Search PubMed⌕ Search

Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 469 records · Page 26Linked to original sources
PubMed1997

CTL induction using synthetic peptides delivered in emulsions--critical role of the formulation procedure.

Emulsions have been used with variable degrees of success to deliver antigen to stimulate immune responses. We have investigated three different ways of incorporating peptide antigen into soybean emulsions to induce CTL responses in mice. Two of these emulsions (oil-in-water, o/w, and water-in-oil-in-water, w/o/w) had peptide incorporated at the formulation stage, while the third had peptide added to a pre-formed o/w emulsion. High levels of CTL activity were induced when peptide was dispersed into the o/w or w/o/w emulsions, in contrast to addition of peptide to the pre-formed o/w emulsion, which did not stimulate a CTL response. Induction of CTL activity was independent of emulsion globule size but was correlated with a negative zeta potential and dispersion of peptide in the oil phase. The ability of peptide in soybean oil emulsion to induce CTL is critically dependent on dispersion of peptide at the time of emulsion formation.

Adjuvants, Immunologic↗
PubMed1997

Controlled release microparticles as a single dose hepatitis B vaccine: evaluation of immunogenicity in mice.

Hepatitis B surface antigen (HBsAg) was encapsulated in microparticles prepared from polylactide-co-glycolide (PLG) and polylactide (PLA) polymers using a solvent evaporation process. The immunoreactivity of the entrapped antigen was investigated by SDS-PAGE and Western blot. The microencapsulation process was modified to obtain both small (< 10 microns) and large microparticles (10-100 < microns). 80% of the antigen was encapsulated. Various combinations of small and large microparticles with controlled release characteristics were investigated in CD1 mice. Groups of animals were immunized with 30 micrograms equivalent of HBsAg in microparticles per animals. The control group received, three injections of 10 micrograms of HBsAg on alum at 0, 1 and 6 months. Results indicated that a single injection of HBsAg in microparticles could maintain the antibody response at a level comparable to the three-injection alum schedule for at least 1 year. An in vitro inhibition assay was developed to demonstrate that antigen-antibody reactivity were comparable for the microparticle immunized mice and the alum immunized mice. A competition assay with a monoclonal antibody specific for the neutralizing epitope of HBsAg demonstrated comparable binding for the sera from the microparticle and alum immunized mice.

Animals↗
PubMed1997

Management of giardiasis by a herbal drug 'Pippali Rasayana': a clinical study.

Pippali Rasayana (PR), an Indian ayurvedic drug prepared from Palash (Butea monosperma (Lamk) Kuntze; Leguminaceae) and Pippali (Piper longum L.; Piperaceae), was administered at a dose of 1 g p.o. three times daily for a period of 15 days to patients (25 treated, 25 placebo controls) suffering from giardiasis with clinical signs and symptoms, and stools positive for trophozoites/cysts of Giardia lamblia. After 15 days of drug treatment there was a complete disappearance of G. lamblia (trophozoites/cysts) from the stools of 23 out of 25 patients. General signs and symptoms of ill health and abdominal discomfort, presence of mucus, pus cells and RBCs were significantly reduced. There was a marked improvement in the clinical and haematological profile of the patients. Spontaneous recovery in 20% cases was recorded in placebo controls.

Adjuvants, Immunologic↗
PubMed1997

A modified HPLC method for monensin analysis in liposomes and nanocapsules and its comparison with spectrophotometric and radioactive methods.

Monensin is a carboxylic ionophore which can potentiate the immunotoxin activity against human tumors in vitro and in vivo. Currently monensin is being encapsulated in liposomes and nanocapsules in our laboratory. The reported methods for monensin analysis by spectrophotometric and HPLC lack the required sensitivity. We have developed a sensitive HPLC method for analysis on monensin. Separation was achieved on a Beckman C18 reverse phase column with methanol-acetonitrile-methylene chloride-water-acetic acid (45:20:25:9.5: 0.5) as the mobile phase. The eluent was reacted with vanillin reagent in the post column reactor at 70 degrees C. The reagent reacted with monensin and formed a pink color, which was detected at 520 nm. The retention time of monensin was found to be 6 min. By using this method it was possible to quantify monensin down to 100 ng ml-1, with a signal to noise ration of > 17:1. Linearity was observed within the range of 10 to 100 ng (r2 > 0.99). Inter-day standard deviations for monensin samples of 20, 50 and 80 ng were 0.675, 0.543 and 0.736 respectively. Alternative methods of analysis include using radioactive [3H]monensin in liposomes which can be quantified by scintillation counter. The results from the HPLC, spectrophotometric and radioactive method were compared and were found to be within acceptable limits. The HPLC method is being utilized in our laboratory for quantitative analysis of monensin in liposomes and nanocapsules.

