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Background: To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438)., Methods: We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections., Results: Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts., Conclusions: Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.

Introduction: After infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and can enter the brain via retrograde axonal transport. Recurrent reactivation of HSV1 may lead to neurodegeneration and Alzheimer's disease (AD) pathology. HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid beta-protein (Aβ) aggregation and HSV1 DNA is common in amyloid plaques. Anti-HSV drugs reduce Aβ and phosphorylated tau accumulation in cell-culture models. Cognitive impairment is greater in patients with HSV seropositive, and antiviral drugs show robust efficacy against peripheral HSV infection. Recent studies of electronic health records databases demonstrate that HSV infections increase dementia risk, and that antiviral medication treatment reduces this risk. The generic antiviral drug valacyclovir was superior to placebo in improving memory in a schizophrenia pilot trial but has not been tested in AD., Methods and Analysis: In patients with mild AD who test positive for HSV1 or HSV2 serum antibodies, valacyclovir, repurposed as an anti-AD drug, will be compared with placebo (lactose pills) in 130 patients (65 valacyclovir and 65 placebo) in a randomised, double-blind, 78-week phase II proof-of-concept trial. Patients on valacyclovir, dose-titrated from 2 g to a targeted oral dose of 4 g daily, compared with placebo, are hypothesised to show smaller cognitive and functional decline, and, using 18 F-Florbetapir positron emission tomography (PET) and 18 F-MK-6240 PET imaging, to show less amyloid and tau accumulation, respectively. In the lumbar puncture subsample, cerebrospinal fluid acyclovir will be assayed to assess central nervous system valacyclovir penetration., Ethics and Dissemination: The trial is being overseen by the New York State Psychiatric Institute Institutional Review Board (protocol 7537), the National Institute on Ageing, and the Data Safety Monitoring Board. Written informed consent is obtained for all subjects. Results will be disseminated via publication, clinicaltrials.gov, media and conferences., Trial Registration Number: ClinicalTrials.gov identifier (NCT03282916) Pre-results., Competing Interests: Competing interests: AM, QR, KMP, DAD, WCK, EA, HA, JP, MK have no competing interests. DPD is a consultant to Acadia, Eisai, Genentech, Avanir, Neuronix, Grifols and BXcel Therapeutics and has grant support from the National Institute of Aging. EDH is a consultant to Biogen and Ionis. TW is a consultant to Alzemend Neuro, Inc. and Grifols and has grant support from the National Institute of Health and the National Institute on Aging. KLB has grant support from Lilly, Amylx and Biohaven. AAG is contracted with Merck. GHP has grant support from the National Institute on Aging. YS is a consultant to Eli Lilly, Axovant, Takeda, and AbbVie, has donated to Piramal Imaging Limited, has grant support from California Walnut Commission, and has a license for the Dependence Scale., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens. Abnormalities in complement functions occur in many infectious and autoimmune disorders that have been linked to schizophrenia. Many older reports indicate altered serum complement activity in schizophrenia, though the data are inconclusive. Compellingly, recent genome-wide association studies suggest repeat polymorphisms incorporating the complement 4A (C4A) and 4B (C4B) genes as risk factors for schizophrenia. The C4A/C4B genetic associations have re-ignited interest not only in inflammation-related models for schizophrenia pathogenesis, but also in neurodevelopmental theories, because rodent models indicate a role for complement proteins in synaptic pruning and neurodevelopment. Thus, the complement system could be used as one of the 'staging posts' for a variety of focused studies of schizophrenia pathogenesis. They include GEI studies of the C4A/C4B repeat polymorphisms in relation to inflammation-related or infectious processes, animal model studies and tests of hypotheses linked to autoimmune diseases that can co-segregate with schizophrenia. If they can be replicated, such studies would vastly improve our understanding of pathogenic processes in schizophrenia through GEI analyses and open new avenues for therapy.

