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Biomedical subjects

R H Kennedy

Publications and source records attributed to R H Kennedy.

At least 19 recordsLinked to original sources
PubMed2001

Eye banking and screening for Creutzfeldt-Jakob disease.

OBJECTIVES: To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States. METHODS: Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated. RESULTS: Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD. CONCLUSIONS: Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.

Adolescent↗
PubMed2001

Estimated incidence of open-angle glaucoma in Olmsted County, Minnesota.

PURPOSE: To determine the incidence rates of open-angle glaucoma (OAG) in Olmsted County, MINNESOTA: DESIGN: Retrospective population-based estimate of incidence. PARTICIPANTS: From the medical histories of 60,666 residents of Olmsted County, Minnesota, who had ocular diagnoses during the study period, 114 subjects with newly diagnosed OAG were identified. METHODS: The database of the Rochester Epidemiology Project was used to identify all Olmsted County residents with a coded diagnosis of OAG, glaucoma suspect, or ocular hypertension during the period 1965 to 1980. Subjects newly diagnosed with and treated for OAG who also had documented clinical evidence of elevated intraocular pressure, optic nerve damage, and/or visual field loss consistent with glaucoma were included as incident cases. Population data for Olmsted County were drawn from United States Census data. Crude incidence data were adjusted to the age and gender distribution of the 1990 United States white population. MAIN OUTCOME MEASURES: Estimated incidence rates of OAG. RESULTS: The overall age- and gender-adjusted annual incidence rate of OAG in a predominantly Caucasian population is conservatively estimated to be 14.5 per 100,000 population. The rates increased with age from 1.6 in the fourth decade of life to 94.3 in the eighth decade. There was no significant difference in incidence by gender. The average annual rate of OAG in the last 2 years of the study was 27.7 compared with 12.3 before 1979. This difference is suggestive of the effect of the introduction of a new medical therapy (timolol) for OAG during the last 2 years. CONCLUSIONS: The incidence rates of OAG increase markedly with advancing age, and screening efforts should be targeted at both men and women in the older age groups. The advent of new diagnostic and therapeutic modalities can have an effect on incidence rates.

Adolescent↗
PubMed2001

Endonasal dacryocystorhinostomy: a report by the American Academy of Ophthalmology.

OBJECTIVE: This document describes endonasal dacryocystorhinostomy (DCR) and examines the evidence to answer key questions about the effectiveness of the procedure compared with external DCR; the relative indications, contraindications, advantages, and limitations of the procedure; and patient selection, surgical technique, postoperative care, and complications. METHODS: A literature search conducted for the years 1968 to 2000 retrieved 93 citations. The panel members reviewed 71 of these articles and selected 64 for the panel methodologist to review and rate according to the strength of evidence. A level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a level II rating is assigned to well-designed cohort and case-control studies; and a level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. RESULTS: The published literature includes two reports that describe clinical trials comparing endonasal with external DCR with a 1-year follow-up. The success rate was 91% for the external DCR group in both reports and 63% and 75% for the endonasal DCR groups, defined by patency to irrigation. A longitudinal cohort study included a control group of age-matched external DCR patients who were compared with a study group of endonasal DCR patients. The reported success rate at 9 months following surgery for the endonasal cohort was 90% and was not statistically significantly different from the 94% success rate noted in the external DCR control group. Remaining data on reported success rates of primary and revision endonasal DCR were obtained from a collection of uncontrolled observational case studies with varying periods of follow-up and success rates ranging from 59% to 100%. CONCLUSIONS: It is difficult to make definite evidence-based determinations about the relative efficacy of endonasal and external DCR because of the deficiencies in the reported literature. Based on level III evidence, the available data suggest that endonasal DCR may be a viable option for the correction of acquired nasolacrimal duct obstruction and complex forms of congenital dacryostenosis in selected patients. This procedure may be indicated on a primary basis or as revisional surgery following failed external or endonasal DCR. Some studies comparing endonasal DCR with external DCR suggested lower success rates in the endonasal group; other studies yielded success rates comparable with or exceeding those of external surgery. Reported complications of endonasal DCR do not generally appear to be greater in frequency or magnitude than those associated with external DCR. Disadvantages of endonasal DCR include the preferred use of general anesthesia by many surgeons, the high cost of expensive equipment and instrumentation, and the relatively steep learning curve for this procedure. Depending on the preference of the surgeon, more postoperative care may be required for patients undergoing endonasal DCR than external DCR. Both the advantages and the limitations of endonasal DCR relative to external DCR should be carefully discussed with patients who are contemplating endonasal surgery.