Capsules↗
PubMed1997

Evolution of neonatal and pediatric critical care in India.

During the last decade, the disciplines of neonatal and pediatric critical care have rapidly progressed in India. The growth of Neonatal Intensive Care has paced the growth of Pediatric Critical Care. The substantial growth of discipline and the positive improvements in neonatal outcomes are the results of the concerted efforts of the National Neonatal Forum and commitment of expatriate physicians residing in the United States. This article provides the background information regarding perinatal, neonatal, and infant mortalities in India. It also describes the maternal child health care delivery system in the Indian subcontinent.

Child↗
PubMed1997

Biodegradable microparticles with an entrapped branched octameric peptide as a controlled-release HIV-1 vaccine.

Polyactide-co-glycolide microparticles, with an entrapped branched octameric peptide from human immunodeficiency virus (HIV-1), were prepared by a solvent evaporation method. The microparticles were characterized for size distribution, antigen loading level, and integrity. Mice in one group were each immunized with a single dose of a controlled-release microparticle formulation containing 300 micrograms of peptide and the serum IgG responses to the antigen were compared with those of mice from a second group that were immunized at 0, 4, and 26 weeks with 100-microgram doses of the same peptide immunogen adsorbed to alum. The controlled-release microparticles induced an antibody response comparable to that from the alum-immunized group. The subcutaneous and the intramuscular routes of administration were compared in additional groups of mice for the microparticles, and both routes induced similar responses. A suspending vehicle for the microparticles was also evaluated and did not affect the immunogenicity of the controlled-release formulation containing both small and large microparticles, although the immunogenicity of smaller microparticles immunized alone was affected.

AIDS Vaccines↗
PubMed1997

Contraceptive efficacy of norethindrone encapsulated in injectable biodegradable poly-dl-lactide-co-glycolide microspheres (NET-90): phase III clinical study.

Safety, contraceptive efficacy, and acceptability of norethindrone, encapsulated in biodegradable poly-dl-lactide-co-glycolide injectable microspheres (NET-90), was evaluated for 12 months in one hundred women. Fifty-one volunteers received 65 mg, and 49 received 100 mg of NET-90, at three month intervals, intramuscularly in the gluteal region. The mean NET levels at 3-month intervals for the 65 and 100 mg groups were, respectively, 0.32 +/- 0.16 ng/ml and 0.49 +/- 0.25 ng/ml. No local or systemic side-effects were observed in either group. Body weight, blood pressure, and laboratory parameters, namely hemoglobin, hematocrit, lipid profile, sequential multichannel autoanalyzer computer profiles (SMAC), as well as PAP smear, remained within normal limits throughout the study in both groups. There was no pregnancy in the 65 mg group; however, one volunteer became pregnant in the 100 mg group. In the 65 mg group, 52.9% of menstrual cycles were normal, 34.5% were amenorrheic, and 12.6% showed prolonged bleeding. In the 100 mg group, 40.6% of the cycles were normal, 52.3% were amenorrheic, and 7.1% had episodes of prolonged bleeding. A total of 40.3% and 36.6% of the cycles showed increased spotting in the 65 and 100 mg group, respectively. Our observations indicate that NET-90 microsphere injectables can provide a safe, efficacious, and acceptable method of contraception.

Adult↗
PubMed1997

Health outcomes by self-report: validity of the SF-36 among Australian hospital patients.

This paper examines the performance of the SF-36 as a self-reported outcome measure in a diverse sample of Australian hospital in-patients. The data derive from the Care Continuum and Health Outcomes Project with a total of 2088 randomly selected patients, yielding a response rate of 80%. Distributions, completion rates and, in particular, correlates of measures were used to investigate the validity of the SF-36 according to clinical and psychometric criteria. Physical functioning, bodily pain, role limitations-physical, general health and vitality scales better represented physical than mental health, with the relative strength decreasing in that order; while mental health, role limitations-emotional and social functioning scales better represented mental health, with the relative strength decreasing in order. A cultural dimension was a strong independent correlate of all scales. While the SF-36 performed satisfactorily, there were weaknesses: the social functioning scale was too narrow to cover social health, both role limitations scales had crude response categories and particular subgroups, the frail elderly and those with complex health conditions, required measures with finer gradings for scales such as physical functioning and bodily pain. Further testing is needed to develop self-reports for use in hospital outcomes measurement which is already proposed in Australia.

Adult↗
PubMed1997

An iterative method for improved protein structural motif recognition.

We present an iterative algorithm that uses randomness and statistical techniques to improve existing methods for recognizing protein structural motifs. Our algorithm is particularly effective in situations where large numbers of sufficiently diverse examples of the motif are not known. These are precisely the situations that pose significant difficulties for previously known methods. We have implemented our algorithm and we demonstrate its performance on the coiled coil motif. We test our program LearnCoil on the domain of 3-stranded coiled coils and subclasses of 2-stranded coiled coils. We show empirically that for these motifs, our method overcomes the problem of limited data.

