Androgen replacement therapy in male patients with rheumatoid arthritis.

A hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P less than 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+:CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P less than 0.05). There was a concurrent significant reduction in the number of affected joints (P less than 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P less than 0.01). The well-known immunosuppressive action of androgens probably contributed to our findings in these RA patients.

Accelerated chemotherapy with or without GM-CSF for small cell lung cancer: a non-randomised pilot study.

Two series of five consecutive patients with small cell lung cancer were treated with an "accelerated" chemotherapy regimen of cyclophosphamide-doxorubicin-vincristine (CAV) and cisplatin-etoposide (PE) alternated possibly every week. In the first group of patients (median age 49 years, range 46-52) recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was given as soon as grade IV leukopenia occurred, while in the second group (median age 59 years, 55-68) no growth factor was administered. The mean interval between chemotherapy courses and the mean duration of chemotherapy were 10 and 57 days, respectively, in the patients supported with GM-CSF compared with 13 and 72 days in the control group. One GM-CSF treated patient was withdrawn after the third cycle because of severe toxicity. The mean white blood cell and platelet nadirs were 600 and 46,000/microliters in the first group vs. 840 and 105,000/microliters in the controls. Overall chemotherapy dose-intensity was increased by two fold in the patients given GM-CSF compared with a 1.5 fold increase in the control patients. In all cases, irrespective of their treatment, there was an impaired colony forming capacity of circulating and marrow haemopoietic progenitor cells when grade IV leukopenia occurred, with recovery after the end of leukopenia. This pilot study suggests that accelerated CAV/PE chemotherapy is feasible both with and without GM-CSF. Different GM-CSF schedules as well as combinations of different haemopoietic growth factors may further improve dose-intensity.

The systemic effect of cancers on human sera proton NMR relaxation times.

In animal models of cancer, an elevation of T1 and T2 in uninvolved tissues and in the blood of tumor bearing animals has been termed "the systemic effect." This study reports T1 values in sera of human patients from Genoa, Italy, with several types of cancer and non-cancerous diseases. T1 values were significantly elevated over normal controls (1628 +/- 113 ms) in colorectal cancers (1725 +/- 149 ms) and stomach cancers (1817 +/- 219 ms). However a systemic effect was not demonstrated in acute myeloid leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, or plasma cell myeloma, or in pancreatic and lung cancers. Noncancerous states of cirrhosis, chronic hepatitis, and monoclonal gammapathies did not show a T1 elevation. In general, T1 values of sera correlated with protein content of the sera; however, a disproportionate contribution of gamma-globulin protein on water proton relaxation times was observed in several cases.