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Biomedical subjects

G Hemstreet

Publications and source records attributed to G Hemstreet.

8 recordsLinked to original sources

Drake Chemical Workers' Health Registry Study: I. Notification and medical surveillance of a group of workers at high risk of developing bladder cancer.

A medical surveillance program and epidemiologic study of 408 former workers of the Drake Chemical Company (now a Superfund waste site) was established in 1986. The Drake Health Registry Study was initiated because these workers had probable past exposures to beta-naphthylamine (BNA), a potent bladder carcinogen. The registry is widely viewed as a model for notification of workers at high risk of disease due to past occupational exposures. By the 40th month, 90% of the 366 living workers had been notified of the existence of the registry; 262 had been enrolled in the annual or semi-annual screening for bladder cancer. Among these, 27 persons have had abnormal screening results indicating moderate to high risk of bladder cancer and have been made eligible for further diagnostic tests. While no invasive bladder tumors were found among 18 persons completing the extended diagnostic evaluation, two diagnoses of moderate to severe dysplasia have been made. The registry has also identified three living and three deceased cases of bladder cancer in the cohort; a mortality analysis showed a 20- to 30-fold excess of bladder cancer. An incidence projection, based on the six identified cases, reveals that between six and ten new bladder cancer cases are likely to occur among the Drake cohort over the next 20 year period.

2-Naphthylamine

Pharmacokinetics of recombinant interleukin 2 in humans.

This report summarizes the pharmacokinetics in humans of recombinant interleukin 2 (IL-2) given as an i.v. bolus, i.v. or i.p. infusion, and i.m. or s.c. injection. Immediately after an i.v. bolus the serum IL-2 level equals the dose divided by the plasma volume, in a typical human 650 units/ml for a dose of 10(6) units/m2. The level initially decreases with a half-life of 12.9 min, followed by a slower phase with a half-life of 85 min out to 4 h after the bolus. The median steady state level during an i.v. infusion of 10(6) units/m2 over 6 h is 41 units/ml. A clearance rate of approximately 120 ml/min is obtained from either the i.v. bolus or infusion data and is consistent with the renal filtration being the major route of clearance. Serum levels remain fairly constant for about 8 h after s.c. or i.m. injection but are approximately 2% of the level seen immediately after an i.v. bolus. The area under the time-concentration curve suggests that about 30% of the IL-2 activity is transported from the site of an i.m. injection to the blood. After i.p. infusion IL-2 is only slowly transported to the blood. The median serum IL-2 levels are 430-fold lower than levels in the i.p. fluid and decrease with a median half-life of 6.3 h.

Biological Assay

A protocol for bladder cancer screening and medical surveillance among high-risk groups: the Drake Health Registry experience.

In 1986, the Drake Health Registry Study initiated bladder cancer screening for 366 persons at high risk because of occupational exposure to beta-naphthylamine. The Drake Health Registry Study screening protocol consists of urinalysis, Papanicolaou cytology, and quantitative fluorescence image analysis. A positive screening test qualifies participants for a full diagnostic evaluation. The screening protocol has been modified during the first 3 years of the program's existence to address unexpected patterns of test results and to incorporate advances in screening technology. The current protocol, which has a two-tiered screening schedule, has been utilized successfully for 15 months. Of the 26 positive results to date most have been based on abnormal Papanicolaou cytology and/or quantitative fluorescence image analysis. Bladder abnormalities were cited among most of the 18 study members who underwent diagnostic evaluation, including chronic cystitis, inflammation, hyperplasia, and dysplasia. We conclude that the screening program is detecting very early changes in a relatively young cohort and that these persons must be monitored over a number of years to ensure adequate medical surveillance.

2-Naphthylamine

Automated quantitative fluorescent image analysis of cervical cytology.

Cervical cytology from 122 patients with histories of one or more abnormal Pap smears were studied using slide-based automated quantitative fluorescence image analysis (QFIA) in order to determine the usefulness of the QFIA technique in detecting neoplasias. The purpose of the study was to evaluate the accuracy and validity of QFIA as a cytological method for the early detection of cervical cancer, based on comparisons with the conventional Pap smear and histopathology. The results of the analysis demonstrated that the sensitivity of the automated QFIA cytology was 100% for high-grade neoplasms (CIN III and invasive carcinoma), compared with 82% for the Pap smear. Evaluation of lower grade neoplasms was also performed. Initial analyses of the data indicate that QFIA, which uses objective biochemical criteria to identify cells with increased nuclear nucleic acid content, is a more sensitive detector of cervical neoplasia of all grades than is conventional Pap cytology.

Acridine Orange

A phase II evaluation of a 3-drug combination of cyclophosphamide, doxorubicin and 5-fluorouracil and of 5-fluorouracil in patients with advanced bladder carcinoma or stage D prostatic carcinoma.

The Southeastern Cancer Study Group has evaluated 5-fluorouracil administered intravenously weekly at a dosage of 600 mg. per M.2 as a single agent, and the 3-drug combination of cyclophosphamide, doxorubicin and 5-fluorouracil in patients with metastatic carcinoma of the bladder and of the prostate previously untreated with cytotoxic chemotherapy in a prospectively randomized phase II study. In 4 of 18 patients with bladder carcinoma 5-fluorouracil induced an objective response, and cyclophosphamide, doxorubicin and 5-fluorouracil induced an objective response in 3 of 21 patients. In patients with prostatic carcinoma 5-fluorouracil induced an objective response as measured by a 50 per cent decrease in prostatic acid phosphatase determined in a central reference laboratory in 3 of 25 patients and objective stability by National Prostatic Cancer Project criteria in 14 of 29 patients. Cyclophosphamide, doxorubicin and 5-fluorouracil induced an objective response in 7 of 22 patients and objective stability in 20 of 29. Thus, 5-fluorouracil administered in an adequate weekly dosage is established as an effective single agent in some patients with stage D carcinoma of the bladder or prostate. However, there is no significant added benefit as measured by survival obtained for these patients by combining cyclophosphamide and doxorubicin with 5-fluorouracil.

Adenocarcinoma

Cytologic detection of urothelial cancer and other abnormalities in a cohort of workers exposed to aromatic amines.

A total of 541 members of a cohort at increased risk for occupational bladder cancer underwent a 33-month program of screening with urine cytology. Selected workers received further urologic study with cystoscopy and bladder biopsies. Eight workers had positive or suspicious cytologic findings. Only one of the eight had a prior history of bladder cancer. Biopsies showed invasive carcinoma and/or nonpapillary carcinoma in situ in five workers in this group, severe atypia in one, and no significant abnormality in two. Of 56 workers who had atypical cytologic findings, 16 had bladder biopsies, which showed atypia of flat urothelium in 11, nonpapillary carcinoma in situ in one, noninfiltrating papillary carcinoma in one, and no significant abnormality in three. The cytologic detection of urothelial abnormalities often required more than a single specimen. Since the cohort in this study may develop more bladder cancers with the passage of time, continued follow-up is indicated.

Adult