one-minute intervals for 5 minutes (T6~T10).</AbstractText>The values of the baseline ONSD (T0) in both eyes were 4.1 ± 0.4 mm. The ONSD significantly increased from T1 to T10 (P < 0.05) compared with T0. The maximum value of the ONSD was measured as 5.1 ± 0.4 mm at T4, and the mean difference between the baseline ONSD and its maximum value was 1.0 mm, which represented about 27%. There was no increase in ICP-related complications such as dizziness, headache, visual acuity, or retinal hemorrhage.</AbstractText>This was an observational study without a control group. All patients were presumed to have no intracranial pathology.</AbstractText>The 14 mL CEI resulted in an increase in the ONSD by ultrasonography over time. The most critical increase in ONSD was observed 4 minutes after CEI, but this increase was not sustained. Further work is needed to confirm the effects of the speed and volume of the injection and of the position.</AbstractText>Registered in the Clinical Research Information Service of the Korea National Institute of Health, registration number: KCT0001487. Key words: Analgesic techniques, epidural block, intracranial pressure, optic nerve sheath diameter, ultrasonography Analgesic techniques, epidural block, intracranial pressure, optic nerve sheath diameter, ultrasonography.</AbstractText>
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