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Biomedical subjects

D P Sinha

Publications and source records attributed to D P Sinha.

At least 19 recordsLinked to original sources
PubMed2004

Pseudoaneurysm following lateral wall myocardial infarction.

Pseudoaneursym (PA) formation of left ventricle (LV) following acute myocardial infarction (AMI) is uncommon and is usually believed to be associated with a grave prognosis. We describe a case of 55 year old male patient presented with AMI and heart failure with a systolic murmur later diagnosed to have PA of the lateral wall of LV on echocardiography (transthoracic and transesophageal, TTE andTEE). Cardiac MRI and coronary angiogram (CAG) were performed. CAG showed 60% lesion at origin of major obtuse marginal artery (OM1). The patientwas advised surgical treatment, but he refused and took discharge against medical advice on 27th dayof admission on stable condition.

Aneurysm, False↗
PubMed1999

Pharmacokinetically guided dose escalation of carboplatin in epithelial ovarian cancer: effect on drug-plasma AUC and peripheral blood drug-DNA adduct levels.

BACKGROUND: Platinum based drugs are active agents in epithelial ovarian cancer and increased platinum drug dose intensity is thought to lead to improved survival, because of the largely untested assumption that increased dose intensity results in an increased interaction of the platinum drug with its target, DNA. In a previously reported phase I trial (Lind et al., J Clin Oncol 1996; 14: 800-5), carboplatin dose intensity was increased by the use of G-CSF to support the bone marrow and using pharmacokinetically-guided carboplatin dosing. The objectives of this study were to validate the carboplatin dosing formula during high dose intensity therapy and evaluate the relationship between systemic carboplatin exposure and Pt-DNA adduct levels in peripheral blood leucocytes. PATIENTS AND METHODS: A total of 17 patients were studied over four levels of dose intensification. The carboplatin dose was calculated using the 'Calvert formula'. Levels of drug-target interaction in peripheral blood leukocytes were measured using an immunoassay based on a monoclonal antibody that recognises DNA-platinum adducts. Pharmacokinetic measurements were carried out using a previously validated single sample method. RESULTS: The area under the curve of concentration of unbound carboplatin in plasma versus time (AUC) for target AUC values of 5, 7 and 9 mg/ml x min were: 5.6 +/- 1.0, 7.3 +/- 0.7 and 9.8 +/- 0.5 mg/ml x min (mean +/- S.D.). There was a good correlation between target and achieved dose intensities (r2 = 0.899) and the slope of the linear regression line was 0.95 (+/- 0.09 SD) not significantly different to 1.0 (P > 0.6). The levels of immunoreactive DNA adducts were not detectable at a target AUC of 5 mg/ml x min but increased progressively at the higher AUC levels. Accumulation of adducts between courses was not detected. CONCLUSIONS: Pharmacokinetically-based carboplatin dosing during high intensity therapy accurately predicted the dose required to achieve a target AUC and resulted in consistent patient exposure to active drug. During the dose escalation study, peripheral blood leucocyte DNA platinum-DNA adduct levels were positively related to drug dose and drug AUC.

Adult↗
PubMed1998

Coronary artery lesions in Takayasu's arteritis--clinical and angiographic study.

Two hundred and twenty five patients of Takayasu's arteritis were studied over 13 years. Male:Female ratio was 1:7. Mean age of the study population was 19 +/- 4 years. Of these 225 patients, 75 patients had symptoms and/or signs of cardiac involvement and these patients were subjected to coronary angiography. Significant coronary artery occlusion (i.e. more than 50% narrowing of luminal diameter) was present in 9 patients. Incidence of coronary artery lesions in Takayasu's arteritis is 12% in this study. The proximal segments of coronary arteries were involved while the distal segments were spared. Out of 34 patients with angina pectoris, only 3 patients had significant coronary arterial narrowing.

Adolescent↗
PubMed1997

Safety evaluation of recombinant human interleukin-4. I. Preclinical studies.

Recombinant human IL-4 (rhuIL-4) has been evaluated in a series of preclinical studies. These studies have demonstrated that rhuIL-4 is a very potent cytokine with a wide range of pharmacologic and toxicologic effects. Target systems/organs included the cardiovascular system, liver, spleen, and bone marrow. The incidence and severity of effects correlated strongly with both the dose level and the duration of rhuIL-4 administration. The major dose-limiting toxicities identified included death, cardiac inflammation and necrosis, hepatitis, and hepatic necrosis and occurred at sc doses > or = 25 micrograms/kg/day, while a sc dose of 5 micrograms/kg/day was the highest tested that did not result in major dose-limiting toxicity. Clinical trials in humans have demonstrated that sc administration of Escherichia coli-derived rhuIL-4 is safe and well tolerated at doses up to and including 5 micrograms/kg/day and up to 10 micrograms/kg when administered 3 times/week.