Academies and Institutes↗
PubMed2001

Doxorubicin affects the cardiac muscarinic system in the rat.

During the study on the mechanism of doxorubicin-induced cardiotoxicity, we observed that a long incubation (4 hr) with doxorubicin reduced the maximal negative inotropic effects of a muscarinic receptor agonist, carbachol. The mechanism responsible for this doxorubicin-induced reduction of the efficacy of carbachol was examined in isolated guinea pig hearts. In isolated left atrial muscle preparations, 1 hr incubation with 100 microM doxorubicin caused a parallel right-ward shift of the concentration-response curves for carbachol, but a longer (4 hr) incubation with this agent (30, 100 or 200 microM), caused a significant reduction of the magnitude of the negative inotropic effect of carbachol in addition to the concentration-dependent parallel right-ward shift. The 4-hr incubation with these concentrations of doxorubicin also reduced the maximal negative inotropic effect of an adenosine A1 receptor agonist, R-phenylisopropyl adenosine (R-PIA), without affecting the potency of this agonist. Doxorubicin (1 to 100 microM) reduced [3H]quinuclidinyl benzilate (QNB) binding in a concentration dependent manner, but failed to alter [3HIR-PIA binding. The decrease in the magnitude of the maximal negative inotropic effect by doxorubicin was caused by changes in the muscarinic system at steps common to the transduction of muscarinic and adenosine A1 receptor mechanisms.

Adenosine↗
PubMed2000

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and insulin resistance.

High exposures of Vietnam veterans to 2,3,7, 8-Tetrachlorodibenzo-p-dioxin, a dioxin contained in the herbicide mixture Agent Orange, have previously been demonstrated to be associated with an increased prevalence of diabetes and hyperinsulinemia in non-diabetic subjects. Sixty-nine persons were identified who were in good health and had normal glucose levels during glucose tolerance testing. These subjects lived within 25 miles of the Vertac/Hercules Superfund site located in Jacksonville, Arkansas. The blood sera lipid concentrations of TCDD for the 69 subjects ranged between 2 and 94 ppt. When subjects with blood sera lipid TCDD levels in the top 10% (TCDD > 15 ppt, n = 7) were compared to subjects with lower levels (2-15 ppt, n = 62), there were no group differences in age, obesity, gender distribution, total lipids, or glucose levels. However, plasma insulin concentrations, at fasting and 30, 60, and 120 min following a 75 g glucose load, were significantly higher in the group with high blood TCDD levels. These finding could not be explained by other known risk factors for hyperinsulinemia. The finding of the TCDD-hyperinsulinemia relationship is consistent with studies of Vietnam veterans and suggests that high blood TCDD levels may cause insulin resistance.

Adult↗
PubMed2000

Induction of Ca-independent PLA(2) and conservation of plasmalogen polyunsaturated fatty acids in diabetic heart.

Diabetes-induced changes in phospholipase A(2) (PLA(2)) activity have been measured in several tissues but are undefined in diabetic myocardium. We measured ventricular PLA(2) activity in control, streptozotocin-induced diabetic, and insulin-treated diabetic rats and characterized myocardial phospholipids to determine whether diabetes altered myocardial phospholipid metabolism. Increased membrane-associated Ca(2+)-independent PLA(2) (iPLA(2)) activity was observed in diabetes that was selective for arachidonylated phospholipids. Increased iPLA(2) activity was accompanied by an increase in choline lysophospholipids. Diabetes was associated with marked alterations in the phospholipid composition of the myocardium, characterized by decreases in esterified arachidonic and docosahexaenoic acids and increases in linoleic acid. The decrease in polyunsaturated fatty acids was confined to diacylphospholipids, whereas the relative amount of these fatty acids in plasmalogens was increased. Diabetes-induced changes in PLA(2) activity, lysophospholipid production, and alterations in phospholipid composition were all reversed by insulin treatment of diabetic animals. Diabetes-induced changes in membrane phospholipid content and phospholipid hydrolysis may contribute to some of the alterations in myocardial function that are observed in diabetic patients.

