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Highlights • COVID-19 pandemic has changed the risk-benefit balance for cardiopulmonary resuscitation [CPR]. • Amongst many aerosol producing procedures performed on patients, CPR is a highly aerosol-generating procedure. • Available literature is inadequate to direct clinicians towards keeping low or high threshold for performing CPR in COVID-19 patient.

Clinicians can use mechanical waveform analysis as a diagnostic tool to identify pulmonary pathophysiology. This review offers an approach to develop a hypothesis of a patient’s lung pathophysiology.

Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020. In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.

Objective The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. Methods This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th–April 24th 2020) at a large medical center in NYC (n = 657). Results Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. Conclusions NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

Delirium is associated with increased hospital costs, health care complications, and increased mortality. Long-term consequences of delirium on cognition have not been synthesized and quantified via meta-analysis.To determine if an episode of delirium was an independent risk factor for long-term cognitive decline, and if it was, whether it was causative or an epiphenomenon in already compromised individuals.A systematic search in PubMed, Cochrane, and Embase was conducted from January 1, 1965, to December 31, 2018. A systematic review guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses was conducted. Search terms included delirium AND postoperative cognitive dysfunction; delirium and cognitive decline; delirium AND dementia; and delirium AND memory.Inclusion criteria for studies included contrast between groups with delirium and without delirium; an objective continuous or binary measure of cognitive outcome; a final time point of 3 or more months after the delirium episode. The electronic search was conducted according to established methodologies and was executed on October 17, 2018.Three authors extracted data on individual characteristics, study design, and outcome, followed by a second independent check on outcome measures. Effect sizes were calculated as Hedges g. If necessary, binary outcomes were also converted to g. Only a single effect size was calculated for each study.The planned main outcome was magnitude of cognitive decline in Hedges g effect size in delirium groups when contrasted with groups that did not experience delirium.Of 1583 articles, data subjected from the 24 studies (including 3562 patients who experienced delirium and 6987 controls who did not) were included in a random-effects meta-analysis for pooled effect estimates and random-effects meta-regressions to identify sources of study variance. One study was excluded as an outlier. There was a significant association between delirium and long-term cognitive decline, as the estimated effect size (Hedges g) for 23 studies was 0.45 (95% CI, 0.34-0.57; P .001). In all studies, the group that experienced delirium had worse cognition at the final time point. The I2 measure of between-study variability in g was 0.81. A multivariable meta-regression suggested that duration of follow-up (longer with larger gs), number of covariates controlled (greater numbers were associated with smaller gs), and baseline cognitive matching (matching was associated with larger gs) were significant sources of variance. More specialized subgroup and meta-regressions were consistent with predictions that suggested that delirium may be a causative factor in cognitive decline.In this meta-analysis, delirium was significantly associated with long-term cognitive decline in both surgical and nonsurgical patients.

PURPOSE: Lung protective ventilation (LPV), defined as a tidal volume (Vt) ≤8cc/kg of predicted body weight, reduces ventilator-induced lung injury but is applied inconsistently. MATERIALS AND METHODS: We conducted (1) a prospective, quasi-experimental, cohort study of adults mechanically ventilated admitted to intensive care units (ICU) in the year before, year after, and second year after implementation of an electronic medical record based LPV order, and (2) a cross-sectional qualitative study of ICU providers regarding their perceptions of the order. We applied the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate the implementation. RESULTS: There were 1405, 1424, and 1342 in the control, adoption, and maintenance cohorts, representing 95% of mechanically ventilated adult ICU patients. The overall prevalence of LPV increased from 65% to 73% (p

