Difficulties in the diagnosis of acute aortic dissection.
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Aged↗
Biomedical subjects
R Anand
Publications and source records attributed to R Anand.
Expression of inducible nitric oxide synthase in cutaneous adnexal tumours of the head and neck.
Adnexal tumours are a rare heterogeneous group of neoplasms, most commonly found in the head and neck region. Although most are benign, malignant adnexal tumours often behave aggressively, resulting in early metastasis. There is increasing interest in the role that nitric oxide (NO) plays in the behaviour of many cancers. It is thought that NO, produced by the enzyme inducible NO synthase (iNOS), facilitates tumour growth and dissemination. iNOS has been studied in the common skin cancers, where its expression correlates with tumour behaviour, but it has not been previously investigated in cutaneous adnexal tumours. An immunhistochemical study was performed using a monoclonal antibody to iNOS in 37 cases of adnexal tumours (19 benign, 18 malignant). iNOS expression was weakly expressed by basal keratinocytes of adjacent skin in all cases and it was variably expressed in the tumours. Malignant tumours had significantly increased iNOS expression when compared to both adjacent skin (P<0.001) and the benign tumour group (P<0.001). No significant difference was found between iNOS expression in benign tumour and adjacent skin (P=0.5). The role of iNOS in this rare group of tumours and the possibility of pharmacologically inhibiting it in the clinical setting warrants further investigation.
Adenocarcinoma, Sebaceous↗
Collaborative iIslet Transplant Registry.
The Collaborative Islet Transplant Registry (CITR) was established in 2001 with support from the National Institute of Diabetes and Digestive Diseases to collect and analyze information on islet transplants in North America. Thirteen of 27 invited islet transplant centers from the United States and Canada were already participants as of January 2004 with 5 additional centers awaiting IRB approval. In October 2003, CITR had preliminary data on 58 recipients of 107 islet transplants performed at the 13 member centers. These islet recipients averaged 41 years of age (SD 8.9), had diabetes for almost 28 years (SD 10.2) and were predominantly (67%) female. Islets were procured from 118 deceased donors whose average age was 42 (SD 12.2), weight was 90 kg (SD 23.5), and BMI was 30.5 (SD 7.9). The time from cross-clamp to pancreas recovery averaged 56 minutes (SD 134.6). An average of 7,127 islets (SD 2,973) were infused per kg of the recipient's weight. Outcome data are still pending as the Registry prepares its first annual report. Here we describe the organization, goals and design of the data collection instruments for CITR.
Data Collection↗
Studies of Pediatric Liver Transplantation (SPLIT): a summary of the 2003 Annual Report.
The SPLIT database is accumulating comprehensive data on both pre- and posttransplant outcomes after pediatric liver transplantation. The relatively small numbers of children receiving any solid organ transplant, even at the largest single centers makes it difficult to study outcomes and changing trends from any single center and necessitates the formation of a large multi-center database. SPLIT has designed its data collection specifically to address outcomes relevant to children after liver transplantation such as growth and school performance and which are not collected by any other exisiting database. From the outcome data generated to date, a subset of which is presented above, hypothesis-driven studies can be designed. The first example of such a study was the development of the Pediatric Endstage Liver Disease (PELD) score. This model, which predicts death on the liver transplant waiting list for children with chronic liver disease was developed using data from SPLIT, has been adopted, and subsequently verified within the national cadaveric organ allocation system.
Adolescent↗
Partial VP1/2A gene sequence based molecular epidemiology of wild type 1 poliovirus isolates from some parts of India.
Genomic variability within the sequences of VP1/2A junction among polioviruses from across the globe has revealed the existence of several endemic genotypes and their epidemiological inter-relationships; but such data on Indian isolates are scanty. The present work was intended to ascertain the persistence and transmission pattern of different genotypes of wild type 1 polioviruses circulating in India. Forty-eight wild type 1 poliovirus isolates obtained from different parts of India during 1996-8 were subjected to RT-PCR and nucleotide sequencing using M13 tailed primers. A 293 base pair region was amplified and sequenced for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, the isolates from six different states of India confirmed a single dominant genotype 4. Phylogenetic analysis revealed the circulation and active inter-state transmission of many genetically distinct strains of wild poliovirus type 1 belonging to genotype 4. This warrants the need for insisting on more efficient surveillance mechanisms so as to assess the impact of an extensive pulse polio immunization programme in India.
Amino Acid Sequence↗
A prospective randomised trial of two treatments for wound seroma after breast surgery.
