PubMed Health⌕ Search

Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 199 records · Page 11Linked to original sources
PubMed2000

A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group.

The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20-68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open-label, randomized, active controlled study. Patients received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for 24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg orally daily. Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related reductions in white cells, neutrophils and platelets. Addition of ribavirin reduced hemoglobin levels in a dose-related manner, did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count, and increased platelet counts. Neutrophil function tests (C5a and FMLP migration, killing curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in all dose groups. Anti-HCV activity, as measured by loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy. There was no evidence of pharmacokinetic interactions with either drug. We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were numerically superior to those obtained with PEG-Intron monotherapy.

Adult↗
PubMed2000

Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.

AIMS: The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. METHODS: Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. RESULTS: Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow-up. Both pegylated and nonpegylated interferon-alpha2b were rapidly absorbed, with maximal concentrations occurring approximately 8 to 12 hours after dose administration. Pegylated interferon-alpha2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon-alpha2b concentrations declined rapidly. Volume of distribution for both compounds was similar (approximately 1 L/kg). Pegylated interferon-alpha2b elimination half-life was approximately 10-fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon-alpha2b. CONCLUSIONS: Pegylated and nonpegylated interferon-alpha2b safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

Absorption↗
PubMed2000

Comparison of various calpain inhibitors in reduction of light scattering, protein precipitation and nuclear cataract in vitro.

PURPOSE: To compare effects of calpain inhibitors on in vitro light-scattering in rat lens soluble protein and calcium-ionophore (A23187)-induced cataract formation in cultured rat lenses. METHODS: Rat lens soluble protein was hydrolyzed for 24 hours by activation of endogenous lens calpain. Ten calpain inhibitors were tested in this model at 10 and 25 microM concentration. As an index of protein precipitation, light scattering was measured daily at 405 nm for 8 days. Lens proteins were analyzed by isoelectric-focussing. Subsequently, rat lenses were cultured for 5 days with 10 microM A23187. Calpain inhibitors (SJA6017, MDL28170, AK295 and PD150606), which inhibited light-scattering were tested at 100 microM concentration in this model. Cataract evaluation, isoelectric-focussing and calcium determinations were performed. RESULTS: At 25 microM concentration AK295, SJA6017, E-64, PD-150606 and MDL28170 produced greater than 25% inhibition of light-scattering. Isoelectric-focussing revealed that addition of Ca(2+) produced characteristic crystallin proteolysis and aggregation patterns. AK295, SJA6017, MDL28170 and E64c prevented these changes. Lenses cultured in A23187 exhibited nuclear cataract, elevated calcium and proteolysis and aggregation of crystallins. Co-culture with SJA6017, MDL28170 and E64c reduced A23187-induced nuclear opacities, proteolysis and aggregation of crystallins without affecting increased total calcium. CONCLUSIONS: Endogenous calpain-activation model and A23187-induced cataract model can be used sequentially to screen calpain inhibitors for potential anti-cataract activity. Proteolytic changes in lens cortex after exposure to A23187 are also due to calpain activation. AK295, SJA6017 and MDL28170 possess efficacy against calcium-induced models of rodent cataracts. Use of calpain inhibitors represents a promising approach to cataract therapy.

Animals↗
PubMed2000

Ultrasound-guided transthoracic co-axial biopsy of thoracic mass lesions.

PURPOSE: To compare the diagnostic yield of fine-needle aspiration biopsy (FNAB) and cutting needle biopsy in thoracic lesions. MATERIAL AND METHODS: Thirty patients with thoracic mass lesions were subjected to ultrasound-guided co-axial FNAB and cutting needle biopsy using 0.7 mm aspirating and 1.0-mm cutting needles, respectively. The diagnostic yield of the individual modalities was compared with the combined yield. RESULTS: A conclusive diagnosis was obtained in 76.6% (n=23) of patients by FNAB and in 66.6% (n=20) by cutting needle biopsy. The combined diagnostic yield of FNAB and cutting needle biopsy was 93.3% (n=28) with a significant statistical difference (p<0.03) as compared to cutting biopsy alone. Of the patients, 23.2% (n=7) had benign and 76.6% (n=23) malignant aetiologies. The diagnostic yield of FNAB versus cutting needle biopsy in benign lesions was 57.1% (n=4) and 100% (n=7), respectively. The diagnostic yield of FNAB versus cutting needle biopsy in malignant lesions was 82.6% (n=19) and 56.5%, (n=13). Two patients remained undiagnosed by either modality. There were no complications. CONCLUSION: FNAB and cutting needle biopsy are complementary to each other and attempts should be made to obtain small tissue cores in addition to routine cytologic specimens in diagnosing thoracic lesions, especially in benign pathologies. US provides a safe guidance modality for lesions abutting the chest wall.