A theoretical model of time-dependent peristaltic viscous fluid flow through a curved channel in the presence of an applied magnetic field is investigated. The results for stream function, pressure distribution and mechanical efficiency are obtained under the assumptions of long wavelength and low Reynolds number approximation. Pressure fluctuations due to an integral and a non-integral number of waves along the channel length are discussed under influence of channel curvature and magnetic parameter. Two inherent characteristics of peristaltic flow regimes (trapping and reflux) are discussed numerically. The mechanical efficiency of curved magnetohydrodynamic peristaltic pumping is also examined. The magnitude of pressure increases with an increasing channel curvature and magnetic parameter. Reflex phenomenon is analyzed in the Lagrangian frame of reference. It is observed that reflex in the curved channel is higher than in the straight channel. The trapped fluid in a curved channel is studied in the Eulerian frame of reference and it contains two asymmetric boluses. The size of the lower bolus grows and the upper bolus decreases with increasing effect of magnetic strength. Pumping efficiency of the peristaltic pump is low for curved channel flow than for straight channel flow. Also, the pumping efficiency is comparatively low at the high effect of the magnetic parameter., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development.

Background: Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens., Results: PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (β = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status., Conclusions: Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.

Effect of incorporation of graded levels (4, 6, 8, 10, 25 ppm) of lac dye on coloring efficacy and possible use of this natural color in processed meat products was studied. Inclusion of lac dye at different concentrations did not affect the pH significantly whereas a linear increase in the Lovibond red color unit of chicken nuggets was noted with raising the level of lac dye from 4 to 10 ppm. The sensory rating for color was highest at addition level of 25 ppm of lac dye and it was comparable to color score of the product containing 200 ppm sodium nitrite. Lac dye inclusion in nuggets at all concentrations studied had better antimicrobial properties as compared to 200 ppm sodium nitrite. It was concluded that lac dye from 10 to 25 ppm could be incorporated in comminuted meat products as a natural colorant with antimicrobial action.

Newly isolated serotypes of AAV readily cross the endothelial barrier to provide efficient transgene delivery throughout the body. However, tissue-specific expression is preferred in most experimental studies and gene therapy protocols. Previous efforts to restrict gene expression to the myocardium often relied on direct injection into heart muscle or intracoronary perfusion. Here, we report an AAV vector system employing the cardiac troponin T (cTnT) promoter. Using luciferase and enhanced green fluorescence protein (eGFP), the efficiency and specificity of cardiac reporter gene expression using AAV serotype capsids: AAV-1, 2, 6, 8 or 9 were tested after systemic administration to 1-week-old mice. Luciferase assays showed that the cTnT promoter worked in combination with each of the AAV serotype capsids to provide cardiomyocyte-specific gene expression, but AAV-9 followed closely by AAV-8 was the most efficient. AAV9-mediated gene expression from the cTnT promoter was 640-fold greater in the heart compared with the next highest tissue (liver). eGFP fluorescence indicated a transduction efficiency of 96% using AAV-9 at a dose of only 3.15 × 10(10) viral particles per mouse. Moreover, the intensity of cardiomyocyte eGFP fluorescence measured on a cell-by-cell basis revealed that AAV-mediated gene expression in the heart can be modeled as a Poisson distribution, requiring an average of nearly two vector genomes per cell to attain an 85% transduction efficiency.

Identification of causative factors for common, chronic disorders is a major focus of current human health science research. These disorders are likely to be caused by multiple etiological agents. Available evidence also suggests that interactions between the risk factors may explain some of their pathogenic effects. While progress in genomics and allied biological research has brought forth powerful analytic techniques, the predicted complexity poses daunting analytic challenges. The search for pathogenesis of schizophrenia shares most of these challenges. We have reviewed the analytic and logistic problems associated with the search for pathogenesis. Evidence for pathogenic interactions is presented for selected diseases and for schizophrenia. We end by suggesting 'recursive analyses' as a potential design to address these challenges. This scheme involves initial focused searches for interactions motivated by available evidence, typically involving identified individual risk factors, such as candidate gene variants. Putative interactions are tested rigorously for replication and for biological plausibility. Support for the interactions from statistical and functional analyses motivates a progressively larger array of interactants that are evaluated recursively. The risk explained by the interactions is assessed concurrently and further elaborate searches may be guided by the results of such analyses. By way of example, we summarize our ongoing analyses of dopaminergic polymorphisms, as well as infectious etiological factors in schizophrenia genesis., Competing Interests: None, (Copyright © 2009 Elsevier Inc. All rights reserved.)