Animals↗
PubMed2000

Aging-associated changes in whole cell K(+) and L-type Ca(2+) currents in rat ventricular myocytes.

The effect of aging on cardiac membrane currents remains unclear. This study examined the inward rectifier K(+) current (I(K1)), the transient outward K(+) current (I(to)), and the L-type Ca(2+) channel current (I(Ca,L)) in ventricular myocytes isolated from young adult (6 mo) and aged (>27 mo) Fischer 344 rats using whole cell patch-clamp techniques. Along with an increase in the cell size and membrane capacitance, aged myocytes had the same magnitude of peak I(K1) with a greater slope conductance but displayed smaller steady-state I(K1). Aged myocytes also had a greater I(to) with an increased rate of activation, but the I(to) inactivation kinetics, steady-state inactivation, and responsiveness to L-phenylephrine, an alpha(1)-adrenergic agonist, were unaltered. The magnitude of peak I(Ca,L) in aged myocytes was decreased and accompanied by a slower inactivation, but the I(Ca,L) steady-state inactivation was unaltered. Action potential duration in aged myocytes was prolonged only at 90% of full repolarization (APD(90)) when compared with the action potential duration of young adult myocytes. Aged myocytes from Long-Evans rats showed similar changes in I(to) and I(Ca,L) but an increased I(K1). These results demonstrate aging-associated changes in action potential, in morphology, and in I(K1), I(to), and I(Ca,L) of rat ventricular myocytes that possibly contribute to the decreased cardiac function of aged hearts.

Adrenergic beta-Antagonists↗
PubMed2000

Partnering through telemedicine to improve the quality of health-care.

In order to assist health-care reform in eastern Slovakia, a partnership was established with health-care institutions in Rhode Island. The aim of the partnership was to improve maternal and child health in Slovakia. Thirty-seven telemedicine sessions were conducted via a satellite link. A number of workshops, case studies, demonstrations and interactive discussions took place between various health-care professionals. The use of telemedicine accelerated the adoption of new procedures in Slovakia.

Cross Infection↗
PubMed2000

Reducing the progression of myopia with atropine: a long term cohort study of Olmsted County students.

BACKGROUND: Myopia is an important public health problem because it is common and is associated with increased risk for chorioretinal degeneration, retinal detachment, and other vision- threatening abnormalities. In animals, ocular elongation and myopia progression can be lessened with atropine treatment. This study provides information about progression of myopia and atropine therapy for myopia in humans. METHODS: A total of 214 residents of Olmsted County, Minnesota (118 girls and 96 boys, median age, 11 years; range 6 to 15 years) received atropine for myopia from 1967 through 1974. Control subjects were matched by age, sex, refractive error, and date of baseline examination to 194 of those receiving atropine. Duration of treatment with atropine ranged from 18 weeks to 11.5 years (median 3.5 years). RESULTS: Median followup from initial to last refraction in the atropine group (11.7 years) was similar to that in the control group (12.4 years). Photophobia and blurred vision were frequently reported, but no serious adverse effects were associated with atropine therapy. Mean myopia progression during atropine treatment adjusted for age and refractive error (0.05 diopters per year) was significantly less than that among control subjects (0.36 diopters per year)(P<.001). Final refractions standardized to the age of 20 years showed a greater mean level of myopia in the control group (3.78 diopters) than in the atropine group (2.79 diopters) (P<.001). CONCLUSIONS: The data support the view that atropine therapy is associated with decreased progression of myopia and that beneficial effects remain after treatment has been discontinued.

Adolescent↗
PubMed1999

Effects of chronic ethanol consumption on aortic constriction in male and female rats.