Animals↗
PubMed1996

The relationship between tumour glutathione concentration, glutathione S-transferase isoenzyme expression and response to single agent carboplatin in epithelial ovarian cancer patients.

There is evidence to suggest that glutathione (GSH) and glutathione-S-transferases (GST) are important factors in determining sensitivity to cytotoxic drugs in vitro and in preclinical in vivo model systems. To define the relationship between tumour GSH concentration, GST isoenzyme expression and response to carboplatin in epithelial ovarian cancer (EOC), tumour samples from 39 patients with assessable disease after primary surgery were analyzed for GSH content and GST expression. Response was assessed after completing six courses of single agent carboplatin therapy. GSH was measured by high performance liquid chromatography (HPLC) in fresh tumour samples taken at primary laparatomy. GST isoenzyme expression was assessed by immunohistochemistry of fixed tumour material using antibodies specific for pi, alpha and mu classes. GST isoenzyme expression was defined as positive if the staining intensity was strong and more than 10% of tumour cells were involved. The mean GSH concentrations were: 8351 +/- 4496, 7211 +/- 5026, 6559 +/- 4573 and 3758 +/- 1885 (nmol g-1 tissue dry weight mean +/- s.d.) for tumours from patients who subsequently achieved a complete response (CR, n = 18), partial response (PR, n = 10) or who had static disease (SD, n = 7) or progressive disease (PD, n = 4) respectively. There was no relationship between GSH concentration and response (ANOVA, P = 0.32). There were also no relationship between GST isoenzyme expression and response (P Fisher's exact test 0.51-0.55 and chi-squared test 0.98-0.99). In conclusion, there was no association between the concentration of GSH or expression of GST isoenzymes and response to single agent carboplatin in primary previously untreated EOC.

Antineoplastic Agents↗
PubMed1996

Studies on prosthetic valve function--a transesophageal echocardiographic assessment.

Haemodynamic assessment was done by colour flow mapping and Doppler interrogation by both Transthoracic (TTE) and Transesophageal echocardiography (TEE) in 40 consecutive patients (mean age 36.6 +/- 12.35 years) with prosthetic valves. There were 30 cases of mitral (MVR) and 12 aortic (AVR) valve replacement. Major purpose of the study was to detect the sensitivity of TEE in detecting prosthetic valve malfunction particularly in comparison to TTE. Pannus was detected in 3 and 8 cases of MVR (p < 0.01) by TTE and TEE respectively; however, TEE was found to be of equal status in detecting pannus over AV (2 cases). Physiological regurgitation in MVR and AVR was detected in 13% and 25% by TTE and 20% and 33% by TEE respectively. Paravalvular leak was detected in 3 cases of MVR by TEE compared to only case by TTE. Though it is difficult to deduce any specific conclusion from this small number of patients, there is definite trend to higher sensitivity in detecting disorders with TEE specially for mitral prostheses.

Adult↗
PubMed1992

Bioelectrical-impedance analysis as a measure of body composition in a West Indian population.

Percent body fat (%BF) was estimated in 50 males and 50 females aged 8-21 y by using hydrodensitometry (%BFd) and a bioelectrical-impedance analyzer (%BF-BIA). The sample population was racially heterogeneous, though predominantly of African origin. Percent body fat was computed from density by using an equation derived specifically for blacks. The BIA predicted %BF with r2 = 0.77 (SEE = 3.7%BF), underestimating by a mean of 1.7%BF. Residuals (%BFd - %BF-BIA) were normally distributed but were significantly correlated with age (P less than 0.01), although this effect was small. The theoretical bases for impedance analysis and for hydrodensitometry would appear for different reasons to impair applicability of these techniques to the present population and age group. However, for our population sample the BIA estimated %BF as precisely as other simple techniques applied to other populations.

Adipose Tissue↗
PubMed1992

Project lifestyle: developing positive health lifestyles for schoolchildren in Antigua.

