Search PubMed⌕ Search

Biomedical subjects

A Verma

Publications and source records attributed to A Verma.

At least 109 records · Page 6Linked to original sources
PubMed1997

Liquid chromatographic assay of dityrosine in human cerebrospinal fluid.

A micro-scale method for separation and measurement of dityrosine in human cerebrospinal fluid (CSF) is described utilizing liquid-liquid extraction and ion-paired, reversed-phase high-performance liquid chromatography with fluorimetric detection. A mobile phase containing 1-heptanesulfonic acid linearly increased in methanol from 0 to 100% over 30 min allows the resolution of dityrosine from other fluorescent compounds with excitation at 285 nm and emission at 410 nm. As little as 0.15 ml CSF sample can be utilized with a detection limit of 60 pg dityrosine on the column. This method facilitates the use of CSF dityrosine as a measure of free radical mediated protein damage in the central nervous system.

Chromatography, High Pressure Liquid↗
PubMed1997

Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.

Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal lobe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC function in part by interacting with dopamine neurotransmission in this region. This study sought to determine the mechanism by which ketamine may disrupt dopaminergic neurotransmission in, and cognitive functions associated with, the PFC. A thorough dose-response study using microdialysis in conscious rats indicated that low doses of ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the PFC, suggesting that at these doses ketamine may increase glutamatergic neurotransmission in the PFC at non-NMDA glutamate receptors. An anesthetic dose of ketamine (200 mg/kg) decreased, and an intermediate dose of 50 mg/kg did not affect, glutamate levels. Ketamine, at 30 mg/kg, also increased the release of dopamine in the PFC. This increase was blocked by intra-PFC application of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione CNQX. Furthermore, ketamine-induced activation of dopamine release and impairment of spatial delayed alternation in the rodent, a PFC-sensitive cognitive task, was ameliorated by systemic pretreatment with AMPA/kainate receptor antagonist LY293558. These findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Active vision therapy for pseudophakic amblyopia.

PURPOSE: To study the benefit of active vision therapy using various pleoptic methods in pseudophakic amblyopic children and young adults. SETTING: Daljit Singh Eye Hospital, Amritsar, India. METHODS: This study comprised 160 consecutive pseudophakic amblyopic patients who had had iris-claw lens implantation for congenital or traumatic cataract. Their ages ranged from 3.5 to 25.0 years. Before active vision treatment, visual acuity was worse than 20/200 in 63 patients (39.3%), 20/200 in 77 (48.1%), 20/120 to 20/80 in 14 (8.7%), and 20/60 in 6 (3.7%). The methods included Haidinger brushes on the synoptophore, after images, CAM stimulator, drawings on the cheiroscope, Pigeon-Cantonnet stereoscope, video games with the amblyopic eye, and exercises for promoting eye-hand coordination. Mean duration of therapy was 6 months. RESULTS: After therapy, visual acuity was worse than 20/200 in 31 patients (19.4%), 20/200 in 38 (23.7%), 20/120 to 20/80 in 41 (25.6%), 20/60 to 20/40 in 36 (22.5%), and 20/20 in 14 (8.7%). In 20 patients (12.5%), all younger than 15 years, visual acuity decreased within 1 month after treatment stopped. However, vision was rapidly restored after another session of active vision therapy. CONCLUSIONS: Active vision therapy helped improve visual acuity in the majority of young pseudophakic amblyopes.

Adolescent↗
PubMed1997

Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: effect of ursodeoxycholic acid and immunosuppressive therapy.

OBJECTIVES: Soluble intercellular adhesion molecule-1 (sICAM-1) is thought to be released by a variety of cells at sites of inflammation, and their serum levels have been used as markers of inflammatory and immune activity. Our aim was to determine the effect of therapy with ursodeoxycholic acid alone and in combination with azathioprine and prednisone on serum sICAM-1 levels in primary biliary cirrhosis. DESIGN/METHODS: Twenty-four patients with primary biliary cirrhosis and 17 healthy subjects were studied. Primary biliary cirrhosis patients received ursodeoxycholic acid for 12 months and were then randomized in a double-blind fashion to receive prednisone and azathioprine, or placebo in addition to ursodeoxycholic acid. RESULTS: sICAM-1 levels were significantly higher in primary biliary cirrhosis patients than healthy subjects and fell by a median of 20% after 12 months' therapy with ursodeoxycholic acid (P<0.0004). Addition of azathioprine and prednisone to ursodeoxycholic acid resulted in a further reduction of sICAM-1 levels by a median of 25% (P< 0.01). Reductions in sICAM-1 were accompanied by improvement in liver function tests but not in the lymphocyte activation marker, soluble interleukin-2 receptor. CONCLUSION: sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid. Further reductions were achieved by adding prednisone and azathioprine. These reductions probably reflect an improvement in hepatobiliary excretion and a reduction in cellular production of sICAM-1.