Infectious agents have been proposed as one of the risk factors for schizophrenia. However, the data on the association of infectious agents with in vivo brain changes are scant. We evaluated the association of serological evidence of exposure to herpes simplex virus 1 (HSV1) with in vivo brain structural variations among first-episode antipsychotic-naive schizophrenia/schizoaffective disorder patients and control subjects. We assayed HSV1 immunoglobulin G (IgG) antibody in serum samples from 30 patients and 44 healthy subjects and obtained structural magnetic resonance imaging scans from the same individuals. There were proportionately more patients with elevated HSV1 antibody ratios than healthy comparison subjects (chi2=3.98, 1 df, P=0.046) and patients had significantly higher HSV1 IgG antibody ratios compared with healthy subjects. Using optimized voxel-based morphometry, we examined diagnosis by HSV1 serological status interaction followed by within- and between-group comparison across the serological status. We observed a diagnosis by HSV1 serological status interaction and a significant main effect of HSV1 serological status in the prefrontal gray matter. Patients exposed to HSV1 had decreased gray matter in Brodmann area 9 (dorsolateral prefrontal cortex) and 32 (anterior cingulate cortex) compared with patients without serological evidence of exposure to HSV1. HSV1-associated differences in brain structure were not detected among healthy subjects. These findings suggest that HSV1 exposure in schizophrenia is associated with specific regional gray matter differences that may not be attributable to medications, illness chronicity or comorbid substance use. This study provides suggestive evidence for a link between HSV1 exposure and some of the cerebral morphological changes often reported in schizophrenia.

Polymorphisms of the gene encoding the regulator of G-protein signaling subtype 4 (RGS4) may confer risk for schizophrenia.(1) DNA microarray studies of postmortem brain samples have shown RGS4 underexpression in the dorsolateral prefrontal cortex (DLPFC, area 9), motor and visual cortices in schizophrenia patients relative to control subjects.(2) Underexpression of RGS4 in DLPFC is pathophysiologically significant because DLPFC pathology in schizophrenia has been supported by neurocognitive,(3,4) structural(5) and functional(6,7) imaging, postmortem,(8) cellular(9,10) and molecular(11) pathological studies. For these reasons, we examined the association of DLPFC gray matter volume with RGS4 polymorphisms in a series of antipsychotic-naive first-episode schizophrenia patients and control subjects. We hypothesized that volumetric alterations of the DLPFC would be associated with RGS4 polymorphisms and that these differences would be more pronounced in patients than in controls. We observed robust volumetric differences across the genotypes in the pooled sample of patients and control subjects; when separately analyzed, we observed differences within the patient group (n = 30) but not in control subject (n = 27) group. The findings suggest that RGS4 polymorphisms may contribute to structural alterations in the DLPFC.

Background: In spite of a perception that alcohol use is rampant in Nepal, there has been no survey to assess the extent of alcohol dependence in the country., Aims: (i) To assess prevalence of alcohol dependence in the community of Dharan and (ii) to correlate this with various socio-demographic characteristics., Design: The CAGE questionnaire was administered to all adult individuals in houses selected randomly in the township of Dharan., Findings: Among 2344 adults assessed, the prevalence of alcohol dependence was found to be 25.8%. The prevalence of alcohol dependence increased with age to peak in the age group 45-54 years and was more than twice as common in men as in women. Also, alcohol dependence was more common among those with lower level of education, widowers and divorcees and those belonging to the Matwali community. The extent of dependence was influenced by socio-cultural sanctions., Conclusions: The prevalence of alcohol dependence is too high for comfort in Dharan, a town in eastern Nepal. There is an urgent need to formulate a policy for substance abuse in the country taking into account the findings of this study.

Insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes is an autoimmune disease that results in destruction of the insulin-producing pancreatic islet beta cells. Several factors induce the invasion of immune cells into islets and trigger inflammation. Gene therapy approaches targeting the islet cells could be an effective treatment to prevent the onset or reverse type 1 diabetes. Allogeneic islet transplantation provides short-term treatment. However, genetically modified islets, which resist the host immune response, could provide long-term solutions. Adeno-associated virus (AAV) is emerging as a prominent vector system for delivering therapeutic genes for human gene therapy. AAV vector can transduce nondividing cells and provide long-term gene expression by integrating into host chromosome. Therefore, it is an appropriate vector system for islet cell gene therapy. To test the efficacy of AAV vector to transduce pancreatic endocrine cells, we constructed AAV vectors using plasmid pSub201. Wild-type AAV DNA analogue from plasmid psub201 was subcloned into a cloning plasmid pSP72 and AAV vectors were constructed by inserting the transgenes with heterologous promoter in place of AAV open reading frames (rep and cap). In this report we demonstrate the transduction of pancreatic islet cells with AAV vectors encoding bacterial -galactosidase enzyme or enhanced green fluorescent protein (EGFP) as reporter gene. Dispersed porcine and rat islet cells can be transduced by AAV vector, with an efficiency of 47% and 38%, respectively. In particular porcine islet insulin producing beta cells were transduced with an efficiency of 39%. Intact rat islet cells were transduced with an efficiency of 26% as estimated by FACS analysis following transduction with an AAV vector encoding EGFP. Transduction of intact rat islets with an AAV vector did not alter glucose-induced insulin secretion. AAV vector transduction was higher in transformed islet cell lines INS-1 and RIN m5F with an efficiency of 65% and 57%, respectively. These new results suggest that AAV vectors will provide an improved method of gene delivery to pancreatic islets and isolated pancreatic beta cells.

The effect of acute normovolemic haemodilution on haemodynamics, serum osmolality and coagulation parameters was studied in 20 patients undergoing intracranial surgical procedures. After induction of anaesthesia, 740+/-153 ml of blood was collected and the same was replaced with an equal volume of 6% hexaethyl starch. Heart rate (HR), blood pressure (BP), central venous pressure (CVP) and end tidal carbon dioxide tension (Et CO2) were monitored for 45 min. Haemoglobin concentration (Hb), haematocrit (Hct), serum osmolality (Osm), bleeding time (BT), prothrombin time (PT) and platelet count were determined before and 45 min after haemodilution. Hb and Hct were significantly lower following haemodilution (13.1+/-1.8 and 10.3+/-1.7 g/dL for Hb and 38.0+/-4.6%. and 30.1+/-4.5% for Hct). There was no significant change in the HR, BP and Et CO2 throughout the study period. CVP increased marginally from 35 to 45 min but was within normal limits. There was no significant change in serum osmolality, bleeding time and prothrombin time following haemodilution. Platelet count decreased following haemodilution but the values were within normal limits. The brain relaxation, as assessed by a semiquantitative scale, was satisfactory in all cases. None of the patients developed intraoperative brain swelling. In conclusion, acute normovolemic haemodilution with hexaethyl starch is tolerated well haemodynamically. It does not cause changes in serum osmolality which can increase brain oedema. It has no adverse effect on intraoperative haemostasis. It is a safe technique to decrease homologous blood transfusion during intracranial surgery.

A girl, aged 20 years presented with diarrhoea, vomiting, pain abdomen and loss of weight, the routine Stool examination revealed Fasciolopsis buski (giant intestinal fluke) in large numbers. Despite treatment with Praziquantel, she died after three days.

