Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 253 records · Page 14Linked to original sources

PubMed1999

Epidemiology of cataract in India: combating plans and strategies.

Blindness due to cataract presents an enormous problem in India not only in terms of human morbidity but also in terms of economic loss and social burden. The WHO/NPCB (National Programme for Control of Blindness) survey has shown that there is a backlog of over 22 million blind eyes (12 million blind people) in India, and 80.1% of these are blind due to cataract. The annual incidence of cataract blindness is about 3.8 million. The present annual level of performance is in the order of about 1.6-1.9 million cataract operations. To clear the backlog of cataract cases by the year 2000 and to tackle the rising incidence, 5-6 million cataract operations annually will have to be performed as against the present rate of 1. 7 million per year. India is undertaking a new long-term initiative to expand the capability of cataract surgery and service levels with financial assistance from the World Bank. An important feature of this initiative is the attention given to spread the cataract blindness programme in rural and tribal areas. The second feature is the emphasis placed on modern extracapsular cataract extraction with intra-ocular lens implantation as the preferred surgical technique. Another noteworthy feature is developing institutional capacity and appropriate co-ordination mechanisms for collaboration between the non-government organization and the public sector to expand coverage to the most disadvantaged populations. The fourth and the most important strategy is to carry out intensive campaigns at the state and national levels against cataract blindness in order to substantially increase the demand for cataract services. A country like India has more significance for such a plan in view of the fact that various social, economic and environmental factors contribute to cataract blindness in populations at a much younger age.

Blindness↗

PubMed1999

Feasibility and functionality of OROS melatonin in healthy subjects.

OROS (melatonin), an oral osmotic system for controlled drug delivery, was evaluated in an open-label, two-way crossover study to test the feasibility of continuous overnight melatonin delivery. Twelve healthy subjects with no sleep disorders, ranging from 60 to 73 years of age, were enrolled in the study. Two doses of melatonin (1 x 110 micrograms and 4 x 110 micrograms) were administered on two separate occasions. Endogenous baseline nighttime serum melatonin concentrations were measured the night before each treatment. Following treatment at 2100 hours, the lights were extinguished at 2200 hours and remained so, except during blood sample collection, which was performed under dim light (< 50 lux) at specified times. Serum samples were analyzed for melatonin by an LC/MS/MS method. In addition, safety measurements such as vitals and serum samples for endocrine functions were measured both prior to and after melatonin dosing. The serum melatonin concentration profile following OROS (melatonin) dosing mimicked the normal endogenous serum melatonin concentration-time profile. The mean maximal melatonin concentration occurred at 3 a.m. The mean AUCs of endogenous melatonin before the two treatment days were 248 and 234 pg.h/mL, respectively. Serum concentrations of melatonin corrected for endogenous production increased proportionally with dose, with AUCs of 288 and 1069 pg.h/mL, respectively. Deconvolution of the serum concentration data showed good correlation between the in vitro amount released and the in vivo amount absorbed, suggesting continuous absorption throughout the gastrointestinal tract. Less than 5% residual content was observed in the recovered OROS system. Minimal changes in serum hormone concentrations (luteinizing hormone, follicular stimulating hormone, and prolactin) and no serious adverse events were observed following OROS treatment in these subjects. Delivery of melatonin with OROS formulation may result in a physiologic nocturnal profile in elderly subjects.

Adjuvants, Immunologic↗

PubMed1999

Ultrasound guided fine needle aspiration biopsy of splenic lesions.

Fine needle aspiration biopsy (FNAB) of focal splenic lesions has been infrequently utilized because of the risk of haemorrhage. This study was carried out to evaluate the safety and efficacy of ultrasound guided FNAB of splenic lesions. 35 patients with focal splenic lesions underwent FNAB under real-time ultrasound guidance using a free hand technique. Ultrasound findings were single or multiple focal hypoechoic lesions (n = 33), focal hyperechoic lesion (n = 1) and diffuse heterogeneous echotexture (n = 1). Aspirations were performed with 22 G spinal needles using either the subcostal or the intercostal approach. Definite cytological diagnosis was made in 22 patients (62.8%), including tuberculosis in 10 patients, lymphoma in seven patients, extramedullary haematopoiesis in two patients and aspergillosis, histoplasmosis and bacterial abscess in one patient each. FNAB was negative in 12 patients because the aspirates were either scanty or contained only blood. FNAB was falsely positive in one patient. Only one patient had significant intraabdominal bleeding, which was managed conservatively. In conclusion, splenic FNAB performed under ultrasound guidance is a safe and accurate method in the diagnosis of focal splenic lesions.

