Search PubMed⌕ Search

Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 253 records · Page 14Linked to original sources
PubMed1982

Benzo(a)pyrene metabolism in primary cultures of mouse epidermal cells and untransformed and transformed epidermal cell lines.

The metabolism of [3H]benzo(a)pyrene [B(a)P] by cultures of primary mouse epidermal cells and untransformed and transformed epidermal cell lines was investigated. All three cell types effectively metabolized [3H]B(a)P. The major organic solvent-extractable metabolites found intracellularly in primary cultures were trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene, although quantities of 9-hydroxybenzo(a)pyrene, trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene, and quinones also were present. The major organic solvent-soluble metabolites found in the extracellular medium were trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene and trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, with smaller quantities of unconjugated phenols and quinones. The major water-soluble metabolites found in the extracellular medium were conjugated with glucuronic acid [primarily 3-hydroxybenzo(a)pyrene and several quinones]. No sulfate conjugates of [3H]B(a)P metabolites were detected. [3H]B(a)P metabolism was similar in cultures of untransformed and transformed epidermal cell lines but differed from the primary cultures. The major intracellular and extracellular organic solvent-soluble metabolites were diols. Little or no unconjugated phenols were detected. Both the untransformed and transformed epidermal cell lines converted [3H]B(a)P to water-soluble metabolites, primarily glucuronide conjugates. In contrast to the primary cells, a major pathway of trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene metabolism in the untransformed and transformed cell lines was a glucuronide conjugate. Primary mouse epidermal cells provide an important model system for studying factors affecting the activation and detoxification of hydrocarbon carcinogens.

Animals↗
PubMed1982

Phase II study of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992) in children with acute leukemia and lymphoma.

Phase I clinical studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA) using several dose schedules have shown acceptable toxicity and antitumor responses in acute leukemia and several carcinomas. Thirty-eight children with acute leukemia and non-Hodgkin's lymphoma were treated with AMSA in a total dose of 140 to 600 mg/sq m given as a daily i.v. infusion in 2 to 5 days. Maximal tolerated dose was 600 mg/sq m given in 5 days. Complete and partial remissions were seen in four of 18 patients with acute lymphocytic leukemia, zero of eight patients with acute nonlymphocytic leukemia, and one of five patients with non-Hodgkin's lymphoma. Marrow aplasia and remissions were also seen with lower doses. The major toxic effects were mucositis, fever, and sepsis which were dose related. Mild nausea and vomiting, transient elevation of serum glutamic oxaloacetic-acid-transaminase, and bilirubin were noted. All of these patients had had prior anthracycline therapy. Abnormal echocardiograms were seen in 14 of 23 patients who had echocardiograms done before and after AMSA. Seven developed congestive heart failure in association with sepsis in five and with epicardial disease in one. We conclude that AMSA possesses significant activity in childhood leukemia and lymphoma and that studies of AMSA in combination with other effective agents should be done.

Acute Disease↗
PubMed1982

Cardiac abnormalities after AMSA administration.

AMSA produced changes on echocardiograms of 18 of 27 patients. Seven patients developed clinical congestive heart failure. The occurrence of cardiac abnormalities was influenced by the previous anthracycline dose and the rate and dose of AMSA administered. No changes were seen in six patients, with a total anthracycline dose less than or equal to 400 mg/m2 and less than 200 mg/m2 of AMSA given on 2 consecutive days. Seven of eight patients had abnormalities with an anthracycline dose less than or equal to 400 mg/m2 but greater than or equal to 200 mg/m2 of AMSA in 48 hours. Nine of 11 patients had abnormalities when AMSA was given after a total anthracycline dose of 400 mg/m2. When the total combined anthracycline and AMSA dose was greater than or equal to 900 mg/m2, 13 of 14 patients had abnormalities while only three of 11 who received less than this dose had abnormalities. The abnormalities may be reversible with prompt treatment and discontinuation of drug.

Adolescent↗
PubMed1982

Chronic granulomatous disease and selective IgA deficiency.

The clinical and laboratory features of a child with chronic granulomatous disease (CGD) and IgA deficiency and his family are presented. Bactericidal and NBT dye reduction studies confirmed the diagnosis of CGD in the patient and the carrier state in the mother. No other family member had IgA deficiency. The manifestations of the IgA deficiency include multiple autoimmune antibodies, progressive pulmonary dysfunction but no gastrointestinal or rheumatoid symptoms. The etiology of the IgA deficiency appears to be a failure in terminal B cell differentiation as evidenced by the presence of normal numbers of IgA bearing cells detected by a fluorescent monospecific antisera, a normal profile of T cell subpopulations, normal responses to the mitogens PHA, Con A, PWM, and antigens C. albicans, E. coli, and S. aureus, and the absence of suppressor cell activity in co-culture assays. The significance of the association of these two disorders is discussed.

