Biomedical subjects

H T Thaler

Publications and source records attributed to H T Thaler.

At least 91 records · Page 5Linked to original sources

PubMed1984

NHL-3 protocol. Six-drug combination chemotherapy for non-Hodgkin's lymphoma.

Combination chemotherapy and radiotherapy (RT) were administered to 73 adults with non-Hodgkin's lymphoma (NHL). Ten cycles of the following drugs were given: intravenous Adriamycin (doxorubicin) (25 mg/m2), cyclophosphamide (700 mg/m2) and vincristine (1.5 mg/m2) on day 1; arabinosylcytosine (100 mg/m2) and methotrexate (10 mg/m2) on days 3 to 5; and oral prednisone (60 mg/m2) on days 1 to 5. Radiotherapy was given to resistant or initially bulky disease (2000 rad). Patients were also randomized to receive pseudomonas vaccine or no immunotherapy. Of 61 evaluable patients, 33 (54%) achieved a complete response (CR) and 18 (30%) a partial response (PR). Among 44 evaluable patients with diffuse histiocytic lymphoma (DHL), 22 (50%) had a CR, and 15 (34%) a PR. For 17 evaluable patients with nodular (4) and diffuse (11) mixed and poorly differentiated lymphocytic and diffuse "undifferentiated" (2) lymphomas, CR and PR rates were 65% and 18%, respectively. No statistically significant differences in response rate or duration and survival have been observed between the patients randomized to receive pseudomonas vaccine or no immunotherapy. Median follow-up time from start of treatment was 47.5 months. Median survival for all 73 patients (including inevaluables ) and for 52 DHL patients was 30.7 months. Poor prognostic features influencing survival included: female sex (P = 0.003), poor response to therapy (CR versus PR; P = 0.001), prior chemotherapy, (P = 0.01) and high levels of lactic dehydrogenase (P = 0.001). It can be concluded that this combination of cycle and phase-active agents is of similar efficacy to other reported regimens in inducing major responses and that it has the potential to prolong disease-free survival. The analysis of prognostic factors has been used to dissect poor prognostic categories that might require different modalities of treatment.

Adult↗

PubMed1984

Metronidazole in the treatment of metastatic brain tumors. Results of a controlled clinical trial.

We measured the effect of the radiation enhancer metronidazole on patients with metastatic brain tumors undergoing radiation therapy (RT) in a randomized controlled study. Metronidazole was given in a dose of 6 g/m2 4 hr before each of the first 3 doses of RT to the whole-brain. A total of 3000 rad was delivered in 6 doses. Patients were followed by serial neurological examinations and CT scans. The metronidazole group did not differ from the control group when measured in terms of survival, clinical improvement or improvement on CT scan, whether measured 2 months or 6 months following treatment. Nausea and vomiting was a significant side effect, preventing about 10% of patients from completing the treatment. Metronidazole appears to have no substantial radiation enhancing effect on metastatic brain tumors.

Anticonvulsants↗

PubMed1984

Prostaglandins in carcinomas of the head and neck.

Abnormalities of 5 cyclooxygenase products were studied in tumours from patients with head and neck cancer. The studies were designed to measure tissue prostaglandin content (ng/g wet tissue) as well as production in vitro by tumour microsomes (ng/mg protein/10 min). Head and neck tumours contained large amounts of 5 eicosanoids in the order. PGE2 greater than PGE1 greater than 6-keto-PGF1 alpha greater than PGF2 alpha greater than TXB2. When tumours less than or equal to 2 cm were compared with tumours equal to or more than 3 cm in size, amounts of all but PGF2 alpha were higher in the larger tumours. However, the capacity of tumour microsomes to synthesize PGs in vitro was inversely related to tumour size. These results suggest a defect in removal of eicosanoids from large tumours. The physiological significance of this increase in local levels of eicosanoids remains to be determined in head and neck cancer.

6-Ketoprostaglandin F1 alpha↗

PubMed1984

Effects of nutrition on disease and life span. I. Immune responses, cardiovascular pathology, and life span in MRL mice.