Adolescent↗
PubMed2000

Platelet agonist F11 receptor is a member of the immunoglobulin superfamily and identical with junctional adhesion molecule (JAM): regulation of expression in human endothelial cells and macrophages.

The stimulatory mAb F11 binds two platelet membrane proteins of 32 and 35 kDa and causes activation of platelets when cross-linked with the FcgammaRII receptor. We used bioinformatics to identify expressed sequence tags from libraries of cytokine-stimulated human endothelial cell (EC) cDNAs. The protein sequence deduced from full-length F11 cDNA was identical to partial sequences of peptides derived from affinity-purified platelet F11 antigen. F11 mRNA is expressed in human EC, macrophages, and a variety of non-hematopoietic vascular tissues. Expression of F11 mRNA is modulated by cytokines in EC and is up-regulated by oxidized low-density lipoprotein in human macrophages. The F11 receptor contains two immunoglobulin-like domains in its 236-amino-acid-long extracellular region, and has identity to the recently described junctional adhesion molecule. The data indicate that the F11 antigen is a novel receptor or cell adhesion molecule belonging to the immunoglobulin superfamily.

Amino Acid Sequence↗
PubMed2000

Intravitreal pharmacokinetics of plain and liposome-entrapped fluconazole in rabbit eyes.

The objective of our experiment was to study the pharmacokinetics of plain and liposome-encapsulated fluconazole after an intravitreal injection (100 microg/0.1 ml) in rabbit eyes. Equal concentrations of plain and liposome-entrapped fluconazole were injected intravitreally into albino rabbits through the pars plana after intravenous pentobarbitone anesthesia. The rabbits were sacrificed at various time intervals, and the concentration of fluconazole in vitreous, retina-choroid, aqueous humor and cornea was estimated using High Performance Liquid Chromatography (HPLC). Plain fluconazole showed a rapid vitreal clearance and a short half-life (3.08 hr), whereas liposome-entrapped fluconazole showed a longer half-life (23.40 hr). The terminal elimination constant (Ke) of the liposome-loaded drug from the vitreous was seven times less than the plain drug. In the plain fluconazole group, at 1 hr, a high concentration of the drug was found in the retina. To conclude, the elimination of fluconazole was primarily transretinal and was very rapid. Liposome encapsulation significantly increased the half-life of fluconazole in the vitreous cavity.

Animals↗
PubMed2000

Delineation of a conserved B cell epitope on bonnet monkey (Macaca radiata) and human zona pellucida glycoprotein-B by monoclonal antibodies demonstrating inhibition of sperm-egg binding.

To circumvent autoimmune oophoritis after immunization with zona pellucida (ZP) glycoproteins, synthetic peptides encompassing B cell epitope(s) and devoid of oophoritogenic T cell epitopes as immunogens have been proposed. In this study, bonnet monkey (Macaca radiata) ZP glycoprotein-B (bmZPB) was expressed as polyhistidine fusion protein in Escherichia coli. Rabbit polyclonal antibodies against recombinant bmZPB (r-bmZPB) significantly inhibited human sperm-oocyte binding. To map B cell epitopes on ZPB, a panel of 7 murine monoclonal antibodies (mAbs) was generated against r-bmZPB. All 7 mAbs, when tested in an indirect immunofluorescence assay, reacted with bonnet monkey ZP, and only 6 recognized human zonae. Monoclonal antibodies MA-809, -811, -813, and -825 showed significant inhibition in the binding of human spermatozoa to human ZP in a hemizona assay. Epitope-mapping studies using multipin peptide synthesis strategy revealed that these 4 mAbs recognized a common epitope corresponding to amino acids (aa) 136-147 (DAPDTDWCDSIP). Competitive binding studies revealed that the synthetic peptide corresponding to the identified epitope (aa 136-147) inhibited the binding of MA-809, -811, -813, and -825 to r-bmZPB in an ELISA and to bonnet monkey ZP in an indirect immunofluorescence assay. The epitopic domain corresponding to aa 136-147 of bmZPB was completely conserved in human ZPB. These studies will further help in designing ZP-based synthetic peptide immunogens incorporating relevant B cell epitope for fertility regulation in humans.