Adult↗
PubMed1982

Hodgkin's diseases in adolescents presenting as a primary bone lesion. A report of four cases and review of literature.

Bone involvement of Hodgkin's disease usually occurs late in the course of the illness, together with extensive nodal involvement. In the past 5 years, we have seen four adolescents with Hodgkin's disease who presented with primary bone lesions. All had disseminated lymphoid involvement when the final diagnosis was made 3-11 months later. A review of the literature showed 13 more cases of similar presentation. The patient characteristics are discussed and the diagnostic difficulties are emphasized. Hodgkin's disease should be considered in the differential diagnosis of primary osseous malignancies.

Adolescent↗
PubMed1982

A comparison of collagen synthesis by different categories of human chondrosarcoma in organ culture.

Accurate diagnosis of the degree of malignancy of individual chondrosarcomas is a difficult problem for the orthopedist. To determine whether certain biochemical and metabolic parameters might provide a useful supplement to roentgenologic and histologic evaluations, 19 human chondrosarcomas were analyzed for DNA and collagen content, and for 3H-proline incorporation into 3H-hydroxyproline and total protein. When these values were compared by estimated tumor grade (benign, low, or high) and by tissue type (hyaline, fibrous, myxoid, or mixed), collagen content, synthesis, and total protein synthesis appeared to vary inversely with apparent degree of malignancy, suggesting that different levels of transformation may be represented in these tumors. These measurements may provide a useful adjunct to histologic and roentgenologic evaluations to more accurately predict the degree of malignancy and the tendency of individual tumors to metastasize.

Chondrosarcoma↗
PubMed1981

Dural sinus thrombosis in children with acute lymphoblastic leukemia.

Dural sinus thrombosis developed in two children with acute lymphoblastic leukemia during induction treatment with vincristine sulfate, prednisone, and asparaginase. Headache, nausea, emesis, and lethargy were the presenting signs. The diagnosis was confirmed by arteriography. The cause is presumed to be secondary to hypercoagulability due to asparaginase-induced antithrombin III deficiency. The patients received anticoagulation therapy and recovered completely. Only two of the six reported patients without heparinization survived.

Age Factors↗
PubMed1981

Acute promyelocytic leukemia in children.

Sixteen children (ages 2--17) with acute promyelocytic leukemia (APL) were studied retrospectively. Diagnosis was based on clinical features and morphological criteria of the FAB classification. Bleeding diathesis was the predominant presenting symptom (greater than 85%), associated with laboratory findings of disseminated intravascular coagulation (DIC). Extramedullary manifestations included skin rash in six patients, gum infiltration in two, and meningeal leukemia in two. Induction therapy consisted of cytosine arabinoside and an anthracycline, with or without other agents. Prophylactic heparinization was given to 12 patients. Six patients (37.5%) failed to achieve remission and died, secondary to hemorrhage in three, and secondary to infection in the remaining three patients. The median duration of remission was 14 months, and the median survival for responders was 21 months. One meningeal leukemia preceded bone marrow relapse despite intermittent intrathecal chemotherapy for prophylaxis. Three patients remain in continuous complete remission 3 years after initial diagnosis. Although childhood APL shares many features of its adult counterpart, the high frequency of extramedullary manifestations and mortality secondary to neutropenia deserves separate attention.

Adolescent↗
PubMed1981

Acute myeloblastic leukemia following non-Hodgkin lymphoma in an adolescent. A report of a case with preleukemic syndrome, and review of the literature.

Reports of acute nonlymphoblastic leukemia occurring after successful treatment of Hodgkin and non-Hodgkin lymphoma (NHL) are appearing with increasing frequency. Two years after completion of LSA2-L2 therapy for stage III, poorly differentiated lymphocytic lymphoma, a 16-year-old boy developed a preleukemic state characterized by a refractory macrocytic anemia with excess blasts, dyshematopoiesis, abnormal cluster:colony ratio on in vitro bone marrow culture, and acquired deficiencies of erythrocyte pyruvate kinase, triose phosphate isomerase, and adenylate kinase. Four months later acute myeloblastic leukemia was evident. The RNA index determined by flow cytofluorometry was increased. Four marker chromosomes were found and involved complex translocation of chromosomes 11 and 17 (t11;l17) in 100% of the cells, and chromosomes 4 (t4q;4) in 10% of the cells. A thorough literature search uncovered four other reports of acute nonlymphoblastic leukemia occurring in children treated for NHL and a total of 58 cases in the adult and pediatric age groups. Over 50% of the patients had AML, were mean over 50 years of age, and were treated with radiotherapy and chemotherapy. It is anticipated that additional cases of second malignancies will be reported in this population of patients whose outlook for the curability of the primary malignancy is 75%.

Adolescent↗
PubMed1981

Phase I trial of rubidazone (NSC 164011) in children with cancer.