As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can differ greatly in etiology and treatment from what is described by the American Heart Association advanced cardiac life support algorithms, which were largely developed for use in out-of-hospital cardiac arrest and in-hospital cardiac arrest outside of the perioperative space. Specifically, there are several life-threatening causes of PPCA of which the management should be within the skill set of all anesthesiologists. However, previous research has demonstrated that continued review and training in the management of these scenarios is greatly needed and is also associated with improved delivery of care and outcomes during PPCA. There is a growing body of literature describing the incidence, causes, treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia, massive trauma, and local anesthetic systemic toxicity) and the need for a better awareness of these topics within the anesthesiology community at large. As noted in part 1 of this series, these events are always witnessed by a member of the perioperative team, frequently anticipated, and involve rescuer-providers with knowledge of the patient and the procedure they are undergoing or have had. Formulation of an appropriate differential diagnosis and rapid application of targeted interventions are critical for good patient outcome. Resuscitation algorithms that include the evaluation and management of common causes leading to cardiac in the perioperative setting are presented. Practicing anesthesiologists need a working knowledge of these algorithms to maximize good outcomes.

Cardiac arrest in the operating room and procedural areas has a different spectrum of causes (ie, hypovolemia, gas embolism, and hyperkalemia), and rapid and appropriate evaluation and management of these causes require modification of traditional cardiac arrest algorithms. There is a small but growing body of literature describing the incidence, causes, treatments, and outcomes of circulatory crisis and perioperative cardiac arrest. These events are almost always witnessed, frequently known, and involve rescuer providers with knowledge of the patient and their procedure. In this setting, there can be formulation of a differential diagnosis and a directed intervention that treats the likely underlying cause(s) of the crisis while concurrently managing the crisis itself. Management of cardiac arrest of the perioperative patient is predicated on expert opinion, physiologic rationale, and an understanding of the context in which these events occur. Resuscitation algorithms should consider the evaluation and management of these causes of crisis in the perioperative setting.

Cardiac arrest systems of care are successfully coordinating community, emergency medical services, and hospital efforts to improve the process of care for patients who have had a cardiac arrest. As a result, the number of people surviving sudden cardiac arrest is increasing. However, physical, cognitive, and emotional effects of surviving cardiac arrest may linger for months or years. Systematic recommendations stop short of addressing partnerships needed to care for patients and caregivers after medical stabilization. This document expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac arrest survivorship.

Objective Recognition of potential for neurological recovery in patients who remain comatose after cardiac arrest is challenging and strains clinical decision making. Here, we utilize an approach that is based on physiological principles underlying recovery of consciousness and show correlation with clinical recovery after acute anoxic brain injury. Methods A cohort study of 54 patients admitted to an Intensive Care Unit after cardiac arrest who underwent standardized bedside behavioral testing (Coma Recovery Scale – Revised [CRS-R]) during EEG monitoring. Blinded to all clinical variables, artifact-free EEG segments were selected around maximally aroused states and analyzed using a multi-taper method to assess frequency spectral content. EEG spectral features were assessed based on pre-defined categories that are linked to anterior forebrain corticothalamic integrity. Clinical outcomes were determined at the time of hospital discharge, using Cerebral Performance Categories (CPC). Results Ten patients with ongoing seizures, myogenic artifacts or technical limitations obscuring recognition of underlying cortical dynamic activity were excluded from primary analysis. Of the 44 remaining patients with distinct EEG spectral features, 39 (88%) fit into our predefined categories. In these patients, spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness and favorable clinical outcome at the time of hospital discharge (P = 0.014). Interpretation Predicted transitions of neocortical dynamics that indicate functional integrity of anterior forebrain corticothalamic circuitry correlate with clinical outcomes in postcardiac-arrest patients. Our results support a new biologically driven approach toward better understanding of neurological recovery after cardiac arrest.