Adolescent↗

PubMed1999

Tyrosinemia type 1 should be suspected in infants with severe coagulopathy even in the absence of other signs of liver failure.

Tyrosinemia type l is an inherited metabolic disorder attributable to deficiency of fumarylacetoacetate hydrolase, a terminal enzyme in the degradation pathway of tyrosine. Affected individuals may present with any of a number of signs and symptoms, including failure to thrive, fever, vomiting, diarrhea, hepatomegaly, ascites, jaundice, renal Fanconi syndrome, or conditions such as rickets and hepatocellular carcinoma.1 If untreated, the patient may die of acute liver failure before the second year of life, or from chronic liver failure or hepatocellular carcinoma before the end of the second decade of life.2 Although overt liver failure with coagulopathy may be part of the presentation of tyrosinemia, a significant coagulopathy in the absence of overt signs of liver disease has not been emphasized as a clue to the diagnosis of this condition. We report two tyrosinemic infants who presented with severe coagulopathies and no other signs of liver failure to stress this diagnostic point.

Amino Acid Metabolism, Inborn Errors↗

PubMed1999

Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin.

Oxybutynin is used for the treatment of urge urinary incontinence. In this randomized, open-label, two-way crossover, multiple-dose study, the pharmacokinetics of a once-daily, controlled-release formulation, OROS oxybutynin chloride, was compared with that of immediate-release (IR) oxybutynin (Ditropan). Thirteen healthy female volunteers received three 5 mg OROS oxybutynin chloride tablets once daily for 4 days or IR oxybutynin 5 mg administered every 8 hours for 4 days. On day 1, with OROS oxybutynin chloride, mean plasma concentrations rose slowly over approximately 6 hours following dosing (mean Cmax 4.2 ng/mL) and remained fairly constant over the 24-hour dosing interval, whereas with IR oxybutynin, mean plasma concentrations rose rapidly within the first hour after dosing (mean Cmax 12.0 ng/mL), then declined. The mean oxybutynin degree of fluctuation was much lower for OROS oxybutynin chloride (78%) than for IR oxybutynin (371%). For both formulations, the plasma concentration-time profiles for the metabolite N-desethyloxybutynin paralleled those of oxybutynin but at higher concentrations. Steady-state oxybutynin concentrations were achieved by day 3 for both formulations. Mean area under the concentration-time curve (AUC) values for both oxybutynin and its metabolite were similar between day 1 and day 4 for each treatment, suggesting time-invariant pharmacokinetics. With OROS oxybutynin chloride, mean relative bioavailability was higher (153%) for oxybutynin and lower (69%) for N-desethyloxybutynin compared with IR oxybutynin. This increased bioavailability may be due to reduced first-pass metabolism; within 3 to 5 hours after dosing, OROS systems are thought to reach the colon, where cytochrome P450-mediated oxidation (oxybutynin's primary metabolic pathway) may be less extensive than in the small intestine. Fewer subjects reported any adverse event with OROS oxybutynin chloride than with IR oxybutynin (including dry mouth, oxybutynin's most frequently reported anticholinergic adverse effect).

Administration, Oral↗

PubMed1999

Suprasellar arachnoid cyst presenting with precocious puberty : report of two cases.

Suprasellar arachnoid cysts (SSAC) are uncommon intracranial lesions. Two patients of SSAC presenting with precocious puberty are described. In both the cases partial excision of the cyst wall, through a pterional craniotomy, establishing communication with the basal subarachnoid spaces was carried out. The endocrinological symptoms regressed after surgery. The clinical presentations of SSAC and the treatment options available are reviewed.

Child↗

PubMed1999

Fomes pectinatis: an aeroallergen in India.

This work is focused on the aerobiology and allergenicity of Fomes pectinatis in India. The atmospheric concentration of Fomes basidiospores was recorded and the antigens were prepared from spore (FSE) and whole body (FWBE) materials. The intradermal (ID) and prick (PT) skin tests were conducted on 172 patients having respiratory allergy. The period from July to October has been recorded as having a higher concentration of Fomes spores. The maximum counts (67 spores/m3) were observed from the North Delhi site in the month of July, 1989, compared with 550 spores/m3 in the South Delhi site. Marked skin positivity (2+ and above) varied from 9.8% to FSE to 22% to FWBE. Nine out of twelve ID positive patients (2+ to 3+) to FSE also gave PT positive response. For FWBE, similar ID and PT response was obtained in 80% of cases. The soluble protein content of FSE was 0.37 mg/ml, whereas, for FWBE it was 0.70 mg/ml. It was observed through ELISA that almost all patients had significantly raised FP specific IgE levels in their sera. The current study, therefore, indicates that Fomes pectinatis may be a prevalent aeroallergen in India.

