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Biomedical subjects

V Mehta

Publications and source records attributed to V Mehta.

At least 37 records · Page 2Linked to original sources

Late results and reoperation after repair of complete and partial atrioventricular canal defect.

Advances in surgical technique and postoperative care have resulted in substantial improvement in the operative mortality after repair of atrioventricular canal defects. However, significant late morbidity and the need for reoperation complicate the medium and long-term results in these patients. Left atrioventricular valve regurgitation, residual or recurrent intracardiac shunting, and subaortic stenosis are the principle causes of late morbidity after repair of complete and partial atrioventricular canal defects. This article describes the incidence and etiology of these complications, as well as the methods of diagnosis and management.

Aortic Valve Stenosis↗

Working memory in temporal lobe epilepsy: an event-related potential study.

Event-related potentials (ERPs) were recorded to a digit-probe identification and matching task (modified 'Sternberg paradigm') in 29 patients with temporal lobe epilepsy (TLE) and 26 healthy subjects. Our main aim was to identify the neurophysiological correlates of abnormal short term memory function in patients with TLE. Neuropsychological tests allowed the definition and comparison of two patient groups according to the presence or absence of memory dysfunction. These two groups did not differ significantly in mean age, education years, IQ, seizure duration, seizure frequency, anti-epileptic drug (AED) regimes, or on findings on neuroimaging. ERPs recorded under different levels of memory load were analysed both by conventional component identification and by an objective computer method of determining mean amplitudes of multiple 50 ms epochs (MMA analysis). We found that some significant abnormalities were common to both groups of patients; these included slow reaction times, a reduced amplitude of the N170 wave (and the corresponding 157-210 ms epoch in the MMA analysis) and a broad late negative shift between 577 and 735 ms. Other findings, including a significantly reduced performance accuracy as the level of memory load increased, were restricted to patients with abnormal memory function. The ERP changes that were specific to these patients occurred within a latency band of 200-420 ms and included a relatively preserved, but delayed P250 component and a delayed and attenuated N290 wave. When compared with either healthy subjects or with patients with normal memory, the responses in patients with abnormal memory showed an abnormal 'positive shift' between 262 and 315 ms after probe presentation and a further positive shift between 315 and 420 ms as memory load increased. These abnormalities of 'memory scanning' ERPs in patients with TLE which paralleled neuropsychological and behavioural evidence of memory dysfunction, and which occurred in the section of the response that is sensitive to memory loading in healthy subjects, provide further objective evidence that abnormalities of short term memory processes contribute to the memory deficits of TLE.

Adult↗

Acute hydrocephalus following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Acute hydrocephalus is a potentially treatable cause of early neurological deterioration after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A retrospective study of 105 consecutive cases of aneurysmal SAH was undertaken to determine those factors significantly related to the development of acute hydrocephalus. Acute hydrocephalus was diagnosed when the bicaudate index was greater than the 95th percentile for age on a CT scan within 72 hours of the ictus. RESULTS: Thirty-one percent of the patients developed acute hydrocephalus. Grade of SAH was a significant factor for the development of acute hydrocephalus on univariate analysis as 87% of patients with acute hydrocephalus (29/32) presented with at least grade 3 (Hunt-Hess) SAH (P < 0.05). In addition, posterior circulation aneurysms on univariate analysis were associated with acute hydrocephalus (p < 0.05). Both premorbid hypertension and intraventricular blood (p < 0.05) were predictors for acute hydrocephalus, whereas intracisternal blood, age and sex were not. On multivariate linear regression analysis, factors found to be significantly associated with acute hydrocephalus were premorbid hypertension, intraventricular blood, CSF diversion and definitive shunt procedures. External ventricular drainage was not associated with any instances of rebleeding. Thirty-seven percent (10/27) of patients with acute hydrocephalus who survived were improved by pre-operative external ventricular drainage. CONCLUSIONS: Patients with acute hydrocephalus following SAH can be safely treated with external ventricular drainage. Multiple factors can be identified to predict those patients who will develop acute hydrocephalus post aneurysmal rupture. Approximately 30% of those patients with acute hydrocephalus will require definitive shunt placement. Acute hydrocephalus occurred in 31% of aneurysmal SAH patients in this series.

