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Biomedical subjects

J Ziegler

Publications and source records attributed to J Ziegler.

At least 127 records · Page 7Linked to original sources

Brain metastases from ovarian cancer.

Brain metastasis from ovarian carcinoma is a relatively rare phenomenon. At NYU Medical Center five patients were treated for this entity from 1982 to 1985. The stage at presentation ranged from stage I to stage III, and all patients had received or were receiving chemotherapy. Two patients had active disease elsewhere at diagnosis of brain metastasis, but three patients were otherwise NED. Three patients had solitary cerebellar disease, and two patients had multiple lesions. All patients were treated with whole brain radiotherapy to 3,000 cGy, with neurological improvement in three of the five patients. The central nervous system may need special consideration for prophylactic treatment in those patients with ovarian cancer who receive adjuvant chemotherapy.

Adenocarcinoma↗

Leukocyte migration inhibitory factor (LIF) to sperm from autoimmune men in infertile couples.

Leukocyte migration inhibitory factor (LIF) is produced by lymphocytes with receptors specific to sensitizing antigens. This principle was used to detect possible antigenic differences between sperm of autoimmune and nonautoimmune men. Sixteen fertile and 91 infertile couples were screened for cytotoxic and hemagglutinating antibodies to sperm from their husbands and controls. Their lymphocytes were tested for the production of LIF to sperm extracts and seminal plasma from the husbands and controls by a direct leukocyte migration inhibition assay. Twenty-nine of 35 men producing LIF to sperm and/or seminal plasma were positive for sperm antibodies (p = 0.0004, vs sperm antibody-negative controls). Twenty-three of 29 wives with LIF production had sperm-autoimmune husbands (p = 0.04). Leukocyte migration was significantly inhibited in sperm-autoimmune men by autologous sperm extracts and seminal plasma in contrast to control sperm extracts and seminal plasma (p = 0.0006 and 0.001, respectively). The wives of autoimmune men had significantly higher LIF responses to their husbands' sperm extracts than to other antigens (p = 0.02). Men with cytotoxic antibodies in their seminal plasma produced LIF to autologous sperm (p = 0.001). It is suggested that certain sperm and seminal plasma antigens of autoimmune men may lead to specific humoral and cell-mediated immune responses in both partners.

Antilymphocyte Serum↗

A computerized sperm motion analysis [published erraturm appears in Fertil Steril 1986 Nov;46(5):980].

Semen samples from 35 fertile men and husbands of 32 infertile couples were evaluated with the use of a rapid computerized sperm motion analysis (CSA). The counts and percentages of motile sperm measured by routine semen analysis (RSA) and CSA were comparable in both groups. In CSA, mean values of swimming speed (microns per second), linearity, and motility index of sperm in the fertile men were significantly higher than those in the infertile group. At 3 hours, the number of sperm moving at a speed of 21 to 30 microns/second were higher in the infertile group than in the fertile group. In contrast, the number of sperm moving at a speed of 31 to 50 microns/second and higher was increased in the fertile group over the infertile group. Good correlations were obtained between RSA and CSA sperm counts and percentages of progressively motile sperm. Sperm counts, percent motility, indices of motility, and mean sperm speed obtained by two observers with the use of CSA correlated well. It seems that the sperm speed and the motility index remain unaltered in repeat semen analyses of fertile men. It is concluded that a computerized analysis of sperm swimming speed is a reliable and rapid mode for evaluating semen samples and offers more discriminatory sperm motion characteristics than the RSA.

Computers↗

Bone marrow transplantation for malignant histiocytosis in childhood.

This report describes a girl who was diagnosed with malignant histiocytosis at the age of 5 years. The disease was controlled initially with chemotherapy for 3 years and had then recurred with meningeal involvement on three occasions. Four years and 8 months from diagnosis, bone marrow transplantation (BMT) was undertaken from an HLA-identical and mixed lymphocyte culture (MLC) nonreactive brother after conditioning with VP-16-213 5 mg/kg/day X 2, cyclophosphamide 60 mg/kg/day X 2, and total body irradiation 200 rad twice daily to a total dose of 1000 rad delivered at 7 rad/minute. At the time of transplant, the disease was in remission. Currently, more than 48 months after the transplant, the child remains free of disease, with a normally functioning donor marrow and with no evidence of graft versus host disease. This is the first recorded case of BMT in the treatment of malignant histiocytosis. The outcome in this patient in late-stage disease suggests that BMT could be considered early in management as definitive therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Incidence of the acquired immunodeficiency syndrome in San Francisco, 1980-1983.