Air Pollutants↗

PubMed1999

Effect of cadmium on the hatching of Metaphire posthuma cocoons.

Earthworms are considered ideal soil organisms for use in terrestrial ecotoxicology. Due to their susceptibility of heavy metals, the effect of cadmium on the hatching of M. posthuma cocoons was studied. The hatching was observed by the water incubation method and the doses of Cd were 0, 1.25, 2.5, 5.0, 10.0 and 40.0 ppm. The 0 and 1.25 ppm treated cocoons hatched within 45-60 days at 20 degrees C with 80% hatching rate and one juvenile per cocoon; no hatching was observed at higher concentrations. Furthermore, there was a linear increase in Cd residue in the treated cocoons. These results are apparently ill effects of Cd on embryonic development of the earthworms.

Animals↗

PubMed1999

Adaptation of cytochrome-b5 reductase activity and methaemoglobinaemia in areas with a high nitrate concentration in drinking-water.

An epidemiological investigation was undertaken in India to assess the prevalence of methaemoglobinaemia in areas with high nitrate concentration in drinking-water and the possible association with an adaptation of cytochrome-b5 reductase. Five areas were selected, with average nitrate ion concentrations in drinking-water of 26, 45, 95, 222 and 459 mg/l. These areas were visited and house schedules were prepared in accordance with a statistically designed protocol. A sample of 10% of the total population was selected in each of the areas, matched for age and weight, giving a total of 178 persons in five age groups. For each subject, a detailed history was documented, a medical examination was conducted and blood samples were taken to determine methaemoglobin level and cytochrome-b5 reductase activity. Collected data were subjected to statistical analysis to test for a possible relationship between nitrate concentration, cytochrome-b5 reductase activity and methaemoglobinaemia. High nitrate concentrations caused methaemoglobinaemia in infants and adults. The reserve of cytochrome-b5 reductase activity (i.e. the enzyme activity not currently being used, but which is available when needed; for example, under conditions of increased nitrate ingestion) and its adaptation with increasing water nitrate concentration to reduce methaemoglobin were more pronounced in children and adolescents.

Adolescent↗

PubMed1999

A novel PAX6 frameshift mutation in a kindred from Atlantic Canada with familial aniridia.

BACKGROUND: Many mutations in PAX6, a member of a family of genes essential for normal development, have been described. We carried out a study to identify the mutation in PAX6 responsible for aniridia, an autosomal dominant disorder, in a kindred from Atlantic Canada. METHODS: Polymerase chain reaction amplification of coding exons, single-strand conformation polymorphism analysis and DNA sequencing. RESULTS: A novel deletion of an adenosine residue at position 1030 (1030delA) was detected. INTERPRETATION: The mutation responsible for aniridia in this kindred is expected to cause a frameshift in the PAX6 coding sequence and truncation of the homeodomain, which is essential for the function of the pax6 protein.

Adult↗

PubMed1999

Midline and far lateral approaches to foramen magnum lesions.

Twenty patients with foramen magnum lesions were operated upon in the last 5 years at Postgraduate Institute of Medical Education and Research, Chandigarh. The common presenting features were quadriparesis, quadriplegia, diminished sensations, neck pain and respiratory insufficiency. The lesions encountered were meningiomas, neurofibromas, posterior inferior cerebellar artery aneurysms, neurenteric cyst and chordoma. Patients with posterior or posterolaterally placed lesions were operated by the midline posterior approach while those with anterior or anterolateral lesions were managed by the far lateral approach. All mass lesions were excised completely and the aneurysms were clipped. Seventeen patients made good neurological recovery while three died. The latter three patients presented very late. The merits of various surgical approaches to the foramen magnum are discussed.

Adolescent↗

PubMed1999

Pure extradural approach for skull base lesions.

Lesions in the parasellar and paracavernous regions can be removed by various skull base approaches involving basal osteotomies. A major complication of intradural skull base approaches is CSF leak and associated meningitis. We have managed 5 patients with skull base lesions with a pure extradural approach using wide basal osteotomies. The operative techniques are described.

Adolescent↗

PubMed1999

Qualitative research in ophthalmic sciences.