Objectives To evaluate the association between length of ICU stay and 1-year mortality for elderly patients who survived to hospital discharge in the United States. Design Retrospective cohort study of a random sample of Medicare beneficiaries who survived to hospital discharge, with 1- and 3-year follow-up, stratified by the number of days of intensive care and with additional stratification based on receipt of mechanical ventilation. Interventions None. Patients The cohort included 34,696 Medicare beneficiaries older than 65 years who received intensive care and survived to hospital discharge in 2005. Measurements and main results Among 34,696 patients who survived to hospital discharge, the mean ICU length of stay was 3.4 days (± 4.5 d). Patients (88.9%) were in the ICU for 1-6 days, representing 58.6% of ICU bed-days. Patients (1.3%) were in the ICU for 21 or more days, but these patients used 11.6% of bed-days. The percentage of mechanically ventilated patients increased with increasing length of stay (6.3% for 1-6 d in the ICU and 71.3% for ≥ 21 d). One-year mortality was 26.6%, ranging from 19.4% for patients in the ICU for 1 day, up to 57.8% for patients in the ICU for 21 or more days. For each day beyond 7 days in the ICU, there was an increased odds of death by 1 year of 1.04 (95% CI, 1.03-1.05) irrespective of the need for mechanical ventilation. Conclusions Increasing ICU length of stay is associated with higher 1-year mortality for both mechanically ventilated and non-mechanically ventilated patients. No specific cutoff was associated with a clear plateau or sharp increase in long-term risk.

BackgroundIt is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses.MethodsIn this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category.ResultsPatients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively).ConclusionsCortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder.In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1).The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen's d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine's effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.

Few valid and reliable grading checklists have been published for the evaluation of performance during simulated high-stakes perioperative event management. As such, the purposes of this study were to construct valid scoring checklists for a variety of perioperative emergencies and to determine the reliability of scores produced by these checklists during continuous video review.A group of anesthesiologists, intensivists, and educators created a set of simulation grading checklists for the assessment of the following scenarios: severe anaphylaxis, cerebrovascular accident, hyperkalemic arrest, malignant hyperthermia, and acute coronary syndrome. Checklist items were coded as critical or noncritical. Nonexpert raters evaluated 10 simulation videos in a random order, with each video being graded 4 times. A group of faculty experts also graded the videos to create a reference standard to which nonexpert ratings were compared. P0.05 was considered significant.Team leaders in the simulation videos were scored by the expert panel as having performed 56.5% of all items on the checklist (range, 43.8%-84.0%), and 67.2% of the critical items (range, 30.0%-100%). Nonexpert raters agreed with the expert assessment 89.6% of the time (95% confidence interval, 87.2%-91.6%). No learning curve development was found with repetitive video assessment or checklist use. The κ values comparing nonexpert rater assessments to the reference standard averaged 0.76 (95% confidence interval, 0.71-0.81).The findings indicate that the grading checklists described are valid, are reliable, and could be used in perioperative crisis management assessment.

The paper describes HPLC, UV spectrophotometric and non aqueous titrimetric method for the estimation of poorly water soluble protease inhibitor. Ritonavir in raw material and tablet dosage form. HPLC analysis was carried out in a C18 column using acetonitrile, methanol, and buffer in the ratio 60: 20: 20 (v/v/v) at 240 nm. For the spectrophotometric determination, methanolic solution of Ritonavir was reacted with 3-methyl benzothiazolin-2-one hydrazone (MBTH). The oxidative coupled green coloured chromogen was analysed at 633 nm. Non aqueous titration was carried out using perchloric acid as titrant and the end point was determined using crystal violet as indicator. The three methods were validated and statistically evaluated to correlate the difference between the methods for estimation of Ritonavir in pharmaceutical dosage form.

Patients with liver disease have multisystem organ dysfunction that leads to physiological perturbations ranging from hyperbilirubinaemia of no clinical consequence to severe coagulopathy and metabolic disarray. Patient-specific risk factors, clinical scoring systems, and surgical procedures stratify perioperative risk for these patients. The anaesthetic management of patients with hepatic dysfunction involves consideration of impaired drug metabolism, hyperdynamic circulation, perioperative hypoxaemia, bleeding, thrombosis, and hepatic encephalopathy.

Anesthesiologists face several perioperative challenges when patients need cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion. To adequately care for these patients, anesthesiologists must understand the goals and objectives of the operation in addition to having a basic knowledge of the chemotherapeutic drugs that are frequently used. Optimal anesthetic management of patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion requires control of a complex interplay of physiologic mechanisms, including hyperthermia, abdominal hypertension, electrolyte abnormalities, coagulopathies, increased cardiac index, oxygen consumption, and decreased systemic vascular resistance. As this surgery continues to gain popularity among oncologic surgeons, further studies that clearly define the chemistry, pharmacokinetics, pharmacodynamics, and end points of efficacy need to be performed to elucidate optimal perioperative management.

Background: Ritonavir is a protease inhibitor and mostly used as a booster for increasing the bioavailability of other protease inhibitors like Atazanavir Sulfate and Lopinavir. Aims: Quality assessment of the new dosage form of Ritonavir i.e. tablets is very essential, so two sensitive, simple and precise methods are developed for quantification of Ritonavir in bulk and tablet dosage forms. Materials and Methods: The first method is based on first order derivative method and the second is based on area under curve method. Both the methods are validated according to international conference of harmonization (ICH) guidelines. A stability study of Ritonavir is done in UV - Visible Spectrophotometer under different stress conditions recommended by ICH guidelines. Results: The absorption maximum is found to be 239nm in methanol. The absorption maximum in first method is chosen at 253.2nm, and the linearity is found between 4 - 20 ΅g/ml with coefficient of correlation value 0.9981. In the second method, the range for area under curve selected is 237 - 242nm. The linearity is found between 4 -20 ΅g/ml with coefficient of correlation value 0.9992. Conclusion: The developed methods are validated and found to be simple, rapid, precise and cost-effective. The degradation study in tablet dosage form can be used as a stability indicating assay method.

Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis. In yeast, SPT is composed of a heterodimer of 2 highly-related subunits, Lcb1p and Lcb2p, and a third subunit, Tsc3p, which increases enzyme activity markedly and is required for growth at elevated temperatures. Higher eukaryotic orthologs of Lcb1p and Lcb2p have been identified, but SPT activity is not highly correlated with coexpression of these subunits and no ortholog of Tsc3p has been identified. Here, we report the discovery of 2 proteins, ssSPTa and ssSPTb, which despite sharing no homology with Tsc3p, each substantially enhance the activity of mammalian SPT expressed in either yeast or mammalian cells and therefore define an evolutionarily conserved family of low molecular weight proteins that confer full enzyme activity. The 2 ssSPT isoforms share a conserved hydrophobic central domain predicted to reside in the membrane, and each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis. The presence of these small subunits, along with 2 hLCB2 isofoms, suggests that there are 4 distinct human SPT isozymes. When each SPT isozyme was expressed in either yeast or CHO LyB cells lacking endogenous SPT activity, characterization of their in vitro enzymatic activities, and long-chain base (LCB) profiling revealed differences in acyl-CoA preference that offer a potential explanation for the observed diversity of LCB seen in mammalian cells.

Basic life support (BLS), advanced cardiovascular life support (ACLS), and post–cardiac arrest care are labels of convenience that each describe a set of skills and knowledge that are applied sequentially during the treatment of patients who have a cardiac arrest. There is overlap as each stage of care progresses to the next, but generally ACLS comprises the level of care between BLS and post–cardiac arrest care. ACLS training is recommended for advanced providers of both prehospital and in-hospital medical care. In the past, much of the data regarding resuscitation was gathered from out-of-hospital arrests, but in recent years, data have also been collected from in-hospital arrests, allowing for a comparison of cardiac arrest and resuscitation in these 2 settings. While there are many similarities, there are also some differences between in- and out-of-hospital cardiac arrest etiology, which may lead to changes in recommended resuscitation treatment or in sequencing of care. The consideration of steroid administration for in-hospital cardiac arrest (IHCA) versus out-of-hospital cardiac arrest (OHCA) is one such example discussed in this Part. The recommendations in this 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) after the publication of the ILCOR 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 1 and was completed in February 2015.2 In this in-depth evidence review process, the ILCOR task forces examined topics and then generated prioritized lists of questions for systematic review. Questions were first formulated in PICO (population, intervention, comparator, outcome) format,3 and then a search strategy and inclusion and exclusion criteria were defined and a search for relevant articles was performed. The evidence was evaluated by using …