Mice of the autoimmune, lymphoproliferative strain MRL/lpr and the congenic, nonlymphoproliferative strain MRL/n were fed one of six diets from weaning on-ward. These mice were sacrificed at 3 or 5 months of age. Low fat diets resulted in lower cholesterol and higher triglyceride levels than did cholesterol-containing high-fat diets. Caloric restriction of MRL/lpr mice was associated with an increased plaque-forming cell response to trinitrophenylated polyacrylamide beads, less lymphoproliferation, and less severe glomerulonephritis. Diet did not affect the incidence of autoimmune vasculitis in MRL/lpr mice sacrificed at 5 months. MRL/lpr mice fed a low-fat, calorically restricted diet from 5 months of age to death lived longer than mice which were fed ad libitum a cholesterol-containing, high-fat diet. At death, MRL/lpr mice fed the former diet had the autoimmune vasculitis which had been evident in mice killed at 5 months, whereas mice fed the latter diet, in addition to the vasculitis, had a high incidence of atherosclerotic lesions of intrarenal and aortic branch arteries.

Animal Nutritional Physiological Phenomena↗

PubMed1984

Effects of nutrition of disease and life span. II. Vascular disease, serum cholesterol, serum thromboxane, and heart-produced prostacyclin in MRL mice.

Mice of the autoimmune strain MRL/1, the congenic strain MRL/n, and two control strains, Balb/c and C57BL/6 mice, were fed diets which varied in the content of lipid and cholesterol. Serum cholesterol levels were highest in mice fed diets containing cholesterol and lowest in mice fed laboratory "chow." Animals fed diets that increased serum cholesterol had decreased production of prostacyclin by vascular tissue and increased production of thromboxane A2 by platelets. Prostacyclin production by heart tissue in response to arachidonic acid showed a negative correlation (r = -0.86) with serum cholesterol. In contrast, serum thromboxane demonstrated a positive correlation (r = 0.70) with serum cholesterol. The prevalence of autoimmune vasculitis seen in MRL/lpr mice was not affected by diet. However, MRL/lpr mice fed a high-fat, cholesterol-containing diet had intimal vascular lesions containing foam cells typical of arteriosclerosis. It is suggested that diets that raise serum cholesterol may influence the nature of autoimmune-mediated vascular disease by altering the balance between thromboxane and prostacyclin.

Animal Nutritional Physiological Phenomena↗

PubMed1984

On the apparent clustering of clonal albumin production and enzyme activity levels.

This communication is a critique of a novel, but inappropriate, use of the correlation coefficient to demonstrate the clustering of biological activity levels about a purported geometric progression. The data are re-examined by using a Fourier analysis approach to test for periodicity on a logarithmic scale; this approach follows from the methods of Kendall (1974, Philosophical Transactions of the Royal Society, Series A 276, 231-266) and Fisher (1929, Proceedings of the Royal Statistical Society, Series A 125, 54-59).

Albumins↗

PubMed1984

Prostaglandins in cells of the lymphoid system in AKR leukemia.

AKR mice develop spontaneous lymphoid leukemia late (8 to 12 months) in life, although persistent murine leukemia virus production occurs throughout their life. This suggests that age-related changes are involved in development of leukemia. Prostaglandin biosynthesis was therefore studied in 24-hr cultures in vitro at 37 degrees of peritoneal macrophages, splenocytes, thymocytes, bone marrow, and lymph node cells. AKR mice of 2, 6, and 8 to 12 months of age were studied. Prostaglandin E1, prostaglandin E2, prostaglandin F2 alpha, 6-ketoprostaglandin F1 alpha, and thromboxane B2 were measured. In cultures of peritoneal macrophages and cells from spleen, thymus, and lymph nodes, the biosynthesis of all five prostaglandin moieties was higher in those cultures prepared from 8- to 12-month-old spontaneously leukemic mice in comparison with those from 2-month-old nonleukemic AKR mice. However, when leukemia was transplanted in 3-month-old AKR mice, synthesis of all five compounds was reduced significantly in cultures of peritoneal macrophages and splenocytes prepared from these 3-month-old leukemic mice. The present data demonstrate abnormalities in prostaglandin synthesis by various cells of the immune system in leukemic mice. However, the nature of these changes was different in cultures of cells from spontaneously leukemic mice from those with transplanted leukemia. Age-related increases in prostaglandin synthesis by various lymphoid cells from spontaneously leukemic AKR mice (8 to 12 months old) occurred at a much earlier age than in BALB/c mice and may be related to the leukemic condition.

