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Biomedical subjects

W A Andes

Publications and source records attributed to W A Andes.

At least 37 records · Page 2Linked to original sources

Bisantrene hydrochloride in gastric adenocarcinoma: a Southwest Oncology Group Study.

Because "the standard" chemotherapy for advanced gastric adenocarcinoma, the FAM combination of 5-fluorouracil, adriamycin, and mitomycin, is only minimally effective, there is a clear need for other choices. Therefore, the Southwest Oncology Group tested the new adriamycin analog, bisantrene, hoping that it might be more effective than the "parent drug." Twenty-six patients with gastric adenocarcinoma were treated on a program of every-3-week 2-hour bisantrene infusions. The starting dose was 260 mg/m2 (208 if poor risk), with subsequent doses based on prior toxicity. The regimen caused sufficient toxicity (especially local phlebitis with pain and swelling) to assure an adequate test. One person (3.8% of eligible patients) experienced a clinically useful 3-month response. He had previously had progressive disease on FAM. Nevertheless, we conclude that bisantrene is not an addition to the small list of drugs useful in the management of gastric adenocarcinoma.

Adenocarcinoma↗

Immunologic studies in homosexual and hemophiliac subjects with persistent generalized lymphadenopathy: a comparative analysis.

Hemophiliac patients receiving factor VIII replacement therapy and homosexual subjects are at risk for the acquired immune deficiency syndrome. Immunologic abnormalities, especially depletion of helper T cell populations, have been noted in members of these groups and may parallel their clinical state. We have evaluated the peripheral blood immunologic status of a group of hemophiliac and homosexual subjects with and without persistent generalized lymphadenopathy (PGL). Although individuals with PGL had more abnormal T-lymphocyte parameters, including lower helper/suppressor ratios, than group members without lymphadenopathy, there were no significant differences noted within each respective risk group. However, differences between hemophiliac and homosexual patient groups were noted. T-lymphocyte subpopulations of hemophiliac patients with lymphadenopathy were significantly more abnormal than the corresponding homosexual groups. All groups had decreased lymphocyte proliferative responses to mitogen. Homosexual subjects with lymphadenopathy exhibited the most profoundly depressed lymphocyte mitogenic responses. We conclude that, although abnormalities of T-lymphocyte subpopulation and lymphocyte mitogenic responses exist within each risk group, homosexual subjects (both asymptomatic and with PGL) had lower mitogenic responses than would be expected for their T-lymphocyte helper/suppressor ratios as compared to either control subjects or hemophiliac patients. These findings suggest that additional factors are operative in the mononuclear cell populations of homosexual subjects that depress lymphocyte function. An analysis of these factors may help explain the higher incidence of AIDS in homosexual subjects as compared to hemophiliac patients.

Acquired Immunodeficiency Syndrome↗

Hemoglobin production in human bone marrow cultures is inhibited by lyophilized coagulation factor concentrates.

Transfusion of blood products may be followed by viral hepatitis and aplastic anemia despite improved techniques for prevention. In view of the need for intensive therapy of hemophilia with blood products, the authors investigated the capacity of these concentrates to influence cultures of human bone marrow cells. Factor VIII concentrates contained a heat-stable dialyzable substance(s) that drastically impaired 59Fe incorporation in normal human bone marrow. Factor IX concentrates had less and cryoprecipitate had no such inhibitory activity. These studies may offer information regarding the effects of various blood products on bone marrow function.

Bone Marrow↗

Coagulation factor concentrate usage and the risk of lymphadenopathy: a prospective study.

A prospective evaluation of 115 patients with hemophilia was performed between July 1982 and July 1983. During that period, 24 patients were seen with unexplained, generalized lymph node enlargement. The date lymphadenopathy occurred was recorded. No lymphadenopathy was found in 22 patients who did not receive coagulation factor concentrate. Factor usage was most closely related to the risks of lymphadenopathy (p = 0.004) even after controlling for age. A patient's age affected the risk of lymphadenopathy when the data were analyzed categorically (p = 0.008). A tendency was seen for heavily treated patients to develop lymph node enlargement earlier in the study period. Twenty-one of twenty-four (88%) patients with lymphadenopathy eventually developed HTLV-III/LAV antibodies and had abnormal T4/T8 ratios. These studies emphasize a close relationship between patients with hemophilia using coagulation factor concentrates and those with other risks for immune deficiency and lymphadenopathy. Close follow-up, optimal use of blood products, and further efforts to understand the importance of such changes are indicated in patients with hemophilia.

