Biomedical subjects
Publications and source records attributed to B W Brown.
The two-period crossover or changeover design for clinical trials is compared with other simple designs in terms of statistical precision and cost. The sensitivity of the crossover to bias due to carryover effects is examined. The feasibility of using the crossover data to test for the existence of carryover effects is investigated and found to be uneconomical. A numerical example is presented.
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A multiple logistic regression analysis of 12,914 pregnancies and 10,523 live births, based on a mail survey of professional women in medicine, was carried out to determine the relationship between maternal cigarette smoking, and spontaneous abortion and congenital abnormality. After controlling for interfering variables (age, exposure to trace anesthetic gases, pregnancy history, and mailing response), a statistically significant increase in risk associated with maternal cigarette smoking was found for spontaneous abortions and congenital abnormalities. The risk of spontaneous abortion for the heavy smoker is estimated to be as much as 1.7 times that of the nonsmoker in certain risk groups. The risk for congenital abnormality for babies born of smoking mothers is estimated to be as much as 2.3 times that of the nonsmoker, depending on age, pregnancy history, and other factors.
Combination chemotherapy utilizing high-dose vinblastine, bleomycin, and cisdichlorodiammineplatinum(II) (CDDP) is effective treatment for metastatic testicular cancer. Unfortunately, it is frequently associated with serious toxicity. In a series of 14 patients receiving 65 treatment cycles, several variables were examined as putative risk factors for prediction of serious toxicity. These included drug dose normalized to body weight or surface area, interval since previous cycle, prior therapeutic experience with either radiation therapy or other cytotoxic chemotherapy, and Karnofsky performance status. The strongest determinant of serious toxicity was the vinblastine dose calculated according to body weight. The next most influential prognostic variables were the performance status and a history of previous treatment with either radiation therapy or chemotherapy. Serious toxicity may be anticipated at a frequency of 40% when vinblastine is administered at a total dose of 0.36 mg/kg with bleomycin and CDDP. In our group of patients, the nephrotoxicity of CDDP appeared to be cumulative despite intensive diuresis at the time of administration. Pulmonary toxicity was not observed. Modest reductions in vinblastine dose, especially in patients with poor performance status or a history of previous radiation or other chemotherapy, will substantially lower the frequency of serious toxicity.
Comparative analysis of data from three large retrospective surveys in the United States and the United Kingdom reaffirms an increased incidence of spontaneous abortion among female physicians working in the operating room. The live-born children of female physicians exposed in the operating room also had substantially more congenital abnormalities. Male anesthetists, compared with nonanesthetist physicians, had an increased incidence of hepatic disease; there was also an increased frequency of congenital abnormality in their children. The incidence of spontaneous abortion in wives of male anesthetists and in the rate of cancer among exposed male anesthetists was similar to control. Despite differences in survey methods and analysis, there was remarkable agreement in conclusions to be drawn from the independent studies.
To determine whether community health education can reduce the risk of cardiovascular disease, a field experiment was conducted in three northern California towns. In two of these communities there were extensive mass-media campaigns over a 2-year period, and in one of these, face-to-face counselling was also provided for a small subset of high-risk people. The third community served as a control. People from each community were interviewed and examined before the campaigns began and one and two years afterwards to assess knowledge and behaviour related to cardiovascular disease (e.g., diet and smoking) and also to measure physiological indicators of risk (e.g., blood-pressure, relative weight, and plasma-cholesterol). In the control community the risk of cardiovascular disease increased over the two years but in the treatment communities there was a substantial and sustained decrease in risk. In the community in which there was some face-to-face counselling the initial improvement was greater and health education was more successful in reducing cigarette smoking, but at the end of the second year the decrease in risk was similar in both treatment communities. These results strongly suggest that mass-media education campaigns directed at entire communities may be very effective in reducing the risk of cardiovascular disease.
In a double-blind, single-dose study, dextroamphetamine combined with morphine was compared with morphine alone to determine the relative efficacy of the combination given intramuscularly for postoperative pain. Each of 450 patients received one treatment of morphine sulfate (3, 6 or 12 mg) with dextroamphetamine (0, 5 or 10 mg). Analgesia, as measured by the patients' subjective responses to questions about relief of pain, was augmented when dextroamphetamine was given with morphine; the combination of dextroamphetamine, 10 mg, with morphine was twice as potent as morphine alone, and the combination with 5 mg was 1 1/2 times as potent as morphine. In simple performance tests, and in measures of side effects, dextroamphetamine generally offset undesirable effects of morphine (sedation and loss of alertness) while increasing analgesia. Effects on blood pressure, pulse and respiratory rate were minimal.