The genus Coccolithovirus is a recently discovered group of viruses that infect the globally important marine calcifying microalga Emiliania huxleyi. Surprisingly, the viral genome contains a cluster of putative sphingolipid biosynthetic genes not found in other viral genus. To address the role of these genes in viral pathogenesis, the ehv050 gene predicted to encode a serine palmitoyltransferase (SPT), the first and rate-limiting enzyme of sphingolipid biosynthesis, was expressed and characterized in Saccharomyces cerevisiae. We show that the encoded protein is indeed a fully functional, endoplasmic reticulum-localized, single-chain SPT. In eukaryotes SPT is a heterodimer comprised of long chain base 1 (LCB1) and LCB2 subunits. Sequence alignment and mutational analysis showed that the N-terminal domain of the viral protein most closely resembled the LCB2 subunit and the C-terminal domain most closely resembled the LCB1 subunit. Regardless of whether the viral protein was expressed as a single polypeptide or as two independent domains, it exhibited an unusual preference for myristoyl-CoA rather than palmitoyl-CoA. This preference was reflected by the increased presence of C16-sphingoid bases in yeast cells expressing the viral protein. The occurrence of a single-chain SPT suggested to us that it might be possible to create other fusion SPTs with unique properties. Remarkably, when the two subunits of the yeast SPT were thus expressed, the single-chain chimera was functional and displayed a novel substrate preference. This suggests that expression of other multisubunit membrane proteins as single-chain chimera could provide a powerful approach to the characterization of integral membrane proteins.

We previously identified BTBD1 and BTBD2 as novel topoisomerase I-interacting proteins that share 80% amino acid identity. Here we report the characterization of their subcellular localization. In a number of mouse and human cells, BTBD1 and BTBD2 (BTBD1/2) colocalized to punctate or elongated cytoplasmic bodies (< 5 microm long and several per cell) that were larger and more elongated in cancer cell lines than in fibroblasts and myoblasts. A search for potential colocalizing proteins identified TRIM family members that localize to morphologically similar cytoplasmic bodies, which were then tested for colocalization with BTBD1/2. TRIM5delta, expressed as a GFP fusion, colocalized with BTBD1/2 immunostaining and appeared to serve as a scaffold for the assembly of endogenous BTBD1/2 proteins. TRIM family members contain a RING domain, B-box(es), and coiled-coil regions, which have a characteristic order and spacing (RBCC domain). RING-dependent ubiquitin ligase activity and multimerization via the coiled-coil region may be defining properties of the RBCC/TRIM protein family. We found that TRIM5delta with a deleted coiled-coil region or a mutated RING domain failed to colocalize with BTBD1/2. Additionally, TRIM5delta ubiquitylated itself in a RING finger- and UbcH5B-dependent manner. BTBD1/2 each contain a PHR-similarity region, repeated twice on the putative ubiquitin ligases PAM, highwire and RPM-1, which also contain a RING and B-box. Thus, four protein modules found on each of these putative ubiquitin ligases, a RING, a B-box and two PHR repeats, are present on BTBD1/2 and TRIM5delta that are colocalized to cytoplasmic bodies.

Evidence accumulated over the years suggests that human erythrocyte membrane protein 4.2 is one of the proteins involved in strengthening the cytoskeleton-membrane interactions in the red blood cell. Deficiency of protein 4.2 is linked with a variety of hereditary haemolytic anaemia. However, the interactions of protein 4.2 with other proteins of the erythrocyte membrane remain poorly understood. The major membrane-binding site for protein 4.2 resides on the cytoplasmic domain of band 3 (CDB3). In order to carry out an initial characterization of its interaction with the CDB3, protein 4.2 was subjected to proteolytic cleavage and gel renaturation assay, and the 23-kDa N-terminal domain was found to interact with band 3. This domain contained two putative palmitoylatable cysteine residues, of which cysteine 203 was identified as the palmitoylatable cysteine. Recombinant glutathione S-transferase-fusion peptides derived from this domain were characterized with respect to their ability to interact with the CDB3. Whereas these studies do not rule out the involvement of other subsites on protein 4.2 in interaction with the CDB3, the evidence suggests that the region encompassing amino acid residues 187-211 is one of the domains critical for the protein 4.2-CDB3 interaction. This is also the first demonstration that palmitoylation serves as a positive modulator of this interaction.