Adolescent↗

A longitudinal immunologic evaluation of hemophiliac patients.

Over an average span of one year, we performed a prospective clinical and immunologic evaluation of 30 patients with hemophilia. No patient developed life-threatening opportunistic infection or malignancy; however, the immunologic abnormalities and lymphadenopathy initially present in nine patients (lymphadenopathy group) persisted. In addition, five patients, representing 24% of the initial group without lymphadenopathy, developed generalized lymphadenopathy (converter group). One episode of idiopathic thrombocytopenia (ITP) and one episode of staphylococcal sepsis occurred in this "converter" group; one episode of ITP also occurred in the lymphadenopathy group. Sixteen patients remained asymptomatic. At the time of the follow-up evaluation, those differences in mononuclear cell (MNC) percentages and numbers noted initially among the three hemophiliac groups were no longer present. Natural killer cell function alone or in the presence of biologic response modifiers was not different among hemophiliac and control groups. Before developing lymphadenopathy, the converter group of patients had significantly better lymphocyte mitogenic function than did the other two groups of patients with hemophilia. However, lymphocyte mitogenic responses of all groups of patients with hemophilia significantly deteriorated over the course of the study. The abnormal mitogenic responses noted in these patients was explained in part by higher levels of spontaneous suppressor cell activity in mononuclear cell preparations from patients with hemophilia. We conclude that long-term immunologic studies of this patient population requires both quantitative and qualitative evaluations. Our data show that patients with hemophilia have progressive dysfunction of cell-mediated immunity.

Adolescent↗

Studies of lymph nodes from patients with classical hemophilia.

Within the last 18 months, we have noted the development of unexplained lymph node enlargement in otherwise asymptomatic patients with hemophilia. Because such changes are poorly understood and, in some patient groups, may be related to the acquired immunodeficiency syndrome (AIDS), we studied the enlarged lymph nodes in four patients with severe factor VIII deficiency and abnormally low peripheral blood helper-inducer/suppressor cell (OKT4/OKT8) ratios. Surgically excised lymph nodes were studied for histopathologic, electron microscopic, and chromosomal changes. Cell suspensions from these and normal nodes were also studied using monoclonal antibodies. Excised lymph nodes showed follicular hyperplasia. Electron microscopy revealed no viral particles or vesicular rosettes. Chromosomal aberrations included an acrocentric marker chromosome in one patient and monosomy 21 in another. T lymphocyte ratios (OKT4/OKT8) in lymph node suspensions were lower than those in nodes from normal controls (1.2 v 6.1) and reflected the lymphocyte ratio in peripheral blood. Mature B cell percentages were increased in the lymph nodes from patients with hemophilia (38% v 27% in controls). Patients treated with factor VIII concentrates and male homosexuals have similarities in persistent lymph node enlargement, histologic features of follicular hyperplasia, and changes in lymph node and circulating lymphocyte subpopulations.

Adult↗

Head trauma in hemophilia. A prospective study.

Intracranial hemorrhage (ICH) remains a serious problem in hemophilia. Consecutive episodes of ICH or reports of head trauma were prospectively recorded in 140 patients with hemophilia seen during a two-year period. Forty of 48 consecutive episodes of ICH or trauma occurred in 37 patients with severe disease (less than 1% factor VIII or IX). Five injured patients had inhibitors to factor VIII. Two fatalities occurred following injury and one patient died following a spontaneous bleed. Injury in 40 instances warranted replacement therapy. No patient given coagulation factor within six hours of injury experienced ICH. The risk of ICH following head trauma (13% in this series) warrants aggressive use of coagulation factor replacement. Watchfulness in dealing with such patients and early therapy may be more necessary than often realized.

Adolescent↗

Hemarthroses and warfarin: joint destruction with anticoagulation.