This study was designed to determine if gender influences the effects of chronic ethanol intake on vasoconstrictive responsiveness. Ethanol-preferring rats were allowed ad libitum access to tap water or tap water containing 20% or 30% ethanol for 16 weeks. All of the ethanol groups consumed more daily calories than their respective controls, and female rats consumed more ethanol calories per unit body mass than their male counterparts. Following treatment, endothelium-intact and endothelium-denuded thoracic aortic rings were used to examine the contractile response to phenylephrine. Ethanol consumption did not alter vasoconstriction in endothelium-intact aortae from either gender. In contrast, males, but not females, demonstrated an ethanol-associated increase in the maximum response to phenylephrine in endothelium-denuded preparations. Aortae from male rats that consumed 20% and 30% ethanol showed an increased contractility of 37% and 85%, respectively. These data indicate that gender influences the vasoconstrictive effects elicited by chronic ethanol consumption and suggest that males may be more susceptible to the associated hypertension.

Animals↗
PubMed1999

Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness.

UNLABELLED: Propofol (iv) depresses cardiovascular function in both humans and animals. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that this effect of propofol results in part from an antagonism of adrenergic control of the heart. Experiments examined effects of propofol on: 1) [3H]CGP12177 (a beta-adrenoceptor antagonist) binding in rat myocardial membranes; and 2) the inotropic and chronotropic actions of isoproterenol in rat left atrial muscle and right atria, respectively. Propofol (25-200 microM) increased the apparent dissociation constant for [3H]CGP12177 without affecting binding site density. Similarly, 200 microM propofol increased the 50% effective concentration values for the dose-dependent positive chronotropic and inotropic actions of isoproterenol in right and left atria, and depressed the maximum increase in spontaneous rate elicited by this beta-adrenoceptor agonist. Other experiments demonstrated that propofol does not alter muscarinic receptor binding as monitored using [3H]quinuclidi-nylbenzilate. In conclusion, these results indicate that propofol can decrease cardiac beta-adrenoceptor responsiveness; however, the concentrations of propofol required suggest that this action contributes to the cardiovascular depression produced by this anesthetic only during large-dose bolus injection. IMPLICATIONS: Experiments in membranes and cardiac preparations isolated from rat heart demonstrate that relatively high concentrations of propofol (25-200 microM) are required to antagonize beta-adrenoceptor binding and tissue responsiveness.

Adrenergic beta-Agonists↗
PubMed1999

Suppression of beta-adrenergic responsiveness of L-type Ca2+ current by IL-1beta in rat ventricular myocytes.

The possible mechanism by which interleukin-1beta (IL-1beta) affects beta-adrenergic responsiveness of L-type Ca2+ current (ICa,L) was examined in adult rat ventricular myocytes by use of whole cell patch-clamp techniques. In the presence of isoproterenol (Iso), exposure for 3 min to IL-1beta suppressed the Iso-activated ICa,L. In the presence of IL-1beta, the response of ICa,L to Iso was decreased, and the EC50 for Iso stimulation was increased. However, IL-1beta had no effect on [3H]CGP-12177 binding, displacement of [3H]CGP-12177 binding by Iso, or on basal and Iso-enhanced cAMP content. When ICa,L was activated by extracellular application of forskolin or 8-(4-chlorophenylthio)-cAMP, a membrane-permeable cAMP analog, or by intracellular dialysis with cAMP, IL-1beta had little effect on ICa,L. In contrast, in the presence of cAMP, IL-1beta still suppressed the Iso-enhanced ICa,L. These results show that the IL-1beta-induced decrease in beta-adrenergic responsiveness of ICa,L does not result from inhibition of beta-adrenoceptor binding, adenylyl cyclase activity, or cAMP-mediated pathways, suggesting a cAMP-independent mechanism.

Animals↗
PubMed1998

Effects of gender on the sensitivity of rat cardiac muscle to extracellular Ca2+.

Experiments were designed to determine if the inotropic response to increasing buffer calcium concentration differs in male and female cardiac muscle. Left atrial and papillary muscles were isolated from hearts of 3-4-month old male and female rats, bathed in Krebs-Henseleit solution (30 degrees C), and stimulated at 1.5 Hz. Isometric developed tension was monitored continuously as extracellular Ca2+ was increased in a cumulative fashion. When compared to male atrial muscle, female atrial preparations were more sensitive to the resulting positive inotropic action; EC50 values were 2.89 +/- 0.22 and 1.86 +/- 0.21 mM in male and female atria, respectively. Two-way analysis of variance (ANOVA) also indicated that there was a significant gender-associated difference in the Ca2+ dose-response curves in atrial muscle. In contrast, papillary muscle did not show a significant gender-related difference in EC50 values (0.88 +/- 0.07 and 0.74 +/- 0.06 mM in males and females); however, the Ca2+ dose-response curves obtained from male and female preparations were found to be significantly different when compared by ANOVA.