Acute Disease↗

Sucrose reduces the efficiency of protein denaturation by a chaotropic agent.

Sugars and polyols are used to stabilize proteins. The degree of stabilization conferred on a model protein by sucrose was calculated in terms of the free energy of folding. Phosphoglycerate kinase (PGK) was denatured by guanidine hydrochloride (GuHCl) in different sucrose concentrations. The linear extrapolation method [1,2] was used to calculate the free energy of folding in the absence of denaturant. Although sucrose increased the concentration of GuHCl required to unfold the protein, the free energy of folding in water was unchanged. In order to probe the nature of the stabilizing effect of sucrose, an FT-Raman spectroscopic study of denaturant-polyol systems was undertaken. Investigations of interactions between GuHCl, urea or formamide and polyhydric compounds, revealed no evidence for hydrogen bonding or dipole-dipole associations. Polyhydric compounds caused minor changes in denaturant spectra although the converse was not observed. The structure of deuterated water changed on addition of denaturants. For non-ionic denaturants, addition of polyhydric solutes countered this change in water structure. Thus polyhydric compounds oppose the effect of denaturants on water structure. The observed increase in GuHCl concentration required to unfold PGK in the presence of sucrose may be attributed to this property of sucrose.

Formamides↗

Surface expression of beta 2-microglobulin-associated thymus-leukemia antigen is independent of TAP2.

Mouse thymus-leukemia antigen (TL), like other major histocompatibility complex (MHC) class I-b antigens, displays signs of a specialized function. It is normally expressed at high levels on immature thymocytes and at moderate levels on gut epithelium and activated mature T cells. A promoter/enhancer region unique among class I genes accounts for this narrow range of tissue distribution. Like most other class I molecules, TL is dependent upon endogenous beta 2-microglobulin (beta 2m) for transport to the surface. However, here we show that unlike most other MHC class I molecules, TL is expressed efficiently in the absence of functional transporter associated with antigen processing subunit 2 (TAP2). A putative fourth TLa gene cloned from A.SL1 cells was expressed in RMA and RMA-S cells. In bulk transformants, TL expression is higher in TAP2-RMA-S cells than in wild-type RMA cells, and is not elevated by incubation at reduced temperatures or exposure to exogenous beta 2m. Analysis of immunoprecipitated molecules by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicates that TL is processed normally in RMA-S cells and is associated with beta 2m both intracellularly and at the cell surface. However, TL heavy chains expressed on the cell surface in the absence of TAP2 are cleaved to a predominant 38 kDa fragment, presumably the result of an altered conformation that renders TL more susceptible to proteolysis. These results suggest that while TL may normally acquire TAP2-dependent peptides, this class I-b molecule does not require them for efficient export to, and stable expression at the cell surface.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

N-acetylaspartate as an acetyl source in the nervous system.

To understand the role of N-acetylaspartate (NAA) as an acetyl donor, we investigated the metabolism of NAA in brain and liver slice preparations. The tissue slices were incubated with [14C-acetyl]NAA (SA = 3 microCi/mumol) or [14C]acetate (SA = 3 microCi/mumol) for 2 h. The tissue was homogenized and was extracted using chloroform/methanol (2:1). The aqueous phase was initially analyzed using anion exchange HPLC while the lipid phase was analyzed using a two-dimensional TLC system. Further resolution of the NAA peak from the anion exchange HPLC was performed using a reverse phase HPLC system. The aqueous phase of both the liver and brain samples incubated with [14C-acetyl]NAA revealed similar patterns of three distinct radioactivity peaks corresponding to NAA, acetate and an early eluting unknown molecule. Further resolution of the NAA peak using reverse phase HPLC indicated that it corresponded to NAA and acetyl CoA. There was significant incorporation of radioactivity into various lipid components in both the brain and liver samples. Patterns similar to that observed with NAA were detected in the case of [14C]acetate in both the brain and liver slice preparations. These results demonstrate that NAA metabolism is not restricted to the nervous system, although its biosynthesis is. It is clear that acetyl moiety of NAA is incorporated into lipids and partially hydrolyzed to free acetate in both brain and liver preparations. Further, production of acetyl CoA from NAA indicates that the acetyl group of NAA is incorporated into lipids and perhaps other acetylated molecules via the acetyl CoA route. A working hypothesis on the metabolic role of NAA is presented.

