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Biomedical subjects

R A Hahn

Publications and source records attributed to R A Hahn.

At least 37 records · Page 2Linked to original sources
PubMed1992

The state of federal health statistics on racial and ethnic groups.

OBJECTIVE: To examine assumptions underlying federal health statistics on racial and ethnic groups in the United States. DATA SOURCES: Studies conducted by federal agencies and other investigators, and technical appendices of published vital statistics and census reports. DATA SYNTHESIS: Several assumptions underlying federal health statistics on racial and ethnic groups are not well supported. Conceptual (as opposed to operational) definitions of race and ethnicity are not available, and scientific grounds for definition are not considered. Procedures for the ascertainment of race and ethnicity vary within and among data-collection agencies. Miscounting and misclassification may vary by an order of magnitude between whites and other races. The responses of individuals to questions of racial and ethnic identity differ for different indicators, in different surveys, and at different times. As a result, counts, rates, and rate ratios may not be meaningful or accurate. Particularly for Hispanics and for races other than whites or blacks, there are inconsistencies in statistical information that may hinder health research and program development. CONCLUSIONS: Improvement of federal health statistics for racial and ethnic groups requires (1) clarification of goals for classification, (2) adoption of scientific principles for the validation and definition of the categories "race" and "ethnicity," (3) assessment of perceived social identity in the population, and (4) periodic evaluation.

Data Collection↗
PubMed1992

beta-D xyloside alters dermatan sulfate proteoglycan synthesis and the organization of the developing avian corneal stroma.

Corneal transparency is dependent upon the development of an organized extracellular matrix containing small diameter collagen fibrils with regular spacing, organized as orthogonal lamellae. Proteoglycan-collagen interactions have been implicated in the regulation of collagen fibrillogenesis and matrix assembly. To determine the role of dermatan sulfate proteoglycan in the development and organization of the secondary corneal stroma, its synthesis was disrupted using beta-D xyloside. The secondary corneal stroma contains two different proteoglycans, dermatan sulfate and keratan sulfate proteoglycan. beta-D xyloside interferes with xylose-mediated O-linked proteoglycan synthesis, and thus disrupts dermatan sulfate proteoglycan synthesis. Corneal keratan sulfate proteoglycan, a mannose-mediated N-linked proteoglycan, should not be altered. Biochemical analysis of corneas treated both in vitro and in ovo revealed a reduced synthesis of normally glycosylated dermatan sulfate proteoglycans and an increased synthesis of free xyloside-dermatan sulfate glycosaminoglycans. Keratan sulfate proteoglycan synthesis was unaltered in both cases. Corneal stromas were studied using histochemistry and electron microscopy after in ovo treatment with beta-D xyloside. The observed biochemical alterations in dermatan sulfate proteoglycans translated into disruptions in the organization of beta-D xyloside-treated stromas. There was a reduction in the histochemical staining of proteoglycans, but no alteration in collagen fibril diameter. In addition, focal alterations in collagen fibril packing, and a disruption of lamellar organization were observed in beta-D xyloside-treated corneas. These data suggest that dermatan sulfate proteoglycans are not involved in the regulation of corneal collagen fibril diameter, but are important in the fibril-fibril spacing as well as in lamellar organization, and cohesiveness.

Animals↗
PubMed1992

Evaluation of LY203647 on cardiovascular leukotriene D4 receptors and myocardial reperfusion injury.

