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Biomedical subjects

A Hoque

Publications and source records attributed to A Hoque.

16 recordsLinked to original sources

In vivo evidence that L-S-nitrosocysteine may exert its vasodilator effects by interaction with thiol residues in the vasculature.

This study examined the effects of the lipophobic thiol chelator, para-hydroxymercurobenzoic acid (25 and 50 micromol/kg, i.v.) on the falls in mean arterial blood pressure and regional vascular resistances produced by L-S-nitrosocysteine (400 nmol/kg, i.v.) and the nitric oxide (NO)-donors, (Z)-1-&z. sfnc;N-methyl-N-[6(N-methylammoniohexyl)amino]&z.sfnc; diazen-1-ium-1, 2-diolate (MAHMA NONOate, 25 nmol/kg, i.v.) and sodium nitroprusside (10 microg/kg, i.v.), in urethane-anesthetized rats. The L-S-nitrosocysteine-induced responses were markedly diminished whereas the MAHMA NONOate- and sodium nitroprusside-induced responses were minimally affected by para-hydroxymercurobenzoic acid. These results suggest that the vasodilator actions of L-S-nitrosocysteine involves the interaction with membrane thiols in vascular smooth muscle of resistance arteries and that para-hydroxymercurobenzoic acid does not markedly affect NO-mediated vasodilation.

Animals↗

Interobserver reproducibility of the Lagios nuclear grading system for ductal carcinoma in situ.

Several studies have shown an association between high nuclear grade or necrosis of ductal carcinoma in situ (DCIS) lesions and the risk of local disease recurrence in patients with DCIS treated surgically with less than mastectomy. Although criteria for separating low from high nuclear grade lesions have been published, no information exists regarding interobserver reproducibility (IR). To assess IR in the classification of DCIS, six surgical pathologists from four institutions used the Lagios grading system to grade 125 DCIS lesions. Before meeting to evaluate the cases, a training set of 12 glass slides, including cases chosen to present conflicting cues for classification, was mailed to the participants with a written criteria summary. This was followed by a working session in which criteria were reviewed and agreed on. The pathologists then graded the lesions independently. The area of interest was marked on each slide before grading. After initial grading, the pathologists met again to resolve discrepant lesion classifications. A complete agreement among raters was achieved in 43 (35%) cases, with five of six raters agreeing in another 45 (36%) cases. In no case did two raters differ by more than one grade. The pairwise kappa agreement values ranged from fair to substantial (0.30 to 0.61). Generalized kappa value indicated moderate agreement (0.46, standard error = 0.02). Kappa statistics for the distinction between grades 1 and 2 and 2 and 3 were 0.29 and 0.48, respectively, (standard error = 0.02). Only one of the six raters differed significantly in scoring. With adherence to specific criteria, IR in the classification of DCIS cases can be obtained in most cases. Although these pathologists made a few grading system modifications, further refinements are needed, especially if grading will influence future therapy.

Breast Neoplasms↗

Durable clinical and pathologic response of hepatocellular carcinoma to systemic and hepatic arterial administration of platinol, recombinant interferon alpha 2B, doxorubicin, and 5-fluorouracil: a communication.

The case described here illustrates the antitumor activity of a four-drug systemic combination chemobiotherapy with platinol, recombinant interferon alpha 2b, doxorubicin (Adriamycin), and 5-fluorouracil (5-FU) (PIAF) in a patient with diffuse hepatocellular carcinoma involving the liver and lungs.

Aged↗

Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States?

Previous research showed that risk factors associated with hepatocellular carcinoma (HCC) include infection with hepatitis B (HBV) and hepatitis C (HCV) viruses, exposure to aflatoxin B1 (AFB1), and liver cirrhosis, due primarily to alcohol consumption. To determine whether AFB1 may play a role in HCC in the United States, a search for AFB1 adducts and p53 alterations, potentially induced by AFB1, was conducted in the United States in 23 HCC patients with available tissue samples. The presence of AFB1 tumor-DNA and -serum lysine adducts and mutant p53 product was determined by immunoassays and codon 249 p53 mutation by restriction enzyme analysis. HBV and HCV serology and serum HBV-DNA were also determined. Thirteen patients were positive for HBV by HBs antigen or anti-HBc antigen or by polymerase chain reaction for HBV-DNA sequences. Nine patients were free of HBV and HCV markers; 5 of 22 sera tested were anti-HCV positive. p53 Protein expression, determined by immunohistochemical staining, was present in 5 of the 23 tumor tissues, whereas p53 codon 249 mutations were not observed in the 5 cases in which tissue was available for study. AFB1 tumor-DNA adducts were present in 3 of 19 tumor tissues, and in 1 of these 3 samples p53 protein was also detected. Sera from only 5 of the patients were tested for AFB1-lysine adducts, and all were positive. In these five patients, neither p53 protein nor a mutation on codon 249 was detected. The demonstration that AFB1-DNA and -lysine adducts are present in HCC patients in the United States is intriguing but requires further substantiation because of the small number of subjects in this pilot study. To elucidate the pathogenetic significance of these findings, further investigation, including studies in larger patient cohorts and properly selected controls, is warranted.