Acetylation↗

Prenatal testosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in the developing sheep.

In sheep, prenatal exposure to androgens during a critical period for sexual differentiation can masculinize tonic luteinizing hormone (LH) secretion and defeminize the LH surge. The present study investigated the possible independent control of these two modes of LH secretion, as revealed by their developmental history. Specifically, we tested the hypothesis that separate critical periods exist for androgenization of tonic and surge LH secretion. Pregnant ewes were treated weekly with testosterone cypionate (200 mg in oil). As a control and to induce robust masculinization of reproductive neuroendocrine function, one group of females received testosterone from day 30 to 86 of gestation (LONG group). To determine if masculinization of tonic LH secretion develops separately from that of the LH surge, two additional groups were treated from day 30 to 51 (EARLY group) or 65-86 (LATE group). At birth, the external genitalia of the LONG- and EARLY-treated females were masculinized; those of the LATE-treated group were normal. At 2 weeks of age, all androgenized females, together with normal males and females (n = 8 each), were gonadectomized and steroids replaced using an estradiol-filled Silastic capsule. First, to determine the timing of the pubertal decrease in steroid sensitivity, circulating LH was monitored twice weekly. Second, to test the function of the LH surge system, LH was measured every 1-2 h for 60 h after an acute increase in estradiol at 9 months of age. With regard to tonic LH secretion, in control males and LONG-treated females, a sustained increase in tonic LH in the presence of constant steroid feedback occurred at 7.1 +/- 0.3 and 10.9 +/- 1.7 weeks of age, respectively (mean +/- SE). In control females, tonic LH increased at 27.1 +/- 0.8 weeks. Despite the differences in their genitalia, EARLY and LATE testosterone treatment produced intermediate effects: LH secretion increased at 19.3 +/- 1.2 and 20.4 +/- 0.8 weeks, respectively. In response to acute estradiol stimulation, all control females produced a surge of LH that peaked 18.4 +/- 0.6 h after steroid treatment. For the control males and LONG-treated females, LH concentrations were not sustained above unsuppressed pretreatment levels throughout the 60-hour sampling period. All but 4 of the 18 EARLY- and LATE-treated females responded to estradiol stimulation with a surge of LH that peaked at 29.8 +/- 1.6 and 31.8 +/- 1.3 h, significantly later than that of control females.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Surgical management of the patient with a thyroid disorder.

In this article, fundamental thyroid physiology and diagnostic procedures in the elderly patient are described. Emphasis is placed on performing nonthyroid surgery in elderly patients with hypo- or hyperthyroidism. The management of the thyroid nodule in the elderly patient is also described with a detailed algorithmic approach. Preoperative and intraoperative cardiac risk assessment and monitoring in elderly patients undergoing nonthyroid as well as thyroid surgery are also described.

Aged↗

Reduced frequency of percutaneous injuries in surgeons: 1993 versus 1988.

OBJECTIVE: To compare the frequency of occupational injuries reported by surgeons in 1993 with similar data obtained in 1988. DESIGN AND SETTING: Two point-prevalence studies of percutaneous injuries of surgeons practicing in tertiary and non-tertiary-care hospitals in the New York metropolitan area. PARTICIPANTS: A total of 202 surgeons and surgical residents surveyed in 1988 and 347 surveyed in 1993 (67 and 65% of the eligible groups, respectively), including 85 surgeons in 1993 (71% of the eligible group) who had participated in the 1988 survey. OUTCOME MEASURES: Yearly frequency of percutaneous injuries, and injury frequency per 1000 operative hours. RESULTS: There was a significant decrease in the frequency of reported percutaneous injuries over the 5-year period. For all surgeons, the mean number of yearly injuries decreased from 5.5 +/- 14.4 SD to 2.1 +/- 6.0 SD (P < or = 0.001). Paired analysis of the subgroup of 85 surgeons who participated in both surveys showed a nearly identical decrease (P = 0.001). Significant decreases were observed in general surgeons, specialists and residents. CONCLUSIONS: During the 5 years studied, surgeons practicing in the greater New York metropolitan area reported a significant reduction in the frequency of occupationally associated percutaneous injuries. The reduced risk of percutaneous injuries should substantially lower the rate of acquired infections from blood-borne pathogens.

