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A set of computer programs which collect and analyze data on the temperature dependence of neuronal activity is described. Data on the response to thermal stimulation of cultured neurons of the rat preoptic area were collected and displayed on-line and were stored on disk for off-line analysis. Statistical analysis of the data examined two alternate models of thermosensitivity: one that the relationship between neuronal activity and temperature was well fit by a linear relationship and the other, that it was well fit by semi-log regression. For each of the models, a neuron was considered to have temperature-dependent activity if two criteria were met: first, that the model was considered adequate by a lack-of-fit F-test and second, that the slope of the regression line differed from zero using a t-test. A statistical method was also used to test the hypothesis that the neuronal response to temperature displays a change point. This method did not identify any neurons whose thermal response relationship could be better fit by two intersecting regression lines than by one regression line.

We have reviewed a 44-year experience with previously untreated carcinomas arising in major salivary glands to compare 319 patients treated before 1966 with 155 who received therapy between 1966 and 1982. Actuarial analysis indicates that five- and ten-year survival of our more recently treated patients was 80% and 65%, compared with 60% and 50% in patients treated before 1966. Explanation for this includes the higher proportion of patients with less aggressive histologic subtypes seen in recent years, as well as the fact that many of our patients treated before 1966 had surgical procedures considered inadequate by current standards. We also believe that adjunctive radiation oncology enhanced survival, but it could not be proved in this retrospective study. Multivariate analysis confirms that the clinical stage was the most important prognostic variable.

4'Deoxydoxorubicin (25 mg/m2 iv every 3 weeks) was evaluated in 20 patients with advanced breast cancer. The patients had good performance status and had not been heavily pretreated. Although all patients experienced leukopenia, no major therapeutic responses were observed. Nonhematologic toxicity was mild. Further evaluation of 4'-deoxydoxorubicin at this dose and schedule is not warranted in patients with advanced breast cancer.

The in vitro release of IL-1 by monocytes in response to endotoxin was subnormal in many patients with breast cancer, malignant melanoma or colorectal cancer but not in patients with benign tumors of the breast or colon. In each of these groups, IL-1 release was low in patients with early cancer, normal in patients with regional metastases, and low in patients with disseminated cancer.

Treatment comparisons in randomized clinical trials usually involve several endpoints such that conventional significance testing can seriously inflate the overall Type I error rate. One option is to select a single primary endpoint for formal statistical inference, but this is not always feasible. Another approach is to apply Bonferroni correction (i.e., multiply each P-value by the total number of endpoints). Its conservatism for correlated endpoints is examined for multivariate normal data. A third approach is to derive an appropriate global test statistic and this paper explores one such test applicable to any set of asymptotically normal test statistics. Quantitative, binary, and survival endpoints are all considered within this general framework. Two examples are presented and the relative merits of the proposed strategies are discussed.

Study Objective: To determine the effectiveness of chemotherapy and adjunctive surgery in managing patients with advanced seminoma., Design: Nonrandomized prospective clinical trial of chemotherapy in a cohort of patients with advanced seminoma., Setting: Referral cancer hospital., Patients: Consecutive sample of 62 patients with primary extragonadal, stage IIC (greater than 5-cm retroperitoneal adenopathy) and stage III seminoma; 45 patients were previously untreated, 13 had received radiotherapy, and 4 had previously received radiotherapy and chemotherapy., Intervention: Cisplatin-based chemotherapy (100 to 120 mg/m2 body surface area per cycle of treatment); 45 patients received vinblastine, bleomycin, cisplatin, dactinomycin, and cyclophosphamide; 15, etoposide and cisplatin; and 2, both regimens., Measurements and Main Results: Fifty-three of the sixty (88%) evaluable patients achieved a complete remission, and only 6 patients had relapses. Fifty-three of the sixty-two patients (85%) remain alive and disease-free. The regimen of etoposide and cisplatin was equivalent to regimens using more drugs. An elevated level of human chorionic gonadotropin at the initiation of treatment was associated with a worse prognosis., Conclusions: Cisplatin-based chemotherapy is effective treatment for patients with extragonadal, stage IIC, and stage III seminoma and should be considered as initial therapy.