Amino Acid Sequence↗
PubMed2000

Direct measurement of pancreatic enzymes after stimulation with secretin versus secretin plus cholecystokinin.

BACKGROUND: Direct measurement of pancreatic enzymes after administration of pancreatic secretagogues is the gold standard in the assessment of exocrine pancreatic function. Recent experience at the authors' institution showed that endoscopic collection of pancreatic secretions 5, 10, and 15 minutes after intravenous administration of secretin is useful in screening for pancreatic insufficiency. Concomitant administration of intravenous cholecystokinin has been a subject of debate. The purpose of this study was to compare pancreatic enzyme levels after administration of secretin versus secretin plus cholecystokinin and to validate the timing of collection of duodenal fluid. METHODS: A prospective, randomized, double-blind study was conducted from September 1997 through September 1998. Patients scheduled for pancreatic enzyme sampling were randomly assigned to receive intravenous secretin (2 U/kg) plus placebo (group 1) or intravenous secretin (2 U/kg) plus cholecystokinin (0.02 microg/kg [Group 2]). Duodenal fluid was collected 5, 10, and 15 minutes later and placed in dry ice. Samples were measured for the levels of trypsin, amylase, lipase, and chymotrypsin. RESULTS: Twenty patients were assigned to each group. The age range was similar in both groups: 12 months to 16 years, 8 months in group 1 (median, 2.1 years) and 15 months to 13 years, 7 months in group 2 (median, 2.5 years). Group 2 had a greater number of patients with all four enzymes at normal levels during at least one of the time points, 75% versus 50% (P = 0.102). The difference in enzyme levels at the 5-, 10-, and 15-minute collections was statistically significant. For all four enzymes in both groups, values varied from highest to lowest with time (P = 0.0001). The enzyme levels at 10 minutes were close to the enzyme levels at 5 minutes; the lowest values occurred at 15 minutes. CONCLUSIONS: Higher pancreatic enzyme levels were obtained after administration of secretin plus cholecystokinin, although the trend did not reach statistical significance. Pancreatic enzyme levels are highest at 5 and 10 minutes, indicating that collections of duodenal fluid should be completed within 10 minutes of the administration of the secretagogues.

Adolescent↗
PubMed2000

Single- and multiple-dose pharmacokinetics of an oral once-a-day osmotic controlled-release OROS (methylphenidate HCl) formulation.

Methylphenidate is used for the treatment of attention deficit hyperactivity disorder (ADHD). OROS (methylphenidate HCl) is an osmotic controlled-release delivery system designed for once-daily oral dosing. The pharmacokinetics of OROS (methylphenidate HCl) 18 mg qd, sustained-release (SR) methylphenidate 20 mg qd, and the immediate-release (IR) formulation given as three 5 mg doses every 4 hours (tid) were compared in adults. In addition, the single- and multiple-dose pharmacokinetics of the OROS formulation were studied. Following OROS (methylphenidate HCl), there was a gradual increase in the mean methylphenidate plasma concentrations with peak concentrations noted at 6 to 8 hours. With the SR formulation, peak plasma concentrations were noted at approximately 4 hours. Following the IR regimen, methylphenidate plasma concentrations fluctuated in tandem with oral dosing; peak concentrations were noted at 6.5 hours. The terminal half-life of methylphenidate was similar for the three formulations. The dose-normalized methylphenidate Cmax for OROS (methylphenidate HCl) was significantly lower than for IR and SR methylphenidate. The bioavailability of methylphenidate and PPA from OROS (methylphenidate HCl) relative to the IR and SR formulations was complete. Mean methylphenidate AUC and terminal half-life were similar after single (32.9 ng.h/mL and 3.9 hours) and multiple doses (35.2 ng.h/mL and 3.9 hours) of OROS (methylphenidate HCl).

Administration, Oral↗
PubMed2000

Modeling of circadian testosterone in healthy men and hypogonadal men.

