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Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 469 records · Page 26Linked to original sources
PubMed1987

Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography.

To impact on the development of clinical congestive heart failure as a complication of doxorubicin therapy, left ventricular ejection fraction was monitored with serial resting radionuclide angiocardiography in 1,487 patients with cancer over a seven-year period in both university and community hospital environments. A high-risk subset of 282 patients was selected for retrospective analysis of their clinical outcome. High-risk patients were identified by one or two of the following three criteria: decline of 10 percent or more in absolute left ventricular ejection fraction from a normal baseline to 50 percent or less; high cumulative dose of doxorubicin (more than 450 mg/m2); abnormal baseline left ventricular ejection fraction (less than 50 percent). Clinical congestive heart failure occurred in 46 (16 percent) during the treatment period, and in an additional three patients (1.3 percent) at last follow-up examination 11.8 +/- 14.2 months following discontinuation of doxorubicin. Total cumulative dosages of doxorubicin that precipitated congestive heart failure (75 to 1,095 mg/m2) and those that did not (30 to 880 mg/m2) varied widely. Decline of 10 percent or more in absolute left ventricular ejection fraction to a value of 50 percent or less preceded administration of the final dose of doxorubicin that precipitated clinical congestive heart failure in the majority of patients in whom congestive heart failure developed. Clinical congestive heart failure improved in 87 percent given routine therapy with digitalis, diuretics, and/or vasodilators. Criteria for monitoring left ventricular ejection fraction and discontinuing doxorubicin were formulated. The occurrence of clinical congestive heart failure was compared in those patients whose management was concordant with proposed criteria (Group A) and in those whose management was not (Group B). Group A had a lower incidence of congestive heart failure compared with Group B (2.9 percent versus 20.8 percent, p less than 0.001) and had only mild congestive heart failure that resolved with treatment (n = 2) and no deaths due to congestive heart failure. Multivariate analysis with proportional-hazards regression (Cox's model) demonstrated a fourfold reduction in the incidence of congestive heart failure independent of other clinical predictor variables in those patients whose management was concordant with proposed guideline criteria. The incidence, persistence, late development, predictability, and reversibility of clinical congestive heart failure were comparable in university and community hospital settings.(ABSTRACT TRUNCATED AT 400 WORDS)

Doxorubicin↗
PubMed1987

Comparative genotoxic effects of IQ and MeIQ in Salmonella typhimurium and cultured mammalian cells.

The food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) were studied for their genotoxic potential using hepatocytes isolated from untreated and Aroclor 1254 (PCB) pretreated rats as an activation system. Monolayers of hepatocytes co-incubated with Salmonella typhimurium TA98 activated IQ and MeIQ to bacterial mutagens, with MeIQ being about twice as potent as IQ. The mutagenic activities of IQ and MeIQ were increased by using hepatocytes from PCB-pretreated rats. IQ and MeIQ also caused primary DNA damage in the hepatocytes as determined by increases in the rate of alkaline elution of DNA, as well as increases in DNA-repair synthesis. Furthermore, exposure of V79 cells co-cultured with PCB-pretreated hepatocytes to IQ and MeIQ showed evidence of increased sister-chromatid exchanges and a low and variable increase in the number of 6-thioguanine-resistant mutants. The genotoxic potency of IQ and MeIQ in mammalian cells was low or virtually absent compared to their extreme potency in bacteria. This could be due to a lower capacity of mammalian cells to further metabolize the so-called directly acting bacterial mutagens, formed by a cytochrome P-450 dependent N-hydroxylation, to their ultimate reactive forms.

Animals↗
PubMed1987

Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis.

Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decreased plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is cleared by the parenchymal tissues, the tissue distribution of 59Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congenital hypotransferrinemia. In control animals, injected 59Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected 59Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound 59Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected 59Fe was removed with a half-time of less than 30 s. Analysis of the distribution of 59Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of 59Fe not bound to transferrin. These results demonstrate the existence of and an uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is a consequence of reduced concentrations of apotransferrin.