When chronic renal failure becomes advanced, the serum levels of most hormones are altered because of several interplaying mechanisms. This study was carried out to evaluate the level of total thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) in 96 clinically euthyriod patient with chronic renal failure and 25 healthy individual as control. The patients were grouped into two groups, 62 patient on conservative management and 34 patients on chronic haemodialysis. The patient of both groups showed significant decrease in total T3 and T4 level as compared to normal control. Serum TSH level were similar in both groups as well as in control and were with in normal limit except 3 patients on conservative management which showed TSH level above normal chronic haemodialysis did not have positive effect in alteration of serum T3, T4 and TSH level.

We report a rare case of Retroperitonial teratoma containing Axial Skeleton long bone. Jaw, pelvis & scapula in a 27 yrs old male. Aberration in monozygotic twinning may rarely present as Fetus in Fetu. Rarer is presentation in Adult.

Seizure thresholds were determined by titration in consecutive electroconvulsive therapy (ECT) patients at the first (n = 146) and sixth (N = 83) ECT sessions. Equations to predict the threshold at the first and sixth ECT were computed from these data using a stepwise linear regression model. These equations were tested prospectively at the first ECT (n = 48) and sixth ECT (n = 26) sessions. Stimulus dose derived from the corresponding equations yielded adequate seizure (successful) in 82% and 84% of patients, respectively. Predictions based on age alone (disregarding two other significant variables--illness severity and inion-nasion distance) were estimated at these two ECT sessions. This would not appreciably compromise the success rate. The "formula" method using age alone may therefore be used in routine clinical practice.

Research on determinants of ECT seizure threshold is inadequate. In view of differences in ECT populations and confounding factors, there is a need for examining this in our population. Consecutive consenting inpatients (N=100), referred for bilateral (BL) ECT by treating psychiatrists at National Institute of Mental Health and Neuro Sciences Hospital, Bangalore, formed the sample for the study. Thiopentone, succinylcholine and atropine were used for modification. Seizure threshold (dependent variable) was determined by titration method at the first ECT. The independent variables were age, gender, diagnosis, illness severity (Clinical Global Impression; CGI), concurrent drugs, head circumference (HC) and inion-nasion distance (IND). Age, IND and CGI severity predicted seizure threshold in forward, stepwise, linear regression model.

The effect of electrode placement on cardiovascular responses was studied. Rate pressure product and diastolic blood pressure before anesthesia and 30 s after electroconvulsive therapy (ECT) seizure were recorded. Recordings were made at the first (threshold ECT) session in 124 bilateral ECT (BLECT) and 95 unilateral ECT (ULECT) consenting patients. Postictal rate pressure product (RPP) was significantly higher after BLECT than ULECT. Mean increase in RPP from pre- to postictal phase was 31% in the former. The corresponding change with ULECT (20%) was significantly smaller. In the stepwise, multiple regression model, pre-ECT RPP, age, and stimulus laterality significantly contributed to postictal RPP. No cardiovascular complications occurred in any of the 219 ECT sessions.

The adeno-associated virus (AAV) replication proteins Rep78 and Rep68 regulate viral gene expression and DNA amplification. Their effects on both processes suggest that they play roles in all phases of the virus life cycle. We have investigated Rep protein phosphorylation to determine if this modification might alter Rep function. All four Rep proteins were found to be phosphorylated in AAV and adenovirus co-infected cell cultures, and Rep proteins contained phospho-serine whereas no phospho-threonine or -tyrosine was detected. We also observed that when viral DNA synthesis was inhibited, there was a significant decrease in the level of Rep78/68 phosphorylation. Our results suggest a plausible mechanism whereby AAV Rep 78/68 function may be regulated by phosphorylation.