In vitro studies have shown LY203647 to be a selective antagonist of contractile responses to leukotriene (LT) D4 and LTE4 in guinea pig ileum, trachea and lung parenchyma. In pithed rat, i.v. injection of LTD4 produced pressor responses that were selectively antagonized by LY203647 in a dose-dependent manner [ED50 7.5 (6.0-9.5) mg/kg, i.v.]. In normal anesthetized rats and dogs, LTD4 reduced aortic blood flow and stroke volume in association with systemic vasoconstriction, variable blood pressure responses and no change in cardiac rate. LTD4 did not alter myocardial contractility corrected for alterations in afterload. Pretreatment of rats and dogs with LY203647 (1-10 mg/kg, i.v.) produced dose-related inhibition of the myocardial and systemic hemodynamic effects of LTD4, whereas coadministration of LY203647 reversed established myocardial depression and systemic and pulmonary vasoconstriction during continuous infusion of LTD4 in dogs. LY203647 (10 mg/kg over 90 min, i.v.) infusion in normal dogs abolished or greatly antagonized hemodynamic responses to LTD4 for 6 hr. In subsequent experiments, myocardial infarct size was measured after 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion. LY203647 (10 mg/kg over 90 min, i.v.) treatment did not alter cardiovascular parameters when compared to time-related alterations observed in control dogs. ST segment deviation and the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion also were similar between groups. Resultant infarct sizes were 46 +/- 1 and 45 +/- 1% of the left ventricular mass placed at risk in control and LY203647-treated dogs, respectively. Present data illustrate the prominent cardiac and systemic hemodynamic effects of LTD4 and indicate that LY203647 produces selective and sustained antagonism of cardiovascular LTD4 receptors. Lack of containment of infarction by LY203647 suggests that endogenous cysteinyl-LT do not contribute to reperfusion injury of ischemic myocardium.

Acetophenones↗
PubMed1991

(Phenylmethoxy)phenyl derivatives of omega-oxo- and omega-tetrazolylalkanoic acids and related tetrazoles. Synthesis and evaluation as leukotriene D4 receptor antagonists.

Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists. In the omega-[(phenylmethoxy)phenyl]-omega-oxoalkanoic acid series, 5-[4-[(4-acetyl-2-ethyl-3-hydroxyphenyl)methoxy]phenyl]-3,3-dimethyl-5- oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pKB of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv). Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds. In the omega-[5-[[(phenylmethoxy)phenyl]alkyl] tetrazolyl]alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat. The pKB value in the guinea pig ileum for 1-[2-hydroxy-3-propyl-4- [[4-[[2-[3-(1H-tetrazol-5-yl)propyl]-2H-tetrazol-5-yl]methyl ] phenoxy]methyl]phenyl]ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv. The sodium salts of 8 (9) and 25 (26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner. Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.

Acetophenones↗
PubMed1991

Profound bilateral blindness and the incidence of breast cancer.

This case-control study addressed the hypothesis that uninterrupted exposure to light is associated with increased rates of breast cancer. We compared the odds of profound binocular blindness among women with a diagnosis of breast cancer with the odds of profound binocular blindness among women with diagnoses of coronary heart disease or stroke. All hospital discharges in the National Hospital Discharge Survey from 1979 through 1987 were analyzed, after exclusion of women with diabetes. Profoundly blind women were half as likely to have breast cancer as women who were not profoundly blind. This effect diminished substantially with increasing age.

Adolescent↗
PubMed1991

Xanthine oxidase inhibition does not limit canine infarct size.

BACKGROUND: Evidence supporting the role of xanthine oxidase in myocardial reperfusion injury is based on studies with pharmacological interventions used to inhibit enzyme function. Controversy exists, however, regarding the true role of xanthine oxidase in reperfusion injury. This study was performed to determine whether xanthine oxidase inhibition limits myocardial injury due to coronary artery occlusion and reperfusion. METHODS AND RESULTS: Anesthetized dogs underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours). Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3 hours after reperfusion. Regional myocardial blood flow was determined with radiolabeled microspheres. Infarct size was determined with the tetrazolium method. Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%. Infarct size for the amflutizole-treated dogs, 40 +/- 21%, was not significantly different from that of the control group. There were no differences in rate-pressure product or collateral blood flow to account for differences in infarct size. Uric acid concentration in the coronary venous plasma increased after reperfusion in the dogs treated with vehicle but not in the drug-treated dogs. Xanthine oxidase inhibition was demonstrated in each of the drug treatment groups, but only oxypurinol limited the extent of myocardial injury. CONCLUSIONS: Previously reported cardioprotective effects of allopurinol, noted to occur only when the drug was administered chronically, may be related to a property of oxypurinol, a major metabolite of allopurinol. The beneficial effect of oxypurinol is unrelated to inhibition of superoxide formation during xanthine oxidase-catalyzed oxidation of xanthine and hypoxanthine.

Animals↗
PubMed1991

Characterization of LY233569 on 5-lipoxygenase and reperfusion injury of ischemic myocardium.

LY233569 produced concentration-dependent inhibition of isolated guinea pig 5-lipoxygenase (5-LPO) and 5-LPO activity of human polymorphonuclear leukocytes in vitro; IC50 values were 0.4 and 0.1 microM, respectively. LY233569 also inhibited (IC50 approximately 1.8 microM) zymosan-stimulated production of leukotriene B4 in canine whole blood but had little or no concomitant effect on the production of thromboxane B2. Concentrations of LY233569 as high as 10 microM did not inhibit production or scavenge superoxide from activated human neutrophils. In normal anesthetized dogs, infusion of LY233569 (0.11 mg/kg/min, i.v.) for 6 hr produced persistent inhibition (approximately 80%) of leukotriene B4 production in blood challenged ex vivo with zymosan; the plasma concentration (approximately 4 microM) of LY233569 was consistent with in vitro data illustrating selective and maximal inhibition of 5-LPO. In subsequent experiments, myocardial infarct size was measured after 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion. Continuous infusion of LY233569 (0.11 mg/kg/min, i.v.) had little or no effect on base-line systolic arterial pressure, cardiac rate and the pressure rate product when compared with time-related changes observed in control dogs. LY233569 infusion also did not alter the degree of ST-segment deviation or the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion. Resultant myocardial infarct sizes were 45 +/- 5% of the left ventricle placed at risk in control dogs and 43 +/- 4% in dogs given LY233569. Myeloperoxidase activity of infarcted myocardium did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Excess deaths from nine chronic diseases in the United States, 1986.

To assess excess mortality from chronic disease in the United States, state age-adjusted combined mortality rates for nine chronic diseases in 1986 were compared with three "minimum" rates--two calculated from rates actually achieved in states and a third estimated as the mortality remaining after elimination of one risk factor for each disease. Hawaii had the lowest mortality rate of combined diseases (305/100,000); state excesses ranged from 0% to 37%. The sum of lowest disease-specific rates in any state was 284 per 100,000, indicating excesses of between 7% and 41%. A minimum mortality rate of 224 per 100,000 was estimated to result from elimination of one risk factor for each of the nine diseases, indicating state excesses from 26% to 54%, or 524,000 US deaths. Reduction of US mortality from the nine diseases to the risk factor--eliminated rate is estimated to be associated with an increased life expectancy at birth of 4 years.

Chronic Disease↗
PubMed1990

Antagonism of leukotriene B4 receptors does not limit canine myocardial infarct size.

Injection of leukotriene (LT)B4 (0.1-3 micrograms/kg i.v.) in normal anesthetized dogs produced dose-related leukopenia that was accompanied by arterial hypotension and tachycardia at higher tested doses. LTD4 (0.1-3 micrograms/kg i.v.), in contrast, increased arterial blood pressure, lowered cardiac rate and produced little change in arterial blood leukocyte count. Continuous infusion of LY255283 [(1-(5-ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)- heptyloxy)phenyl)ethanone] (0.33 mg/kg/min i.v.), a selective LTB4 receptor antagonist, resulted in near complete inhibition of leukopenic, hypotensive and tachycardic responses to LTB4 (3 micrograms/kg i.v.) challenge over a 6-hr test period. Persistent antagonism of canine LTB4 receptors was associated with high circulating levels of LY255283 that were bound extensively to plasma proteins. In subsequent experiments, myocardial infarct size was measured following 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion in control dogs infused with vehicle, and in dogs receiving LY255283 (0.33 mg/kg/min i.v.). Drug and vehicle were infused continuously beginning 15 min before coronary artery occlusion. LY255283 treatment essentially did not alter base-line cardiovascular parameters or myocardial oxygen demand when alterations were compared to time-related changes observed in control dogs. LY255283 infusion also did not alter the degree of myocardial ischemia or the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion. Resultant infarct sizes were 43 +/- 5% of the left ventricle placed at risk in control dogs and 32 +/- 5% in dogs given LY255283; this difference was not statistically significant. The extent of left ventricle placed at risk was similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Prevalence of HIV infection among intravenous drug users in the United States.