Animals↗

PubMed1984

Accuracy of stable xenon/CT measurements of regional cerebral blood flow: effect of extrapolated estimates of brain-blood partition coefficients.

Stable xenon/computed tomographic (Xe/CT) measurements of regional brain-blood partition coefficients for xenon (lambda) and of regional cerebral blood flow (rCBF) have been reported for animal models of stroke and for patients with a variety of neurological diseases. We estimated the uncertainty in reported measurements of lambda and rCBF using computer simulations based on Kety's blood flow equation. Anesthetized baboons were scanned repeatedly for 30-60 min while inhaling an 80:20% xenon-oxygen mixture, and the resulting CT enhancement values for user-defined regions of interest were used to define a mathematical function with which to fit simulated CT enhancement data. In computer simulation studies, extrapolated and fit values of lambda for the same dataset were used to calculate rCBF, and the calculated flow values were compared. Computer simulations for heterogeneous (gray-white matter) regions indicate that better estimates of flow are obtained by fitting lambda than by using extrapolated values of lambda to calculate flow, although, paradoxically, better estimates of lambda are obtained by extrapolation than by fitting lambda.

Animals↗

PubMed1983

The non-Hodgkin's lymphomas. I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969.

A retrospective clinical and histopathological review was made of 499 previously untreated cases of non-Hodgkin's lymphoma with adequate initial biopsy material diagnosed at Memorial Hospital between 1958 and 1969. Three hundred-eighty-four cases (77%) had diffuse, 104 (21%) nodular, nine (2%) nodular and diffuse, and two (less than 1%) unclassifiable histologic types. Overall median survival was 16 months, and 79% of the patients died with lymphoma. For all treatments, survival of responding patients was the same as that of nonresponders, a reflection of the palliative approach. Significant differences in survival were found between patients in the various Ann Arbor stages. Median survival was 42 months for the nodular group and 11.5 months for the diffuse (P less than 0.001). The ten-year survival was 12% for the diffuse and 22% for the nodular patients. The overall difference in survival was due to early deaths in the diffuse group. Long-term follow-up is necessary to appreciate the usual fatal course of patients with all types of non-Hodgkin's lymphomas treated conservatively.

Adolescent↗

PubMed1983

Prostaglandin concentrations and prostaglandin synthetase activity in N-nitrosomethylurea-induced rat mammary adenocarcinoma.

A comparison of tissue concentrations and biosynthesis of prostaglandin (PG)E2, PGF2 alpha, 6-keto-PGF1 alpha (degradation production of PGI2) and thromboxane (TX)B2 (degradation product of TXA2) was made in normal mammary glands obtained from virgin female Sprague-Dawley rats and in N-nitrosomethylurea (NMU)-induced mammary adenocarcinomas. The tissue concentrations (ng/g wet weight) of all 4 compounds were significantly higher in the NMU-induced tumor than in normal mammary tissue: PGE2, 210 +/- 37 vs 25 +/- 6; PGF2 alpha, 287 +/- 48 vs 23 +/- 8; 6-keto-PGF1 alpha, 294 +/- 42 vs 31 +/- 8; and TXB2, 260 +/- 49 vs 27 +/- 5 (mean +/- S.E.M.). Microsomal prostaglandin synthetase activity in NMU-induced tumors was also significantly higher than in normal tissue for all but 6-keto-PGF1 alpha: PGE2, 226 +/- 16 vs 50 +/- 9; PGF2 alpha, 28 +/- 3 vs 4 +/- 1; 6-keto-PGF1 alpha, 14 +/- 2 vs 11 +/- 2; and TXB2, 17 +/- 1 vs 10 +/- 1 ng/mg protein (mean +/- S.E.M.). There was no apparent relationship between either tumor size or age and the ability of microsomal enzyme to synthesize prostaglandins, although the content of prostaglandins extracted from tumor tissue was inversely related to the tumor size.