Adult↗

Cancer among a Michigan cohort exposed to polybrominated biphenyls in 1973.

The long-term health effects of human exposure to polybrominated biphenyls are not known. In this nested case-control study, we evaluated the association between site-specific cancer risk and serum polybrominated biphenyl levels among a Michigan cohort accidentally exposed to polybrominated biphenyls in 1973. The Michigan Department of Public Health has followed 3,899 people through 1993, among whom 195 primary cancers were identified in 187 persons. Controls were 696 randomly selected cancer-free individuals who were frequency matched to cases by sex and age (in 5-year strata). Baseline serum polybrominated biphenyl levels were measured using standard methods. We found an increasing dose-response relation for digestive system cancer risk with higher serum polybrominated biphenyl category [4-20 parts per billion (ppb), 21-50 ppb, and > 50 ppb] after adjustment for age, family cancer history, cigarette smoking, alcohol drinking, and baseline serum polychlorinated biphenyl level. Adjusted odds ratios (ORs) for each category were 8.23 [95% confidence interval (CI) = 1.27-53.3], 12.3 (95% CI = 0.80-191), and 22.9 (95% CI = 1.34-392), respectively. Univariate analysis for polybrominated biphenyl level and lymphoma risk also showed a dose-response relation, with corresponding ORs of 3.24 (95% CI = 0.24-95.9), 20.5 (95% CI = 1.51-608), and 32.6 (95% CI = 3.33-861).

Adult↗

Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin.

PURPOSE: To determine the toxicity, response rate, and survival in patients treated with hepatic arterial infusion (HAI) of fluorouracil (5-FU) plus recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron-A; Schering-Plough, Inc, Kenilworth, NJ) for colorectal carcinoma (CRC) liver metastases refractory to systemic 5-FU plus leucovorin (LCV). PATIENTS AND METHODS: Forty-eight patients were given a 6-hour HAI of rIFN-alpha 2b 5 MU/m2 followed by an 18-hour HAI of 5-FU, 1,500 mg/m2 daily for 5 days. Twenty-nine patients were treated through percutaneously placed catheters and 19 through implantable infusion pumps (Shiley Infusaid Inc, Noorwood, MA). Treatment cycles were repeated every 28 to 35 days. RESULTS: There were three (6.6%) complete remissions (CRs) and 12 (26.6%) partial remissions (PRs), for a CR plus PR rate of 33.3% among 45 assessable patients (95% confidence interval [CI], 20% to 49%). The median response duration was 7 months, while median survival duration was 15 months. Grade 3 to 4 treatment-related toxic effects included mucositis (40%), neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity was encountered in any of the patients. Treatment was discontinued because of progressive liver disease in 23 patients and extrahepatic progression in 16, while six patients continue treatment through an infusaid pump. CONCLUSION: HAI of 5-FU plus rIFN-alpha 2b is well tolerated, devoid of hepatobiliary toxicity, and can produce a response rate of 33.3% among patients refractory to bolus intravenous (IV) 5-FU plus LCV. The lack of hepatobiliary toxicity may permit salvage HAI with floxuridine (FUDR) in patients whose liver tumors fail to respond to HAI of 5-FU plus rIFN-alpha 2b. Because diarrhea was not a common side effect of HAI of 5-FU plus rIFN-alpha 2b, it would be of interest to investigate whether alternating HAI of 5-FU and rIFN-alpha 2b with systemic irinotecan (CPT-11) will decrease the incidence of both hepatic and extrahepatic disease progression.

Adult↗

In vitro propagation of Rauvolfia serpentina through tissue culture.

Multiple shoots were induced from nodal segments and shoot apices of Rauvolfia serpentina and MS medium containing 1.0 mg/l BA and 0.1 mg/l NAA was found to give the best shoot proliferation rate. Callus formed at cut bases of the explants which produced shoots when subcultured on media containing low concentration of BA (0.5 or 0.1 mg/l) and NAA (0.1 mg/l). The in vitro proliferated shoots were rooted and later transferred to the soil.

Cell Division↗

Phase II study of paclitaxel therapy for unresectable biliary tree carcinomas.

