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A new device for the continuous monitoring of oxygen uptake and carbon dioxide delivery is presented, which is based on a continuous expired gas analysis using a paramagnetic oxygen and an infrared-absorption carbon dioxide sensor. To validate the results, data of measured oxygen uptake and cardiac output calculated by the Fick principle were compared to synchronous thermodilution measurements at rest and during exercise. Measurements were performed at rest on 18 patients, additionally 13 of the patients were exercised with either 25 W or 50 W workload. The results indicate, for both measurement series, a significant correlation (r greater than 0.95, p less than 0.001) and exemplify that the measurement of oxygen uptake by expired gas analysis permits a precise analysis of the cardiovascular transport function during exercise.

Relationships between ovarian cancer and ability to conceive were explored in a case-control study of 188 women with histologically confirmed epithelial ovarian cancer and 539 control women in the San Francisco Bay Area. Control women consisted of two groups: those hospitalized without cancer, matched to cases by age, race, and hospital of diagnosis (n = 280); and those selected from the general population by random digital dialing, matched to cases by age, race, and telephone prefix (n = 259). Ovarian cancer risk among nulliparous (but not parous) women was positively associated with a history of unsuccessful attempts to conceive, of physician-diagnosed infertility, and of doubts about ability to conceive. Among all women, risk increased with increasing years of unprotected intercourse (P value for trend = 0.02). Risk among women having 10 or more yr of unprotected intercourse was 1.8 relative to that among women having less than 2 such yr (P = 0.01). This association was independent of parity, oral contraceptive use, and estimated years of ovulation, each associated with ovarian cancer. Further, duration of unprotected intercourse combined multiplicatively with each of these latter characteristics in increasing ovarian cancer risk. For example, while cancer risk exhibited a 2-fold range from lowest to highest years of unprotected intercourse and a 4-fold range from lowest to highest years of ovulation, risk among women in the highest joint category of these characteristics was 8 times that of women in the lowest category. We believe that some abnormality of ovulation that reduces the likelihood of conception plays a role in epithelial ovarian cancer.

Data on rodents exposed to carcinogens indicate that their tumor probabilities are proportional to effective concentrations of parent compound or metabolites at the target tissues. This proportionality suggests that observed nonlinear dose-response curves reflect dose-dependent kinetics between applied dose rate and effective concentrations. Therefore low dose extrapolation procedures that include pharmacokinetic data could improve extrapolation accuracy. To test such procedures, we simulated bioassay and pharmacokinetic "data." Then, ignoring the mechanisms generating the data, we used four extrapolation procedures to estimate tumor probability at a low applied dose rate. Two of the procedures use a pharmacokinetic model and simulated pharmacokinetic data, and two do not. The pharmacokinetic model used for extrapolation was only an approximation to the one used to generate the pharmacokinetic data. The procedures that include pharmacokinetics often performed better and never did much worse than those that ignore them, regardless of the relations used to generate the data, the amount of experimental error in the pharmacokinetic data, and the appropriateness of the pharmacokinetic and extrapolation models used. Moreover they performed substantially better when effective concentration and tumor probability were concave-up functions of applied dose rate.

Mortality rates among 838 white female breast cancer patients were examined for relationships to personal characteristics assessed at time of diagnosis. These included weight and body mass index, oral contraceptive use, and prior menstrual and reproductive events. Multivariate analyses were used to determine the importance of these characteristics in predicting death rates specific for age and extent of disease at time of diagnosis. Weight was associated with poor prognosis among premenopausal patients, but not among postmenopausal patients. Premenopausal women weighing more than 140 lbs at diagnosis had death rates 1.7 times those of lighter women (P = 0.04). This effect was not explained by differences in the distribution of disease stage between the two groups. Body mass index was positively associated with mortality in both premenopausal and postmenopausal patients. In the entire group, the death rate ratio was 1.4 (P = 0.02) for obese (body mass index greater than 30.4 X 10(-3) lbs/in.2) vs lean women. Among premenopausal patients, parous women had higher mortality rates than nulliparous women (death rate ratio = 2.0, P = 0.06). Although the data were sparse, death rates were higher for women having a full-term pregnancy within 2 years of diagnosis than for premenopausal women with earlier pregnancies. Oral contraceptive use, age at menarche, age at first full term birth, and age at menopause were unrelated to mortality.

After a scraping injury to the skin a 47-year-old man developed a generalized Nocardia brasiliensis infection with cutaneous, pulmonary and cerebral dissemination. There was no predisposing underlying illness. High-dosage cotrimoxazol and short-term intrathecal and systemic gentamycin administration achieved extensive healing. This form of treatment would thus seem capable of reversing the otherwise poor prognosis of generalized N. brasiliensis infection.

The noninvasive determination of the respiratory gas exchange (measurement of oxygen uptake and carbon dioxide delivery) permits the calculation of cardiac output by Fick principle and of the actual energy requirement of the patient (indirect calorimetry). A system is presented for the continuous measurement of oxygen uptake and carbon dioxide delivery, that bases on simple components, which are available on most intensive care units. The methodical problems are discussed and the improvement of the signal of the oxygen sensor by digital signal processing is described. Clinical measurements on 16 patients are presented, whose metabolic rate early after extracorporal circulation was measured. The results reveal, that 4.4 hours after ECC the metabolic rate is close to the calculated basic metabolic rate. They demonstrate the importance of indirect calorimetry as a future bedside monitoring routine.

Tumor growth in a 72-year-old male patient with malignant haemangiopericytoma in the left hemithorax could be followed radiologically for 4 years before symptoms of recurrent hypoglycaemia appeared. The endogenous insulin level in serum was maximally and serum IGF-1 and IGF-2 markedly reduced. An intravenous arginine load test showed a normal stimulation capacity of the pancreatic glucagon secretion but not that of insulin. After resection of the tumor, blood sugar metabolism was completely normalised. The insulin level, IGF-1 and IGF-2 in serum returned to normal.