Animals↗
PubMed1987

Fluorometric detection of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and their N-acetylated metabolites excreted by the rat.

A sensitive fluorometric method has been developed for the determination of carcinogenic amino imidazoazaarenes (AIA compounds) which are formed during the cooking of food. They are separated by t.l.c. followed by spraying with dimethylsulfoxide and visualization by long-wave u.v. light. Quantification is done by fluorescence scanning. This method was applied to the determination of the metabolites in urine and feces from rats given 5 mg/kg body wt i.p. of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). Metabolites extractable by organic solvents were identified as the parent compound and their N-acetylated derivatives (AcIQ, AcMeIQ). Between 0.1 and 1% of the administered dose was recovered as these metabolites in urine during 24 h. The amounts of MeIQ and AcMeIQ found in feces were approximately 1 and 3% respectively. AcIQ was not detected in feces while IQ, MeIQ and their N-acetylated derivatives were found in bile. The metabolites in urine were identified by m.s. and in feces by t.l.c. and their fluorescent properties. When IQ or MeIQ were incubated with rat liver cytosol in the presence of acetyl-CoA, N-acetylated derivatives were formed. The reverse reaction, deacetylation, also took place in the liver cytosol, with Km values of 67 and 32 microM for AcIQ and AcMeIQ respectively.

Acetylation↗
PubMed1987

The correlation between delayed hypersensitivity, lymphocyte activation and protective immunity in experimental murine leishmaniasis.

The growth of Leishmania major and Leishmania mexicana lesions and the concomitant development of delayed-type hypersensitivity (DTH) to homologous or heterologous soluble antigen was studied in BALB/c and CBA/Ca mice. Although CBA/Ca mice are highly susceptible to L. mexicana, developing non-healing lesions, they are resistant to L. major; while BALB/c mice develop non-healing lesions when infected with either species. The development of resistance was associated with the acquisition of DTH which peaked at 48 h (L. major infected CBA/Ca mice). Non healing lesions were associated with either negative DTH (L. major infected BALB/c mice) or DTH that peaked at 24 h but had significantly subsided by 48 h (L. mexicana infected CBA/Ca and BALB/c mice). The latter response was associated with basophilic infiltration of the skin test site. Pre-irradiating (600 rad) CBA/Ca and BALB/c mice induced resistance against L. mexicana and L. major respectively in conjunction with the appearance of 48 h DTH to the homologous antigen. There was clear dissociation in the skin reactivity produced by the heterologous antigen. Thus L. major-derived antigen failed to produce DTH in L. mexicana infected mice of either strain. L. mexicana-derived antigen on the other hand produced a quicker response and of greater magnitude than the homologous antigen in L. major infected CBA/Ca mice. This correlated well with the strong cross-immunity induced by L. major in these mice to L. mexicana infection.

Animals↗
PubMed1987

Parental smoking, breast feeding, and respiratory infection in development of allergic diseases.

Environmental factors were examined as determinants of clinical disease in a five year prospective study of 73 children born to atopic parents. Clinical follow up for evidence of eczema and wheezing was combined with regular skin testing, immunoglobulin assay, and respiratory viral culture where appropriate. Thirty six children developed eczema, which was often associated with a positive result of a skin test to ingestants in the first year and inhalants by the fifth year. Thirty two children developed one or more episodes of wheeze. Fifteen children wheezed once only, and not all of these developed atopy. No pattern of respiratory infection in early life was characteristic of children with recurrent wheeze. There was a significant difference in parental smoking habits between children with and without episodes of wheeze at the fifth birthday. No protective effect of breast feeding could be shown. The development of allergic disease in susceptible children is influenced by many environmental factors. Advice to families about reduction of environmental allergens continues to pose problems, but parents should be advised to avoid smoking in the child's presence.

Allergens↗
PubMed1987

Deep venous thrombosis: US assessment using vein compression.