A 56 year old man was seen because of recurrent right shoulder hemarthroses and a superior vena caval syndrome. Intermittent symptoms had occurred for six years and resulted in marked destructive changes in the right shoulder. Arthroscopy added pathological evidence of this unusual mechanism of arthropathy. Patients on anticoagulants deserve close attention to symptoms of occult bleeding.

Chronic Disease↗

An immunologic evaluation of hemophiliac patients and their wives. Relationships to the acquired immunodeficiency syndrome.

Recently, hemophiliac patients receiving factor VIII concentrate therapy have developed the acquired immunodeficiency syndrome. Because abnormalities of cell-mediated immunity are found in this syndrome, we evaluated the peripheral blood immunologic status of 24 patients with classic hemophilia and 5 patients with factor IX deficiency. Both groups had decreased percentages and numbers of helper-inducer lymphocytes (OKT4+) and increased percentages of suppressor-cytotoxic T-lymphocytes (OKT8+) which resulted in depressed OKT4/T8 ratios. Abnormalities of the T-lymphocyte subpopulation were most severe in 7 patients with factor VIII deficiency with lymphadenopathy who also had increased Ia+ cells and profoundly suppressed lymphocyte mitogenic responses. No correlation was found between OKT4/OKT8 ratios or lymphocyte responses to mitogen and the amount of factor VIII concentrate used per year. Evaluation of five wives of factor-VIII-deficient patients who had abnormal OKT4/OKT8 ratios showed decreased percentages of OKT4 cells, but normal lymphocyte mitogenic responses. Serum levels of IgG were elevated in factor-VIII-deficient patients but not their wives or factor-IX-deficient patients. We conclude that T-lymphocyte subpopulation abnormalities and lymphocyte mitogenic responses are depressed in asymptomatic hemophiliac patients receiving either factor VIII or factor IX concentrates. These abnormalities are most severe in otherwise asymptomatic hemophiliac patients who have developed lymphadenopathy.

Acquired Immunodeficiency Syndrome↗

IgM anticoagulant with acquired abnormalities in factor VIII.

The effects of an IgM lupus anticoagulant on coagulation tests and factor VIII related antigen (FVIIR:Ag) were investigated on a 62 year old man with lymphocytic lymphoma. He experienced no abnormal bleeding despite a prothrombin time of 29 seconds, PTT 84 seconds and inhibition of multiple coagulation factors. One course of chemotherapy induced a clinical response, normalization of coagulation studies and a rapid fall in IgM from 1120 to less than 30 mg%. Studies revealed a monoclonal IgM, immediate-acting lupus anticoagulant. This IgM could not be shown to affect normal FVIIIR:Ag but the patient's FVIIIR:Ag was grossly abnormal on crossed immunoelectrophoresis with a normal and a rapidly-migrating peak. The anodal component disappeared after chemotherapy. These studies suggest that the anticoagulant was temporally related to but did not cause the abnormality in FVIIIR:Ag. Such antibodies may occasionally serve as disease markers and may point out the disparity between coagulation tests and hemostasis.

Antigens↗

Spontaneous clostridial sepsis and sudden death.

A neutropenic patient with leukemia treated successfully several times for infectious complications died suddenly after developing widespread gas formation in many tissues due to C septicum sepsis. Localized severe pain in a susceptible patient with few other signs or symptoms should alert the practitioner to the possibility of clostridial infection.

Aged↗

The measurement of human plasma antiplasmin activity by radial diffusion assay.

An assay of human antiplasmins has been developed utilizing radial diffusion of plasma from wells cut in plasmin-enriched, fibrinogen-agarose plates. After diffusion the fibrinogen is clotted. Zones of fibrin protected from background fibrinolysis develop as the result of plasma antiplasmin activity. A pooled plasma standard was taken to contain 100% antiplasmin activity. Antiplasmin activity of 52 normal subjects varied from 64 to 132%. Washed platelets contained 1-5% antiplasmin activity. Using antisera to precipitate individual inhibitors, physical methods of separation, and electrophoresis of plasma in agarose, several different proteins were found to have antiplasmin activity in this assay. Thus, alpha2-macroglobulin contributed 56%, alpha1-antitrypsin 20%, antithrombin III 2%, and other proteins 22% of the total antiplasmin activity. 1 ml of whole plasma neutralized 7.0 CTA units of plasmin.

Antithrombins↗