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K Shah

Publications and source records attributed to K Shah.

At least 145 records · Page 8Linked to original sources
PubMed1986

The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers.

Eight healthy volunteers received slow release nifedipine 20 mg 12 hourly, for six doses. A nifedipine pharmacokinetic profile was performed after the fifth dosing interval using 12 sampling times over 12 h. A specific high pressure liquid chromatography (h.p.l.c.) nifedipine assay was used. Six of the volunteers subsequently received an i.v. infusion of 3.5 mg of nifedipine after an identical period (five dosing intervals) of chronic oral dosing with slow release nifedipine 20 mg 12 hourly. An identical pharmacokinetic profile was performed after the infusion. Bioavailability, clearance (CL), apparent volume of distribution (V), apparent half life (t1/2) and area under the curve (AUC) were calculated. The geometric mean apparent t1/2 for the slow release preparation was 6.3 +/- 2.0 h. In the six volunteers, the mean bioavailability was 46% (range 29-86%), the mean CL was 588.0 +/- 67.1 ml min-1, the mean apparent V was 160.1 +/- 61.7 l. The pharmacokinetics of slow release nifedipine during chronic dosing appear similar to those derived from single dose studies.

Administration, Oral↗
PubMed1986

The interaction between i.v. theophylline and chronic oral dosing with slow release nifedipine in volunteers.

Eight healthy volunteers received a 5 min i.v. infusion of lysine theophylline, equivalent to 197 mg anhydrous theophylline, both before (day 1) and during (day 5) steady state chronic oral dosing with slow release nifedipine 20 mg 12 hourly. A theophylline pharmacokinetic profile was performed on day 1 and day 5 and a nifedipine pharmacokinetic profile was performed on day 4 and day 5. The greatest difference in serum theophylline concentrations was seen at the first sampling time (5 min after completion of the infusion) with a mean concentration of 9.9 mg l-1 during nifedipine administration and 14.6 mg l-1 with theophylline alone. Thereafter, the difference fell to approximately 1 mg l-1 until 6 h when they became almost identical. Repeated measures analysis of variance using the theophylline serum concentrations at each of ten time points over 8 h as the repeated measures showed a small but significant effect of nifedipine (F(1,151) = 7.0, P less than 0.01) on serum theophylline concentrations. Mean volume of distribution (V) rose from 0.33 +/- 0.07 to 0.39 +/- 0.06 1 kg-1 corrected body weight (CBW) in the presence of nifedipine (t = 2.23, P = 0.052). Theophylline clearance, area under the curve to 8 h AUC (0-8), area under the curve to infinity AUC (0-infinity) and elimination half-life (t1/2) did not change appreciably. No statistically significant changes in nifedipine pharmacokinetics occurred in the presence of theophylline.

Administration, Oral↗
PubMed1986

Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity.

We evaluated the cellular immunity of 408 clinically stratified subjects at risk for acquired immune deficiency syndrome (AIDS), to define the role of interferon-alpha production deficits in the pathogenesis of opportunistic infections (OI). We followed 115 prospectively for up to 45 mo. Onset of OI was associated with, and predicted by, deficiency both of interferon-alpha generation in vitro, and of circulating Leu-3a+ cells. Interferon-alpha production is an index of the function of certain non-T, non-B, large granular lymphocytes (LGL) that are independent of T cell help. Leu-3a+ cell counts are a marker of T cell function. OI did not usually develop until both of these mutually independent immune functions were simultaneously critically depressed, leading to a synergistic interaction. These data suggest that the AIDS virus affects a subset of LGL, and that cytokine production by these cells is an important component of the host defense against intracellular pathogens that becomes crucial in the presence of severe T cell immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Comparison of effects of lysine aspirin, soluble aspirin and conventional aspirin on buccal potential difference in healthy volunteer subjects.

The effects of aspirin, soluble aspirin and lysine aspirin on buccal mucosal potential difference (p.d.) were compared in a double-blind trial. Placebo and three doses of each preparation containing 150, 300 and 600 mg of aspirin were allocated according to a latin square design. Six volunteer subjects were studied; each received a total of 10 treatments at least 24 h apart. All doses of each preparation considered, a significant treatment effect was seen [F (d.f. = 2,306) = 6.2, P less than 0.003]. Lysine aspirin showed the least effect of the active treatments on buccal p.d. with a change from baseline of +8.5 mV compared with +13.3 for soluble aspirin +14.4 for conventional aspirin and -5.2 mV for placebo.

