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Biomedical subjects

J L Ziegler

Publications and source records attributed to J L Ziegler.

At least 73 records · Page 4Linked to original sources

Clinical trial methodology.

A number of recent conferences have emphasized the importance of clinical trials methodology. The most significant of these was the one held in France in January, 1978. Much discussion centered around the use of matched historical controls from the same institution in comparison with randomized, prospectively controlled clinical trials. It was concluded that controlled clinical trials are required to answer comparative therapeutic questions in a convincing manner and that statistical advice is critical at all stages of such trials.

Clinical Trials as Topic↗

Treatment results of 54 American patients with Burkitt's lymphoma are similar to the African experience.

Burkitt's lymphoma in Africa may be curable by chemotherapy alone; in nonendemic regions results are reportedly less favorable. Fifty-four Americans with Burkitt's lymphoma were treated with two sequential combined treatment regimens that incorporated therapeutic approaches from clinical trials in Africa. Four patients died during induction therapy, and 48 of the remaining 50 achieved complete remissions. Twenty-two relapsed at a median of three months from the start of therapy. The overall two-year actuarial survival was 54 percent: younger patients ( less than 12 years old) and patients with minimal tumor burden (stages A, B and AR) had significantly better survivals than older patients (P less than 0.02) and patients with advanced abdominal tumors (stages C and D) (P less than 0.01). No differences in survival were detected between patients treated at the National Institutes of Health and those treated in regional institutions on either protocol. Complete response rates, relapse frequency and survival in American patients are similar to results in Africa.

Adolescent↗

A phase II study of adriamycin (NSC 123127) in patients with hepatocellular carcinoma from Zambia and the United States.

Nineteen Zambian and 22 American patients with hepatocellular carcinoma were treated with Adriamycin every three weeks in intravenous doses ranging from 20-75 mg/m2 (depending upon their initial serum bilirubin levels). Four of 16 (25%) "good risk" Zambian and American patients who received 75 mg/m2 had objective responses, while in five additional patients there was evidence of either transient tumor regression or disease stabilization. In contrast three of 25 "poor risk" patients who received 20-60 mg/m2 had objective responses. Even in this latter group, however, transient, objective signs of tumor regression were noted in four patients. The results of the present study confirm previous reports suggesting anti-tumor activity for high doses of Adriamycin in hepatocellular carcinoma. Since those responses seen were generally incomplete and transient, further clinical trials of this agent used in combination or sequentially with other agents are indicated.

Adult↗

Epstein-Barr virus and human malignancy.

The association of the Epstein-Barr virus and two human malignancies, Burkitt's lumphoma and nasopharyngeal carcinoma, is reviewed. Seroepidemiologic, virologic, and immunologic evidence is summarized, and several hypotheses regarding a possible etiologic role for the Epstein-Barr virus in these tumors are presented. With our current state of knowledge we cannot conclude that the Ipstein-Barr virus is oncogenic in man, nor can we yet ascertain the biological and clinical significance of its association with Burkitt's lymphoma and nasopharyngeal carcinoma.

Antibodies, Viral↗

Non-endemic Burkitt's lymphoma. A B-cell tumor related to germinal centers.

To investigate the nature of non-endemic Burkitt's lymphoma, we examined neoplastic cells from eight American patients for receptors for sheep erythrocytes (E), complement (EAC), and Fc fragment of lgG (igGEA), and for surface immunoglobulins (Slg) and hydrolytic enzymes. In addition, we reviewed 47 biopsies and 17 autopsies from American patients to ascertain patterns of involvement by tumor in lymph nodes, spleens and Peyer's patches. Neoplastic cells in all cases studies bore monoclonal surface immunoglobulins of the igM class. Receptors for EAC and igGEA were identified on a minority of the cells. Little or no hydrolytic enzyme activity was demonstrable. These results indicate that, like Burkitt's lymphoma in Africans, this histologically identical tumor in American patients consists of B lymphocytes. In 10 biopsies and two autopsies, germinal centers were selectively involved by tumor, suggesting that these neoplastic cells may be related to some B lymphocytes of normal germinal centers.

Africa↗

Detection of Epstein-Barr virus DNA in American Burkitt's lymphoma.

Twenty American patients with Burkitt's lymphoma (BL) were studied serologically and biochemically to detect an association with Epstein-Barr virus (EBV). A wide range of antibody reactivities was encountered. Five patients had serological profiles similar to those of African patients with BL: one and possibly two of these patients harbored EBV-DNA in their tumors. Fifteen patients had low or absent antibody to EBV: tumors from 10 of these patients lacked evidence of EBV-DNA. An unexplained association between elevated antibody (greater than or equal to 1:80) to EBV virus capsid antigen (VCA) and a favorable prognosis was noted in this series; this prognostic observation requires further substantiation. Thus, it appears that EBV-associated BL is inversely proportional to tumor endemicity. An etiological role for EBV in BL remains speculative.