The polymyxins (polymyxin B and E) are bactericidal polypeptide antibiotics first discovered in 1947 and used for the treatment of gram-negative bacterial infections. Renal and neurologic toxicities coupled with the increasing availability of effective alternatives led to declining use in the 1960s. The emergence of multidrug-resistant organisms in the past decade has resulted in a resurgence in the use of polymyxins in critically ill patients, yet the side effects are not well known. We report two cases of respiratory arrest likely due to polymyxin B infusions in the context of a 10-fold increase in the use of polymyxin B in our institution over the past 10 years.

1used in the treatment of human immunodeficiency virus (HIV) Type II infection. ATV is re ported as poorly water soluble and a known substrate for both hepatic metabolizing enzyme Cytochrome 450 (CYP3A) and intestinal drug efflux pump, P-glycoprotein (Pgp) so have low oral bioavailability. 2 So co-administration of small dose of Ritonavir (RTV) is recommended as booster. This new drug is official in IP - 2010, but not included in BP or USP. The reported analytical methods for the determination of ATV are based on high performance liquid chromatography (HPLC) 3-12 in biological samples like blood plasma, biological cells, cerebrospinal fluid (CSF) and blood serum. Stress degradation studies were reported analysed by HPLC and ultraviolet spectrophotometry. 13, 14 The present work was aimed to develop a visible spectrophotometric method, which is simple, sensitive, accurate and cost effective to evaluate the quality of the bulk and pharmaceutical formulations. The novelties of the developed methods are that the reagents used in both the methods are easily available and the mechanisms of reactions of the reagents are already well established. The reactions involved with these reagents are simple, rapid and sensitive. Spectrophotometric methods involve simple instrumentation which is cost effective as compared to other instrumental techniques. The present method involves the determination of ATV, which is a second line drug for treatment of type II HIV infection. Still now, the 2 nd line drugs are available at higher price, than the 1 st line drugs. The high

Background Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5α restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5α splice variant TRIM5δ in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction. Results We show that the interaction of BTBD1 and BTBD2 with TOP1 requires hu-TOP1 residues 236 and 237, the same residues required to enhance the infectivity of progeny virions when hu-TOP1 is expressed in AGM producer cells. Additionally, interference with the expression of BTBD2 in AGM and human 293T target cells increased their permissiveness to HIV-1 infection two- to three-fold. Conclusions These results do not exclude the possibility that BTBD2 may modestly restrict HIV-1 infection via colocation with TRIM5 variants in cytoplasmic bodies.

Hyperglycemia and elevated glycosylated hemoglobin (HbA(1c)) are associated with perioperative morbidity in patients with diabetes, but the relationship between long-term glycemic control and perioperative glucose control is unknown. The purpose of this study was to determine the relationship between glycosylated hemoglobin (HbA(1c)) and perioperative glucose in fasting patients with type 2 diabetes undergoing elective non-cardiac surgery.This was a prospective observational study of 244 adult patients with type 2 diabetes who were evaluated before elective non-cardiac surgery at a preoperative medicine clinic in a tertiary care medical centre during the period September 2004 to May 2005. Preoperative HbA(1c) levels were determined, and preoperative and postoperative glucose values were measured on the day of surgery. The primary outcome variables were preoperative and postoperative blood glucose values.Half of all study patients had an HbA(1c)or = 7%, including 23% of patients with HbA(1c)/= 8%. HbA(1c) levels predict preoperative glucose levels, and preoperative glucose levels and duration of surgery predict postoperative glucose levels. Glucose levels in one-third of the patients with type 2 diabetes decreased during surgery without administration of insulin or glucose-regulating medications.HbA(1c) values may serve as biomarkers for glucose control during the immediate perioperative period in patients with type 2 diabetes undergoing elective surgery.

