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Biomedical subjects

M Coleman

Publications and source records attributed to M Coleman.

At least 235 records · Page 13Linked to original sources

Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome.

The hallmark of chronic myelocytic leukemia is the presence of the Philadelphia chromosome (Ph1). In recent studies, we obtained data that strongly suggested the involvement of an oncogene, c-abl, in this type of leukemia. This oncogene, normally located on chromosome 9, is translocated to chromosome 22 as a result of the Ph1 translocation. In addition, we identified a region on chromosome 22, the breakpoint cluster region (bcr), which contains the chromosomal breakpoint in all patients with chronic myelocytic leukemia who are positive for Ph1. Recent studies have suggested that the bcr is part of a gene that is truncated as a consequence of the Ph1 translocation. The deleted part of this gene could be replaced by c-abl sequences; to test this hypothesis we analyzed the RNA of five patients with chronic myelocytic leukemia. All five had chimeric bcr/c-abl messenger RNA, suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c-abl oncogene.

Adult↗

HAC-Cytoxan (cyclophosphamide) chemotherapy for ovarian carcinoma. Alternating chemotherapy with intensification.

Twenty-two previously untreated patients with adenocarcinoma of the ovary were treated with 28 day cycles of hexamethylmelamine, Adriamycin (doxorubicin), and cisplatin (HAC) for 9 months followed by three monthly cycles of intense intravenous cyclophosphamide. An overall response frequency of 82% (18/22) was achieved. Complete pathologic responses (CPR) documented by second look operations were found in 50% (11/22); however, patients considered to be free of disease (prolonged complete clinical response refusing "second look" and CPR) totaled 59%. Median survival has not been reached after a median follow-up of 34 months. No major or life threatening toxicity was encountered. HAC followed by cyclophosphamide is a highly effective regimen that may be easily administered on an outpatient basis with comparatively little toxicity.

Adenocarcinoma↗

Unusual translocations involving chromosomes 12;22 and 9;12 in a case of chronic myelogenous leukemia.

A case of chronic myelogenous leukemia (CML) with highly unusual translocations involving both chromosomes #12 is reported. The origin of the Ph1 chromosome was due to a 12p/22q translocation. Chromosome #9 was involved in a translocation with the other chromosome #12. By critical examination of the "size" of the Philadelphia chromosome, it was noted that the breakpoints on 22q were different when compared with a previous case (see Verma and Dosik [16]), although the short arm of chromosome #12 (12p) was involved in both instances. So far, no apparent differences in the course of the disease have been attributed to the types of translocation observed in these cases.

Adult↗

Autism and lactic acidosis.

Four patients are described who have two coexistent syndromes: the behavioral syndrome of autism and the biochemical syndrome of lactic acidosis. One of the four patients also had hyperuricemia and hyperuricosuria. These patients raise the possibility that one subgroup of the autism syndrome may be associated with inborn errors of carbohydrate metabolism.

Acidosis↗

Studies on the mechanism of immunosuppression with adenine.

Studies on the mechanism of immunosuppression shown by adenine comprised two areas: (1) Toxicity studies on hepatic, muscle and renal tissues were undertaken to ascertain if immunosuppression was a result of a non specific toxicity. (2) Studies to determine whether immunosuppression is a function of the inhibitory effect on de novo and salvage pathways of purine nucleotide metabolism. Toxicity studies in mice indicated that adenine caused an acute, reversible renal tubular necrosis and that allopurinol, when combined with adenine, could abrogate both the renal toxicity and immunosuppressive activity of the purine base. This result indicated that the toxic and/or immunosuppressive compound may be a xanthine oxidase catalysed product of adenine. Further studies indicated that it was unlikely that a major part of the immunosuppressive activity of adenine was due to the renal toxicity exerted by this compound. Splenic PRPP levels were found to peak on day 4 after antigen administration (day 0) and this corresponded with the peak in antibody plaque response which occurred at day 4 to 5. Adenine given at an immunosuppressive dose of 25 mumoles/mouse on day 0, 1 resulted in a significant inhibition of splenic PRPP levels on day 2 of the response. This effect on splenic PRPP levels on day 2 was also found with hypoxanthine given at an immune enhancing dose and therefore would indicate that depression of splenic PRPP per se is not responsible for the immunosuppression. Adenosine given at immunosuppressive doses was found not to affect PRPP levels in the spleen and hepatic PRPP levels were unaffected by adenine, adenosine and hypoxanthine. The in vivo effects of adenine on hypoxanthine-guanine phosphoribosyltransferase showed that adenine could inhibit significantly this salvage pathway in spleen and liver and that this inhibition could be overcome with concomitant administration of allopurinol. A metabolite of adenine which could contribute to its immunosuppressive activity may be 2-hydroxyadenine since it is derived from the xanthine oxidase catalysed oxidation of adenine inhibited hypoxanthine-guanine phosphoribosyltransferase gave similar renal toxicity to adenine and was immunosuppressive.