6-Ketoprostaglandin F1 alpha↗

PubMed1983

Prostaglandins in breast cancer: relationship to disease stage and hormone status.

Tissue prostaglandin (PG) content and production by human breast cancers were measured in 24 human mammary carcinoma specimens. The 5 compounds studied were PGE1, PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TXB2. The tissue content of all 5 compounds was higher in neoplastic tissue in comparison with the paired noncancerous breast tissue. However, microsomal PG synthetase activity in vitro in noncancerous and neoplastic breast tissue was comparable. Increased thromboxane formation was associated with three clinical variables--tumour size, axillary lymph node metastases and distant metastasis. A lesion negative for either oestrogen or progesterone receptor content tended to produce more TXB2 but lower PGE2 and 6-keto-PGF1 alpha. Results obtained in this pilot study may provide clues as to what direction future larger studies could take in the search for reliable prognostic indicators for breast cancer.

6-Ketoprostaglandin F1 alpha↗

PubMed1983

Influence of diet on vascular lesions in autoimmune-prone B/W mice.

Autoimmune-prone B/W mice, which are known to develop severe glomerulonephritis and vasculitis, also are found to develop arteritis and proliferative and fatty-proliferative lesions of the aorta and its branches as well as renal inflammatory lesions. High intake of saturated fat in the diet enhances the development of these atherosclerotic and autoimmune lesions significantly in female mice, whereas restriction of dietary calories and fat inhibits their development. Ad lib feeding of laboratory chow, high in fiber and low in fat, does not foster development of vascular lesions but does permit the development of autoimmune renal disease.

Animals↗

PubMed1983

Association of cell cycle expression of Ia-like antigenic determinations on normal human multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells with regulation in vitro by acidic isoferritins.

An association has been established between human Ia-like antigenic determinants, expression during DNA synthesis on multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells, and the regulatory action of acidic isoferritins in vitro. Treatment of human bone marrow cells with monoclonal anti-Ia (NE1-011) plus complement inhibited colony formation of CFU-GEMM) and BFU-E by 50%-70%. Reduction of colonies was similar whether bone marrow cells were exposed to anti-Ia plus complement, high specific tritiated thymidine (3HTdr), or acidic isoferritins. No further decrease was apparent with 3HTdr or acidic isoferritins after Ia-antigen+ CFU-GEMM or BFU-E were removed, or with anti-Ia plus complement or acidic isoferritins after S-phase CFU-GEMM or BFU-E were removed. Anti-Ia, in the absence of complement, had no effect on colony formation but blocked the inhibition of CFU-GEMM and BFU-E by acidic isoferritins. Demonstration of Ia-antigens on BFU-E and inhibition of BFU-E by acidic isoferritins appeared to require the presence of phytohemmagglutinin leukocyte conditioned medium (PHA-LCM) in the culture medium during the 14-day incubation period. these results implicate Ia-antigen+ cells, acidic isoferritins, and PHA-LCM in the regulation of multipotential and erythroid progenitor cells in vitro.

Antibodies, Monoclonal↗

PubMed1982

Treatment of advanced diffuse histiocytic lymphoma: an analysis of prognostic variables.

Sixty-five patients with Stages III and IV diffuse histiocytic lymphoma (DHL) were treated with two different and successive combination chemotherapy protocols. Twenty-seven patients were treated with the cyclophosphamide (CTX) L2 protocol, which included maintenance chemotherapy for three years. Thirty-eight patients received the NHL-3 program. Both protocols included radiotherapy (1350--4000 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system prophylaxis with intrathecal methotrexate or cytosine arabinoside in patients with bone marrow involvement. Two-year survival rates were 44 and 56%, respectively, for the CTX-L2 and NHL-3 protocols. Of the 65 patients, 59 were evaluable for response to therapy. The CTX-L2 produced a 58% total response (TR) rate, 39% complete (CR), and 19% partial (PR). The patients on NHL-3 achieved a TR rate of 82%, 33% CR, and 48% PR. The difference in TR was significant (P = 0.05), but in CR was not. Prior chemotherapy (P = 0.077) and serum lactic dehydrogenase (LDH) level above 500 U/liter (P = 0.01) significantly lessened the chances for achievement of a CR. However, sex, age, the presence of systemic symptoms, stage (III vs. IV), and prior RT were not found to be significantly related to CR rate. This analysis suggests that a high level of serum LDH characterizes a subgroup of patients with particularly aggressive DHL that requires a more intensive modality of treatment.