The testosterone circadian rhythm has been reported extensively in the literature and has been described by a cosine function. Typically, these data are measured at frequent and regular (e.g., hourly) intervals. However, modeling circadian rhythm with data collected sparsely at irregular intervals and/or data that are not collected at the same time in all individuals has not been reported. The population nonlinear mixed-effects approach can handle such data and also allows covariates to be incorporated into the model. Frequent hourly testosterone concentration data available in the literature for young and elderly healthy volunteers were analyzed first. In the elderly, blunted or completely absent circadian rhythm has been reported, but a full circadian model was significantly better than a model containing one or no circadian component. Therefore, data from both the elderly and young were modeled together, and age was included as a categorical variable (young or elderly). Consistent with literature, the rhythm-adjusted mean testosterone concentrations was lower, and the deviation from the mean, especially to the maximum daily value, was less than half in the elderly (7%) compared to young subjects (16%). The testosterone concentration data measured infrequently and at varying intervals in young normal men and hypogonadal men were evaluated next. Although not measured at regular frequency in each individual, the data were obtained at different clock times for different subjects. Since for population mixed-effects analysis, data from all subjects are pooled, there was enough information to profile the 24-hour circadian cycle. In healthy young subjects, the mean Cnadir, Cpeak, Tnadir, and Tpeak values estimated from the model were 420 ng/dL, 577 ng/dL, 21:42 hours, and 0600 hours, respectively, and were similar to the parameters obtained for the frequently sampled young subjects. In hypogonadal men (testosterone concentrations < 300 ng/dL), the mean testosterone concentrations were much lower than the healthy young or elderly men, and a straight-line model was the best descriptor (i.e., no circadian rhythm was detected). It was also shown that with the application of a transdermal testosterone system, the mean testosterone concentrations in the treated men were within the 95% confidence interval for healthy young men. The results presented here suggest that the advantages of the analysis approach--namely, handling of covariates and handling of sparse, infrequently collected data--can be used in characterizing testosterone circadian rhythm or the lack of it.

Adolescent↗
PubMed2000

Recurrent acute respiratory tract infections in areas with high nitrate concentrations in drinking water.

A review of the literature indicated an association among high nitrate ingestion, methemoglobinemia, and pathologic changes in bronchi and lung parenchyma. The present study examined a possible correlation among drinking water nitrate concentration, methemoglobin levels, cytochrome b(5) reductase activity, and acute respiratory tract infection with a history of recurrence (RRTI). Our study was conducted in five village units in the state of Rajasthan, India, with nitrate concentrations of 26, 45, 95, 222, and 459 mg NO(3) ion/L. We randomly selected 88 children. The children were up to 8 years of age, age matched, and represented 10% of the total population of these areas. We obtained detailed RRTI histories and conducted medical examinations. Methemoglobin levels and cytochrome b(5) reductase activity were estimated biochemically. The data collected were statistically analyzed using spreadsheet software on a personal computer. We observed strong interdependence between methemoglobin levels and RRTI in children up to 8 years of age. Methemoglobin levels alone explained 80% of the variation in the RRTI cases. This study indicates that methemoglobinemia, secondary to high nitrate ingestion in drinking water, causes RRTI. Increased production of methemoglobin and free radicals of nitric oxide and oxygen due to nitrate metabolism in the body lead to alveolar damage and mismatching of ventilation and perfusion, which may be the reason for high mortality in children due to RRTI.

Acute Disease↗
PubMed2000

Hunger in legal immigrants in California, Texas, and Illinois.

OBJECTIVES: This study determined the prevalence of food insecurity and hunger in low-income legal immigrants. METHODS: We conducted a cross-sectional survey of Latino and Asian legal immigrants attending urban clinics and community centers in California, Texas, and Illinois with a food security questionnaire. RESULTS: Among 630 respondents, 40% of the households were food insecure without hunger and 41% were food insecure with hunger. Independent predictors of hunger were income below federal poverty level (odds ratio [OR] = 2.72, 95% confidence interval [CI] = 1.72, 4.30), receipt of food stamps (OR = 2.53, 95% CI = 1.57, 4.09), Latino ethnicity (OR = 2.39, 95% CI = 1.49, 3.82), and poor English (OR = 1.76, 95% CI = 1.10, 2.82). CONCLUSIONS: The prevalence of hunger among low-income legal immigrants is unacceptably high. Access to food assistance programs is important for the health and well-being of this population.