Incidence data for the acquired immunodeficiency syndrome (AIDS) are presented on the basis of a surveillance file maintained by the San Francisco Bureau of Communicable Disease Control. The incidence of AIDS among residents of San Francisco rose steadily from the first case diagnosed in the last quarter of 1980 through the last quarter of 1983. New cases were diagnosed at a rate of 25 per month in the last quarter of 1983. Reported incidence declined in mid-1983, but the decline was probably a case-finding artifact. Smoothed incidence rates show a steady progressive rise, which is approximated equally well by quadratic or exponential curves. Among the patients diagnosed in San Francisco, 99% were homosexual or bisexual men. The cumulative incidence rate among homosexual or bisexual men was estimated to be 770 per 100,000 in the last quarter of 1983. The incidence rate of AIDS increased with age, and the increase was greater than that found with other sexually transmitted diseases. The difference in the age distributions between cases of AIDS and syphilis suggests either that susceptibility to AIDS increases with age or that the average latency associated with AIDS is longer than previously thought.

Acquired Immunodeficiency Syndrome↗

Vinblastine therapy for Kaposi's sarcoma in the acquired immunodeficiency syndrome.

Single-agent intravenous vinblastine, 4 to 8 mg/week, was used to treat 38 patients with Kaposi's sarcoma related to the acquired immunodeficiency syndrome. The dose was titrated in relation to the total leukocyte count. Ten patients had an objective response, and 19 had stable disease during therapy. Apart from expected modest neutropenia, toxicity was minimal. A lower response rate was seen in patients with anemia, an elevated erythrocyte sedimentation rate, or any lymphoma-like B symptom. Opportunistic infections were common regardless of type of response but were commoner in patients who did not respond. Vinblastine used in low doses weekly is effective in treating Kaposi's sarcoma related to the acquired immunodeficiency syndrome and has minimal associated toxicities.

Acquired Immunodeficiency Syndrome↗

B-cell immunodeficiency in acquired immune deficiency syndrome.

To investigate B-cell function in acquired immune deficiency syndrome (AIDS), we immunized a group of patients with AIDS with pneumococcal polysaccharide (tetradecavalent) and protein (keyhole-limpet hemocyanin) antigens. Antibody responses were determined three to four weeks after immunization. Compared with controls, patients with AIDS had significantly lower geometric mean antibody levels to polysaccharide before and after immunization. Levels before and after immunization were frequently below a level thought to correlate with protection. Patients with AIDS also had a significant reduction in their primary antibody response to the protein antigens. The results of these studies indicate that AIDS is associated with an acquired B-cell as well as T-cell immunodeficiency. It is suggested that future studies should consider the evaluation of passive antibody in the prevention of infection and/or prevention of progressive immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Antagonism between epidermal growth factor and phorbol ester tumor promoters in human breast cancer cells.

It has been suggested that the phorbol ester tumor promoters act via the receptor-effector system for epidermal growth factor (EGF), since they interact with the EGF receptor system and mimic many of the effects of EGF in cultured cells. We have studied the interaction of phorbol esters with the EGF-responsive MCF-7 human breast cancer cell line. Similar to other systems, phorbol esters inhibit EGF binding in MCF-7 cells in a manner paralleling their potency as tumor promoters in mice. The effect is specific for EGF since the membrane binding of insulin is unaffected. Like EGF, the potent phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) stimulates protein synthesis as indicated by a twofold increase in [(3)H]leucine incorporation into protein after 24 h in TPA. Cell morphology, however, is significantly different with TPA treatment. After 24-48 h in TPA, cells become markedly enlarged with increased cytoplasmic vacuolization and increased membrane microvilli. This is reflected in a fourfold increase in the protein/DNA ratio (control 13.1; TPA 55.9). Furthermore, TPA inhibits cell division in media with or without serum, and prevents growth stimulation by EGF. Low TPA concentrations (1.0 ng/ml) are active, and 10 ng/ml results in maximal inhibition of cell replication. Other phorbol esters inhibit MCF-7 cells relative to their tumor promoting activity in vivo and their ability to inhibit EGF binding in these cells. After 24 h in TPA, incorporation of [(3)H]thymidine into DNA is markedly reduced and the thymidine labeling index falls (33% to 2%) indicating very few S-phase cells. Growth inhibition is reversible by removing TPA from the medium. Similar inhibitory effects are seen with the two other human breast cancer cell lines studied, ZR75-1 and MDA-MB-231. In conclusion, phorbol esters may interact with the EGF receptor domain in MCF-7 human breast cancer cells, but they have distinct effects on cell morphology and growth suggesting alternative pathways of action. The antineoplastic activity of these compounds needs further investigation.