Adult↗

Tracheal suction in meconium stained infants: a randomized controlled study.

We performed a randomized controlled study of the mortality and morbidity of 49 babies born with thick meconium staining of amniotic fluid. These unasphyxiated babies were consecutively born and were admitted to the intensive care unit for observation as routine. The groups were comparable in regard to sex, birth weight, gestational age, maternal factors like anaemia, toxaemia, antepartum haemorrhage, prolonged rupture of membranes, presentation, and interventions including caesarian section. The control group, comprising 26 babies received only oropharyngeal suction, while the intervention group, comprising 23 babies, underwent oropharyngeal suction followed by tracheal suction. There was no significant difference in the mortality or morbidity in form of evidence of air leak or hypoxic ischaemic encephalopathy.

Female↗

Functional state of the beta cell affects expression of both forms of glutamic acid decarboxylase.

Glutamic acid decarboxylase (GAD) is a candidate target autoantigen involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). The functional state of the beta cells has been suggested to play a pathogenic role in IDDM by altering beta-cell autoantigen expression. In this study, we investigated expression of GAD-65 and GAD-67 in isolated Sprague-Dawley rat islets cultured at different glucose concentrations. Using GAD isoform-specific antibodies in an immunoblot assay, we found that expression of both GAD-65 and GAD-67 in cultured islets was glucose dependent and that increased expression of both forms of GAD correlated with increased functional state of the beta cell. Our data indicate that the functional state of the beta cell influences islet cell expression of GAD. Thus, decreasing islet cell expression of GAD by suppressing beta cells activity may have a potential role in blunting the autoimmune destruction of pancreatic islet beta cells.

Animals↗

Regulation of TL antigen expression. Analysis of the T18d promoter region and responses to IFN-gamma.

Type I (alpha/beta) and type II (gamma) IFN enhance MHC class I gene expression through an IFN-responsive element (IRE) present in the 5' flanking region of the class I-a genes. Comparison of the 5' sequences between classical class I-a genes and T region class I-b genes reveals little homology except for presence of a potential IRE. We have found that cell surface expression of thymus leukemia Ag (TL) was up-regulated by IFN-gamma to a greater extent than H-2K,D in all TL+ T cell lines tested. In contrast, IFN-alpha/beta, which significantly increased H-2K and H-2D Ag expression, had only minor effects on TL expression. Resting peripheral T cells, which were considered to be TL- from previous studies, were found to express TL at a low level as determined by flow cytometry, immunoprecipitation, as well as polymerase chain reaction; the level of expression also could be elevated by IFN-gamma. To examine the control of TL gene transcription and its regulation by IFN-gamma, varying lengths of the T18d 5' flanking region were analyzed in chloramphenicol acetyl transferase assays. By deletion analysis, promoter activity and IFN-gamma responsiveness were localized to an 86-bp fragment that contains the IRE. Both responses were localized further to a 32-bp fragment that contained the IRE at its 3' end. RNase protection assays revealed two major transcription initiation sites, one immediately 5' of the IRE and another approximately 60 bp downstream. Furthermore, polymerase chain reaction analysis of mRNA from resting T cells, thymocytes, and T cell tumor lines confirmed the RNase protection data. Thus, transcription of T18d initiates much further upstream than the classical class I genes, can utilize an unusual promoter element, and can be elevated by IFN-gamma.

Animals↗

Potential of overuse of the inferior vena cava filter.

To examine indications for, and morbidity and mortality rate of, inferior vena cava filter insertion at a community hospital, the records of 69 patients who received inferior vena cava filters were reviewed. Patients were assigned to three groups--group 1, 45 patients with pulmonary embolism or deep venous thrombosis and a contraindication to anticoagulation; group 2, 14 patients with a diagnosis as in group 1, who received filters without consideration to anticoagulation, and group 3, ten patients with clinically suspected deep venous thrombosis and no objective assessment of the process. Indications for filter placement were recorded. Morbidity and in-hospital mortality rates were 29 and 49 percent, 43 and 36 percent and 10 and 30 percent for groups 1, 2 and 3, respectively (29 and 43 percent overall). Only patients in group 1 had documented indications for caval interruption. Results compared unfavorably with complication and mortality rates reported previously. Non-selective use of inferior vena cava filters is associated with unacceptable morbidity and mortality rates. Strict indications for filters must be well documented.

