Anesthesia for patients with liver disease

Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isofurane, Desfurane or Sevofurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient's condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above mentioned rules a safe anesthesia could be achievable in these patients. © 2014, Kowsar Corp.; Published by Kowsar Corp

Lower intrafamilial transmission rate of hepatitis B in patients with hepatitis D coinfection: A data-mining approach

demographic and viral characteristics of family members affect the transmission rate. Objectives: In this study, we have used data mining techniques to investigate the impact of different variables in intrafamilial transmission of HBV infection. Patients and Methods: demographic information, viral markers, and medical history of 330 patients with chronic hepatitis B and their offspring attending a referral center in Tehran were collected. Data-mining techniques were administered to detect patterns. Results: The overall transmission rate was 15.7 (5.4 and 27.3 for male and female index cases respectively). In female patients, HBe Ag positively affected the transmission rate (49 vs. 23.4). There was a dominant change in transmission rate of female patients with negative results for Hbe Ag with HDV coinfection, where the transmission rate changed from 25 in patients with negative results for HDV Ab to 5 in those with positive results. In Hbe Ag negative male index cases, the transmission rate was 1.3 in cases with positive results for HDV Ab compared to 7 in those with negative findings. The overall transmission rate was statistically different between patients with positive and negative results for HDV Ab (P = 0.016). Conclusions: There is a minor but consistent pattern change in the presence of HDV infection which reduces familial transmission of HBV, especially in female patients with negative results for HBe Ag. © 2013, Kowsar Corp

A new approach to estimation of the number of central synapse(s) included in the H-reflex

BACKGROUND: Among the main clinical applications of the H-reflex are the evaluation of the S1 nerve root conductivity such as radiculopathy and measurement of the excitability of the spinal motoneurons in neurological conditions. An attempt has been made to reduce the pathway over which H-reflex can be obtained in a hope to localize a lesion to the S1 nerve root, so the S1 central loop has been suggested. The main goal of this study is the estimation of the H-reflex number of synapse(s) for better understanding of the physiology of this practical reflex. METHODS: Forty healthy adult volunteers (22 males, 18 females) with the mean age of (37.7 ± 10.2) years participated in this study. They were positioned comfortably in the prone position, with their feet off the edge of the plinth. Recording electrodes were positioned at the mid point of a line connecting the mid popliteal crease to the proximal flare of the medial malleolus. Stimulation was applied at the tibial nerve in the popliteal fossa and H, F and M waves were recorded. Without any change in the location of the recording electrodes, a monopolar needle was inserted as cathode at a point 1 cm medial to the posterior superior iliac spine, perpendicular to the frontal plane. The anode electrode was placed over the anterior superior iliac spine, and then M and H waves of the central loop were recorded. After processing the data, sacral cord conduction delay was determined by this formula: * Sacral cord conduction delay = central loop of H-reflex – (delays of the proximal motor and sensory fibers in the central loop). RESULTS: The central loop of H-reflex was (6.77 ± 0.28) msec and the sacral cord conduction delay was (1.09 ± 0.06) msec. CONCLUSION: The sacral cord conduction time was estimated to be about 1.09 msec in this study and because at least 1 msec is required to transmit the signal across the synapse between the sensory ending and the motor cell, so this estimated time was sufficient for only one central synapse in this reflex

Rising burden of Hepatitis C Virus in hemodialysis patients

<p>Abstract</p> <p>Aim</p> <p>High prevalence of Hepatitis C virus (HCV) has been reported among the dialysis patients throughout the world. No serious efforts were taken to investigate HCV in patients undergoing hemodialysis (HD) treatment who are at great increased risk to HCV. HCV genotypes are important in the study of epidemiology, pathogenesis and reaction to antiviral therapy. This study was performed to investigate the prevalence of active HCV infection, HCV genotypes and to assess risk factors associated with HCV genotype infection in HD patients of Khyber Pakhtunkhwa as well as comparing this prevalence data with past studies in Pakistan.</p> <p>Methods</p> <p>Polymerase chain reaction was performed for HCV RNA detection and genotyping in 384 HD patients. The data obtained was compared with available past studies from Pakistan.</p> <p>Results</p> <p>Anti HCV antibodies were observed in 112 (29.2%), of whom 90 (80.4%) were HCV RNA positive. In rest of the anti HCV negative patients, HCV RNA was detected in 16 (5.9%) patients. The dominant HCV genotypes in HCV infected HD patients were found to be 3a (n = 36), 3b (n = 20), 1a (n = 16), 2a (n = 10), 2b (n = 2), 1b (n = 4), 4a (n = 2), untypeable (n = 10) and mixed (n = 12) genotype.</p> <p>Conclusion</p> <p>This study suggesting that i) the prevalence of HCV does not differentiate between past and present infection and continued to be elevated ii) HD patients may be a risk for HCV due to the involvement of multiple routes of infections especially poor blood screening of transfused blood and low standard of dialysis procedures in Pakistan and iii) need to apply infection control practice.</p

A Bcl-x(L)-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis

Following exocytosis, the rate of recovery of neurotransmitter release is determined by vesicle retrieval from the plasma membrane and by recruitment of vesicles from reserve pools within the synapse, which is dependent on mitochondrial ATP. The anti-apoptotic Bcl-2 family protein Bcl-xL also regulates neurotransmitter release and recovery in part by increasing ATP availability from mitochondria. We now find, that Bcl-xL directly regulates endocytic vesicle retrieval in hippocampal neurons through protein–protein interaction with components of the clathrin complex. Our evidence suggests that, during synaptic stimulation, Bcl-xL translocates to clathrin-coated pits in a calmodulin-dependent manner and forms a complex with the GTPase Drp1, Mff and clathrin. Depletion of Drp1 produces misformed endocytic vesicles. Mutagenesis studies suggest that formation of the Bcl-xL–Drp1 complex is necessary for the enhanced rate of vesicle endocytosis produced by Bcl-xL, thus providing a mechanism for presynaptic plasticity

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin