Salman Gailani

Human chorionic gonadotrophins (hCG) in nontrophoblastic neoplasms. Assessment of abnormalities of hCG and CEA in bronchogenic and digestive neoplasms

Evaluation of plasma hCG measurement in the diagnosis of nontrophoblastic neoplasms and assessment of the value of concomitant measurement of plasma hCG and CEA in patients with bronchogenic carcinoma and neoplasms of the digestive tract were undertaken. Only one of 70 normal control subjects had positive plasma hCG (3.5 ng/ml), whereas 54 of 320 patients with nontrophoblastic neoplasms had measurable plasma hCG (1.9 to 160 ng/ml). Forty of these patients had less than 5.1 ng/ml, 10 had 5.1 to 10 ng/ml, and only three had high levels of 96, 110, and 160 ng/ml. Elevated plasma CEA levels of 3.6 to 140 ng/ml were found in 38 of the 70 patients with bronchogenic carcinoma and 30 of the 72 patients with neoplasms of the digestive tract in this series. Concomitant positive hCG was found in only six of the 68 patients who had elevated CEA levels, and positive hCG was found in eight of 74 patients who had normal plasma CEA. The low frequency and the modest elevation of plasma hCG, despite frequent advanced disease, indicate plasma hCG has limited value as a biologic marker for diagnosis and assessment of nontrophoblastic neoplasms.

Comparison of the combination of 1, 3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and vincristine with two dose schedules of 5-(3,3-dimethyl-l-triazino) imidazole 4-carboxamide (DTIC) in the treatment of disseminated malignant melanoma

One hundred twenty patients with inoperable metastatic malignant melanoma were randomly allocated to treatment with either a combination of BCNU 150 mg/m2 and vincristine 2 mg/m2 given every 30 days, or one of two regimens of DTIC: 300 mg/m2/day × 6 or 100 mg/m2/8 hours × 18 given every 30 days. Eight of the 51 (16%) patients who were originally treated with the BCNU and vincristine combination had 50% or more objective tumor regression, compared to 6 out of 25 (24%) patients treated with daily injections of DTIC, and 6 out of 21 (29%) patients treated with DTIC injections every 8 hours. The median duration of response to the BCNU and vincristine combination was 60 days, and the median duration of survival from initiation of treatment was 6.5 months in the responders and 3.3 months in the nonresponders. The median duration of response was 90 and 100 days for the daily and 8‐hour regimens of DTIC respectively, and the median duration of survival from commencement of treatment was 8.5 months for the responders and 3.5 months for the nonresponders. None of the 43 patients who failed to respond to the initial treatment program or whose disease progressed after initial improvement responded to the alternate treatment regimen.

Diabetes in patients treated with asparaginase.

In 5 patients treated with L‐asparaginase, plasma insulin response to intravenous glucose injection was measured by radioimmunoassay. Two of the patients developed a diabetic state (2 and 4 days) after a single dose of L‐asparaginase, while a third patient developed diabetes 2 days after the fourth dose of L‐asparaginase. Plasma insulin was not detectable by radioimmunoassay during the diabetic state in each of them. The normal pattern of insulin response returned completely in one of the 3 patients within 23 days, whereas suboptimal response persisted for 2 weeks and 9 months in the remaining 2 patients. The two remaining patients were studied prior to and 6 days after a single dose of L‐asparaginase; neither developed a diabetic state.

Plasma cell neoplasm involving the thyroid.

Involvement of the thyroid gland by plasma cell neoplasms is very rare. On review of 248 cases, we found 4 cases in which pathological evidence of plasms cell neoplasm in the thyroid was verified. This was a heterogeneous group of patients; the thyroid involvement was clinically recognized as a site of extramedullary plasma cell neoplasm in one patient and as a part of generalized disease in two patients. In another patient with generalized disease, the thyroid involvement was discovered at autopsy.

Treatment of metastatic Ewing's sarcoma with BCNU

Twelve patients with metastatic Ewings sarcoma, ranging in age from 4 to 26 years, were treated with 1‐3‐bis chloroethyl nitrosourea (BCNU). The tumor in five of the patients showed objective tumor shrinkage with BCNU. In one patient, there was complete disappearance of the tumor lasting 21/2 years. In four other patients, there was partial improvement (50% shrinkage) lasting 2, 3, 6, and 8 months. BCNU may be of value in an adjuvant chemotherapy program as part of the initial treatment in an attempt to eradicate subclinical micrometastasis and thus increase the cure rate.

Studies on Hormone Production by Human Fetal Pituitary Cell Cultures

Summary Growth hormone (HGH) elaboration in culture media of 16 human fetal anterior pituitary cell cultures was studied using the rocker incubator system. HGH was measured by radioimmunoassay technique. HGH was demonstrated in all culture media from human fetal pituitaries but no such activity could be demonstrated from media obtained from other tissue cultures. There was a general correlation between the age of the fetus and the amount of HGH elaborated. In each of the cultures established, the daily elaboration of HGH was reduced after a period of time ranging from 1 to 4 weeks. The biologic activity of the hormone was confirmed in one sample by bioassay. Generally, there appeared to be no correlation between the rate of cellular growth, morphologic appearance, and level of hormone elaboration. The growth appeared to be rapid initially and then to reach a plateau. Luteinizing hormone and thyrotropic hormone were tested for and were found in the culture media of one pituitary.

Clinical and biochemical studies of pyridoxine deficiency in patients with neoplastic diseases.

Seventeen patients with advanced neoplastic diseases were fed a formula diet deficient in vitamin B6 for 10 to 80 days. In addition, nine of the patients received the B6 antagonist, 4‐deoxypyridoxine (4‐DOP), for periods ranging from 6 to 46 days. No definite antitumor effect could be observed in any of the patients studied despite ample biochemical and clinical evidence of vitamin B6 depletion. The study confirmed previous reported experiences in man and many other animal species that 4‐DOP accentuates some of the manifestations of vitamin‐B6 deficiency, particularly neurologic and dermatologic side effects. The lymphopenic effect of 4‐DOP was demonstrated only in patients with normal bone marrow. In three of four patients with lymphoproliferative disease the peripheral lymphocyte count rose coincidentally with 4‐DOP administration while in the fourth the rise developed immediately after discontinuation of 4‐DOP and at the peak of toxicity. The study showed evidence of progressive tissue depletion when the patient was fed the deficient diet alone. Addition of 4‐DOP to the deficient diet led to the transient reappearance of measurable pyridoxal phosphate in leukocytes and pyridoxic acid in the urine. This and the slight increase in reticulocyte counts during administration of 4‐DOP raise the possibility that vitamin B6 was mobilized from certain tissue depots by the 4‐DOP and was thus available for oxidation to pyridoxic acid and for use by the less depressed of the enzymes dependent upon vitamin B6.

Pyridoxal phosphate determination in isolated leucocytes and tissue by E. coli apotryptophanase

A reproducible enzymic method for determination of PLP in isolated leucocytes and tissue using E. coli apotryptophanase is described. PLP extraction was achieved by heating at pH 4. Heating at lower pH values gives lower results, most probably due to dephosphorylation of PLP. PLP levels in human isolated leucocytes and liver obtained by needle biopsy, and the effect of vitamin B6 depletion and repletion on liver PLP levels, are reported.

Studies on normal human bone marrow cultures in controlled environment thin-film culture systems

SummaryTwo thin film culture systems, the controlled environment steady state system (SS) and the rocker tube configuration of that system (RT), were used to identify some of the conditions that appear to maintain morphologic and functional characteristics of cells of human bone marrow explants in vitro. The systems configuration assured continual gassing, control and easy monitoring of the cultures. Cytocentrifuge preparations of media of specimens cultured in RT disclosed, though in decreasing numbers, various hematopoietic cells for periods exceeding one month. Hematopoietic cells shed from specimens cultured in the SS system were retained in the culture tubes; cells of the myelocytic series predominated for the first 2 weeks while an increasing number of monocytes and macrophages appeared in the media of older cultures. Histologic examination of cultured explants disclosed preservation of the marrow architecture and the persistence of hematopoietic cells. Specimens cultured in RT tubes tended to be less cellular than similar cultures placed in dialysis bags or as cultured in the SS system. Immunoglobulins (Ig) were released into the culture media at a constant rate throughout the period of culture. Specimens that were cultured at a controlled pH of 7.4 released 2 to more than 4 times as much Ig as similar specimens maintained at a pH level of 7.1. There were no definitive differences in Ig levels in the cultures maintained at comparable pH levels and overlaid with various CO2 concentrations, i.e. 2%, 5%, 10%; similarly, no differences in Ig levels were found in specimens cultured in media containing fetal bovine sera as opposed to horse sera.

Isolation and characterization of 7S IgG, a γ-fragment, β2-microglobulin and a Bence Jones protein in urine of a patient with plasma cell leukemia☆

Abstract Large quantities of a monoclonal 7S IgGκ, a κ type Bence Jones protein, and β 2 -microglobulin along with a smaller amoung of a γ-fragemnt were found in the urine of a patient, TSCH, with plasma cell leukemia. The serum of this patinet also contained a monoclonal 7S IgGκ. Comparison of the isolated urinary IgG and the serum IgG disclosed no significant differences between the two proteins with respect to amino acid composition, amino-terminal amino acid sequence, amino sugar composition, sodium dodecyl sulfate acrylamide gel elecgtrophoresis, ultracentrifugation and antigenicity. Both IgG proteins were intact 7S molecules with a γ chain of γl subclass and with a κ chain of VκIII subgroup. A double immunodiffusion study showed that teh γ-fragment represents a portion of the Fc fragment. This γ-fragment was previously shown to be noncovalently bound to β 2 -microglobulin (Seon & Pressman, 1977). A relatively simple procedure was successfully used to isolate a large amoung of β 2 -microglobulin from the urine of the patient.