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Biomedical subjects

B Bell

Publications and source records attributed to B Bell.

At least 55 records · Page 3Linked to original sources
PubMed1995

A phase I study of acivicin in refractory pediatric solid tumors. A Pediatric Oncology Group study.

Forty-two patients with progressive solid tumors and brain tumors were entered in this Phase I study of the glutamine antagonist acivicin given intravenously over thirty minutes daily for five days. The major toxicities encountered were myelosuppression and central nervous system toxicity (nightmares and somnolence). The maximum tolerated dosage on this schedule was 26 mg/M2 daily for five days. Six patients including three patients with brain tumor had stable disease.

Adolescent↗
PubMed1993

Ifosfamide with mesna uroprotection and etoposide in recurrent, refractory acute leukemia in childhood. A Pediatric Oncology Group Study.

BACKGROUND: Ifosfamide has previously been shown to be active as a single agent and in combination with doxorubicin, etoposide, and teniposide in pediatric solid tumors and adult acute leukemia. The authors performed a dose-escalation trial of ifosfamide with a fixed dosage of etoposide, with mesna uroprotection, in children with multiply recurrent acute leukemia. METHODS: Chemotherapy was administered daily for 5 days. Etoposide 100 mg/m2 was followed by ifosfamide at an initial dosage of 1.6 g/m2. The ifosfamide was escalated in 20% increments to the maximum tolerated dosage in cohorts of three patients. Mesna 400 mg/m2 was given immediately before the ifosfamide and then at 3 and 6 hours after ifosfamide in the initial patients. Subsequent patients were treated with mesna 400 mg/m2 just before ifosfamide, and then every 2 hours to a total dosage equal to the ifosfamide dosage. RESULTS: Forty-four heavily pretreated patients were entered on study. Forty were evaluable for toxicity and 36 for response as well. The maximum tolerated dosage of ifosfamide was 4.0 g/m2/d for 5 days (20 g/m2/course). Overall, 10 patients achieved complete remission, and 3 achieved partial remission. Remissions were brief, although four patients went on to bone marrow transplant while in remission. One patient is still alive. CONCLUSIONS: The combination of etoposide and ifosfamide with mesna uroprotection showed promising activity in children with multiply recurrent acute leukemia.

Acute Disease↗
PubMed1993

Familial adenomatous polyposis (Gardner's syndrome) and thyroid carcinoma. A case report and review of the literature.

The case history of a 24-year-old woman with Gardner's syndrome [familial adenomatous polyposis (FAP)] and papillary thyroid carcinoma is presented, representing the 37th report of this association. Although FAP is transmitted as an autosomal dominant trait with similar penetrance in both sexes, thyroid carcinoma has been found almost exclusively in women (94.3%). The majority have been papillary carcinomas (88.5%), which have become apparent during the third decade (average 23.6, range 16-40 years). Most (55.5%) thyroid carcinomas have been discovered 1-17 years after FAP was identified, although some have been found before (29.6%), or at the same time (14.8%) FAP was diagnosed. Multicentric papillary carcinomas have been reported in 64% (14 of 22) of FAP patients, a frequency at least twofold greater than usual. Although papillary carcinoma found before age 30 (as it was in most patients with FAP) typically has an excellent prognosis, one patient with FAP developed distant metastases from thyroid carcinoma and a 28-year-old woman's death was attributed to papillary carcinoma. The high frequency of multicentric papillary thyroid carcinoma in young patients with FAP and the potential for metastases and death due to thyroid carcinoma warrant aggressive diagnostic screening at regular intervals with neck palpation, ultrasonography, and if necessary, fine-needle aspiration biopsy. When thyroid carcinoma is found, total or near-total thyroidectomy should be considered because of the tumor's high likelihood of being multifocal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Phase I clinical trial of recombinant human tumor necrosis factor in children with refractory solid tumors: a Pediatric Oncology Group study.

PURPOSE: A phase I study was undertaken to determine the toxicity and maximum-tolerated dose (MTD) of recombinant human tumor necrosis factor (rTNF) in children. PATIENTS AND METHODS: Twenty-seven patients with recurrent or refractory solid tumors were enrolled on the study. rTNF was administered daily for 5 days by 30-minute intravenous (IV) infusion, and doses were escalated in cohorts of three to six patients. Courses were repeated after a 9-day rest period, if toxicity was tolerable. Daily doses ranged from 100 to 350 micrograms/m2. RESULTS: Most courses were associated with grade I/II fever, rigors, nausea, or vomiting. Three patients experienced moderate dyspnea that responded to supplemental oxygen. All abnormalities resolved on discontinuation of the infusion. One patient had a cardiac arrest 90 minutes after receiving the first dose of rTNF and died 10 days later of related complications. In two other patients, rTNF was discontinued due to persistent grade IV hypotension. Toxicities were not consistently related to dose and no cumulative effects were noted. The dose-limiting toxicity was transient hepatic dysfunction, which occurred in three of six patients receiving 350 micrograms/m2; this toxicity was rapidly reversed on discontinuation of the rTNF. One patient, whose non-Hodgkin's lymphoma had recurred after bone marrow transplantation, had a partial response. Disease was stabilized in two patients. CONCLUSION: We recommend that phase II testing proceed at a dose of 300 micrograms/m2/d on the schedule described.