Serial changes in tumor mass were evaluated in 61 patients with multiple myeloma who had received intermittent courses of melphalan-prednisone until death. The variations in the kinetics of tumor reduction and relapse could be explained by a mathematical model based on two cell populations, one sensitive to and one resistant to chemotherapy. For all responding patients, the median tumor halving-time was 1.3 months and the median doubling time was 2.9 months. The duration of a constant tumor mass during remission was brief in most patients. A larger fraction of resistant cells prior to therapy was associated with a slower tumor doubling-time during relapse. With a constant fractional reduction of sensitive cells and a tumor halving-time of one month or less, all cells sensitive to alkylating agents would be eliminated with 3 years of uninterrupted intermittent therapy.
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The indicator fractionation technique with [86Rb]rubidium chloride as the indicator was used in conscious animals to determine the relative blood flow (RBF) as a measure of capillary blood flow in regions of the genital tract of cyclic ewes and of hormonally treated ovariectomized ewes. The RBF values in the ampulla, isthmus, uterus and cervix of cyclic ewes were markedly raised at pro-oestrus and declined thereafter to low levels during the remainder of the oestrous cycle. On Day 4 a small secondary rise in flow occurred in the ampulla and isthmus. In ovariectomized ewes, oestradiol induced high levels of RBF in the ampulla, isthmus, uterus and cervix whether the animals had been treated previously with progesterone or given concurrent small doses of progesterone. Though progesterone given alone caused a significant rise in RBF in the uterus, this effect appeared to be one occurring only during active re-growth of regressed tracts. The findings are discussed in relation to oestradiol inducing a stimulatory effect on RBF in the genital tract of the ewe around oestrus but not at Days 3-4 of the oestrous cycle.
Cardiovascular risk factors were assess in 986 women residing in three northern California communities. Women who reported current use of oral contraceptives had higher plasma triglyceride levels and systolic and diastolic blood pressures compared with women not using these agents, after adjusting for age and for the greater relative leannes of oral contraceptive users. Similar increases, albeit of lesser magnitude, were observed in women who used pure estrogens. Mexican-American women appeared to be more susceptible to the effects of estrogens, perhaps as a consequence of their greater degree of obesity.
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To establish the relative potency of naproxen and aspirin for oral analgesia, a 4-point, noncrossover bioassay with placebo control was undertaken with 197 patients. Subjective-response methods were used to determine two measures of postoperative analgesia over a period of 6 hr. With reasonable confidence for an oral analgesic assay, we found 220 mg of naproxen to be equivalent to 600 mg of aspirin for pain relief and 330 mg of naproxen to be equivalent to 600 mg of aspirin for decreased pain intensity.
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The antihistamines diphenhydramine and methapyrilene were compared with pentobarbital for hypnotic effect in two Veterans Administration Hospital populations using subjective-response methods. In the first part of the study, 60 mg and 180 mg of pentobarbital were compared with 50 mg and 150 mg of diphenhydramine. A positive dose-response relationship was obtained only for pentobarbital; neither dose of diphenhydramine was significantly different from 60 mg of pentobarbital for any response variable. In the second part of the study, 100 mg of pentobarbital, 50 mg of diphenhydramine, and 50 mg of diphenhydramine, and 50 mg of methapyrilene were compared with placebo. One hundred mg of pentobarbital and 50 mg of diphenhydramine were significantly different from placebo, but 50 mg of methapyrilene was not.
The incidences of some childhood cancers have been shown to fit a two-mutation hypothesis for cancer initiation. According to this hypothesis, the first mutation can be either germinal or somatic while the second is always somatic. A probabilistic model involving the mean number of tumors per genetically susceptible individual is developed as a function of age and is compared with age incidence data for retinoblastoma. The change in the mean number of tumors with time is interpreted in terms of the growth of retinal cells. In patients who are not genetically susceptible, the times of occurrence of the first and second somatic mutations can be inferred from a comparison of familial and non-familial unilateral case incidences. The total incidences of hereditary and nonhereditary forms of retinoblastoma are related to germinal and somatic mutation rates. The even distribution of certain childhood cancers throughout the world suggests that their incidences are determined by spontaneous mutation rates rather than by local environmental mutagenic carcinogens.