Adenine↗

Evidence for the non-infectious etiology of early postoperative fever.

In a prospective study of infections in 871 general surgery patients, we identified 81 patients who developed unexplained postoperative fevers. The majority of these episodes (72%) occurred early (within the first 48 hours) following surgery. Patients who developed early, unexplained fevers differed significantly from patients who developed documented postoperative infections. Patients with unexplained fevers were younger, had less severe underlying disease and underwent less extensive surgeries than patients who subsequently developed infections. In these respects, they were more similar to non-infected, non-febrile patients. We concluded that episodes of early, unexplained postoperative fever occur frequently in a wide range of general surgery patients. Most of these episodes are non-infectious in origin. Patients with early postoperative fevers should be evaluated to identify any obvious sources of infection. If no focus is identified, empiric antibiotic therapy should not be initiated nor should prophylactic antibiotics be extended for prolonged durations. Unexplained fevers will resolve in time without specific therapeutic interventions.

Age Factors↗

Space-time clustering of nasopharyngeal carcinoma in Greenland Eskimos.

Evidence of epidemicity of nasopharyngeal carcinoma (NPC) was sought in Greenland Inuits, who have a high incidence of this cancer, by examining the births of NPC cases for evidence of clustering in time and space. Births of cases were concentrated in autumn and winter. Fifty-four cases were analysed, and a two-fold excess of clustering within one year was observed, both within single districts and between adjacent districts. This excess was not significant at the 5% level; about 90 cases would have been required to confirm the observed effect at this level of significance. It is suggested that a search for space-time clustering of NPC cases in larger high-risk populations might prove more fruitful.

Age Factors↗

A double blind study of vitamin B6 in Down's syndrome infants. Part 1--Clinical and biochemical results.

Nineteen patients with Down's syndrome participated in a double blind study of the clinical effects of pharmacological doses of vitamin B6 administration, starting under 8 weeks of age and continuing until 3 years of age. Ten patients received the vitamin and nine the placebo. In Part 1 of this study, no statistically significant differences were found between the two groups in mental age, height, weight, cranial circumference or tongue protrusion. A study of side effects conducted on a larger open population found vitamin B6 to be relatively safe when administered over long periods of time with photosensitive blisters as the major complication.

Blister↗

A double blind study of vitamin B6 in Down's syndrome infants. Part 2--Cortical auditory evoked potentials.

Cortical auditory evoked potentials (CAEPs) were recorded at 1 and at 3 years of age in 19 children with Down's syndrome participating in a double blind trial of vitamin B6 and placebo begun in early infancy and continued for 3 years. CAEPs have previously been shown to have abnormally high amplitude in Down's syndrome patients. The CAEPs of the patients in the B6-treated and placebo groups were compared. Only minor effects were found in the CAEPs recorded at 1 year of age. At 3 years of age, however, comparison of the B6-treated group and the placebo group revealed significant differences in both amplitudes and latencies of CAEP components. Peak to peak amplitudes of prominent components were significantly lower in B6-treated patients than in their placebo controls. Amplitude correlated in some cases with whole blood serotonin levels. Latencies for several prominent evoked peaks were significantly longer in B6-treated patients.

Child, Preschool↗

Toxicological assessment of lidocaine in the pregnant rat.

Teratogenic and toxicological effects of lidocaine administered during pregnancy were evaluated in the Sprague Dawley rat. High doses of lidocaine administered during specific periods of gestation were shown to produce no apparent adverse toxicological or teratogenic effects. Histological, enzymological, and physical features of the fetuses, utilizing conventional toxicological parameters, were all found to be normal following maternal administration of lidocaine. Analysis of these data suggests that the administration of lidocaine during pregnancy had no detectable adverse effects on the fetus.