Adult↗
PubMed2000

Far lateral approach for foramen magnum lesions.

Twelve patients with lesions in the anterior or anterolateral regions of foramen magnum were treated through the far lateral approach. The patients presented with neck pain, dysesthesia, quadriparesis, numbness, respiratory distress, and spastic contractures. Most lesions were meningiomas and neurofibromas, with one patient each with a posterior inferior cerebellar artery aneurysm, neurenteric cyst, and chordoma. All mass lesions were excised totally and the aneurysm was clipped. Three patients had severe respiratory problems preoperatively and two of them died. The other patients made a satisfactory neurological recovery. It was not found necessary to resect the condyle or mobilize the vertebral artery in any of the patients.

Adolescent↗
PubMed2000

Anterior surgical approaches to the sub-axial cervical spine.

Anterior cervical spine surgery has come of age, as a golden route for treating anteriorly placed cervical compressions ranging from simple prolapsed disc to long segment pathologies like ossification of posterior longitudinal ligaments and cervical spondylotic myelopathy. Numerous technical modifications of the procedure are described. The role of stabilisation established for several pathologies, is still debateable in surgery for cervical disc. Bone is the ideal tissue for fusion. Hydroxyapetite implants are goods, but costly for our set up. Methylmethacrylate has a limited role in elderly patients with malignancy and a short life expectancy. Anterior cervical instrumentation has mushroomed over the last decade. Acceptable as methods of immediate stabilisation, the choice of the system varies with the surgeon. The authors use simple titanium plates with locking screws for the purpose.

Cervical Vertebrae↗
PubMed2000

Evaluation of groundwater pollution potential of sewage-irrigated vegetable growing areas of the eastern fringe of Calcutta city.

In recent years recycling in agriculture is a common method of disposal or utilisation of waste. However, recycling of wastes may cause contamination of groundwater by toxic elements like heavy metals, cationic and anionic contaminants and pathogens. Groundwater of shallow and deep tubewells was collected during 1991 to 1997 from raw sewage effluent irrigated garbage farming areas on the eastern fringe of Calcutta city. In general raw sewage effluents, sludges and sewage-irrigated soils contain very high amounts of cations, anions, organics and heavy metals. It is found that most of the groundwater contained undesirable pH, total dissolved solids, total hardness, calcium, magnesium, phenolic compounds, iron and manganese and the observed values or concentrations were much above the maximum desirable limits specified by World Health Organisation (WHO) and Bureau of Indian Standards (BIS) for use as drinking water. Groundwater of that area may be used for irrigation. Dispersion by leaching of the metals, cationic and anionic contaminants from irrigated soil and from settled bottom sludge in unlined sewage channels are the principal causes of groundwater contamination. Some management plans have been suggested to control further deterioration of groundwater quality.

Agriculture↗
PubMed2000

Current concepts in the management of pyogenic brain abscess.

Current philosophy of treatment of brain abscess includes aspiration, appropriate antibiotics, treatment of sequelae and eradication of the primary source. Early clinical suspicion and diagnosis with CT is crucial. Small abscesses (<3 cm) in cerebritis or capsular stage located deep in clinically stable, poor surgical risk patients with diagnosis firmly supported by CT, may be treated with medical treatment only. Biweekly CT scan must be done to monitor the treatment response. CT or ultrasound guided aspiration should be performed in the event of clinical deterioration, failure of reduction in size or enlargement of abscesses. Encapsulated abscess (>3 cm), presence of significant neurological deficit or mass effect, doubt in the diagnosis and presumed resistant organisms are best treated with aspiration. Excision is required in large superficial abscesses resistant to multiple aspirations, post-traumatic abscess with a foreign body or fistula and multiloculated abscess of nocardial or actinomycotic aetiology. Results are directly related to the sensorium at the time of presentation. Stereotactic aspiration of all the loculi of multiloculated abscess in single or staged aspiration, and more completed drainage and lavage with endoscopic stereotactic evacuation may cut down indications of excision of brain abscess in future. It is concluded that, with diagnostic and technical advancements, a trend of adequate drainage of brain abscess via minimally invasive surgery is emerging. Confirmation of diagnosis and monitoring of treatment response with magnetic resonance spectroscopy may allow greater number of patients in future to be managed with medical treatment only.

Brain Abscess↗