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D L Coleman

Publications and source records attributed to D L Coleman.

At least 127 records · Page 7Linked to original sources

Blood-materials interactions: the minimum interfacial free energy and the optimum polar/apolar ratio hypotheses.

Numerous hypotheses exist to explain observed blood-materials interactions. It is the purpose of this article to test two popular hypotheses, namely, the minimum interfacial free energy hypothesis and the optimum polar/apolar ratio hypothesis. Methacrylate polymers and copolymers were characterized using the captive bubble underwater contact angle method; bulk water content was determined by gravimetric methods; streaming potential measurements were made; and surface roughness and possible particulate contamination were evaluated by reflected light microscopy. In vitro blood tests include whole blood clotting time measurements on polymer-coated tubes; centrifugal force platelet adhesion on polymer-coated coverslips; and a measure of the partial thromboplastin time, Russell's viper venom time (Stypven time), and the prothrombin time of native whole blood exposed to polymer-coated microscope slides. Results suggest that platelet adhesion correlates in the opposite direction of whole blood clotting time and partial thromboplastin time, emphasizing the need for a multiparameter approach to blood-materials testing. Based on these tests the minimum interfacial free energy hypothesis is not supported. In fact, the data suggest the opposite to be true. It is apparent that platelet adhesion can be a misleading indicator of blood compatibility. Neither hypothesis can explain the apparent conflict between the platelet adhesion data and the coagulation time data.

Animals↗

Thermogenesis in diabetes-obesity syndromes in mutant mice.

The two mouse mutants, obese (ob) and diabetes (db), cause similar diabetes-obesity syndromes that are characterized by a marked increase in apparent metabolic efficiency with regard to utilization of energy. A failure to thermoregulate in a normal fashion would save energy which could then be diverted to other functions and be reflected as increased metabolic efficiency. This study assesses the contribution of a defect in thermogenesis to the increased metabolic efficiency. Thermogenesis in obese (ob) and diabetes (db) mutant mice was quantified at various environmental temperatures. Both mutants maintained body temperatures near normal when maintained at ambient temperatures (23 degrees C), and if exposed to cold at 10 degrees C for a brief period, became cold-adapted and would survive indefinitely at 4 degrees C. Rectal temperatures of mutants maintained at 4 degrees C were only 1 degree -2 degrees C less than those seen in normal mice. This maintenance of nearly normal body temperature at temperatures less than thermoneutral was reflected by increased food consumption in all mice maintained in the cold. The data presented suggest that the defect in thermogenesis in both mutants is not a major cause of the increased metabolic efficiency. Hyperinsulinaemia, a consistent feature of both mutants, might by increasing anabolic processes (synthesis) and decreasing degradation spare energy normally used for tissue turnover and account for some of this increased metabolic efficiency.

Acclimatization↗

Association between serum inhibitory and bactericidal concentrations and therapeutic outcome in bacterial endocarditis.

Several recent reviews on the therapy of bacterial endocarditis have recommended that a serum inhibitory and/or bactericidal concentration (SIC/SBC) of 1:8 or more be achieved to ensure successful therapeutic outcome. We conducted a methodologic and statistical analysis of the available literature on endocarditis to determine the association between SIC/SBC titers of 1:8 or more and therapeutic outcome. We reviewed 17 studies published between 1948 and 1980 in which both SIC/SBC and therapeutic outcome were available. Factors that affect outcome, such as age, duration of symptoms, organism, and valve status, varied widely among the 226 patients. The methods used to measure SIC/SBC differed with respect to the time of obtaining the blood specimen relative to the antibiotic dose, size of the bacterial inoculum, type of broth, and definition of the bactericidal end-point. None of the 17 studies showed a significant association between SIC/SBC titers of 1:8 or more and survival or bacteriologic cure. Fifteen of the 17 also failed to demonstrate a significant association between SIC/SBC titers of 1:8 or more and medical cure. However, each of the studies that failed to demonstrate an association between SIC/SBC titers of 1:8 or more and improved therapeutic outcome had an insufficient sample size to confidently exclude a false-negative result. Analysis of the published data reveals insufficient evidence to demonstrate that SIC and SBC titers are of prognostic value in the therapy of patients with bacterial endocarditis.

Anti-Bacterial Agents↗

Pneumocystis carinii pneumonia in homosexual men.

The clinical records and radiographs of 12 homosexual men with symptomatic biopsy-proved Pneumocystic carinii pneumonia were reviewed. At presentation, the most common radiographic finding in the chest was a diffuse, coarse, ground-glass pattern. Normal findings on chest radiographs or only minimal abnormalities did not preclude P. carinii pneumonia. Progression of the radiographic findings varied. Rapid development of diffuse consolidation in 2--5 days occurred most commonly. Thoracic lymphadenopathy and pleural effusions were each seen in two patients. Clearing of the lungs often took many weeks. Six of the 12 patients died in 2 weeks to 8 months. In the appropriate clinical setting, early transbronchial biopsy should be strongly advocated to ensure initiation of suitable antimicrobial therapy.

Adult↗

Diabetes-obesity syndromes in mice.