Aspirin↗
PubMed1986

Genital tract papillomavirus infection in children.

Genital tract papillomas in five children were examined for the presence of human papillomavirus (HPV) DNA by molecular hybridization. Papillomavirus DNA was detected in each sample and was identified as HPV-6 (three cases), HPV-6 or HPV-11 (one case), or HPV-16 (one case). These viruses are the same as are responsible for genital papillomas (condylomata) of adults. The transmission of adult genital tract viruses to children occurs primarily by a venereal route but may occur by a nonvenereal route.

Child↗
PubMed1986

Rarity of cesarean delivery in cases of juvenile-onset respiratory papillomatosis.

Papillomas of the respiratory and genital tracts are caused by the same papillomavirus genotypes, and mothers of children with respiratory papillomatosis often have a history of genital warts. Only one of 109 cases reviewed gave a history of birth by cesarean section, whereas ten cesarean deliveries would have been the expected number for this group on the basis of national rates. The single case was delivered by elective cesarean section before the rupture of the membranes, and the child developed respiratory papillomatosis in the first year of life. These findings suggest that in juvenile-onset disease, the transmission of infection from mother to child occurs most often during passage through an infected birth canal, but that intrauterine infection of the fetus is also possible. Papillomavirus infection of the female genital tract is common, but respiratory papillomatosis is rare. On the basis of crude estimates of annual number of children born to infected mothers and of new cases of juvenile-onset disease, the risk of developing disease for a child born to an infected mother was calculated to be one in several hundred exposures.

Cesarean Section↗
PubMed1985

Identification of genital tract papillomaviruses HPV-6 and HPV-16 in warts of the oral cavity.

Warty lesions of the oral cavity were examined for etiologic association with genital tract papillomaviruses HPV-6, HPV-11, and HPV-16. DNAs extracted from ten oral biopsies were screened for HPV genomic sequences by Southern transfer hybridization with 32P-labeled viral DNA probes. Nonstringent hybridization with an HPV-6 probe revealed papillomavirus DNA sequences in four of seven tissues with histologic evidence of papillomatosis, in none of two tissues without histologic evidence of papillomatosis, and in one tissue that was not examined by histology. Stringent hybridization tests with HPV-6 and HPV-16 probes identified the genome in one tissue as being HPV-16, in a second tissue as being HPV-6 subtype a, and in a third tissue as HPV-6 (subtype unidentified); papillomavirus DNA sequences in two tissues are as yet not identified. An additional case of HPV-6 or HPV-11 related oral cavity lesion was diagnosed by in situ hybridization of paraffin sections with a 35S-labeled, mixed HPV-6 + HPV-11 probe. The hybridization in the positive section was extensive and confined to epithelial nuclei. The oral lesions associated with genital tract papillomaviruses were asymptomatic, multiple or single, and were located in different parts of the oral cavity, for example, on the gingivae, on the tongue, on the lip, on the tonsillar pillar, and on the floor of the mouth.

Adolescent↗
PubMed1985

Specific identification of human papillomavirus type in cervical smears and paraffin sections by in situ hybridization with radioactive probes: a preliminary communication.

Cervical Papanicolaou smears and paraffin sections of biopsy specimens obtained from women attending dysplasia clinics were examined for viral DNA sequences by in situ hybridization technique using 35S-labeled cloned recombinant DNA probes of human papillomavirus (HPV) types 6, 11, and 16. These and one unrelated DNA probe complementary to measles virus RNA were labeled by nick translation using either one or two 35S-labeled nucleotides. The radiolabeled probes were reduced in size with DNase to 60-160 nucleotides. Paraffin sections and cervical smears were collected on pretreated slides, hybridized with the probes under stringent or nonstringent conditions for 50 h, and autoradiographed. Additional cervical specimens from the same women were examined for the presence of genus-specific papillomavirus capsid antigen by the immunoperoxidase technique. Preliminary results may be summarized as follows. The infecting virus could be identified in smears as well as in sections. Viral DNA sequences were detected only when there were condylomatous cells in the specimen and in only a proportion of the condylomatous cells. Even under stringent conditions, some specimens reacted with both HPV-6 and HPV-11. None of the specimens hybridized with HPV-16 or with the unrelated probe. In some instances, the cells did not hybridize with any of the three probes even when duplicate specimens contained frankly condylomatous, capsid antigen-positive cells. In situ hybridization of Papanicolaou smears or of tissue sections is a practical method for diagnosis and follow-up of specific papillomavirus infection using routinely collected material.