Breast Neoplasms↗

NIH conference. A multidisciplinary approach to non-hodgkin's lymphomas.

Epidemiologic studies show that non-Hodgkin's lymphomas tend to develop after prolonged antigenic stimulation, after loss of normal regulation of lymphoid proliferation, or especially after both processes. Study of these tumors in vitro has greatly increased understanding of their pathophysiology and has provided a conceptual framework for their morphologic diversity. Lymphomas are now understood to be expanded clones of their normal counterparts. The anatomic location, phenotypic characteristics, proliferative capacity, and functional capabilities of the neoplasm often reflect those of the equivalent normal cells. If neoplastic transformation can occur at any stage of lymphoid differentiation, then it is theoretically possible that neoplastic lymphocytes may respond, or could be induced, to normal regulatory influences. Further study of selective cytotoxicity may reveal exploitable differences among lymphocytic subpopulations and permit more rational choices of therapy. Of major aid to future clinical trials should be the recent consensus on nomenclature by an international panel of experts.

Adolescent↗

Cardiotoxicity associated with high-dose cyclophosphamide therapy.

The cardiac effects of chemotherapeutic regimens using high doses of cyclophosphamide (180 mg/kg over four days) were assessed in 32 patients with hematologic malignant neoplasms. Left ventricular systolic function, determined by the fractional shortening on echocardiogram, declined substantially five to 16 days after the initiation of cyclophosphamide therapy. Although pericardial effusion on echocardiogram occurred in 33% of the patients studied, ECG voltage decreased five to 14 days after beginning cyclophosphamide therapy even in those patients without pericardial effusion. Congestive heart failure was noted in nine patients (28%) within three weeks of cyclophosphamide administration. Six of these patients (19%) died of myocardial failure. Pericardial tamponade occurred in six patients (19%), including five who died of myocardial failure. Histopathologic and electron microscopic findings showed endothelial injury and a hemorrhagic myopericarditis. Cyclophosphamide in this high dose is associated with a toxic, often fatal, pericardiomyopathy. Depression of ECG voltage and systolic left ventricular function, though common, do not necessarily predict clinical cardiac deterioration.

Adolescent↗

Prognostic factors in Burkitt's lymphoma: importance of total tumor burden.

In 42 patients with African Burkitt's lymphoma, we have studied biochemical and clinical correlations with prognosis. Clinical stage and anti-EA titer were the best predictive factors, but lactic dehydrogenase (LDH) and uric acid (UA) concentrations also correlated with stage and prognosis, whereas lactic acid (LA), which was significantly elevated in Stage D, did not significantly correlated with prognosis or with LDH and UA levels. All of these factors with the possible exception of LA reflect the total body burden of tumor. We conclude that the tumor burden is the single most important prognostic factor in Burkitt's lymphoma, and that this is reflected directly by LDH and UA concentrations, and probably indirectly by anti-EA titer.

Adolescent↗

Comments on the carcinogenic, mutagenic, and teratogenic properties of anticancer drugs.

Relevance of the carcinogenic effects of anticancer agents has arisen in the context of three circumstances: (a) when patients who have a favorable outlook without treatment receive chemotherapy, (b) when several alternate therapies with varying carcinogenic potential are available, and (c) when considering the introduction of a new drug into clinical investigation and/or clinical practice. Teratogenic effects require special attention when dealing with women in their reproductive years. Techniques to evaluate the mutagenic effects have opened up new areas of research and will be increasingly applied to the study of anticancer drugs.

Antineoplastic Agents↗

Long-term sequelae of cancer chemotherapy.

Long-term sequelae of therapy of neoplastic disease have become an important topic, since many patients exposed to anticancer drugs will have prolonged survival. The advances which have been made in the treatment of pediatric malignancies, in fact, give particular relevance to a study of these complications. Moreover, clues as to the mechanism of action and molecular pharmacology of these agents may emerge from such studies. Herein we review both the specific organ dysfunction and the generalized effects which may become apparent as late consequences of chemotherapy.

Antineoplastic Agents↗