Adult↗
PubMed1997

Profile of ocular trauma in Papua New Guinea.

BACKGROUND: Ocular trauma is a significant cause of blindness in Papua New Guinea (PNG). This study was done to determine the pattern and rates of ocular and adnexal injuries so as to determine the size and extent of the problem. METHODS: A retrospective study of 4157 cases presenting with ocular trauma in three regions of PNG was carried out. The data were analysed with respect to the age, sex, province, type and cause of injury, time interval between injury and presentation to the hospital and the final visual outcome after treatment. RESULTS: Ocular trauma rates in PNG were alarmingly high (39.1 per 100,000). The commonest cause of injury in the younger age group was due to lime. Alcohol-related violence and fights resulted in injuries in the adult age group. Most of the injuries were grievous and 60.7% of patients were left with a visual acuity of less than 6/60 in the injured eye. In addition, 78.7% of the patients were under 30 years of age. CONCLUSIONS: Ocular injuries in PNG are an important cause of visual disability. Some specific injuries, such as those due to lime in children, can easily be prevented by health education.

Adolescent↗
PubMed1997

A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy.

We describe a childhood mitochondrial disorder in which the clinical symptoms began and remained confined to the gastrointestinal (GI) system during the first 4 y. Seizures heralded the onset of progressive encephalopathy at age 7. Peripheral neuropathy, retinitis pigmentosa, and neural deafness developed subsequently. Laboratory investigations disclosed elevated levels of plasma lactate, and a muscle biopsy revealed ragged red fibers lacking cytochrome c oxidase activity and diminished levels of respiratory chain enzyme complexes. Molecular genetic tests failed to show any of the previously reported pathogenic mitochondrial DNA (mtDNA) mutations. We therefore screened the whole mitochondrial genome by coupling restriction digestions with single-strand conformational polymorphism (SSCP) patterns. We identified a unique SSCP in the segment that encompassed the tRNA(Lys) gene, and direct sequencing of this segment revealed a G-->A transition at an evolutionarily conserved nucleotide at mtDNA position 8313. This G8313A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in the white blood cells and platelets from his maternal relatives. This report illustrates how GI symptoms can be the initial manifestation in a mitochondrial disorder and suggests that mitochondrial dysfunction should be considered in differentials of unexplained chronic GI symptoms, especially when lactic acidosis or other unrelated clinical signs or symptoms are present.

Adolescent↗
PubMed1997

Gestational diabetes mellitus. Unresolved issues and future research directions.

OBJECTIVE: To summarize the controversial aspects of gestational diabetes (GDM) and introduce readers to possible relevant research questions that could be examined to provide clinicians with good-quality data on which to base decisions about this relatively common pregnancy-related issue. DATA SOURCES AND STUDY SELECTION: Ongoing review of the English literature related to GDM. Sources were not restricted to prospective, controlled trials, as these are severely limited in number. SYNTHESIS: Controversial issues include the relevance of GDM to clinically meaningful outcomes in the index pregnancy, the effectiveness of current therapy in altering these outcomes, and the resultant questionable relevance of routine screening and diagnosis of an entity with as yet uncertain significance in pregnancy. CONCLUSIONS: Suggested questions to be addressed in multicentre controlled trials include randomization with respect to screening and with respect to treatment. Until such trials are completed, continuing with a standard approach to screening, diagnosis, and treatment, such as that suggested by the third international workshop on GDM, is recommended.

Cost-Benefit Analysis↗
PubMed1996

Utility of a test for chromosomal malsegregation in Saccharomyces cerevisiae strain D61.M for the detection of antianeugens: test of the model combination of chlorophyllin and nocodazole.

Despite the fact that aneuploidy is a major genetic cause of human morbidity and mortality, antimutagenicity studies have used predominantly short-term tests that detect gene mutations, chromosomal aberrations, and micronuclei. Therefore, the major deficiency in the use of short-term tests for antimutagenicity studies is those that detect chromosomal malsegregation leading to aneuploidy. Thus, we initiated a study on the utility of short-term tests for the detection of antianeugenic activity. We selected strain D61.M of Saccharomyces cerevisiae, nocodazole, and chlorophyllin as a model short-term test, aneugen, and antimutagen, respectively, for our initial study. Chlorophyllin strongly inhibited the aneugenic activity of nocodazole, but had no effect on the endpoints when tested alone, in strain D61.M. To our knowledge, this is the first report of an antianeugen. Furthermore, we conclude that strain D61.M can be used as a relatively simple, inexpensive, and rapid short-term test for the study of antianeugenicity.