Rubidazone was administered to 24 children with advanced solid tumors or leukemia. The dose ranged from 80 to 150 mg/m2/IV daily to a total dose of 160 to 450 mg/m2/course. This course was repeated at intervals of approximately three weeks. Eighteen of 24 patients (75%) had received adriamycin and daunomycin as part of prior chemotherapy. The major toxic effects observed were myelosuppression, nausea, vomiting, mucositis, and skin rash. Four patients developed abnormal echocardiograms following the rubidazone therapy, 2 manifested clinical cardiac failure, of which one had anthracycline cardiomyopathic changes on autopsy. One of 7 adequately treated ALL patients achieved M2 marrow and improved peripheral counts for 3 weeks. One of the 2 neuroblastoma patients had subjective improvement of bone pain for 2 months. Rubidazone, in a previous heavily treated group of patients used in this study, had dosages of 360 and 450 mg/m2 which produced marrow hyperplasia to aplasia, with only minimal responses.

Adolescent↗
PubMed1981

Cardiac changes with cyclophosphamide.

Serial echocardiographic (ECHO) studies were obtained on 40 pediatric patients (pts) treated with greater than or equal to 80 mg/kg cyclophosphamide (CPM) (range 80-200 mg/kg) in 1 week. Patients were treated for solid tumors and prior to marrow transplant. Echo changes occurred in 10/13 pts who received CPM greater than or equal to 170 mg/kg over four days, and in 11/19 pts who received 120-140 mg/kg dose over two days and who had previously received greater than or equal to 100 mg/m2 anthracyclines with or without radiation. No changes were seen in eight pts who had 80-160 mg/kg CPM and less than 100 mg/m2 anthracyclines. The observed changes occurred approximately 1 week after CPM and persisted for days to weeks. Pericardial effusion seen in 15 pts was successfully treated with furosemide in 13. Two died with hemorrhagic pancarditis. Other changes seen were increased end diastolic left ventricular diameter, decreased fractional shortening and abnormal left ventricular preejection period/ejection time ratios. Thus, cardiac effects of high dose CPM are not rare in children. Patients receiving greater than 170 mg/kg CPM in 1 week or 120 mg/kg in 1 week after greater than or equal to 100 mg/m2 anthracyclines are at particular risk.

Adolescent↗
PubMed1981

Combination use of nonsteroidal antiinflammatory drugs.

Polypharmacy with nonsteroidal antiinflammatory drugs (NSAIDs) is widely practiced despite being condemned by many rheumatologist. Combination use of aspirin with other NSAIDs might be discouraged for three well-documented reasons. First, aspirin reduces the blood levels of many NSAIDs. Second, multiple drugs are antagonistic or at least less than additive in animal models of inflammation. Third, there is no good clinical data to suggest that combination use of NSAIDs is beneficial. Unless new studies become available, NSAIDs should be used one at a time, with supplementary analgesics added on a prn basis.

Analgesics↗
PubMed1981

Fluorometric assay of DNA in cartilage and correction for interference by matrix components.

A fluorometric assay using 3,5-diaminobenzoic acid for analysis of DNA in alkaline-hydrolyzed calf articular cartilage is described. Additional estimates of DNA content, obtained by counting of cells in cartilage slices and of cells isolated from the tissue by digestion with bacterial collagenase, indicated that falsely high values were obtained with the fluorometric assay and with the indole procedure of Bonting and Jones. Cartilage collagen and proteoglycan were both found to contribute to this interference. Factors to correct for this interference were determined, based upon the hydroxyproline and uronic acid contents of these components. application of these corrections to DNA values obtained by fluorometric assay of the cartilage samples resulted in DNA estimates in agreement with those obtained by counting of cells.

Animals↗
PubMed1981

Prognostic importance of morphology (FAB classification) in childhood acute lymphoblastic leukaemia (ALL).

The French-American-British (FAB) classification has been proposed as a useful and uniform method of defining morphologic subsets of acute leukaemias. As part of a prospective study designed to identify subsets of children with high risk of early relapse (CCG 141), submitted bone marrow slides from 765 of 883 patients entered on study were reviewed by two morphologists blinded as to prognostic factors and treatment regimen. L1, L2 and L3 acute lymphoblastic leukaemia (ALL) comprised 85.1%, 14.1% and 0.8%, respectively, of the total population. Children with greater than 25% L2 lymphoblasts had a significantly higher relapse rate and significantly poorer survival. Results of this study indicate that as a single variable, lymphoblast morphology is a very significant predictor of survival, haematologic remission, and complete continuous remission. Multivariate analyses show that lymphoblast morphology is again significant in determining duration of survival (P = 0.048), and is of borderline statistical significance (P = 0.089) in predicting length of complete continuous remission. The FAB classification, with minor modifications, is reproducible, useful, and prognostic in childhood ALL.

Adult↗