A splenectomized patient with systemic lupus erythematosus, who had previously been treated with high doses of corticosteroids, presented with headaches and symptoms of a respiratory tract infection. A magnetic resonance imaging scan of the brain revealed a ring-enhancing lesion, and Nocardia asteroides was isolated from a stereotactic biopsy specimen. After adverse reactions to a number of antibiotics, infection control was finally achieved by the new oxazolidinone drug, linezolid. Nocardiosis should be considered as a differential diagnosis in all immunocompromised patients who develop an obscure infection; delay in diagnosis and subsequent initiation of appropriate treatment often results in a fatal outcome. Linezolid is a new option for the treatment of nocardiosis and is effective when given orally.

Protein 4.2 is a major component of the red blood cell membrane skeleton. Deficiency of protein 4.2 is linked with a variety of hereditary haemolytic anaemias. However, the interactions of protein 4.2 with other proteins of the erythrocyte membrane remain poorly understood. The major membrane-binding site for protein 4.2 resides on the cytoplasmic domain of band 3. Protein 4.2 interacts directly with spectrin in solution, suggesting that it stabilizes interactions between the membrane skeleton and the erythrocyte membrane. A 30kDa polypeptide, with its N-terminus corresponding to amino acid residue 269, derived by partial proteolysis of protein 4.2, was found to interact with biotinylated spectrin in gel renaturation assays. A series of overlapping glutathione S-transferase fusion peptides were constructed, and an α-helical domain encompassing residues 470–492 was found to be instrumental in mediating protein 4.2—spectrin interactions. Direct binding of a synthetic peptide, with the sequence corresponding to residues 470–492, to spectrin and the ability of the peptide to inhibit spectrin binding of protein 4.2 confirmed that these residues are crucial in mediating protein 4.2—spectrin interactions.

Central Pollution Control Board, East Arjun Nagar, Delhi-110 032 Department of Chemistry, Pt. Ravishankar Shukla University, Raipur-492 010 Manuscript received 8 June 1993, revised 6 January 1994, accepted 6 April 1994 Microgram Determination of Lead(II) using 2-Thioorotic Acid (Ammonium Salt) : Application to Steel Plant Effluent.

Renal perfusion relies upon cardiac output, renal blood fl ow, and autoregulation. HRS infl uences cardiac output and systemic vascular resistance, and establishing a pressure gradient across the glomerulus ensures renal blood fl ow and glomerular fi ltration rate [2,3]. In fl uid responsive patients, volume resuscitation is a key component of HRS management. Th e traditional target mean arterial pressure (MAP) of 65 mmHg to ensure renal perfusion assumes that ‘one size fi ts all’ in HRS. Th e kidneys are in the abdominal compartment, and intraabdominal pressure varies among individuals. Th e pressure of the compartment during disease states that cause ascites decreases renal perfusion pressure and should be overcome, especially when autoregulation is impaired [4]. In other words, the arbitrary suggestion of increasing the MAP by 10 mmHg (Table 6 in [1]) may not be enough (or may be too much). Titrating norepinephrine to a baseline MAP of 65 mmHg plus the intraabdominal pressure [4] and administering terlipressin or vasopressin (which may constrict the eff erent glomerular arteriole [5]) may be an eff ective hemodynamic strategy to ensure renal perfusion pressure. Although this recommendation may not be based on grade A evidence, it is physiologically sound (establishes a pressure gradient) and may inspire further studies of hemodynamic management in patients with HRS.