Adeno-associated virus (AAV) replication proteins Rep78 and Rep68 play major roles in the life cycle of AAV. We have recently provided in vivo evidence for the existence of a covalent association between Rep78 and virion single-stranded (ss) AAV DNA (K. M. R. Prasad and J.P. Trempe(1995) Virology 214, 360-370). In this work we have further characterized the Rep78 protein-AAV DNA covalent linkage. Exonuclease and primer extension analyses revealed that in the majority of isolated ssDNA, Rep78 protein is covalently linked to one of the 5' terminal thymidines. Pulse-chase experiments with radiolabeled methionine suggest that Rep protein remains associated with the virus particle for up to 8 hr after labeling in infected cells. Quantitative immunoprecipitation indicated that approximately 30% of the ssDNA remains associated with the Rep protein after cell fractionation and partial purification. When cells are infected with Rep-associated AAV particles, a significant proportion of viral DNA remains attached to Rep after entry into the nucleus. However, the linkage does not persist after nuclear entry. These observations suggest that covalently linked Rep78 protein may play a key role during wild-type AAV infections and AAV vector transductions.

A simple, sensitive and selective method for the spectrophotometric determination of drugs, viz., sulphamethoxazole, tetracycline HCl, amidopyrine, nifurtimox and isoniazid and biologically important amino acids, cysteine, aspartic acid and arginine based on their reactivity with chloramine-T (CAT) is proposed. The method involves the addition of excess CAT of a known concentration in the presence of 0.25 M HCl and the determination of the unreacted CAT by measurement of the decrease in the absorbance of the dye, gallocyanine (lambda(max): 540 nm), the most suitable of several dyes that were tested. This method was applied to the determination of drug contents in pharmaceutical formulations and to the measurement of the aspartic acid content of some protein hydrolysates. The method is useful for the determination of the target compounds in microgram quantities from 0.4-5.6 microg mL(-1) with the exceptions of arginine (1.0-8.0 microg mL(-1)) and nifurtimox (0.8-5.6 microg mL(-1)). Standard deviations were typically 0.5 mg per dose (RSD 0.5-1.2%). No interferences were observed from common excipients in formulations, and detailed interference studies of other amino acids in the determination of cysteine, aspartic acid and arginine are reported. The validity of the method was tested against spectrophotometric and titrimetric reference methods. Recoveries were 99.8-102.1%.

A detailed account of the specification of colour using the 1931 Commission International de L'Eclairage tristimulus coordinates and subsequent colour spaces for the measurement of small differences in colour is provided along with a review of the application of quantitative parameters for the evaluation of colour changes of acid-base and complexometric indicators. The development of screened indicators to improve the quality of colour changes at the equivalence point is discussed. Various computer programs proposed to calculate the different parameters by different algorithms are reviewed.

This retrospective study aimed to explore the sociodemographic and clinial profile of patients aged 60 years and above attending the psychiatric services of NIMHANS. Two hundred and sixty-five such patients utilized the services during one year. Preliminary analysis of the data revealed that nearly three-fourths of the patients were between 60 and 69 years of age. The family support was adequate for most of the patients. Psychoses made up two-thirds of the sample (nonorganic psychoses = 43% and organic psychoses = 22%). The difference in the distribution of organic and nonorganic psychoses between the two sexes was significant (p=0.01485); men had significantly more organic psychoses than women and the latter had more nonorganic psychoses than the former. It was found that about 70% of the sample had associated physical disorders. The implications are discussed.