The serum values of alphafetoprotein, human chorionic gonadotropin, lactate dehydrogenase, and carcinoembryonic antigen in patients with metastatic testicular cancer were reviewed for the period 1972 to 1982. All values were obtained before chemotherapy was begun. Elevated values of alphafetoprotein were present in 47 percent of patients tested, of human chorionic gonadotropin in 60 percent, of lactate dehydrogenase in 64 percent, and of carcinoembryonic antigen in 11 percent. The frequency of elevated values of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase decreased during the study period. Inverse relations between elevated values of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase and both complete remission rate and survival rate were noted in some of the chemotherapy trials. Carcinoembryonic antigen was believed not to be useful as a marker in this disease. It is concluded that assays of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are important both clinically and prognostically in patients with testicular cancer.

The effect of polyethylene oxide of different molecular weight on the aggregation of erythrocytes has been investigated. It was shown that the addition to blood of polymers with molecular weight of 600 and 1 000 weakens this aggregation, whereas the addition of those with molecular weights of 4 000 and 6 000 completely prevents it, simultaneously decreasing their osmotic resistance. Polyethylene oxide with molecular weight from 20 000 to 1 000 000 increase the aggregation of erythrocytes and do not affect their osmotic resistance. The aggregation of erythrocytes is a reversible process. The decrease in polyethylene oxide concentration leads to decreasing aggregation effect. The mechanism of the effect of polymers on cell aggregation is discussed.

We have conducted a Phase I and initial clinical pharmacological evaluation of 4'-deoxydoxorubicin (4'-DXDX), administering the drug i.v. on an every 21-day schedule to 60 patients with advanced cancer. Patients were treated at six dosage levels ranging from 10 to 35 mg/sq m. Leukopenia was the dose-limiting toxic effect, and no cardiac, renal, or hepatic toxicity was observed; stomatitis was not seen; and there were no drug-related deaths. Significant alopecia was rare at doses less than 35 mg/sq m, mild nausea and vomiting occurred in one-third of patients at myelosuppressive doses; 12 patients had a transient local urticarial reaction. In the 30 patients with measurable disease, two partial remissions were seen, lasting 5 months in a patient with a nasopharyngeal adenocarcinoma, and 7 months in a patient with endometrial adenocarcinoma. The recommended dose of 4'-DXDX for Phase II studies is 30 mg/sq m in good-risk patients and 25 mg/sq m in moderate-risk or heavily pretreated patients. Pharmacokinetic studies were carried out in ten patients, four of whom received 4'-DXDX at a dose of 10 mg/sq m and six at 30 mg/sq m. Disappearance of 4'-DXDX from plasma was triphasic with a rapid initial phase clearance showing a t1/2 alpha of 1 to 2 min and a prolonged terminal phase with a median t1/2 gamma in excess of 90 h in patients receiving 30 mg/sq m.

Mucositis is one of the major problems encountered after the administration of systemic chemotherapy. Leucovorin, routinely used as a rescue agent for methotrexate may reduce toxicity, but may also reduce the effectiveness of the chemotherapeutic agent. If leucovorin is administered as a mouth wash, local toxicity may be reduced without loss of methotrexate efficacy. In order to study this, 15 normal human volunteers were given leucovorin mouth wash and then had plasma determinations of 5-methyl-tetrahydrofolate and citrovorum factor. Small but statistically significant increases in plasma levels of 5-methyl-tetrahydrofolate were observed with no increase in levels of plasma citrovorum factor. It is concluded therefore that a small amount of leucovorin is absorbed systemically when administered as a mouth wash, but such an amount would most likely not be significant enough to reduce the effect of methotrexate therapy, but may reduce mucositis.

A rapid method for the measurement of serum and/or plasma, lipid-associated sialic acid levels has been developed. This test has been applied to 850 human sera of which 670 came from patients with nine categories of malignant disease, 80 from persons with benign disorders, and 100 from normal individuals. Lipid-associated sialic acid concentrations were found to be significantly increased (p less than 0.001) in all groups of cancer patients as compared to both those with benign diseases and normal controls. Test sensitivity in the detection of cancer ranged from 77 to 97%. Specificity was, respectively, 81 and 93% for the benign and normal groups. In small samples of patients, no association between test values and tumor burden was found. This test compares favorably with the most widely used tumor marker test, that for carcinoembryonic antigen.