Algorithms↗
PubMed1997

Efficacy and acceptability of different modes of oxygen administration in children: implications for a community hospital.

Eighty under-five children admitted in the pediatric ward with acute respiratory distress requiring oxygen inhalation were prospectively studied. Oxygen was administered to all the children by head box, face mask, nasopharyngeal catheter, and twin-holed prenasal catheter in a predetermined sequence. Oxygen was delivered at a flow rate of 4 l/min in the head box and by face mask and at a rate of 1 l/min for nasopharyngeal catheter and twin-holed prenasal catheter. There was a significant rise in paO2 and SaO2 values with all the oxygen delivery methods. The number of children who achieved paO2 of > 90 mmHg with oxygen delivered by head box was 53 (69 per cent), with face mask 37 (57 per cent), with nasopharyngeal catheter 13 (26 per cent), and with twin-holed prenasal catheter 18 (25 per cent). In view of high acceptability of twin-holed prenasal catheter, a further pilot study involving 10 children was carried out to compare the efficacy of head box and twin-holed prenasal catheter at an identical oxygen flow rate of 4 l/min. The number of children achieving paO2 of > 90 mmHg were comparable, i.e. seven (70 per cent) and eight (80 per cent) when the oxygen was delivered by head box and twin-holed prenasal catheter, respectively. It is concluded that both head box and twin-holed prenasal catheter are equally effective, acceptable and safe methods for administration of oxygen to children with acute respiratory disorders. In view of the cost-effectiveness, and easy availability and affordability of twin-holed prenasal catheter, it should be popularized in the small hospitals in the community, while head box should be reserved for use in the referral hospitals.

Acute Disease↗
PubMed1997

Distribution pattern of basal cells detected by cytokeratin 34 beta E12 in primary prostatic duct adenocarcinoma.

Primary prostatic duct adenocarcinoma, initially labeled as endometrioid carcinoma of the prostate, is a rare neoplasm that displays exophytic growth into the prostatic urethra with involvement of prostatic ducts. Because this tumour arises from preexisting epithelia, there is a possibility that a remnant basal epithelium may be seen in association with these tumours. If this hypothesis is correct, then prostatic duct adenocarcinoma may possibly be mistaken for high-grade prostatic intraepithelial neoplasia (PIN) on needle biopsies. The distribution of basal cells in this tumour has not been described previously. Nine cases of prostatic duct adenocarcinoma and prostatic adenocarcinoma with focal ductal differentiation were studied immunohistochemically with antibodies specifying cytokeratin 34 beta E12, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP). All cases were positive for PSA and PAP. In some areas of the tumour in eight cases there was a continuous and discontinuous layer of basal cells surrounding islands of carcinoma. This was found with cribriform, comedo, solid, and papillary components of ductal type adenocarcinoma. It is necessary to be aware of the presence of basal cells in association with primary prostatic duct adenocarcinoma. Differentiation of high-grade PIN from this lesion should depend on complex architectural characteristics and Cytologic features rather than presence of a basal cell layer. This finding confirms that the solid, cribriform, papillary, and comedo components initially grow intraluminally within ducts before invasion into surrounding stroma occurs.

Acid Phosphatase↗
PubMed1997

Resident cardiac mast cells and the cardioprotective effect of ischemic preconditioning in isolated rat heart.

Our study was designed to investigate the role of resident cardiac mast cells in the cardioprotective effect of ischemic preconditioning. Ischemic/compound 48/80 preconditioning and treatment with compound 48/80, a mast cell degranulator (1 microg/ml), produced cardioprotective and antiarrhythmic effects in isolated perfused rat heart subjected to 30-min global ischemia followed by 30-min reperfusion. Four episodes of ischemic/compound 48/80 preconditioning and compound 48/80 treatment markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary perfusate and the incidence of ventricular premature beats (VPBs) and ventricular tachycardia or fibrillation (VT/VF) during the reperfusion phase. The release of mast cell peroxidase (MPO), a marker of mast cell degranulation in coronary perfusate, increased immediately after ischemic and compound 48/80 preconditioning. The cardioprotective and antiarrhythmic effect of ischemic/compound 48/80 preconditioning was lost within 60 min. It is proposed that the cardioprotective effect of ischemic preconditioning, which lasts for 60 min in isolated rat heart, may be ascribed to degranulation of resident cardiac mast cells.

Animals↗
PubMed1997

Matrix metalloproteinase-9 in cerebral aneurysms.