Animals↗

Physical exercise, social background, and the well-being of older adult women.

28 older women participating in an exercise program were compared to 30 older women not participating in an exercise program on two behavioral measures. There were no significant main effects for participation-nonparticipation in an exercise program. Significant main effects were found, however, for each of three social variables.

Aged↗

Terminal-phase chronic myelogenous leukemia: approaches to treatment.

The prognosis of patients with CML has improved little in the past 50 years. The relatively benign chronic phase invariably deteriorates to a refractory and rapidly fatal terminal phase. This terminal stage has been found to have two major subtypes as defined by morphologic, cytochemical, immunologic, and enzymatic criteria--myeloblastoid and lymphoblastoid. Aggressive combination chemotherapy has achieved minimal improvement in survival once the terminal phase has begun, perhaps because only Ph1-positive stem cells remain to repopulate the marrow at this stage. Bone marrow transplantation has also been unsuccessful as therapy for the terminal phase, possibly because the patients are too debilitated to tolerate transplantation once the terminal phase has begun. Combination chemotherapy has been applied in an effort to eliminate the Ph1 chromosome-containing clone during the chronic phase. This goal has not yet been consistently achieved. Chemotherapy has also not been able to delay the onset of the terminal phase nor to prolong survival. Even in those patients in whom the Ph1 chromosome-containing clone has been eliminated, relapse to the chronic phase with return of the Ph1 chromosome has generally occurred within a brief period of time. Bone marrow transplantation during the chronic phase may hold the promise of true cure for CML, with permanent elimination of the malignant clone. However, the chronic phase can be unpredictably long and patients in the chronic phase often have few, if any symptoms. Therefore, there has been a reluctance to employ drastic therapy during the chronic phase. Techniques to predict the transformation to the terminal phase prior to overt morphologic or clinical conversion are now being developed. It may be possible in the future to attempt HLA-matched sibling donor bone marrow transplantation at the earliest signs of transformation from the chronic to the terminal phase. In this manner, optimal survival might be achieved by allowing patients to be maintained in the chronic phase for as long as possible prior to the initiation of aggressive therapy. Until this is routinely possible, continued research designed to improve the therapy of the terminal phase must be pursued. These attempts are likely to include the development and evaluation of new chemotherapeutic agents, novel methods of administration of existing drugs to better exploit their pharmacokinetics (for example, continuous infusion), and the utilization of newly described treatment approaches (such as the use of "differentiating" agents in an attempt to prevent progression to blastic transformation).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Multiple myeloma--complete remission with high dose melphalan chemotherapy.

A patient with IgG3 lambda plasma cell myeloma characterized by anemia, hypercalcemia, hypoalbuminemia, renal insufficiency, osteolytic bone lesions, and serum and urinary light chains inadvertently received a dose of intravenous melphalan considerably greater than standard. A complete remission ensued characterized by normal protein and bone marrow studies. Healing of bone lesions occurred. This and two somewhat similar happenstances producing rare complete remissions in myeloma may have significant chemotherapeutic ramifications.

Aged↗

Phase I-II trial of mitoxantrone in acute leukemia.

Mitoxantrone was evaluated in a multi-institution trial to define the effective dose for treating acute leukemia, to evaluate its toxicity, and to assess the induction rates for the different types of acute leukemia. Fifty-seven patients have been treated. Of the 24 patients receiving mitoxantrone (10 mg/m2/day X 5), one of nine with acute nonlymphoblastic leukemia (ANLL) in relapse, one of five with acute lymphoblastic leukemia in relapse, and one of seven with blastic chronic myelogenous leukemia achieved remission. At a dose of 12 mg/m2/day X 5, seven of 16 patients with ANLL in relapse, none of six with acute lymphoblastic leukemia in relapse, and one of five with blastic chronic myelogenous leukemia achieved remission. At both dose levels, there was no response in patients who had failed to achieve a prior remission. Toxic effects included nausea/vomiting, stomatitis, and hepatic dysfunction. Nine of the 57 patients treated experienced cardiac events but cardiac toxicity seemed clinically significant in only three. We conclude that mitoxantrone, at a dose of 12 mg/m2/day X 5, is effective therapy for ANLL. Trials combining mitoxantrone with other agents are needed.

Acute Disease↗