Adolescent↗

PubMed1982

Repeated least squares analysis of simulated xenon computed tomographic measurements of regional cerebral blood flow.

Computer simulations were done as a feasibility study of xenon computed tomographic measurements of regional cerebral blood flow. Accuracy of initial least squares estimates of gray matter and white matter rate constants from a two-compartment model depended very little on the number and timing of scans, but did depend significantly on the enhancement-to-noise ratio as well as on the true values of the rate constants and gray/white ratio. Nonlinear least squares gives an optimal fit of the predicted wash-in--wash-out curve to the data rather than optimal estimates of the rate constants. A polynomial correction factor was obtained by regressing initial estimates on the true values used to generate the simulations. The correction factor substantially reduced error in the estimates and, in particular, eliminated large outliers.

Brain↗

PubMed1982

Clinical classification of cardiac deaths.

One hundred forty-two deaths among 743 men ages 50 - 65 years who had been examined and followed 5 - 10 years were investigated and classified on the basis of clinical information from medical and non-medical observers, ECGs and autopsies. A classification based on the condition of the circulation immediately before death appears to be most relevant to studies of sudden death. In 58% of the cases, the subjects collapsed abruptly and his pulse ceased without prior circulatory collapse (arrhythmic death); in 42%, the pulse ceased only after the peripheral circulation had collapsed (deaths in circulatory failure). Thirty-three percent of arrhythmic deaths and 10% of deaths in circulatory failure occurred in a setting of clinical evidence of acute ischemic heart disease (p less than 0.005). Forty-five percent of arrhythmic deaths were preceded by chronic congestive heart failure without circulatory collapse. Ninety-three percent of final illnesses that lasted less than 1 hour ended in arrhythmic deaths; 74% lasted more than 1 day ended in deaths in circulatory failure (p less than 0.001). Eighty-eight percent of deaths that occurred outside of the hospital were arrhythmic; 71% of deaths that occurred in the hospital were deaths in circulatory failure (p less than 0.001). Ninety percent of deaths in which the primary cause of the final illness was heart disease were arrhythmic; 86% of deaths in which the primary cause was other than heart disease were deaths in circulatory failure (p less than 0.001). Ninety-one percent of deaths precipitated by an acute cardiac event were arrhythmic; 98% precipitated by acute respiratory obstruction, hemorrhage, infection, stroke or other noncardiac events were deaths in circulatory failure (p less than 0.001).

Aged↗

PubMed1982

Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone).

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.

Antineoplastic Agents↗

PubMed1981

Treatment of acute nonlymphocytic leukemia in adults: response to 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine and thioguanine on the L-12 protocol.

Fifty-one adult patients with acute nonlymphocytic leukemia (excluding acute promyelocytic leukemia) were treated on the L-12 protocol. The L-12 differed from the preceding L-6 in that 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine (AAFC), replaced arabinosylcytosine (ara-C) together with 6-thioguanine (TG) for remission induction. Achievement of remission was followed by an extended 14-week multi-drug consolidation program. With this more intense regimen, an overall complete remission rate of 49% and a median remission duration of 23.7 months were achieved; these results were not significantly better than the 57% complete remission rate and 8.6 months median remission duration obtained with the L-6 regimen. Four year disease-free survival was 22% on the L-12 compared with 16% on the L-6 protocol. No relationship between prognosis and FAB classification was found on either the L-6 or the L-12 protocol.

Adolescent↗