Qualitative research was the preserve of social scientists before making inroads into medical sciences, as the medical fraternity was wedded to evidence-based medicine. Qualitative research methods are now being increasingly used in medicine. The goal of qualitative research is to help in the understanding of social phenomenon in their natural settings. These methods help to unravel mysteries relating to complex human interactions and to study the role of human behaviour in health and disease. Recent evidence points to the complementary roles of qualitative and quantitative methods in medical research. Qualitative methods include observations, interviews, focus groups, projective techniques, analysis of personal documents and accounts, sorting and ranking, and case studies. This communication describes the application of qualitative methods in ophthalmic research.

Humans↗

PubMed1998

Hetero-oligomerization-dependent binding of pig oocyte zona pellucida glycoproteins ZPB and ZPC to boar sperm membrane vesicles.

The zona pellucida surrounding the pig oocyte contains two Mr 55,000 glycoproteins, pZPB and pZPC, which are orthologues of mouse zona proteins ZP1 and ZP3, respectively. We previously reported that isolated boar sperm membrane vesicles possess high affinity binding sites for partially purified pZPB, but not pZPC. Interestingly, co-incubation experiments also implicated pZPB-pZPC complexes as potential ligands. We now report that when depleted of a minor pZPC contaminant by size exclusion chromatography, pZPB lacks independent binding activity. In solid phase binding assays employing immobilized boar sperm membranes, pZPB failed to compete with biotin-(pZPB+pZPC) probe, and biotin-labeled pZPB yielded negligible binding. However, when co-incubated with pZPC prior to the binding assays, pZPB acted as a potent competitor, and biotin-labeled pZPB exhibited high affinity, saturable binding. Binding activity was attributed to pZPB-pZPC heterocomplexes, which were detected in co-incubation mixtures by size exclusion chromatography and Western blot analysis. In the pig, therefore, sperm membranes possess a zona-binding protein with high affinity sites for pZPB-pZPC heterocomplexes, but not free glycoprotein subunits. Consequently, associative interactions between zona molecules can contribute toward both the assembly of the zona matrix and generation of ligands important for sperm-zona interactions.

Animals↗

PubMed1998

Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines.

Chemokines play an important role in the regulation of endothelial cell (EC) function, including proliferation, migration and differentiation during angiogenesis, and re-endothelialization after injury. In this study, reverse transcriptase-polymerase chain reaction was used to reveal expression of various CXC and CC chemokine receptors in human umbilical vein EC. Northern analysis showed that CXCR4 was selectively expressed in vascular EC, but not in smooth muscle cells. Compared with other chemokines, stromal cell-derived factor-1alpha (SDF-1alpha), the known CXCR4 ligand, was an efficacious chemoattractant for EC, causing the migration of approximately 40% input cells with an EC50 of 10-20 nM. Of the chemokines tested, only SDF-1alpha induced a rapid, though variable mobilization of intracellular Ca2+ in EC. Experiments with actinomycin D demonstrated that CXCR4 transcripts were short-lived, indicating a rapid mRNA turnover. Interferon-gamma (IFN-gamma) caused a pronounced down-regulation of CXCR4 mRNA in a concentration- and time-dependent manner. In a striking functional correlation, IFN-gamma treatment also attenuated the chemotactic response of EC to SDF-1alpha. IL-1beta, tumor necrosis factor-alpha, and lipopolysaccharide produced a time course-dependent biphasic effect on CXCR4 transcription. Expression of CXCR4 in EC is significant, more so as it and several CC chemokine receptors have been shown to serve as fusion co-receptors along with CD4 during human immunodeficiency virus infection. Taken together, these findings provide evidence of chemokine receptor expression in EC and offer an explanation for the action of chemokines like SDF-1alpha on the vascular endothelium.

Calcium↗

PubMed1998

Molecular cloning and expression in Escherichia coli of cDNA encoding bonnet monkey (Macaca radiata) zona pellucida glycoprotein-ZP2.

Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for an immunocontraceptive vaccine. The efficacy of such a vaccine has to be evaluated in nonhuman primates, thus necessitating the characterization of their ZP glycoproteins. A bonnet monkey (Macaca radiata) ovarian cDNA lambda gt11 library was screened for ZP2 (bZP2) using full-length human ZP2 cDNA as a probe. Two identical full-length clones with an open reading frame of 2235 nt encoding a polypeptide of 745 aa residues were isolated. The deduced aa sequence of bZP2 revealed high sequence identity (94.2%) with human ZP2. The bZP2 cDNA (115-1914 nt, 1.8 kb), excluding sequences coding for N-terminal signal sequence and C-terminal transmembranelike domain, was PCR amplified and Sac1-Sal1 restricted fragment cloned in frame downstream of the T5 promoter under the lac operator control in a pQE-30 vector. Recombinant bZP2 (r-bZP2) was expressed as a polyhistidine fusion protein in Escherichia coli strain M15 [pREP4]. Immunoblot with rabbit polyclonal antibodies against bZP2 synthetic peptide (corresponding to aa residues 429-444; K434 replaced by R and 1436 by V) revealed a major band of 68 kDa. Immunization of male rabbits with the r-bZP2 protein purified on Ni-NTA resin under denaturing conditions generated antibodies reactive with r-bZP2 in ELISA as well as with native protein as revealed by positive fluorescence of ZP of bonnet monkey ovary. The availability of r-bZP2 and its aa sequence will help in the development and evaluation of a contraceptive vaccine based on ZP2.

Amino Acid Sequence↗

PubMed1998

Multiple-dose pharmacokinetics and pharmacodynamics of OROS and immediate-release amitriptyline hydrochloride formulations.

The pharmacokinetics and pharmacodynamics of amitriptyline hydrochloride after oral administration of an OROS osmotic system, which provides controlled drug delivery, and an immediate-release (IR) tablet, were evaluated in 24 healthy volunteers after repeated administration for 14 days. Each morning, subjects received either 75 mg of the OROS (amitriptyline HCl) controlled-release formulation or the 75 mg IR amitriptyline tablet for 14 days on two separate occasions with a washout period of 21 days according to a randomly assigned sequence. Serial blood samples were collected for a period of 58 hours after the day 14 dose, then these samples were analyzed by the gas chromatography method for amitriptyline and nortriptyline. Subjective ratings of dry mouth and drowsiness were collected at specific times throughout each treatment period. Administration of the OROS formulation resulted in much more consistent plasma concentrations of the drug and metabolite compared with the IR formulation at steady state. The mean maximum concentration (Cmax) of amitriptyline was significantly lower after administration of OROS than the IR formulation. Mean values for area under the concentration--time curve (AUC0-24) for the OROS and IR formulations were 1,265 and 1,393 ng. hr/mL, respectively. The drug-to-metabolite ratio was found to be similar for both treatments, suggesting that there was no difference in metabolism between treatments. Incidence and severity of the anticholinergic effects were similar for the two treatments. A clockwise hysteresis between baseline-corrected drowsiness and drug concentration suggests development of tolerance of the anticholinergic effects after both treatments. Using a hypothetical anatagonist metabolite model to explain tolerance development, the shape of the hysteresis curves of the two treatments could be explained by differences in dosing frequency.

Adult↗

PubMed1998

Fentanyl delivery from an electrotransport system: delivery is a function of total current, not duration of current.

This open-label, parallel study of 28 men was conducted to evaluate the pharmacokinetics and safety of fentanyl delivered by the E-TRANS (fentanyl) electrotransport transdermal system (ALZA Corporation, Palo Alto, CA). The E-TRANS (fentanyl) system provided electrically assisted, transdermal, continuous delivery of fentanyl. Treatments consisted of no current (group A); a constant current of 100 microA for 26 hours plus 4 additional doses at varying currents for varying times during hour 25 (groups B, C, D); a constant current of 100 microA for 26 hours plus 4 additional doses at 1,200 microA over 2.5 minutes during hour 1 (group E); or 500 microA for 0.5 hours and 100 microA for 3.5 hours (group F). No fentanyl was detected in serum when no current had been applied. Mean serum fentanyl concentrations were similar regardless of current duration during hour 25 (treatments B, C, D). Increases in mean serum fentanyl concentrations were significantly lower during additional dosing for treatment E compared with treatments B, C, and D. Serum fentanyl concentrations sufficient for analgesia (1-3 ng/mL) were attained in treatments using the E-TRANS (fentanyl) system with basal current of 100 microA for 26 hours. There were no safety issues after treatment with E-TRANS (fentanyl) system with concurrent opioid antagonist (naltrexone) administration. The only adverse event requiring treatment was a headache (n = 1). The majority of subjects had no or barely perceptible erythema at the application site 24 hours after system removal. Application of E-TRANS (fentanyl) resulted in therapeutically significant serum fentanyl concentrations over a range of applied currents. Overall serum fentanyl concentrations were higher when the skin had been primed by constant-current fentanyl delivery.

Administration, Cutaneous↗