Adolescent↗
PubMed1993

Racial differentials in the identification of hypercholesterolemia.

BACKGROUND: African Americans have higher rates of cardiovascular disease than white Americans. To address this differential, barriers to cardiovascular risk reduction need to be identified. This study examines the association of race with the likelihood of screening for and diagnosis of hypercholesterolemia. METHODS: Possible associations between demographic variables and screening for and diagnosis of hypercholesterolemia were examined on data gathered in a prospective fashion in an office-based family medicine residency training program in Rochester, New York. A consecutive sample of all patients seen between December 15, 1988, and April 15, 1990, about whom there was complete data collection (age, sex, insurance, race, and other cardiovascular risk factors) were included in the multivariate analyses (N = 4256). RESULTS: After controlling for age, sex, insurance status, socioeconomic status, number of visits, and other cardiovascular risk factors, it was found that minorities were less likely to have been screened for cholesterol levels than whites (adjusted odds ratio [AOR] = 0.84, 95% confidence interval [CI] = 0.98 to 0.72). The mean cholesterol level did not differ by race (mean cholesterol for whites, 204 mg/dL [5.28 mmol/L], and for minorities, 203 mg/dL [5.25 mmol/L], t = 0.7, P = .47). Among those screened, minorities were less likely than whites to have been diagnosed with hypercholesterolemia (AOR = 0.62, 95% CI = 0.86 to 0.44; and 0.47 (95% CI = 0.28 to 0.78] in those with a cholesterol level greater than 240 mg/dL [6.2 mmol/L]). CONCLUSIONS: Our data suggest that provider behavior in diagnosing hypercholesterolemia varies by the race of the patient.

Adult↗
PubMed1992

GAL4 fusion vectors for expression in yeast or mammalian cells.

We describe two sets of vectors, one for yeast (pY1, pY2 and pY3) and one for mammalian cells (pM1, pM2, and pM3), that simplify the production of fusion proteins containing the DNA-binding domain of GAL4. This protein fragment, consisting of GAL4 amino acid (aa) residues 1-147, binds to a specific 17-bp nucleotide sequence, but is incapable of activating transcription unless fused to a protein that can contribute an activating function. Genetic strategies exploiting this property of GAL4 (aa 1-147) have been developed to characterize transcription factor functional domains, protein-protein interactions, and site-specific proteolysis. The vectors we describe allow fusion to the C terminus of GAL4 (aa 1-147) in any reading frame, and thus facilitate these experimental strategies.

Amino Acid Sequence↗
PubMed1991

Alcohol affects rat testicular interstitial fluid volume and testicular secretion of testosterone and beta-endorphin.

The effects of alcohol on testicular interstitial fluid (TIF) volume and the secretion of testosterone and beta-endorphin (beta E) into this important testicular compartment were assessed in the rat. Alcohol time- and dose-response curves were constructed for changes in TIF volume and the bioactive concentrations of testosterone and immunoreactive beta E (i-beta E). Alcohol (3 g/kg) decreased TIF volumes and increased TIF i-beta E secretion 0.5 to 6 hr after injection and decreased TIF testosterone 1 to 6 hr after injection. These effects were dose-related at 2 hr postinjection. The possible role of alcohol-induced reductions in serum luteinizing hormone and testosterone levels in mediating the effects of alcohol on TIF volume was also examined. We found that pretreating rats with human chorionic gonadotropin, which reversed alcohol-induced suppression in levels of serum gonadotropins and testosterone, failed to reverse the effects of alcohol on TIF volume and the secretion of testosterone and i-beta E. These results indicate that alcohol decreases TIF volume, inhibits TIF testosterone secretion and stimulates TIF i-beta E secretion and, furthermore, suggest that these effects are not indirectly mediated by decreased levels of gonadotropins or testosterone, but by direct effects of alcohol on gonadal function. The strong inverse correlation between TIF i-beta E and testosterone secretion after alcohol administration and previous evidence that testicular opioids inhibit the biosynthesis of testosterone suggest that alcohol may act through testicular beta E to suppress the synthesis and release of testosterone in the testes.

Animals↗
PubMed1990

Phase I study of a 120-hour continuous intravenous infusion of 5-fluorouracil in pediatric patients with recurrent solid tumors: a Pediatric Oncology Group study.

To determine the maximum tolerated dose of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients, we performed a phase I study using a starting dosage of 900 mg/m2/day. The maximum tolerated dosage (MTD) was 1,100 mg/m2/day. At this dosage level 40% of courses were complicated by grade 3 mucositis. Three additional patients were treated at the dosage level of 1,000 mg/m2/day after the MTD was determined. We recommend the dosage level of 1,000 mg/m2/day for phase II studies of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients.

Adolescent↗
PubMed1990

Phase I evaluation of diaziquone in childhood cancer. A Pediatric Oncology Group study.

We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly X 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M2/week X 4 for patients with a solid tumor, and is 30 mg/M2/week X 4 for children with acute leukemia.

Adolescent↗