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Biomedical subjects

M M Oken

Publications and source records attributed to M M Oken.

144 records · Page 8Linked to original sources
PubMed1981

Endogenous pyrogen production by human blood monocytes stimulated by staphylococcal cell wall components.

To determine the properties of Staphylococcus aureus contributing to its pyrogenicity, we compared, in human monocytes, endogenous pyrogen production stimulated by heat-killed S. aureus with that stimulated by purified S. aureus cell walls or by particulate peptidoglycan prepared from the same strain. Peptidoglycan, but not the purified cell wall preparation, was found comparable to S. aureus as an endogenous pyrogen stimulus. This finding was associated with a more effective monocyte phagocytosis of S. aureus and peptidoglycan as compared with that of purified cell walls. Lysostaphin digestion of peptidoglycan markedly reduced its pyrogenicity. To test whether the chemical composition of the ingested particles is important, latex particles were tested as possible stimuli for monocyte endogenous pyrogen release. Although 40 to 68% of monocytes ingested latex particles during the first hour, there was no evidence of endogenous pyrogen activity in the supernatant even when supernatants equivalent to 5.2 X 10(6) monocytes were tested. This study demonstrates that the pyrogenic moiety of the S. aureus cell wall resides in the peptidoglycan component. Phagocytosis is not in itself a pyrogenic stimulus, but rather serves as an effective mechanism to bring about contact between the chemical stimulus and the monocyte.

Cell Wall↗
PubMed1980

Cyclophosphamide, cytosine arabinoside and methotrexate versus cytosine arabinoside and thioguanine for acute non-lymphocytic leukemia in adults.

One-hundred and fifty-one adults with acute non-lymphocytic leukemia (ANLL) were entered into an Eastern Cooperative Oncology Group protocol (EST-1473) comparing twice daily cytosine arabinoside and thioguanine (AT) with weekly cyclophosphamide, cytosine arabinoside, and methotrexate (CAM) for remission induction. Of 111 evaluable patients, 16 treated with CAM and 16 treated with AT entered complete remission (CR) on their initial therapy and 5 additional patients entered CR on crossover for a total of 37 or 33% of the evaluable patients. Of the 71 patients who survived three weeks or longer, the overall CR rate was 52%. Cytochemical studies were performed on 85% of the evaluable cases, Minor disagreements between morphologic subtypes of ANLL occurred in 50% of cases. There was no difference in response rates between the major subtypes of ANLL regardless of whether the investigator's diagnosis or the cytochemical reference laboratory diagnosis was used. The median survival of all evaluable patients was 4.9 weeks; those patients who responded with a CR had a median survival of 60 weeks, while those who did not have a median survival of less than 3 weeks. Age less than 60, ambulatory performance status, or fewer than 50% marrow blasts were also associated with a better response rate and longer survival. CAM had more severe mucositis and vomiting associated with it than did AT, but toxicities were otherwise comparble. Weekly CAM and AT appear to be equally effective regimens in the treatment of ANLL.

Adult↗
PubMed1980

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Activities of Daily Living↗
PubMed1980

Effects of fever and hyperthermia on thyroid function.

Thyroid hormones in man are affected by acute and chronic febrile states. To define these acute changes, we used a previously described rabbit model. Serum levels of T3, rT3, and T4 were measured at 0, 2, 4, 6, and 24 hr following injection of 1 microgram E. coli endotoxin, and during heat-induced hyperthermia. All rabbits receiving endotoxin developed fever with peaks at one hour (delta T = 1.1 degrees C) and three hours (delta T = 1.4 degrees C); they then defervesced to base levels at 6 hr. Similar temperature elevations occurred with heat-induced hyperthermia. Results show that endotoxin-induced fever produces changes similar to those reported during infections to man, and more rapidly than previously recognized. These include a prompt decrease in T3, reciprocal rise in rT3, and an initially reduced T4 that rebounds above basal levels. These findings may represent suppressed TSH release, alteration of peripheral monodeiodination of T4 from T3 to rT3, or enchanced clearance of T3. Heat-induced hyperthermia, except for slight decrease in T4 at 6 and 24 hr, had little effect on thyroid hormones.

Animals↗
PubMed1980

Randomized clinical trial comparing two dose regimens of ICRF-159 in refractory malignant lymphomas.

A clinical trial of ICRF-159 was done in patients with Hodgkin's disease and non-Hodgkin's lymphomas whose tumors had become resistant to conventional chemotherapy. Antitumor effect and toxicity were compared in patients who were randomly assigned to receive either a loading course or a weekly regimen. Among 82 evaluable cases, five of 39 (13%) treated with the loading course schedule and six of 43 (14%) treated with the weekly schedule experienced objective tumor regressions. Response duration tended to be brief (median, 7 weeks). Life-threatening myelosuppression was more frequent in patients receiving the loading course regimen. Survival was somewhat longer among patients receiving the weekly schedule (median survival, 24 versus 12 weeks; P = 0.04). ICRF-159 demonstrated definite but limited therapeutic activity in this population of patients with advanced malignant lymphomas. The weekly schedule was associated with fewer episodes of life-threatening toxicity and longer patient survival.

Adult↗
PubMed1979

Chronic lymphocytic leukemia in association with a second lymphoproliferative disorder: response to chemotherapy in two cases.