Countries of the English-speaking Caribbean are in epidemiological transition. Following 30 years of socioeconomic change, obesity and chronic diseases have almost replaced malnutrition and infectious diseases as major health problems. Major risk factors for this modern epidemic are lifestyle-related. Project Lifestyle seeks to develop positive health lifestyles in schoolchildren gradually, sequentially, and systematically from grades 1-12 and throughout the school system on the island of Antigua. The four health habits addressed include weighing right, eating right, doing daily physical exercise, and having a positive self-concept. Since risk interventions with schoolchildren have produced positive results in several developed countries, this project developed an intervention methodology in the Caribbean context.

Adolescent↗
PubMed1992

Intranuclear inclusions in the pituitary gland of cynomolgus monkeys.

In a 3-month oral toxicity study of a pharmaceutical agent, intranuclear inclusions were seen in the secretory cells of the pars anterior of the pituitary gland of 22 of 40 cynomolgus monkeys, with similar incidences in control and dosed groups. All monkeys were clinically healthy. Electron microscopic examination revealed that the intranuclear inclusions were cytoplasmic invaginations.

Animals↗
PubMed1990

Role of centralization of surgery in Stage IB carcinoma of the cervix: a review of 498 cases.

A review was undertaken of 498 patients with stage IB carcinoma of the cervix managed over a 15-year period in the Regional Gynaecological Oncology Centre, Gateshead. All but 4 were treated by radical hysterectomy, with adjuvant radiotherapy and/or chemotherapy for those with involved pelvic nodes. The overall 5-year survival in those with negative nodes was 91.4% compared with 50.5% in those with positive nodes (P less than 0.05). Of those dying from the disease, 7 patients only (1.4%) developed central recurrence, the remainder experiencing pelvic side-wall or distant recurrence. There was no difference in survival related to patient age. There were three deaths related to surgery and a fistula rate of only 1.2%. Bladder hypotonia and lymphocyst affected a minority of patients in the long term. The data support the case for radical surgery in stage IB carcinoma of the cervix, managed on a centralized referral basis.

Adult↗
PubMed1989

Cytokeratin expression in cervical epithelium: an immunohistological study of normal, wart virus-infected and neoplastic tissue.

In this study using a panel of anticytokeratin antibodies and an indirect immunoperoxidase method, we examined cervical squamous epithelia including mature stratified epithelium, immature squamous metaplasia, CIN 1, 2 and 3, wart virus infection and squamous carcinoma. Changes from the normal patterns of staining were inconsistently seen in CIN 1 and 2, but in CIN 3 the changes were more marked, and consisted of a loss of stratification of the staining pattern and a patchy reduction in staining. Invasive carcinomas showed a similar staining pattern to CIN 3 lesions.

Carcinoma, Squamous Cell↗
PubMed1988

Inflammatory cell infiltration and survival in squamous cell carcinoma of the vulva.

The prognostic significance of tumour infiltration by inflammatory cells in squamous cell carcinoma of the vulva was examined in a cohort of 34 patients surviving without recurrence for at least 5 years after radical surgery, and a comparative cohort of 35 patients who died of their diseases. Overall, heavy inflammatory infiltration correlated with a good prognosis and light infiltration with a poor one, independent of other indices such as differentiation, tumour size and nodal status. IgA-containing cell infiltration also correlated with a good prognosis but the presence of IgA-containing cells did not alone account for all the inflammation in the good prognosis group. An immunological response to the tumour may be influencing prognosis. At a practical level, the extent of inflammation appears, at least in this material, to be as useful a prognostic index as many more conventional ones.

Aged↗
PubMed1987

Preclinical safety evaluation of the benzodiazepine quazepam.

7-Chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4- benzodiazepine-2-thione (quazepam, Sch 16134, Dormalin) was evaluated for evidence of systemic toxicity, carcinogenicity and reproductive toxicity in several laboratory animal species including the hamster. Mutagenic potential was also assessed in one in vivo and three in vitro assays. In some studies, diazepam was used as a comparative control. Oral LD50 values were greater than 5000 mg/kg in the mouse and rat while i.p. LD50 values were approximately 900 and 2900 mg/kg in the mouse and rat, respectively. Studies in hamsters for 4 weeks at doses up to 500 mg/kg/d and for 51 weeks at doses up to 120 mg/kg/d demonstrated that the liver was the principal target organ in this species with the effects upon the liver related to dose and duration of dosing. Studies in the squirrel monkey for 13 and 52 weeks at doses up to 50 mg/kg/d demonstrated a transient ataxia, hypoactivity and somnolence during the initial two weeks of dosing. No unusual necropsy or microscopic observations were noted in the 13-week study. Male reproductive organs of quazepam-dosed monkeys were reduced in weight after 52 weeks. Moderate to marked impairment of spermatogenesis and higher liver weights with moderate to marked fatty change in both sexes were observed in groups given diazepam. Abrupt withdrawal of quazepam or diazepam after 52 weeks of dosing was associated at all dose levels with excitability, hyperactivity and convulsions. Two quazepam- and all diazepam-dosed monkeys died.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats.