Several different rodent models are available for metabolic studies on the development of diabetes. Although the abnormalities associated with each diabetes type have many features in common, the documentation of several different genes being involved makes it unlikely that the various syndromes will be reduced to a single disturbance in one metabolic pathway. The severity of the diabetes produced depends on the interaction of the individual mutation with genetic factors in the inbred background of the host. Establishing the nature of these gene-host interactions in rodents should aid us in understanding similar interactions that occur in human diabetes. The development of the syndrome in most models is similar and includes hyperinsulinemia, hyperphagia, and attempts at increasing insulin supply by beta-cell hyperplasia and hypertrophy in the early stages. Hyperglycemia, obesity, and severe diabetes are secondary features that result from a combination of insulin resistance and a failure to sustain the secretion of the large amounts of insulin. Most models utilize ingested food and stored food reserves more efficiently. This increased metabolic efficiency extends to heterozygotes that are normal in all respects having only one dose of the deleterious gene. Establishing this increased metabolic efficiency in heterozygotes lends credence to the thrifty gene hypothesis of diabetes and suggests a mechanism whereby some deleterious diabetes genes may be favored in the human population. The best studied mouse models, and those for which the most complete information is available, are those caused by single genes, e.g., yellow, obese, diabetes, tubby, and fat. In the other models, the mode of inheritance is either polygenic or otherwise unclear, features which interfere with the interpretation of the data. This report briefly summarizes the developing syndrome in each model, points out any differences, and suggests the most appropriate areas where future research should be most productive in the light of contemporary studies.

Animals↗

Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.

Alloxan↗

Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice.

Dehydroepiandrosterone (DHEA), a major adrenal secretory steroid in humans, was therapeutic when fed in a concentration of 0.4% to C57BL/KsJ mice with either non-insulin-dependent or insulin-dependent diabetes. Genetically diabetic (db/db) mice of both sexes develop obesity and a glucose intolerance and hyperglycemia associated with insulin resistance by 2 mo of age, and exhibit beta-cell necrosis and islet atrophy by 4 mo. In contrast, DHEA feeding initiated between 1 and 4 mo of age, while only moderately effective in preventing obesity, did prevent the other pathogenic changes and effected a rapid remission of hyperglycemia, a preservation of beta-cell structure and function, and an increased insulin sensitivity as measured by glucose tolerance tests. DHEA feeding was also therapeutic to normal C57BL/KsJ male mice made diabetic by multiple low doses of streptozotocin (SZ). While DHEA treatments did not block either the direct cytotoxic action of SZ on beta-cells or the development of insulitis, the steroid significantly moderated the severity of the ensuing diabetes (reduced hyperglycemia and water consumption, and increased plasma insulin and numbers of residual, granulated beta-cells.

Animals↗

Relapse of Paragonimus westermani lung infection after bithionol therapy.

Clinical trials of bithionol in treating Paragonimus westermani lung infection have been conducted in areas of endemic infection. Bithionol has been reported to cure over 90% of infected patients. We report a case of a 32-year-old Laotian man residing in Connecticut who relapsed with P. westermani pneumonitis 4 months after apparent eradication of infection with bithionol (40 mg/kg by mouth every other day for 10 doses). He was successfully treated with a second course of bithionol (40 mg/kg by mouth every other day for 15 doses). The mechanism of relapse of P. westermani infection following bithionol therapy should be evaluated.

Adult↗

An outbreak of Pneumocystis carinii pneumonia in homosexual men.

Pneumocystis carinii pneumonia has rarely been reported in previously healthy persons over the age of 6 months. Five cases of P. carinii pneumonia in adult homosexual men, confirmed by biopsy results, are reported. All five patients were seropositive when tested for antibodies to cytomegalovirus and four had evidence of active concurrent cytomegalovirus infections. Kaposi's sarcoma was shown in two of the patients and one had possible Pneumocystis infection of the central nervous system as well as P. carinii pneumonia. Three patients had second episodes of Pneumocystis pneumonia. Four of the five patients have died. Past or concurrent cytomegalovirus infection and homosexuality were the only common epidemiologic features in all five patients.

Adult↗

Dietary control of pathogenesis in C57BL/KsJ db/db diabetes mice.

Weanling C57BL/KsJ homozygous diabetic (db/db) and normal littermate (+/+ or +/db) mice were maintained for 5 mon on isocaloric diets containing either 60% sucrose, 23% casein, 8% corn oil (diet C) or 0% sucrose, 83% casein, 8% corn oil (diet B). Diabetic homozygotes consumed more diet C than normals, but ate control amounts of diet B. Diabetic mice fed diet C exhibited 57% mortality between 4 or 5 mo of age. All diabetic mutants fed the carbohydrate-free diet B appeared healthy at 6 mo of age; mutant females were normoglycemic and mutant males were only moderately hyperglycemic. Histological examination of pancreatic islets confirmed the absence of islet degeneration. In diet B maintained mutants, increased carcass fat composition, plasma and pancreatic content of insulin and glucagon, and thymidine incorporation into islets, all established that the db gene was being fully expressed. These results indicate that dietary protein stimulates islet growth and function in db/db mice, while high levels of refined carbohydrate in the diet predispose islet beta cells to undefined changes that culminate in necrosis. Restricting mutants' intake of a carbohydrate-containing diet to one-half the caloric intake of normal mice failed to block onset of beta cell necrosis. Thus, dietary composition rather than total caloric intake appears to be critical in the induction of islet necrosis and atrophy in this animal model of genetically transmitted diabetes.

Animals↗

Determination of moxalactam in human body fluids by liquid chromatographic and microbiological methods.

High-performance liquid chromatographic methods for determination of the isomers of moxalactam in plasma and urine have been developed. Conventional reverse-phase chromatography was used for plasma assays, and an ion-pairing reagent was included for urine assays. Detection limits were 1.5 micrograms/ml of plasma and 7.5 micrograms/ml of urine. The high-performance liquid chromatographic assays were extensively compared with a microbiological assay (detection limit, 1 microgram/ml), using samples from human volunteers to whom moxalactam had been administered as well as plasma and urine from untreated humans, to which moxalactam was added. The correlations between the assays were quite good, but the precision and accuracy of the high-performance liquid chromatographic methods were superior. Both types of assays were used in a study of the stability of moxalactam-containing samples at various temperatures.

Biological Assay↗