Adult↗
PubMed1985

Parathyroid carcinoma. A report of five cases.

Parathyroid carcinoma, although rare, represents 0.5-4.0 per cent of the cases of hyperparathyroidism. The authors have encountered five cases of parathyroid carcinoma in their experience treating 445 patients with primary hyperparathyroidism (1.1%) since 1965. All five patients were women, ranging in age fro 29 to 60 years, and had marked hypercalcemia at the time of presentation, with values up to 26 mg/dl in one case. All the tumors were locally adherent to surrounding structures at the time of parathyroidectomy. Pathologically they were characteristic with a dense sclerotic reaction and fibrous bands criss-crossing islands of parathyroid cells. Three patients with local as well as distant metastases have died as a result of recurrent parathyroid carcinoma (follow-up: 2, 3, and 6 years). The remaining two patients became normocalcemic following resection, and have been asymptomatic for 1 and 7 years, respectively. The overall survival and clinical course, in our limited experience with five parathyroid carcinoma cases demonstrates that the morbidity and mortality in these patients is mainly due to local recurrence with the resultant metabolic disturbances, as has been previously noted in the literature.

Adult↗
PubMed1984

Protein hydrophobicity and stability support the thermodynamic theory of protein degradation.

Rat liver enzymes were used to study the relationship between their in vivo half-lives and their apparent hydrophobicity or their resistance to inactivation by mechanical shaking. The apparent hydrophobicity of these enzymes, measured as the percent of the protein recovered from an octyl-Sepharose column, is correlated with their known half-lives (r = 0.75, P less than 0.01). The presence of specific ligands which are known to increase compactness by impeding unfolding of proteins decreased the apparent hydrophobicity of fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase. Resistance of enzymes to inactivation by mechanical shaking correlated well with their in vivo half-lives (r = 0.90, P less than 0.01). When the shaking experiments were done in the presence of substrates, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase were protected from inactivation.

Animals↗
PubMed1984

Adult nesidiodysplasia.

Subtotal pancreatectomy specimens from two adults with hyperinsulinemic hypoglycemia and one adult with watery diarrhea syndrome were investigated. All three specimens were originally diagnosed as "nesidioblastosis"; none had a neoplasm, and all patients were cured of their endocrine dysfunction by the surgical procedure. Tissue samples were studied by light microscopy and light microscopic immunohistochemistry for serotonin, ACTH, bombesin, calcitonin, gastrin, glucagon, insulin, HPP, somatostatin, and VIP. The results were compared with those obtained from the parallel study of ten adult pancreata obtained at autopsy from patients without pancreatic disease or endocrine dysfunction. The total endocrine cell mass was not notably greater in the pancreata from patients with endocrine dysfunction than in the controls. Both groups had an estimated 95% of the endocrine cell population organized in islets while the remaining 5% was irregularly dispersed amidst the exocrine ducts and acini. Findings more conspicuous in patients with endocrine dysfunction but not absent in the controls included: large islets, islets with irregular contours and ragged edges, and large individual islet cells with abundant cytoplasm and bizarre nuclei. Immunoreactivity for insulin, glucagon, and somatostatin was demonstrated in all cases; the ratio among these hormones in the patients with endocrine dysfunction and in the controls was similar. In the patients with hyperinsulinemic hypoglycemia, step sections sequentially stained for insulin and somatostatin showed a close topographic relationship between these cell types. In the patient with the watery diarrhea syndrome, VIP immunoreactive cells were easily identified admixed with exocrine components; they were only rarely seen within islets. We suggest that the hyperinsulinemic hypoglycemia in these adults was not due to simple quantitative abnormalities in total endocrine cell mass nor to its maldistribution nor to lack of topographic proximity between insulin and somatostatin cells. We speculate that the syndrome may be based on still unknown derangements of insulin secretion, release, and/or its degradation. In the case of the watery diarrhea syndrome, the readily identifiable VIP immunoreactive cells represent the emergence of a functional expression regarded as ectopic for the endocrine cells of the pancreas. We conclude that nesidioblastosis per se cannot be viewed as the structural basis of these endocrine dysfunctions since many of its features were present in control pancreata lacking any such association.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Hyperparathyroidism unmasked by the treatment of hypothyroidism secondary to Hashimoto's thyroiditis.