Two subchronic studies were conducted to assess the potential toxicity of N-D-ornithyl amphotericin B methyl ester (OAME). In both studies the comparative control substance was amphotericin B (AMB). Dogs (5/sex/group) were given OAME (82% pure, based on high-pressure liquid chromatographic (HPLC) analysis) at 0.6, 2.5, and 10 mg/kg or AMB at 0.6 mg/kg intravenously once daily for 3 months. Two dogs per sex per group were retained for a 7-week postdose observation period. Rats (15/sex/group) were given daily doses of OAME at 4, 12, 24, and 36 mg/kg or AMB at 5 and 12 mg/kg intraperitoneally for 3 months. The principal organs of toxicity in both species were the liver, kidneys, and circulating erythrocytes. Hepatic changes in dogs consisted of periportal and centrilobular inflammation in animals of all dosed groups and were equivalent in dogs given 0.6 mg/kg OAME or AMB. In rats, acute hepatic necrosis with periportal, centrilobular, or panlobular distribution in animals of all OAME (except 4 mg/kg) and AMB-dosed groups was observed. These changes were equivalent in the 36-mg/kg OAME- and 12-mg/kg AMB-dosed animals. Renal changes, evidenced by increases in serum urea nitrogen water consumption, urine volume, decreased urine osmolality, and renal tubular changes (ranging from degeneration and regeneration to necrosis), were observed in both species. In dogs, these changes in the OAME-dosed animals were less severe at all doses than those observed in the AMB-dosed dogs. Renal changes in rats, which were mild in comparison to the dogs, were equivalent at doses of 5 and 12 mg/kg AMB and 36 mg/kg OAME. Decreased erythrocyte counts, hematocrit, and hemoglobin values were observed in both species. Unique to the dog study, however, were irreversible behavioral (somnolence, ataxia, tremors, and compulsive searching) and/or morphologic brain changes (gliosis with astrocytic hypertrophy and hyperplasia) at doses of 2.5 and 10 mg/kg OAME. Similar changes were observed in two dogs given 10 mg/kg OAME (100% pure, based on HPLC analysis) in a 6-week pilot study, indicating that the neurological changes were induced by OAME rather than by an impurity. These changes appear related to prolonged exposure to high plasma concentrations of OAME.

Alkaline Phosphatase↗
PubMed1984

Tapetal changes in beagle dogs. I. Ocular changes after oral administration of a beta-adrenergic blocking agent--SCH 19927.

SCH 19927 [R,R)-(-)-2-Hydroxy-5-[1-hydroxy-2-[(1-methyl -3-phenylpropyl)amino]ethyl]benzamide hydrochloride) is a beta-adrenergic blocking agent which has vasodilating properties. In a subchronic oral toxicity study in beagle dogs, SCH 19927 was given by gavage at doses of 30, 60, and 90 mg/kg. Lesions were observed at weeks 13 and 19 in the tapetum lucidum, a light reflecting structure of the eye. The lesions consisted of focal to multifocal areas of discoloration of the tapetal portion of the ocular fundus, pigmentation in the tapetal area, and, in one dog, subretinal edema resulting in a focal retinal detachment. Light and electron microscopic examination of the ocular lesions demonstrated tapetal cell degeneration and necrosis with macrophages, lymphocytes, and occasional plasma cells in the tapetum and adjacent choroid. Local cellular infiltrates within the retina internal to the pigmented epithelium were observed in one dog (60 mg/kg) which was demonstrated to have focal retinal edema during the study. In a repeat study the lesion again occurred in tapetal beagle dogs but not in atapetal beagle dogs (90 mg/kg) or cynomolgous monkeys (360 mg/kg). The lesion had not occurred in a previous subchronic study in albino rats. These results demonstrated that the tapetum lucidum was a target organ of toxicity for SCH 19927 and indicated that the finding was without observable toxicological significance in animals, including man, whose eyes do not have this structure.

Animals↗