We reviewed 92 published and unpublished studies of the prevalence of infection with the human immunodeficiency virus (HIV) among intravenous drug users (IVDUs) in the United States. Human immunodeficiency virus seroprevalence among IVDUs in drug treatment programs in the United States ranged from 0% to 65%. Seroprevalence was highest in the Northeast (10% to 65%) and Puerto Rico (45% to 59%); lower in the South Atlantic (7% to 29%) and in the metropolitan areas of Atlanta, Ga (10%), Detroit, Mich (7% to 13%), and San Francisco, Calif (7% to 13%); and 5% or less in other areas of the West, the Midwest, and the South. Among IVDUs seen in drug treatment programs, risk of infection was not associated with gender or age but was associated with black and Hispanic ethnicity, male homosexual orientation, and certain intravenous drug-use practices. Cross-sectional and cohort studies indicated increases in seroprevalence of between 0% and 14% per year among IVDUs in treatment. We estimated that between 61,000 and 398,000 IVDUs in the United States were infected with human immunodeficiency virus, or 5% to 33% of the IVDU population. High rates of infection among IVDUs in treatment in the Northeast indicate the potential for rapid spread in regions where rates are currently low. An urgent need exists to monitor human immunodeficiency virus infection levels and trends more widely and to develop effective programs to reduce the further spread of human immunodeficiency virus infection among IVDUs.

Black or African American↗
PubMed1989

Leukotriene (LT) receptor antagonists. Heterocycle-linked tetrazoles and carboxylic acids. LY203647.

LY171883, 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl] ethanone, is an orally active antagonist of LTD4- and LTE4-induced responses in a variety of test systems. We prepared a new series of LT antagonists based on a proposed model of LY171883 binding to the LTE4 receptor in which the n-propyl and tetrazole moieties of LY171883 occupy those parts of the receptor to which the C1-C5 chain and the cysteinyl carboxyl of LTE4 bind, respectively. The new compounds have an acidic function corresponding to the glycine carboxyl of LTD4 linked through a heterocyclic group which is proposed to bind to the LTD4 receptor where the cysteinyl glycine amide bond of LTD4 binds. LY203647, 1-[2-hydroxy-3-propyl-4-[4-[2-[4-(1H-tetrazol-5-yl)butyl]-2H- tetrazol-5-yl]butoxy]phenyl] ethanone, showed good LTD4 antagonist activity with a suitable pharmacologic and toxicologic profile and has been chosen for clinical evaluation.

Acetophenones↗
PubMed1989

Mechanical properties of collagen fibres: a comparison of reconstituted and rat tail tendon fibres.

This study involves comparison of the mechanical properties of reconstituted collagen fibres with those of collagen fibres obtained from rat tail tendons. Reconstituted collagen fibres were cross-linked in the presence of glutaraldehyde vapour for 2 and 4 d or using a combination of severe dehydration and carbodiimide treatment. Ultimate tensile strengths for reconstituted fibres cross-linked with glutaraldehyde ranged from 50 to 66 MPa while those cross-linked by severe dehydration and carbodiimide treatment had ultimate tensile strengths between 24 and 31 MPa. Rat tail tendon fibres had tensile strengths that ranged from 33 to 39 MPa. These results indicate that high-strength collagen fibres can be reconstituted in vitro and that these fibres may be useful in repair of dermal, dental, cardiovascular and orthopaedic defects.

Animals↗
PubMed1989

Nulliparity, decade of first birth, and breast cancer in Connecticut cohorts, 1855 to 1945: an ecological study.

Risk of breast cancer increases with age at first birth, and is lower in women who bear their first children while young than in nulliparous women. While previous studies have investigated risk of breast cancer in birth cohorts by examining partial aspects of cohort childbearing, the present ecological study assesses total cohort childbearing risk in Connecticut women born between 1855 and 1945. In each cohort, the proportion of women nulliparous and first bearing children in their twenties, thirties, and forties are weighted by relative risks associated with these events as ascertained in previous studies. Summed cohort childbearing risks are compared to the incidence of breast cancer in women 40 years of age and older in the same cohorts. Changes in decade of first birth and nulliparity do not explain the changes in breast cancer incidence observed: while cohort childbearing risk has declined over the period examined, breast cancer incidence has increased in the same cohorts. Alternative explanations for cohort increases in breast cancer incidence are reviewed.