To assess vein compressibility as a simple ultrasound (US) technique to determine the presence of venous thrombi, 51 patients undergoing contrast material venography of the lower extremity because of a clinical suspicion of deep venous thrombosis (DVT) also underwent high-resolution US evaluation of the veins. DVT was diagnosed on 28 venograms. In 25 patients US studies demonstrated non-compressibility of the veins, indicating the presence of clot. In 23 patients with normal venograms, US examinations demonstrated total compressibility of the veins, indicating the absence of DVT. Clots below the knee were not depicted by US. In this study US had a sensitivity of 89% and a specificity of 100%.

Adolescent↗
PubMed1987

Instantaneous pressure-volume relation of the ejecting canine left atrium.

To characterize the pump function of the left atrium, we determined the instantaneous pressure-volume relation of the isolated supported left atrium. A physiologic after-loading system for the low-pressure atrium was created by coupling it to a real-time computer-simulated ventricle and a simulated venous impedance network via a volume servo-pump. In 10 atria loaded with such systems, multiple isochronal sets of pressure-volume data were collected from many ejecting or isovolumic contractions obtained under a constant inotropic state, and the time-varying elastance, E(t), as well as the volume-axis intercepts, VO(t), were calculated. E(t) is the ensemble of slopes, and VO(t), the volume-axis intercepts resulting from the linear regression of instantaneous pressure on instantaneous volume at multiple instants throughout the cardiac cycle. The systolic portion of the left atrial E(t) was insensitive to loading conditions, as was VO(t), which, in addition, proved to be similar to the right atrial and right ventricular VO(t) waveforms in its time dependence. These results indicate that E(t) and VO(t) adequately represent the instantaneous pressure-volume relation of the left atrium in systole irrespective of the mode of contraction. Whatever the underlying mechanism might be, the load insensitivity and similarity of the basic shape of the left atrial E(t) among different atria suggests that the characterization reflects fundamental features of left atrial contraction.

Animals↗
PubMed1987

Evaluation of topical metronidazole gel in acne rosacea.

Topical metronidazole gel (0.75%) was compared to placebo gel in a randomized, double-blind, placebo-controlled, split-face clinical trial for the treatment of 59 patients with acne rosacea. Statistically significant differences in inflammatory lesions, erythema, and global assessments were seen at three, six, and nine weeks post-baseline in favor of the active treatment side. It did not, however, alter the telangiectatic component of the disease. No known drug-related side effects were detected, and the low topical dose along with low serum levels of metronidazole indicate a high safety profile for this therapeutic agent. This work suggests that metronidazole gel, as specifically formulated, is safe and effective in reducing the symptomatology of acne rosacea.

Administration, Topical↗
PubMed1987

The outcome of neurotic disorders after out-patient and day hospital care.

New psychiatric out-patients with depressive, phobic, and anxiety neurosis were randomly allocated to out-patient care or to one of two types of day hospital treatment, one specialising in psychotherapy and the other offering all forms of day care. Of 106 patients who entered the study, 78 had assessments of psychiatric symptomatology and social adjustment both before treatment and after 4, 8 and 24 months. There was no significant difference in outcome between depressive, phobic, and anxiety neurosis, and no overall difference in response to treatment between the three types of care. Suicidal symptoms were significantly less common in out-patients. In many respects, neurotic disorder can be regarded as a single syndrome.

Ambulatory Care↗
PubMed1987

Fatal hepatic necrosis due to pyrimethamine-sulfadoxine (Fansidar).

Pyrimethamine-sulfadoxine has been associated with severe and fatal cutaneous reactions as well as transient liver damage. We report the case of a patient who died of progressive hepatic failure caused by pyrimethamine-sulfadoxine administration. In addition, we summarize reports made to the Food and Drug Administration since 1982 that focus on hepatotoxic reactions to pyrimethamine-sulfadoxine. We suggest that fatal hepatic injury can occur after treatment with pyrimethamine-sulfadoxine and that physicians who prescribe the drug should be aware of this possibility.

Adolescent↗