Objective regressions of T- and B-cell lymphomas in patients following treatment with anti-thymocyte globulin.

We have conducted a clinical trial utilizing anti-thymocyte globulin (ATG) for the treatment of patients with non-Hodgkin's lymphomas. Six patients were treated; 50% reductions in tumor mass of short duration were observed in one patient with a T-cell lymphoma and two patients with B-cell lymphomas. In vitro assays have been performed in an attempt to study the reactivity and potential mechanism of antitumor action of the ATG. The ATG bound to essentially all normal blood mononuclear leukocytes as well as tumor cells from patients with T-, B-, or null cell lymphomas demonstrating its lack of specificity. Furthermore, complement-mediated lysis of normal mononuclear leukocytes, normal T- or B-cells, and tumor cells from two unresponsive patients were all comparable; moreover, since this lysis occurred only at concentrations of ATG that are not attainable in vivo, it is unlikely that complement-mediated cytotoxicity accounts for the responses observed. Peripheral blood lymphocyte counts and total erythrocyte rosettes did decrease during ATG treatment. Thus, objective tumor responses in both B- and T-cell non-Hodgkin's lymphomas can be achieved with a very nonspecific antiserum although significant toxicity resulted. Whether the magnitude or duration of response can be increased with monoclonal antibodies remains to be determined. Future success with serotherapy might require use of either a battery of different monoclonal antibodies or a single monoclonal antibody that can deliver radioisotopes, chemotherapy, or toxins to the tumor cells.

Reduction in the plasma clearance rate of warfarin induced by cimetidine.

The interaction between the histamine H-2 receptor antagonist, cimetidine, and warfarin sodium was prospectively studied in 14 patients who were previously anticoagulated for five years. The patients received warfarin and cimetidine concomitantly for a minimum of ten days. Seven of the patients experienced increases in plasma warfarin concentrations. This correspondingly resulted in abnormal prolongation of their prothrombin times. In these patients the elevation in the steady-state warfarin concentration demonstrates that coadministration of cimetidine significantly reduces the plasma clearance rate of warfarin. The serum and urine metabolite levels of warfarin were not qualitatively different in the absence in contrast to the presence of cimetidine. It is apparent that cimetidine can act as an inhibitory influence on the catabolic degradation of warfarin.

How to assess neurologically impaired patients.

Subtle changes can occur with neuro patients; therefore, it's important to make frequent, careful observations. The main functions that change rapidly and need to be frequently and thoroughly assessed are described in the following article and include: consciousness, mentation, movement, sensation, and integrated regulatory functions.

Behavioral correlates and staff recognition of alcohol use in a university hospital trauma service.

Hospital course and admission blood alcohol levels were compared in 242 consecutive adult trauma admissions. A 33% overall intoxication rate was found. Intoxicated patients were more likely to be young, male, and Hispanic or black and to be involved in fights, stabbings, and automobile accidents in which they were presumed to be at fault. These patients were also more likely to manifest disruptive behavior in the emergency room. Disruptive behavior on the ward was not correlated with alcohol intoxication at admission, but was correlated with the history of head injury. Staff recognition of intoxication was high, but only about 7% of the patients who were intoxicated at admission were referred to alcohol treatment programs. More frequent referrals for such treatment might decrease trauma center admissions and the high costs associated with them.

Deficient helper cell function as a cause of diminished pokeweed mitogen blastogenic responses in patients with non-Hodgkin's lymphomas.

An investigation has been made of immunoregulatory T-cell function in the non-Hodgkin's lymphomas by comparing immunoregulation of healthy control and patient peripheral blood lymphocyte blastogenic responses to pokeweed mitogen. Normal mononuclear leukocytes (MNL) had significantly higher responses than patient MNL. MNL were subsequently separated into T- and non-T-cell fractions by differential E-rosette sedimentation for co-culture experiments. When normal non-T-cells and autologous irradiated T-cells were recombined, the mitogenic response again exceeded the response of patient non-T-cells recombined with their own irradiated T-cells. However, when normal non-T-cells were co-cultured with patient irradiated T-cells, the mitogenic response was diminished. Moreover, when patient non-T-cells were co-cultured with normal irradiated T-cells, a normal proliferative response occurred. These differences in non-T-cell response are not simply a result of allogeneic effects, since normal non-T-cell responses were the same regardless of whether autologous or normal allogeneic irradiated T-cells were used as helpers. Furthermore, co-culture of normal non-T-cells simultaneously with autologous irradiated T-cells and patient irradiated T-cells revealed no diminution of blastogenic response compared with co-cultures of normal non-T-plus autologous irradiated T only, suggesting no net suppression by patient irradiated T-cells. Studies with monoclonal antibodies revealed that patient T-cells had normal to increased ratios of OK-T4+:OK-T8+ cells. These results suggest that peripheral blood T-cells from patients with non-Hodgkin's lymphomas, despite the presence of a normal to increased ratio of OK-T4+:OK-T8+ cells, are functionally deficient in their helper capacity for non-T-cell blastogenic response to pokeweed mitogen. Abnormal helper T-cell function may explain some of the immune deficits in patients with non-Hodgkin's lymphoma and may be important in the pathogenesis of these diseases.

Phase II trial of chlorozotocin in malignant melanoma, breast cancer, and other solid tumors.

We have conducted a broad phase II clinical trial of chlorozotocin in 74 patients including 28 with malignant melanoma, 18 with breast cancer, nine with non-Hodgkin's lymphoma, six with nonseminomatous testicular cancer, five with ovarian cancer, four with sarcoma, three with non-beta islet cell carcinoma of the pancreas, and one with anaplastic carcinoma of the thyroid. Objective responses were noted only in 15% of the patients with melanoma and in 11% of the patients with non-Hodgkin's lymphoma. Significant leukopenia and thrombocytopenia were observed only in previously treated patients. Chlorozotocin does not appear to offer clinically significant advantages over other currently available nitrosoureas.