Adolescent↗

Failure of BCG immunostimulation to affect the clinical course of Burkitt's lymphoma.

A controlled randomised trial was carried out to evaluate the efficacy of BCG immunotherapy in preventing relapse in patients with Burkitt's lymphoma in whom remission had been induced with cyclophosphamide. Twenty-one patients were treated with BCG, and 19 were controls. Eleven patients in each group relapsed during a follow-up period long enough to make it unlikely that further relapses would occur. There were no significant differences in the length of remission or the site of relapse that could be attributed to treatment. Eleven patients died: of these none of the six patients in the BCG group but all of the five in the control group had stage D lymphomas. BCG treatment increased the rate of recovery from tumour-induced immunosuppression, but within the BCG group immunocompetence improved most rapidly in the patients who relapsed-a finding that appears to contradict the tenet retionalising the use of immunological adjuvants as treatment.

Adjuvants, Immunologic↗

Combined modality treatment of American Burkitt's lymphoma.

Fifteen American patients with Burkitt's lymphoma were treated in a clinical trial employing chemotherapy, radiotherapy, and immunotherapy. Two patients died during induction, and 13 achieved complete responses. Eight patients relapsed at a median of 11 weeks from initial treatment, and seven of these have died. The remaining patient has enjoyed a prolonged third remission following intensive chemotherapy and bone marrow autograft. Five patients remain in their first remission in excess of 1 year. The major therapeutic goal in the management of Burkitt's lymphoma is the prevention of relapse; the identification of risk factors and various strategies to achieve this goal are discussed.

Adolescent↗

In vitro correlates of clinical response to methotrexate in actue leukaemia and Burkitt's lymphoma.

The response of drug-resistant patients with acute leukaemia and Burkitt's lymphoma to treatment with a 24 h infusion of methotrexate (MTX) followed, in some cases,by cytosine arabinoside was correlated with in vitro measurements of total intracellular MTX, exchangeable intracellular MTX, and suppressibility of deoxyuridine (UdR) incorporation in isolated marrow blast cells at extracellular MTX concentrations of 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M. Total intracellular MTX levels and exchangeable intracellular MTX levels were not significantly different in responding or non-responding patients at any MTX concentration, but increased four-fold for every ten-fold concentration increment studied. Extracellular MTX levels in excess of 10(-7)M appeared necessary to allow accumulation of exchangeable intracellular MTX. UdR incorporation at 10(-6)M and 10(-5)M differed significantly between responding and non-responding patients, with responders having less than 20% of control values and non-responders having greater than 40% of control values. Further, increasing the extracellular MTX concentration from 10(-6)M to 10(-5)M produced no significant decrease in UdR incorporation in either group. The therapeutic implications of this apparent threshold are discussed.

Adolescent↗

Childhood Kaposi's sarcoma: clinical features and therapy.

Twelve cases of childhood Kaposi's sarcoma seen at the Uganda Cancer Institute over the last 7 years are reported. The disease presents mainly as generalized lymphadenopathy, with sparsely and anomalously distributed cutaneous nodules, and has a higher proportion of females with the disease than in the adult form. The histology is usually of mixed cell type. If not treated, childhood Kaposi's sarcoma runs a fulminating course, but disease control with chemotherapy is associated with prolonged survival.

Adolescent↗

Spontaneous remission in Burkitt's lymphoma.

Three cases of spontaneous regression of Burkitt's lymphoma are reviewed and additional clinical and laboratory observations relevant to the role of host defenses are summarized. Spontaneous regression of Burkitt's lymphoma provides compelling evidence for antitumor immunity.

Adult↗

Management of Burkitt's lymphoma involving the central nervous system.

The clinical features and pathogenesis of CNS involvement in Burkitt's lymphoma have been reviewed, with an emphasis on the relevant therapeutic approaches. Certain "prophylactic" measures have been suggested and several are currently undergoing clinical trial. These include the use of CCNU, a nitrosourea which effectively crosses the blood-brain barrier, and the use of craniospinal irradiation early in the course of treatment. Malignant pleocytosis can be palliated by the use of intrathecal chemotherapy, but malignant cells in peripheral nerves or deep in the sulci of the brain parenchyma will be relatively inaccessible to drugs in the circulating cerebrospinal fluid (CSF). A bilateral approach (i.e. simultaneous systemic plus intrathecal chemotherapy) may kill cells lodged in this anatomic sanctuary, and the increased use of cytotoxic drugs crossing the blood-brain barrier may facilitate this approach.

Antineoplastic Agents↗