AIMS: Seroma formation is a recognised complication of breast surgery causing wound pain and discomfort. It was hypothesised that daily aspiration of symptomatic seromas that formed after breast surgery would encourage flap adherence to the chest wall, thereby allowing swifter resolution of seroma. METHODS: Thirty-six patients undergoing mastectomy and/or axillary clearance who formed seroma post operatively, were randomised into two groups either having daily aspiration of seroma or aspiration as required by patient symptoms. RESULTS: The daily aspiration required significantly more attendances for aspiration (P<0.005) and the time from surgery to final aspiration was not reduced. CONCLUSION: Daily aspiration of symptomatic seroma did not result in swifter resolution.
Aged↗
Endothelin is an important determinant of renal function in a rat model of acute liver and renal failure.
BACKGROUND AND AIMS: Renal failure occurs in approximately 55% of patients with acute liver failure. We have previously shown that plasma endothelin 1 concentrations are elevated in patients with acute liver failure and the hepatorenal syndrome. There are few reported satisfactory animal models of liver failure together with functional renal failure. In this study, a rat model of acute liver failure induced by galactosamine that also develops renal failure was first characterised. This model was used to investigate the hypothesis that endothelin 1 is an important mediator involved in the pathogenesis of renal impairment that occurs in acute liver failure. METHODS: Acute liver failure was induced in male Sprague-Dawley rats by intraperitoneal injection of galactosamine together with treatment with the endothelin receptor antagonist Bosentan. Twenty four hour urine collections were made using a metabolic cage. Renal blood flow was measured in anaesthetised animals. RESULTS: This model developed renal failure and liver failure in the absence of any significant renal pathology, and with an accompanying fall in renal blood flow. Plasma concentrations of endothelin 1 were increased twofold following the onset of liver and renal failure (p<0.05), and there was significant upregulation of the endothelin receptor A (ET(A)) in the renal cortex (p<0.05). Administration of Bosentan prevented the development of renal failure when given before or 24 hours after the onset of liver injury (p<0.05) but had no effect on liver injury itself, or on renal blood flow. CONCLUSIONS: This study demonstrates that this animal model has many of the features needed to be regarded as a model of renal failure that occurs in acute liver failure. The observation that plasma levels of endothelin 1 and ET(A) receptors are increased and upregulated, and that renal failure is prevented by an endothelin antagonist supports the hypothesis originally put forward that ET(A) is important in the pathogenesis of renal failure that occurs in patients with acute liver failure.
Acute Disease↗
Effects of rivastigmine on cognitive function in dementia with lewy bodies: a randomised placebo-controlled international study using the cognitive drug research computerised assessment system.
This study was designed to assess the effects of rivastigmine (Exelon) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.
Aged↗
A critical audit of the surgical management of intractable epistaxis using sphenopalatine artery ligation/diathermy.
An audit of the local practice of sphenopalatine artery (SPA) ligation/diathermy was undertaken following its introduction to the unit in April 1998. The authors looked to the literature for evidence of what was to be taken as a successful result and were surprised at the lack of published data on its efficacy or lack thereof. Fivehundredsixtythree patients were admitted for inpatient management of epistaxis over a two-year period. Ten of these patients required surgical control of epistaxis and went on to have either sphenopalatine artery ligation or diathermy. One had concomitant anterior ethmoidal artery diathermy. Postoperatively, the patients stayed between one to ten days (mean 3.3 days). The mean follow up in the clinic was 42.7 days. A recurrent bleed rate of 33% was found, which is higher than previously published results. Of these failures one had internal maxillary embolization followed by anterior ethmoidal artery ligation. The other two failures were successfully corrected with anterior ethmoidal ligation. The authors discuss and illustrate the possible reasons for failure.
Aged↗
Stabilising the leg to harvest a fibular flap: a new device.
A simple stabilisation device is described that facilitates easy harvesting of a fibular free flap.
Bone Transplantation↗
Herpes simplex virus bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary glaucoma: an unusual presentation.
PURPOSE: To report an unusual case of herpetic bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary glaucoma. RESULTS: A retrospective analysis of the case record of a 60-year-old man who had earlier undergone bilateral cataract surgery, was done. He presented with a complaint of decrease in vision in the right eye of 20 days duration. On examination, cornea showed epithelial bullae all over the surface with stromal and epithelial edema. Intraocular pressure was 30 mm of Hg in RE. He was treated with anti-glaucoma medications. Two dendritic lesions were seen in the cornea during a subsequent visit four days later. Virological investigations confirmed a diagnosis of Herpes simplex keratitis. He was treated with topical acyclovir. CONCLUSIONS: This case highlights the fact that herpes simplex keratitis can present initially as a more diffuse corneal stromal and epithelial edema with epithelial bullae mimicking bullous keratopathy. Herpetic bullous keratitis, although unusual, should be considered in the differential diagnosis under such circumstances.