Adult↗

The functional state of the beta cell modulates IL-1 and TNF-induced cytotoxicity.

Insulin-dependent diabetes is an autoimmune disease specifically targeting the pancreatic beta cells and several observations, both experimental and clinical, suggest that the interaction of the immune system with the beta cells is in part determined by the functional state of the target cells, increased beta cell activity resulting in augmented immunologic mechanisms and vice versa for suppressed beta cell activity and decreased immune attack. In this study we investigated whether cytokine induced islet cell cytotoxicity in vitro was in part dependent on the functional state of the beta cells. Cytotoxicity of cultured rat islets was induced by IL-1 (100 pg/ml) and TNF (62.5 ng/ml) individually and in combination and beta cell activity was modulated by culturing the islets in media containing 3.3, 5.5, 11, and 20 mmol/liter glucose. Both IL-1 and TNF were cytotoxic when administered individually and the combination of IL-1 and TNF was more cytotoxic than either cytokine alone. Maximum cytotoxicity was observed at 11 mmol/liter glucose with cytotoxicity being reduced at 5.5 mmol/liter glucose and further reduced at 3.3 mmol/liter glucose. Interestingly, the degree of cytotoxicity was lower in 20 mmol/liter glucose compared to 11 mmol/liter. These results firmly establish that islet cytotoxicity of IL-1 and TNF is highly dependent on the functional state of the beta cells. This suggests that during the IDDM disease process as some beta cells are destroyed, the compensatory increased activity of the remaining beta cells may increase their susceptibility to cytokine attack. Furthermore, our observations provide rational support for the use of beta cell rest as intervention therapy for IDDM.

Animals↗

Environmental conditions, anthropometric parameters and arterial blood pressure.

The influence of environmental conditions and anthropometric parameters on arterial blood pressure level was studied in 280 healthy Kashmiri subjects, aged 18-50 years (140 males, 140 females) Men in the age group of 18-20 years had higher blood pressure than women and their systolic blood pressure showed significant correlation with height, weight and skinfold thickness. Females (18-20 years) showed association of diastolic blood pressure with weight, skinfold thickness. Females (18-20) years) showed association of diastolic blood pressure with weight, skinfold thickness and mid-arm circumference. After the age of 20 years females had higher blood pressure than males. Height and weight decreased with age in both the sexes. Skinfold thickness and midarm circumference increased with age in females. A comparison between the present study and those reported from Haryana and Delhi revealed a higher diastolic pressure in Kashmiris.

Adolescent↗

Autonomic functions during different phases of menstrual cycle.

Autonomic functions were studied in female healthy human subjects during the pre-menstrual, menstrual and post-menstrual phases. Our findings indicate a higher BP (systolic) and lower GSR in pre-menstrual phase as compared to other phases. Parasympathetic activity on the other hand does not show significant differences.

Adolescent↗

IgE-mediated sensitization to English plantain pollen in seasonal respiratory allergy: identification and partial characterisation of its allergenic components.

Characterisation by SDS-PAGE immunoblotting of plantain pollen extract showed that components of 16,000-20,000 M(r) were frequently reactive with IgE antibody in the sera of subjects with seasonal respiratory allergy. Other, more weakly IgE-binding allergens were seen in the range of 40,000-60,000 M(r). HPLC followed by RAST inhibition demonstrated that components of approximately 17,000 M(r) were also responsible for much of the IgE-binding activity of the extract. These components appeared to have pI values between 4.5 and 5.2. RAST inhibition showed that there were no common IgE-binding epitopes in grass pollen and plantain pollen extracts, indicating that skin test responses should not necessarily be interpreted in terms of cross-reaction. 82 subjects with a clinical history of seasonal, respiratory allergy were screened in a skin prick test survey. 28% were skin test positive to plantain pollen extract. The frequency of positive skin test reactions to plantain pollen extract was greater than that to Betula (23%) and Artemisa (16%), both which are considered to be important allergens. In a larger survey positive RAST scores to plantain pollen were given by 34% of sera from subjects with respiratory allergy. Plantain pollen sensitivity should therefore be considered during diagnosis of seasonal allergy.

Allergens↗