This study was conducted to explore the concerns and coping mechanisms used by patients with head and neck cancer and assess their quality of life. A group of 50 consecutive patients with oral and laryngeal cancers were interviewed using a coping and concerns checklist and a semistructured interview proforma to elicit the common concerns in relation to head and neck cancers and their surgical treatment. The Hospital Anxiety and Depression Scale was used to detect anxiety and depression. Concerns were compared between oral and laryngeal cancers and between preoperative and postoperative patients. Commonest concerns were about the future (64%), subjective physical evaluation (60%), finances (56%), being upset (54%), communication (54%), current illness (52%) and inability to do things (50%). The commonest coping mechanisms used were helplessness and fatalism. Resolution was noted in less than 40% of the frequent concerns. As compared to laryngeal cancer patients, those with oral cancer significantly more often had concerns about current illness, subjective evaluation of health, eating and chewing, social interactions, pain and disfigurement (P < 0.05). Most subjects had numerous unresolved concerns. Mainly ineffective coping mechanisms such as helplessness and fatalism were employed leading to incomplete resolution. Interventions to minimise these concerns and to handle associated anxiety and depression would improve their quality of life.

This retrospective chart review attempts to compare the utility, safety and efficacy of once daily (OD) versus divided dose (DD) lithium therapy in the prophylaxis of mood disorders. Sixty-six patients who met DSM-II1R criteria for mood disorders were grouped into those on OD Lithium (n=31) and those on DD lithium (n=35). The groups were matched on sociodemographic and clinical variables. The total daily dose was similar in the two groups, but the OD group tended to have higher serum lithium levels while the DD group tended to have a greater number of affective episodes during the period of follow up. The implications are discussed.

Resolution of the covalently closed terminus of adeno-associated Virus (AAV) DNA is mediated by viral replication protein Rep78 or Rep68. In vitro studies with purified Rep proteins indicate that concurrent with this resolution is a covalent attachment of one of the proteins to the 5' end of the viral genome. The in vivo existence and fate of the covalently associated Rep protein during the virus life cycle has not yet been elucidated. In this report, we use immunoprecipitation analyses to demonstrate that the Rep78 protein is covalently attached to viral DNA in a preformed virion. The attached Rep78 is susceptible to antibody binding and protease digestion, and the DNA linkage is susceptible to nuclease digestion, therefore Rep78 is probably located on the outside of the particle. Rep proteins are also attached to double-stranded replicative-form monomer (RFM) DNA in extracts from AAV and adenovirus coinfected cells. Rep protein attachment to RFM and encapsidated AAV DNA suggest that the covalent complex is an intermediate in virus assembly. These observations are similar to those noted by others for the autonomous parvoviruses and provide additional insights into parvovirus assembly.

Microcephaly with mental retardation forms a distinct subgroup among mentally retarded individuals. The paucity of studies on the etiology of this condition in India made the investigators to study this population. It HTO aimed to study the demographic and clinical characteristics, and the etiologic pattern in children with microcepltaly and mental retardation The sample consisted of 82 children who were examined by detailed clinical assessment and a battery of investigations. A definite etiology could be found in 56% of children which have been grouped into prenatal embryonic, prenatal maternal/environmental, and birth and neonatal causes. Non-genetic causes were the most common. The prenatal etiology constituted nearly twice that of birth and neonatal causes. Majority of the etiologic factors were preventable. The role of socio-environmental factors has been discussed As a group, the neurological disorders were found to be the most commonly associated medical condition. Malnutrition, specially of severe degree, was significantly associated with this group compared to the general population. The study findings indicate that there is a significant place for prevention.

The aim of the study was to compare once-daily with divided dosage lithium treatment in acute mania. In 79 retrospectively studied subjects who met the DSMIII-R criteria for mania, 26 independent and dependent variables were analyzed. The two groups of patients (categorized according to dosage schedule) were broadly comparable with respect to demographic and clinical characteristics. The two groups also did not differ on the outcome measures of lithium efficacy and lithium adverse effects. It is concluded that single dose lithium therapy is clinically comparable with divided dose lithium therapy in acute mania. Possible advantages of switching over to once-daily lithium regimes are discussed.