Aneuploidy↗
PubMed1996

Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam.

C57BL/6J-Min/+mice (n = 56), heterozygous for a nonsense mutation in the Apc gene, were randomized at weaning to seven groups, including groups treated with piroxicam at 0, 50, 100, and 200 ppm in the AIN93G diet. After only 6 weeks of treatment, intestinal adenomas and aberrant crypt foci were counted, and serum levels of piroxicam and thromboxane B2 were quantitated. Tumor multiplicity was decreased in a dose-dependent manner from 17.3 +/- 2.7 in the control to 2.1 +/- 1.1 (12%) in the high-dose piroxicam group (P < 0.001). Thromboxane B2 levels in plasma also decreased monotonically in parallel to the decrease in tumor multiplicity, consistent with the prostaglandin inhibitory effect of piroxicam. The Min mouse model demonstrates that the nonsteroidal anti-inflammatory drug piroxicam has strong biological and therapeutic effects, potentially useful for prevention of the early adenoma stage of tumor development.

Animals↗
PubMed1996

Motor neuron disease: a paraneoplastic process associated with anti-hu antibody and small-cell lung carcinoma.

Although isolated lower motor neuron disease has been reported as a paraneoplastic complication, it has not been previously described, in association with anti-Hu antibody. We report a 51-year-old man in whom weakness heralded the presence of a small-cell cancer of the lung. His neurological disorder was characterized by an unremitting progression of limb, neck, and chest wall weakness and wasting that commenced and remained predominant in the upper limbs. Electrophysiological studies demonstrated widespread denervation and examination of a muscle biopsy specimen showed evidence of acute and chronic denervation. High titers of anti-Hu antibody were detected in the serum and cerebrospinal fluid. Neither objective measures of strength nor titers of anti-Hu antibody responded to corticosteroids, cyclophosphamide, intravenous immunoglobulins, or plasmapheresis. Death from the complications of motor neuron disease ensued 23 months after the onset of weakness. Autopsy revealed tumor in the lung and on pleural and peritoneal surfaces. There was a loss of anterior horn cells in the spinal cord. Despite the absence of symptomatic cerebellar disease, a decrease in the number of Purkinje cells was also detected.

Anti-Inflammatory Agents↗
PubMed1996

Occipital lobe tumor presenting as migraine with typical aura.

We report the case of a 60-year-old woman in whom migraine with typical aura heralded the presence of an occipital lobe tumor. Her headache was characterized by recurrent episodes of visual aura confined to the left visual field followed by right hemicranial throbbing headaches accompanied by nausea, photophobia, and phonophobia. Interictal neurologic and ophthalmologic examinations were negative, as was an unenhanced brain CT scan. The headaches increased in frequency over 4 months despite a number of medications known to prevent attacks of migraine. A low-grade right occipital lobe tumor was eventually discovered on MR scan. This case illustrates that headache fulfilling the International Headache Society (IHS) criteria for migraine with typical aura can occur in association with an occipital lobe tumor.

Brain Neoplasms↗
PubMed1996

Effects of halothane and isoflurane on carbon monoxide-induced relaxations in the rat aorta.

BACKGROUND: Halothane and isoflurane previously were reported to attenuate endothelium-derived relaxing factor/nitric oxide-mediated vasodilation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic similarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxations and cGMP formation in the isolated rat aorta. METHODS: Isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 microM). This procedure was repeated three times, with anesthetics delivered 10 min before the second procedure. Carbon monoxide responses of rings contracted with the same concentration of norepinephrine (10(-6) M and 2 x 10(-6) M) used in the anesthetic-exposed preparations also were examined. The concentrations of cGMP were determined in denuded rings using radioimmunoassay. The rings were treated with carbon monoxide (176 microM, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM or 0.72 mM). To determine whether the sequence of anesthetic delivery influenced results, vascular rings pretreated with halothane were compared with nonpretreated rings. RESULTS: Carbon monoxide (26-176 microM) caused a dose-dependent reduction of norepinephrine-induced tension, with a maximal relaxation of 1.51 +/- 0.07 g (85 +/- 7% of norepinephrine-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the highest concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 microM) significantly increased cGMP content (+88.1 +/- 7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this increase (-70.7 +/- 6.8% and -108.1 +/- 10.6%, respectively). When aortic rings and carbon monoxide were added simultaneously to Krebs solution equilibrated with halothane (0.72 mM), no inhibition of cGMP formation occurred. CONCLUSION: Carbon monoxide-induced endothelium-independent relaxations of rat aortic rings were decreased by clinically relevant concentrations of halothane and isoflurane. The carbon monoxide-induced elevations of cGMP were attenuated by halothane only when the anesthetic was incubated with aortic rings before carbon monoxide treatment. The possible clinical significance of the actions of the anesthetics on this endogenous vasodilator is yet to be determined.