The development of either histiocytic lymphoma or Hodgkin disease in association with pre-existing chronic lymphocytic leukemia has been described in the literature as a terminal event. We describe two patients in whom the diagnosis of a second malignant lymphoma was made during life and who achieved objective clinical response after a change in therapy to a more aggressive combination of drugs. We conclude that patients with chronic lymphocytic leukemia who have had a sudden change in their clinical course should have thorough reevaluation, looking specifically for the development of a second lymphoproliferative disorder. If this is discovered, more aggressive therapy should be initiated.

Aged↗
PubMed1978

Comparison of two radioimmunoassays and a microbiologic assay for bleomycin.

Recently two radioimmunoassays have been independently developed for determination of bleomycin levels. In this study these assays are compared with each other and with a standard microbiologic assay for bleomycin. Bleomycin levels were determined in serum and urine samples obtained at varying intervals following intramuscular bleomycin injection. There were systematic differences between the assays. One radioimmunoassay indicated bleomycin levels lower than the levels indicated by the microbiologic assay with serum samples. With urine samples, both radioimmunoassays indicated bleomycin levels greater than the microbiologic assay.

Antibody Specificity↗
PubMed1977

A radioimmunoassay for bleomycin.

A radioimmunoassay for bleomycin, suitable for monitoring serum and urine drug levels, has been developed. Antisera were obtained from rabbits immunized with a conjugate of bleomycin and human serum albumin.Bleomycin labeled with 57Co was used as the tracer. Antibody-bound and free bleomycin were separated by precipitation with polyethylene glycol. The assay could determine bleomycin levels down to 0.025 mug/ml. The assay was precise, with a coefficient of variation of 2.8% Other drugs likely to be administered in combination with bleomycin did not interfere with the radioimmunoassay.

Animals↗
PubMed1976

IgM pyroglobulinemia with erythrocytosis presenting as hyperviscosity syndrome. I. Clinical features and viscometric studies.

The hyperviscosity syndrome is described in a patient with erythrocytosis and an immunoglobulin M with kappa light chain (IgMK) macroglobulinemia. Viscometric studies were carried out on whole blood and demonstrated the contribution of both the increased hematocrit value and the macroglobulinemia to the whole blood viscosity. Clinical improvement followed phlebotomy and was accompanied by a decrease in whole blood viscosity. Continued treatment with chlorambucil has been associated with a long symptom-free period. The macroglobulin was characterized as a monoclonal IgMK pyroglobulin which retained its thermoprecipitability was reduced to 7S monomers. The presence of IgMK aggregates in the serum may have contributed to the increase in blood viscosity.

Aged↗
PubMed1976

IgM pyroglobulinemia with erythrocytosis presenting as hyperviscosity syndrome. II. Biochemical properties and mechanisms of pyrogel formation.

An immunoglobulin M with kappa light chains (IgMK) pyroglobulin from a patient with hyperviscosity syndrome, erythrocytosis and coagulation defects has been studied for its immunochemical properties. At physiologic temperatures the purified macropyroglobulin showed a striking tendency to aggregate in the pentamer as well as in the monomer form. This property was also observed in its H chains. Aggregate formation of the pentamers may have contributed to the blood viscosity and coagulation defects. Formation of pyrogel at 56degreesC was observed with pentamers as well as monomers, but not with separated H or L chains. Amino acid analysis showed quantitative abnormalities of aspartic acid, glycine, cystine and leucine within the H chains. Solubility of the pyrogel in sodium dodecyl sulfate, the pyroglobulin's tendency to aggregate and the cystine deficit of H chains implicate conformational changes leading to hydrophobic bonding at 56degreesC in the formation of pyrogel.

Amino Acids↗
PubMedDate not supplied

Neuropeptides and thermoregulation: the interactions of bombesin, neurotensin, TRH, somatostatin, naloxone and prostaglandins.

In this study we have examined the interactions of bombesin (1 microgram ICV), neurotensin (1 microgram ICV), TRH (10 micrograms ICV), somatostatin (10 micrograms ICV), PGE2 (10 micrograms ICV) and naloxone (10 mg/kg SC) on thermoregulation in the rat at room temperature (20 +/- 1 degree C). Given alone, bombesin, neurotensin, somatostatin and naloxone all produced hypothermia (bombesin greater than neurotensin greater than somatostatin congruent to naloxone). PGE2 was hyperthermic, and TRH had no effect. Bombesin and PGE2 neutralized one another's effects. Neurotensin had no effect on PGE2-induced hyperthermia. Naloxone enhanced the hypothermic effect of bombesin and somatostatin enhanced the rate of onset of hypothermia after bombesin. TRH had no effect on bombesin-induced hypothermia. TRH, somatostatin and naloxone had no effect on neurotensin-induced hypothermia. TRH antagonized the hypothermia due to naloxone and somatostatin.

Animals↗
PubMedDate not supplied

Pharmacokinetics of bleomycin after im administration in man.

The pharmacokinetics of bleomycin were studied after im injection in patients with malignant lymphoma. Mean peak serum concentrations of 0.133, 0.326, and 0.587 milliunits/ml were obtained approximately 1 hour after injection of 2, 5, and 10 units/m2, respectively. The mean half-life was 155 minutes, with a range of 65--235 minutes. Thirty-three percent of the administered dose was recovered in the urine after 4 hours. The urinary excretion of bleomycin was 61% during the 24 hours after injection, with some variability that was not explained by differences in dose or creatinine clearance.

Aged↗