OBJECTIVE: Generalized disruption of arterial wall morphological changes in patients harboring cerebral aneurysms has been documented; however, little is known regarding the pathogenesis of these changes. To explore the role of the elastolytic gelatinase, matrix metalloproteinase-9 (MMP-9), levels of this enzyme in the wall of intracranial aneurysms were compared with those in both intracranial and extracranial arteries. The tissue levels of its major inhibitor, tissue inhibitor of metalloproteinase (TIMP), were measured in these tissues as well. The activity of MMP-9 in plasma was also evaluated. METHODS: The aneurysm wall was excised from three of six patients undergoing craniotomies for aneurysm clipping. A 1-cm segment of superficial temporal artery (STA) was obtained from each of six patients. Additional STAs were obtained from six patients in the control group who were undergoing craniotomies for nonvascular disease. An intracranial artery was also obtained from the anterior temporal neocortical resection of a patient undergoing a craniotomy for mesial temporal sclerosis. MMP-9 and TIMP levels were determined via Western blot analysis. Using substrate gel Zymography, MMP-9 plasma activity was determined for a separate cohort of patients with aneurysms (n = 6) and patients in the control group (n = 6). RESULTS: MMP-9 and TIMP levels in the aneurysm wall were markedly increased beyond levels in both extracranial arteries (STAs from patients with aneurysms and patients in the control group) and the intracranial artery. There were no differences in the levels of MMP-9 in the STAs of patients harboring aneurysms when compared with patients in the control group. Also, no differences were noted in plasma MMP-9 activity. CONCLUSION: Local rather than systemic perturbations in MMP-9 levels may contribute to the matrix disruption associated with cerebral aneurysms. This local up-regulation is not the result of TIMP down-regulation. The lack of increased systemic metalloproteinase activity precludes the use of plasma MMP-9 activity as a screening tool for presymptomatic aneurysms. However, local therapeutic modulation of MMP-9 activity may help arrest aneurysm progression.

Aneurysm, Ruptured↗
PubMed1997

Spatio-temporal EEG source localization using simulated annealing.

The estimation of multiple dipole parameters in spatio-temporal source modeling (STSM) of electroencephalographic (EEG) data is a difficult nonlinear optimization problem due to multiple local minima in the cost function. A straightforward iterative optimization approach to such a problem is very susceptible to being trapped in a local minimum, thereby resulting in incorrect estimates of the dipole parameters. In this paper, we present and evaluate a more robust optimization approach based on the simulated annealing algorithm. The complexity of this approach for the STSM problem was reduced by separating the dipole parameters into linear (moment) and nonlinear (location) components. The effectiveness of the proposed method and its superiority over the traditional nonlinear simplex technique in escaping local minima were tested and demonstrated through computer simulations. The annealing algorithm and its implementation for multidipole estimation are also discussed. We found the simulated annealing approach to be 7-31% more effective than the simplex method at converging to the true global minimum for a number of different kinds of three-dipole problems simulated in this work. In addition, the computational cost of the proposed approach was only marginally higher than its simplex counterpart. The annealing method also yielded similar solutions irrespective of the initial guesses used. The proposed simulated annealing method is an attractive alternative to the simplex method that is currently more common in dipole estimation applications.

Algorithms↗
PubMed1997

Encapsulation, stability and in-vitro release characteristics of liposomal formulations of colchicine.

The severe toxicity and low therapeutic index of colchicine limit its therapeutic use. Encapsulation in liposomes might reduce these toxic effects. The objective of this study was to determine the factors influencing encapsulation of colchicine in liposomes and to optimize the encapsulation parameters. Colchicine was encapsulated in multilamellar liposomes and large unilamellar liposomes prepared using various phospholipids. The effects of method of preparation, type of vesicle, charge, and concentration of cholesterol on encapsulation of colchicine in liposomes were investigated. Also, stability of colchicine under stress conditions and at various temperatures, and in-vitro release characteristics were determined. A significant difference in encapsulation of colchicine in multilamellar liposomes was observed when prepared by two different methods. Induction of charge on the liposome surface increased encapsulation of colchicine in multilamellar liposomes, but did not affect large unilamellar liposomes. The liposome preparations could withstand simulated transport conditions and frequent changes in temperature. Particle size and concentration of colchicine did not change significantly during storage at various temperatures for six months. In order to retain encapsulated colchicine in liposomes, storage at or below room temperature was found to be suitable. In-vitro release of colchicine from large unilamellar liposomes was biphasic and was influenced by two rate-limiting barriers, the dialysis membrane and the liposome bi-layers. For optimum encapsulation and stability of colchicine liposomes were prepared from a mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol and either stearylamine or dicetyl phosphate.

Capsules↗
PubMed1997

Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine.

Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization.

Administration, Cutaneous↗