Acyclovir↗
The chaperone protein 14-3-3eta interacts with the nicotinic acetylcholine receptor alpha 4 subunit. Evidence for a dynamic role in subunit stabilization.
By using the large cytoplasmic domain of the nicotinic acetylcholine receptor (AChR) alpha4 subunit as a bait in the yeast two-hybrid system, we isolated the first cytosolic protein, 14-3-3eta, known to interact directly with neuronal AChRs. 14-3-3eta is a member of a family of proteins that function as regulatory or chaperone/ scaffolding/adaptor proteins. 14-3-3eta interacted with the recombinant alpha4 subunit alone in tsA 201 cells following activation of cAMP-dependent protein kinase by forskolin. The interaction of 14-3-3eta with recombinant alpha4 subunits was abolished when serine 441 of the alpha4 subunit was mutated to alanine (alpha4(S441A)). The surface levels of recombinant wild-type alpha4beta2 AChRs were approximately 2-fold higher than those of mutant alpha4(S441A)beta2 AChRs. The interaction significantly increased the steady state levels of the alpha4 subunit and alpha4beta2 AChRs but not that of the mutant alpha4(S441A) subunit or mutant alpha4(S441A)beta2 AChRs. The EC50 values for activation by acetylcholine were not significantly different for alpha4beta2 AChRs and alpha4(S441A)beta2 AChRs coexpressed with 14-3-3eta in oocytes following treatment with forskolin. 14-3-3 coimmunopurified with native alpha4 AChRs from brain. These results support a role for 14-3-3 in dynamically regulating the expression levels of alpha4beta2 AChRs through its interaction with the alpha4 subunit.
14-3-3 Proteins↗
Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.
CONTEXT: Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress. OBJECTIVE: To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999. SETTING: Two tertiary referral centers in the United States. PATIENTS: One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy. INTERVENTION: Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n = 50) or matching placebo (n = 50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy. MAIN OUTCOME MEASURE: Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale. RESULTS: Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%. Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P =.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period. CONCLUSIONS: In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.
Adult↗
Response of patients with Alzheimer disease to rivastigmine treatment is predicted by the rate of disease progression.
BACKGROUND: Evidence suggests that disease severity predicts the response of patients with Alzheimer disease (AD) to cholinesterase inhibitor treatment, raising the question of whether disease progression also predicts response to this treatment. OBJECTIVE: To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartrate therapy for patients with mild to moderately severe AD. DESIGN: A 26-week, open-label extension study following a 26-week, double-blind, randomized, placebo-controlled trial. SETTING: Outpatient research centers at 22 sites in the United States. PATIENTS: We studied 187 of 235 patients originally randomized to receive placebo treatment in the double-blind phase of the trial who continued with open-label (rivastigmine) extension therapy. INTERVENTION: Placebo treatment for 26 weeks followed by rivastigmine treatment, 2 to 12 mg/d, for 26 weeks. MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), Progressive Deterioration Scale, Mini-Mental State Examination, and Global Deterioration Scale scores. RESULTS: Rivastigmine administration during open-label extension therapy benefited patients who had progressed slowly and those who had progressed rapidly during initial double-blind placebo treatment. Slowly progressive patients responded with a mean 1.03-point improvement in the week 26 (ie, start of open-label rivastigmine treatment) ADAS-Cog score at 12 weeks of rivastigmine treatment (week 38 of treatment; P =.02 vs week 26). However, more rapidly progressive patients had a significantly larger mean 4.97-point improvement from the week 26 ADAS-Cog score at 12 weeks (with respect to week 26 of treatment and slowly progressive patient scores, P<.001 for both). Thus, a more rapid disease progression rate while receiving placebo treatment was predictive of a significantly stronger patient response to rivastigmine therapy. This relation also was observed with the other 3 outcome measures and was still apparent when accounting for disease severity. CONCLUSIONS: Rate of disease progression for patients with mild to moderate AD seems to predict response to rivastigmine treatment. Patients with more rapidly progressive disease might be particularly likely to benefit from rivastigmine therapy.
Aged↗
Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.
In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.
Aged↗
Intracellular neuronal calcium sensor (NCS) protein VILIP-1 modulates cGMP signalling pathways in transfected neural cells and cerebellar granule neurones.