Primary hyperparathyroidism masked by untreated hypothyroidism was first noted by Kissin and Bakst in 1947; since then there has been only a single case reported. As a result, it has been thought to be a rare complex of parathyroid disease. During the past 17 years we observed 17 patients who developed primary hyperparathyroidism after their treatment for hypothyroidism (secondary to Hashimoto's thyroiditis) with thyroxine had been well underway. The patients were all women whose ages ranged between 16 and 76 years. The clinical and biochemical manifestations of hyperparathyroidism were noted 2 months to 30 years after thyroxine therapy. All patients underwent standard subtotal parathyroidectomy. Fourteen patients had a single parathyroid adenoma and three had multiglandular adenomatous hyperplasia. It is of interest that all 17 patients were found to have Hashimoto's thyroiditis, based on antimicrosomal antibody titers or histopathologic criteria. Thus we present a series of patients who developed primary hyperparathyroidism in a background of Hashimoto's thyroiditis and hypothyroidism treated with thyroxine. We are intrigued by the association of hyperparathyroidism and Hashimoto's chronic thyroiditis. From this experience it seems appropriate to evaluate parathyroid function in patients with hypothyroidism secondary to Hashimoto's thyroiditis before the initiation of treatment with thyroxine and at intervals thereafter.

Adenoma↗
PubMed1983

Papillomavirus in cervical condylomas with and without associated cervical intraepithelial neoplasia.

The aim of this study was to analyze the cytohistologic features of cervical condylomas with respect to the presence of associated cervical intraepithelial neoplasia (CIN) and to evaluate whether or not the prevalence of virus antigen, as detected by immunologic staining with peroxidase-antiperoxidase technique, varies with the histologic appearance of the lesions. In a series of 94 histologically confirmed condylomas of the cervix, almost half (43) had features of CIN grades 1 and 2, corresponding to mild and moderate dysplasia. The prevalence of papillomavirus antigen decreased markedly as the features of associated dysplasia became more severe. The antigen prevalence was 82% in pure condylomas, 32% in condylomas with CIN 1, and 0% in condylomas with CIN 2. The evidence that virus production decreased as the lesion became more severe does not preclude papillomavirus etiology for the CIN lesions. Cells transformed by papillomavirus may be expected to cease production of virus particles even as they continue to harbor the viral genome.

Adolescent↗
PubMed1983

[Cervical condyloma and dysplasia: histological and virological correlation apropos of 100 cases].

Colposcopy and cytology have pointed at the frequency of cervical condylomas with special consideration to flat types. The association condyloma/dysplasia and the behavior of carcinomas in situ as sexually transmitted diseases, suggest that human papillomavirus (H. P. V.) could play a role in cervical cancer. 100 patients have undergone examination for coloscopy, cytology, histology and virology. Dysplastic features were observed in 47 p. 100 and led to classify the lesions in 3 groups according to their importance: condylomas (53 p. 100), dysplastic condylomas (25 p. 100) with predominance of condylomatous pattern, dysplasia (22 p. 100) with a predominant dysplastic pattern. Virologic data were correlated with this classification and demonstrate a dramatic relationship between viral disappearance and the presence of dysplastic features. Virus was found in 83 p. 100 of pure condylomas, 16 p. 100 of dysplastic condylomas and 0 p. 100 of condylomatous dysplasias. Such a phenomenon of viral absence is observed in animal models (malignant transformation of Shope's papilloma): this could be a new argument to suspect the carcinogenic potential of H. P. V. for cervix and external genitalia.

Adolescent↗