Analysis of Variance↗
PubMed1998

Effects of streptozotocin-induced diabetes on heart rate, blood pressure and cardiac autonomic nervous control.

Diabetes-associated alterations in resting heart rate and blood pressure have been demonstrated in clinical studies and in animal models of insulin-dependent diabetes mellitus (IDDM). These alterations may result from changes in the heart, vasculature or autonomic nervous system control. Using the streptozotocin- (STZ-) treated rat model of IDDM, the current study was designed to: (1) monitor changes in heart rate and blood pressure continually during a 10-week period in conscious unrestrained animals; and (2) determine if observed alterations in heart rate were mediated by changes in sympathetic and/or parasympathetic nervous control. Biotelemetry techniques were used. Heart rate and blood pressure were recorded 24 h a day at 10 min intervals before and after induction of diabetes. Diabetes was induced by i.v. administration of 50 mg/kg STZ. Resting autonomic nervous system tone was estimated by chronotropic responses to full-blocking doses of nadolol (5 mg/kg i.p.) and atropine (10 mg/kg i.p.). STZ-induced diabetes was associated with time-dependent reductions in heart rate and its circadian variation. Diastolic blood pressure and mean arterial pressure did not differ significantly when compared between control and STZ-treated animals; however, pulse pressure was diminished in diabetic rats. Chronotropic responses to both nadolol and atropine were blunted significantly in diabetic animals suggesting that resting levels of both vagal and sympathetic nervous tone to the heart were diminished. Heart rate in the presence of both nadolol and atropine was also decreased in diabetic rats. All effects observed following administration of STZ were reversed, at least in part, by insulin treatment. These results suggest that IDDM is associated with time-dependent reductions in resting heart rate and autonomic nervous control of cardiac function.

Adrenergic beta-Antagonists↗
PubMed1998

Outcome following laparoscopic resection for colorectal cancer.

BACKGROUND: A prospective comparison of laparoscopic or laparoscopically assisted colorectal resection versus open resection has been undertaken to evaluate early benefits and cost implications. METHODS: Consecutive patients with colorectal cancer underwent either elective laparoscopic (n = 25) or open (n = 29) resection. RESULTS: Mean hospital stay was significantly shorter in the laparoscopic group: 10.7 versus 17.8 days. Mean morphine requirements were less in patients who had laparoscopic resection and their recovery, as measured by the dynamometer hand grip and the SF-36 symptom score, was more rapid. Adequate tumour clearance was achieved in the laparoscopic group. In both groups, the number of lymph nodes harvested was similar. Port-site or wound recurrence has not been observed at a median follow-up of 28 months. CONCLUSION: When laparoscopic colorectal resection is possible, there are significant early benefits for patients.

Aged↗
PubMed1998

alpha1-Adrenergic activation of L-type Ca current in rat ventricular myocytes: perforated patch-clamp recordings.

alpha1-Adrenergic stimulation has little effect on L-type Ca2+ channel current (ICa,L) in adult cardiac myocytes measured using conventional whole cell voltage-clamp techniques. In this study using perforated-patch techniques, we reevaluated the effect of alpha1-adrenergic stimulation on ICa,L in adult rat ventricular myocytes. Action potentials and ICa,L were examined in the presence of 1 microM nadolol, a beta-adrenergic antagonist, in myocytes internally dialyzed with Na+- and K+-free solutions (Cs+ and tetraethylammonium as substitutes). Phenylephrine (PE; 30 microM) increased the action potential duration measured at 25 and 70% of repolarization by 104 and 86%, respectively. In the perforated-patch configuration, PE elicited a transient decrease followed by a approximately 60% increase in ICa,L, whereas only the transient decrease in ICa,L was observed in myocytes when the conventional whole cell configuration was used. The PE-induced increase in ICa,L was reversibly blocked by 1 microM prazosin, an alpha1-adrenergic antagonist. These results suggest that alpha1-adrenergic stimulation enhances cardiac ICa,L and that obligatory intracellular mediators for this action are lost during whole cell recordings.

Action Potentials↗