PURPOSE: To evaluate the efficacy of paclitaxel administered to patients with unresectable adenocarcinomas of the gallbladder and biliary tree over 3 hours every 21 days. PATIENTS AND METHODS: Fifteen patients with unresectable and/or metastatic carcinoma of the gallbladder and bile ducts received intravenous paclitaxel over 3 hours after premedication with dexamethasone, diphenhydramine, and cimetidine. Treatment was repeated every 21 days, and one complete course of therapy was comprised of two such 21-day treatment cycles. The initial dose of paclitaxel was 170 mg/m2, and this was elevated to 200 mg/m2 due to tolerance within the initial patient cohort. RESULTS: All patients were assessable for both toxicity and response: 11 with bile duct cancer and four with gall-bladder carcinoma. Forty-three cycles of therapy were delivered during the trial (median, two), and one patient remains on treatment. No complete or partial responses were noted, although two patients achieved minor responses that lasted 2 and 2+ months, respectively. There were no deaths on this study, and all but one of the patients is still alive. The therapy was well tolerated, and hematologic and mucosal toxic effects were moderate and readily reversible, although significant neuromuscular adverse effects were noted. CONCLUSION: These findings indicate that paclitaxel, administered on this schedule, is tolerable, but is unlikely to have activity in metastatic carcinomas of the biliary tree. It is unclear whether a different regimen of paclitaxel, or another taxane, may have activity in these neoplasms.

Adenocarcinoma↗

Phase II trial of intravenous flourouracil and subcutaneous interferon alfa-2b for biliary tract cancer.

PURPOSE: To assess the efficacy of systemic intravenous-fluorouracil (5-FU) and subcutaneous recombinant human interferon alfa-2b (rIFN alpha-2b) in patients with measurable cancer of the biliary tree. PATIENTS AND METHODS: Thirty-five patients (25 with cholangiocarcinoma and 10 with gallbladder carcinoma) were registered onto this phase II protocol between 1992 and 1995. Patients received a continuous infusion of 750 mg/m2/d of 5-FU on days 1 through 5 through a centrally placed venous catheter and a subcutaneous injection of 5 MU/m2 of rIFN alpha-2b on days 1, 3, and 5. Treatment cycles were repeated every 14 days; one course of therapy included four treatment cycles. Disease status was assessed every 8 weeks. Dosages were lowered for grade III mucositis. Fourteen patients had prior treatment and, before initiating this therapy, 17 patients required decompression of the biliary tree. RESULTS: Eleven of 32 (34%) assessable patients had a partial response. The median time to disease progression was 9.5 months, and the median survival time 12 months. Grade III to IV toxic effects were granulocytopenia (14%), mucositis (20%), diarrhea (9%), and dermatitis (11%). Grade III to IV asthenia and fatigue were observed in 6% of patients. CONCLUSION: Drug tolerance was better among previously untreated patients. To achieve a complete response, additional chemotherapy or radiotherapy should be considered when liver resection or transplantation is not feasible. However, if these results can be reproduced by other investigators, the regimen should be studied for adjuvant treatment of gallbladder carcinoma incidentally identified in patients undergoing cholecystectomy.

Adult↗

Birth practice patterns in urban slums of Dhaka, Bangladesh.

This study describes the patterns of birth related practices amongst women from an urban slum population in Dhaka city during December 1988 to May 1989. A household census identified all resident women of childbearing age in Rajabazar ward of Dhaka city. Of the 1017 women so identified, 289 women who had given birth to their last child over the previous five years were randomly selected for interview using a structured interview schedule. To observe actual birth practices, sixteen women pregnant for six months or more at the time of the census were followed-up to the immediate post-natal period. Eight local traditional birth attendants (TBAs) were interviewed informally to obtain insights about birthing techniques. A case study for a typical 'normal' delivery is presented and discussed.

Adolescent↗

Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract.

BACKGROUND: Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors. PURPOSE: We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993. METHODS: For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity. RESULTS: Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors. CONCLUSIONS: Mutagen hypersensitivity increases the risk of developing second malignant tumors. IMPLICATIONS: Future research should focus on the molecular mechanisms underlying mutagen sensitivity.

Adult↗

Patterns of physical growth in a longitudinal study of young children in rural Bangladesh.

Longitudinal field studies of the physical growth of 197 children between 6 and 60 months of age have been completed in two rural villages of Bangladesh. The distribution of weights by age indicated that 90% of the village girls and boyd weighed less than the National Center for Health Statistics 5th percentile by 8 and 15 months of age, respectively. Of the children 90% were shorter than the reference population 10th percentile length by age by 10 to 13 months of age. Since the children's patterns of growth differed from those of the reference populations from North America and Europe, internal standards were created for the village girls and boys by fitting curves to their data for weight by age, length by age, arm circumference by age, triceps skinfold thickness by age, and weight by length. The village references enabled age-independent comparisons of children within the study population by relating their actual anthropometric status to the village norms. Comparisons of the village standards with the international reference data showed the period of poorest nutritional status of the village children persisted from shortly after birth to approximately 2 yr of age.

Bangladesh↗