The family of intracellular neuronal calcium-sensors (NCS) belongs to the superfamily of EF-hand proteins. Family members have been shown by in vitro assays to regulate signal cascades in retinal photoreceptor cells. To study the functions of NCS proteins not expressed in photoreceptor cells we examined Visinin-like protein-1 (VILIP-1) effects on signalling pathways in living neural cells. Visinin-like protein-1 expression increased cGMP levels in transfected C6 and PC12 cells. Interestingly, in transfected PC12 cells stimulation was dependent on the subcellular localization of VILIP-1. In cells transfected with membrane-associated wild-type VILIP-1 particulate guanylyl cyclase (GC) was stimulated more strongly than soluble GC. In contrast, deletion of the N-terminal myristoylation site resulted in cytosolic localization of VILIP-1 and enhanced stimulation of soluble GC. To study the molecular mechanisms underlying GC stimulation VILIP-1 was examined to see if it can physically interact with GCs. A direct physical interaction of VILIP-1 with the recombinant catalytic domain of particulate GCs-A, B and with native GCs enriched from rat brain was observed in GST pull-down as well as in surface plasmon resonance interaction studies. Furthermore, following trituration of recombinant VILIP-1 protein into cerebellar granule cells the protein influenced only signalling by GC-B. Together with the observed colocalization of GC-B, but not GC-A, with VILIP-1 in cerebellar granule cells, these results suggest that VILIP-1 may be a physiological regulator of GC-B.
Animals↗
Nutrient intake and hypertensive disorders of pregnancy: Evidence from a large prospective cohort.
OBJECTIVE: The objective of this analysis was to prospectively determine the effects of nutrient intakes on the incidences of preeclampsia and pregnancy-associated hypertension among women enrolled in the Calcium for Preeclampsia Prevention study. STUDY DESIGN: This was a prospective observational cohort study of women in a randomized clinical trial that included women seeking prenatal care at university medical centers and affiliated clinics and hospitals in 5 US communities. A total of 4589 nulliparous women were recruited between 13 and 21 weeks' gestation. Preeclampsia and pregnancy-associated hypertension were the main outcome measures. RESULTS: Preeclampsia was noted in 326 (7.6%) of the 4314 women with known pregnancy outcomes followed up until > or =20 weeks' gestation, and pregnancy-associated hypertension was noted in 747 (17.3%). As previously reported, there was no significant difference in these outcomes between cohorts randomly assigned to supplementation with calcium or placebo. By means of logistic regression a baseline risk model was constructed for preeclampsia and pregnancy-associated hypertension. After adjustment for treatment and clinical site, body mass index >26 kg/m(2) and race were significantly associated with an increased risk of preeclampsia. Body mass index > or =35 kg/m(2), race, and never smoking were significantly associated with an increased risk of pregnancy-associated hypertension. After adjustment for baseline risks, none of the 28 nutritional factors analyzed were significantly related to either preeclampsia or pregnancy-associated hypertension. CONCLUSION: We found no evidence in this study for a significant association of hypertensive disorders of pregnancy with any of the 23 nutrients measured.
Body Mass Index↗
Creutzfeldt-Jakob disease : report of 10 cases from North India.
Creutzfeldt-Jakob disease (CJD) is increasingly being reported over the last three decades as a result of heightened awareness of the disease. Various studies have reported annual incidence of 0.5-1.5 cases of CJD per million of general population. In India, the disease is still under reported. Over the period spanning from 1968-1997, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore recorded 69 cases of CJD from different parts of India in the CJD registry. This paper describes the clinical experience with cases of CJD managed at the Department of Neurology, G.B. Pant Hospital, New Delhi from 1990-1998. In this series, the mean age of the patients was 53.80 (+/- 7.32) years and there were 5 females and 5 males. Myoclonus was present in all the cases and abnormal behaviour with or without other features was the presenting complaint in 7 of the 10 patients, while one patient of CJD had cerebellar ataxia as the presenting feature. One patient with occipital variant of CJD presented with acute onset cortical blindness and myoclonic jerks. One of the patients had acute psychosis precipitated by emotional stress at the onset. Extrapyramidal features were noted in 7 of the 10 patients before death. The mean duration of symptoms from the onset of disease to death was 6.6 (+/- 6.11) months. Classical EEG changes were observed in all the patients, except in one possible case of occipital variant of CJD, where we did not have access to EEG record. Brain biopsy could be undertaken in 3 patients, and in 2 patients the features of subacute spongiform encephalopathy (SSE) were noted.
Adult↗