Breast Neoplasms↗
PubMed1989

Race and the prevalence of syphilis seroreactivity in the United States population: a national sero-epidemiologic study.

We used the 1978 National Health and Nutrition Examination Survey to examine the prevalence of positive syphilis serologies in the US population. Analysis of risk markers--gender, age, marital status, education, income, and residence--indicates that all except gender are associated with syphilis seroreactivity, independent of race. Controlling for associated risk markers, the Black-White odds ratio of syphilis seroreactivity is 4.7 (95% CI = 2.7, 8.2). Current knowledge of racial differences in sexual and health care behavior does not explain the Black-White difference in the prevalence of syphilis seroreactivity.

Adolescent↗
PubMed1987

Primate myocardial and systemic hemodynamic responses to leukotriene D4: antagonism by LY171883.

Intravenous infusion of leukotriene D4 (LTD4; 0.1-10 micrograms/kg) produced dose-related depression of myocardial contractility, stroke volume index and mean aortic blood flow index in anesthetized monkeys. These alterations occurred in association with increments in systemic and pulmonary vascular resistances, reductions in calculated left ventricular stroke and minute work indices and relatively little or no dose-dependent change in cardiac rate, mean arterial blood pressure and mean pulmonary arterial blood pressure. Left atrial pressure did not increase in response to LTD4, although cardiac afterload was increased and myocardial contractility and stroke volume index were reduced. LTD4-induced alterations of aortic blood flow index, stroke volume index and systemic and pulmonary vascular resistances were sustained during a 60-min observation period after drug infusion. Pretreatment of monkeys with LY171883 (10 mg/kg i.v.), a selective LTD4-LTE4 receptor antagonist, inhibited the magnitude and duration of hemodynamic responses to LTD4 challenge. For example, LTD4 dose-response curves for depression of mean aortic blood flow index, stroke volume index and left ventricular stroke and minute work indices were shifted to the right approximately 10-fold by LY171883. The plasma concentration of LY171883 effective in this regard was 32 +/- 7 micrograms/ml. Attenuation of LTD4 responses by LY171883 was selective in that antagonist pretreatment did not result in concomitant reduction of vascular and cardiac responses mediated by adrenergic receptors, and LY171883 administration produced little or no change in base-line parameters. The composite data provide evidence of the presence of LT receptors in the primate cardiovascular system and suggest that LY171883 is a selective antagonist of these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗
PubMed1984

Depletion of cardiac norepinephrine in rats and mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a commercially available chemical reagent. Although little has been known about its biological effects, recently MPTP has been reported to cause irreversible Parkinson's disease-like symptoms in humans and in monkeys. We describe here another pharmacologic effect of MPTP, the ability to deplete cardiac norepinephrine in rats and mice. In mice, cardiac norepinephrine concentration decreased within 1 hr, was maximally depleted at 24 hr, and recovered by 4-7 days after i.p. injection of a 32 mg/kg dose of MPTP. The depletion was antagonized by desipramine pretreatment, as was norepinephrine depletion by tyramine. In rats, cardiac norepinephrine depletion by 10-30 mg/kg, i.p., doses of MPTP was accompanied by depletion of cardiac dopamine and of norepinephrine in the mesenteric artery. In rats and in mice, norepinephrine in brain was affected to a smaller degree than was norepinephrine in heart, and dopamine in brain was depleted very little if at all. In spontaneously hypertensive rats, the depletion of cardiac norepinephrine was associated with a marked antihypertensive effect. The p-hydroxy analog of MPTP did not deplete cardiac norepinephrine in rats, indicating that its possible formation as a metabolite of MPTP was not involved in the depletion of cardiac norepinephrine. These findings extend the spectrum of known pharmacologic effects of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