We present a detailed analysis of the nature of electronic eigenfunctions in one-dimensional quasiperiodic chains based on a clustering idea recently introduced by us [Sil et al., Phys. Rev. B 48, 4192 (1993)], within the framework of the real-space renormalization-group approach. It is shown that even in the absence of translational invariance, extended states arise in a class of such lattices if they possess a certain local correlation among the constituent atoms. We have applied these ideas to the quasiperiodic period-doubling chain, whose spectrum is found to exhibit a rich variety of behavior, including a crossover from critical to an extended regime, as a function of the Hamiltonian parameters. Contrary to prevailing ideas, the period-doubling lattice is shown to support an infinity of extended states, even though the polynomial invariant associated with the trace map is nonvanishing. Results are presented for different parameter regimes, yielding both periodic as well as nonperiodic eigenfunctions. We have also extended the present theory to a multiband model arising from a quasiperiodically arranged array of \ensuremath{\delta}-function potentials on the atomic sites. Finally, we present a multifractal analysis of these wave functions following the method of Godreche and Luck [J. Phys. A 23, 3769 (1990)] to confirm their extended character.

A new type of correlated disorder is shown to be responsible for the appearance of extended electronic states in one-dimensional aperiodic systems like the Thue-Morse lattice. Our analysis leads to an understanding of the underlying reason for the extended states in this system, for which only numerical evidence is available in the literature so far. The present work also sheds light on the restrictive conditions under which the extended states are supported by this lattice., Comment: 11 pages, LaTeX V2.09, 1 figure (available on request), to appear in Physical Review Letters

School of Studies m Chemistry, Ravishankar University, Raipur-492 010 Central Pollution Control Board, Motinagar, Shillong-793 014 Manuscript received 19 May 1992, revised 23 February 1993, accepted 9 March 1993 2-Thioorotic Acid (Pyridinium Salt) as a New Spectrophotometric Reagent for Copper(II) Determination

We discuss a very simple model of a 1-d disordered lattice, in which {\em all} the electronic eigenstates are extended. The nature of these states is examined from several viewpoints, and it is found that the eigenfunctions are not Bloch functions although they extend throughout the chain. Some typical wavefunctions are plotted. This problem originated in our earlier study of extended states in the quasiperiodic copper-mean lattice [ Sil, Karmakar, Moitra and Chakrabarti, Phys. Rev. B (1993) ]. In the present investigation extended states are found to arise from a different kind of correlation than that of the well-known dimer-type., Comment: 9 pages, 1 figure available on request, LaTex version 2.09, SINP-SSMP93-02

A non-perturbative theory is proposed in this article in which an energy independent effective Hamiltonian is obtained for open-shell systems. We have given a diagrammatic version of theory to facilitate the analysis of the problem. The theory has been applied to a model 4-π electron problem, for calculating the lowestπ-π* singlet and triplet energy levels of transbutadiene. Comparison with full Cl calculation indicates the excellent workability of the theory.

The appearance of phosphatidylserine (PS) on the outer surface of red cells is an important signal for their uptake by macrophages. We report for the first time that procaspase 3 present in the anucleated mature human erythrocyte is activated under oxidative stress induced by t-butylhydroperoxide leading to impairment of the aminophospholipid translocase, PS externalization and increased erythrophagocytosis. This is the first report linking caspase 3 activation to inhibition of flippase activity and uptake of red cells by macrophages.

The constellation of advanced cardiac life support (ACLS) events, such as gas embolism, local anesthetic overdose, and spinal bradycardia, in the perioperative setting differs from events in the pre-hospital arena. As a result, modification of traditional ACLS protocols allows for more specific etiology-based resuscitation.Perioperative arrests are both uncommon and heterogeneous and have not been described or studied to the same extent as cardiac arrest in the community. These crises are usually witnessed, frequently anticipated, and involve a rescuer physician with knowledge of the patient's comorbidities and coexisting anesthetic or surgically related pathophysiology. When the health care provider identifies the probable cause of arrest, the practitioner has the ability to initiate medical management rapidly.Recommendations for management must be predicated on expert opinion and physiological understanding rather than on the standards currently being used in the generation of ACLS protocols in the community. Adapting ACLS algorithms and considering the differential diagnoses of these perioperative events may prevent cardiac arrest.