Anesthetics, Inhalation↗
PubMed1996

A MERRF/PEO overlap syndrome associated with the mitochondrial DNA 3243 mutation.

We describe a two-generation family with combined clinical features of myoclonic epilepsy, progressive external ophthalmoplegia (PEO), proximal myopathy, pigmentary retinopathy, progressive deafness, basal ganglia calcification, and ragged-red fibers in a muscle biopsy specimen. One family member died unexpectedly at age 22 years. The molecular tests revealed an A-to-G transition at nucleotide position 3243 of the mitochondrial tRNA(Leu(UUR)) gene. No one in this family had stroke-like episodes. Although the propositus (a 28-year-old woman) had a significant number of white hairs, the percentage of mutant mtDNA in white-hair roots was not different from that in the colored-hair roots. Our findings suggest that the 3243 mutation can be associated with mixed clinical features of myoclonic epilepsy with ragged-red fibers (MERRF) and PEO and that a preferential increase in the levels of the mutant mtDNA is not related to graying of hair, and hence to the hypothesized production of premature aging of cells.

Adult↗
PubMed1996

Painful vasculitic neuropathy in HIV-1 infection: relief of pain with prednisone therapy.

Painful distal sensory polyneuropathy (DSP) is the most common peripheral neuropathy in patients with human immunodeficiency virus-1 (HIV-1) infection. There is no specific therapy for DSP, and nonspecific treatment with pain blockers and narcotic agents generally fails to adequately control the symptoms. We report two patients who had subacute painful neuropathy in the B2 (formerly AIDS-related complex [ARC]) stage of HIV-1 infection. Neurophysiologic studies revealed predominantly axonal sensorimotor neuropathy. Sural nerve biopsy in both cases showed a necrotizing vasculitis. Treatment with corticosteroids resulted in rapid relief of pain, followed by arrest of the neuropathic process. Although not previously emphasized, vasculitic neuropathy must be considered among the treatable causes of painful sensory neuropathy in HIV-1-infected individuals.

HIV Infections↗
PubMed1996

NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine.

The present study was performed to assess the role of excitatory amino acid and dopamine receptors on associative functions of the prefrontal cortex (PFC) of the rat. Spatial delayed alternation was used as a PFC-sensitive cognitive task. In addition, in vivo microdialysis was used to assess the release of dopamine in the PFC. The noncompetitive NMDA antagonists ketamine (10-30 mg/kg) and MK-801 (0.1 and 0.5 mg/kg) dose-dependently impaired the spatial delayed alternation performance compared with the saline-treated control group. Administration of the dopamine antagonists raclopride (0.1 and 0.5 mg/kg), SCH-23390 (0.1 mg/kg), or haloperidol (0.1 mg/kg) was without a significant effect. However, haloperidol and raclopride (but not SCH-23390) reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance. Microdialysis studies revealed that this dose of ketamine preferentially increased the release of dopamine in the PFC compared with the striatum. These findings indicate that attenuation of glutamatergic neurotransmission at the NMDA receptor impairs PFC-dependent cognitive functions. Furthermore, activation of dopamine neurotransmission contributes, at least in part, to this impairment.

Animals↗
PubMed1996

Estradiol attenuates directed migration of vascular smooth muscle cells in vitro.

Although the cardiovascular benefits of the hormone estrogen are at least, in part, mediated by its antiproliferative effect on vascular smooth muscle, its action on the migration of these cells is unknown. To explore this relationship, female rat aortic smooth muscle cells were grown in hormone-free medium, and the effect of various concentrations of beta-estradiol on directed cellular migration was measured in vitro using a microwell Boyden chamber apparatus. Migration of smooth muscle cells to the known chemoattractants platelet-derived growth factor, insulin-like growth factor-1, and fibronectin (all at peak doses for migratory activity) was attenuated by beta-estradiol (0.5 to 10 ng/ml) in a concentration-dependent manner relative to control cells treated with vehicle (0.01% ethanol). This response was insensitive to pretreatment with indomethacin and was stereospecific (17 alpha-estradiol lacked response). Like beta-estradiol, the synthetic estrogen diethylstilbestrol attenuated directed smooth muscle cell migration whereas the male hormone testosterone was ineffective. Additional studies showed that beta-estradiol-mediated suppression of migration was inhibited by the anti-estrogen ICI 164,384 and the gene transcription inhibitor actinomycin D. These are the first results demonstrating a reduction in directed smooth muscle cell migration by beta-estradiol. The mechanism of this estrogen-mediated response appears to involve conventional estrogen receptors.

Animals↗