Trichromatic colorimetry was applied to the specification of colour changes of metallochromic indicators viz., murexide, pyrocatechol violet, bromopyrogallol red, pyrogallol red and chromazurol S in the complexometric titration of Nickel(II) with ethylene-diaminetetraacetic acid (EDTA), in order to assess the quality of colour change at the equivalence point with the help of CIE L*a*b* 1976 system and the values of SCD (Specific Colour Discrimination) parameter. A screened indicator, a mixture of murexide and methylene blue in the ratio 10:1 (m/m), is proposed as an ideal indicator in this titration as evidenced by the plots of a* vs. b* and from the numerical values of standard deviation for a large number of visual titrations.

Since 1967, when the first intracardiac repair was performed in this centre, until 1991, 840 symptomatic subjects with tetralogy of Fallot have undergone corrective surgery. Cardiac catheterization and angiocardiography were carried out in all patients. Cardinal findings on the clinical status of these subjects are outlined. A substantial number of patients (244; 29.0%) were > 15 years of age. Historically, a transannular pericardial gusset has been utilized in 578 (68.8%), and in 423 (93.0%) during the past decade. The incidence of residual interventricular septal defects has been 0.68% and occurrence of complete heart block after surgery 0.4%. Death occurred in 86 patients (10.2%) within 30 days of operation and later in 40 subjects (4.8%). Long-term results have been excellent with good haemodynamic status in > 90% of subjects in the follow-up period. Associated features including absent pulmonary valve, absent left pulmonary artery, and previous palliative shunts did not alter the outcome; however, a raised haematocrit (> 0.65) was associated with an increased mortality rate.

A variant line (CEM-7A) "overproducing" the reduced folate/MTX carrier system was isolated from human CCRF-CEM leukemia cells grown under selective conditions in medium containing 0.25 nM 5-formyl-THF as the sole folate source. This line exhibits a 95-fold increased Vmax for [3H]-MTX influx as compared to parental cells. The values for [3H]-MTX influx Km, efflux t1/2 and structural specificity for other (anti)folate compounds were unchanged. The amount of carrier protein, estimated by NHS-[3H]-MTX affinity labeling, was approximately 30-fold higher in CEM-7A cells than in parental cells. Influx of [3H]-MTX in CEM-7A cells was found to be down-regulated 6-7-fold after preincubation of cells with adenosine, 5-formyl-THF or 5-methyl-THF, but could be prevented exclusively by inhibitors of dihydrofolate reductase. The underlying mechanism(s) of these effects have not as yet been elucidated. A radioiodinated photoaffinity analog of MTX was used to prove the molecular events in carrier-mediated MTX uptake in parental CCRF-CEM cells, CEM-7A cells, and a line exhibiting a MTX-transport defect (CEM-MTX). Specific labeling of an 80-85 kDa membrane protein was observed in parental cells, but not in CEM/MTX cells. Uptake of photoprobe and levels of the 80-85 kDa membrane protein were significantly increased in CEM-7A cells. Due to extensive glycosylation the MW of the carrier protein in human cells seems to be substantially higher than that of its counterpart in murine L1210 leukemia cells (46-48 kDa). Pulse-labeling experiments at 37 degrees C demonstrated that in CEM-7A cells photoprobe uptake proceeds via a specific pathway. The 80-85 kDa membrane protein is involved in the initial binding and translocation of photoprobe, after which a 38 kDa cytosolic protein is responsible for further intracellular distribution. At this time, the combination of photoaffinity labeling techniques and the availability of variant cell lines overexpressing the reduced folate/MTX carrier protein has provided new insights into the MTX transport process in human leukemia cell lines. In the near future this approach should also allow a further elucidation of the regulatory aspects of carrier function.

The quality of the colour changes at the end-point in the complexometric titration of bismuth(III) with EDTA, using the indicators Hemotoxylin, PAN [1-(2-Pyridylazo)-Naphthol-2], PAR [4-(2-Pyridylazo)-Resorcinol], Xylenol Orange and Thoran is studied by means of the CIE 1931 trichromatic system, using specific colour discrimination (SCD) and colour difference (DeltaE*). The indicators are arranged in order of colour change quality. Of the indicators studied, Hemotoxylin is recommended as the most suitable for this titration.