Search PubMed⌕ Search

Biomedical subjects

R H Kennedy

Publications and source records attributed to R H Kennedy.

At least 55 records · Page 3Linked to original sources
PubMed1995

Progression of myopia.

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 follow-up 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↗
PubMed1994

Effects of extracellular Cl- on the inotropic response to alpha-adrenoceptor stimulation.

This study was designed to determine if the sustained positive inotropic action of alpha-adrenergic stimulation is affected by the absence of extracellular chloride ion (Clo-). Atrial and papillary muscle were isolated from adult male rats, bathed in Krebs-Henseleit solution (30 degrees C) with and without Cl- (methane-sulfonate substitution), and stimulated at 0.5 Hz. Isometric developed tension was monitored during cumulative addition of phenylephrine, isoproterenol and Ca2+. The dose-dependent positive inotropic effects of isoproterenol and Ca2+ were not altered by the absence of Clo-. However, the magnitude of the response to phenylephrine was diminished in both tissues. In atrial muscle, the maximum positive inotropic effect of phenylephrine was reduced from 2.05 +/- 0.17 g in the presence of Clo- to 0.39 +/- 0.06 g in the absence of Clo-; control developed tension was 0.60 +/- 0.08 and 0.47 +/- 0.10 g in these two groups before exposure to the alpha-adrenoceptor agonist. In papillary muscle, control developed tension was 1.40 +/- 0.11 and 1.17 +/- 0.18 g in the presence and absence of Clo-, respectively; and the maximum inotropic responses to phenylephrine were 0.71 +/- 0.12 and 0.27 +/- 0.13 g. EC50 values for phenylephrine were not significantly affected by substitution for Cl-. Similar results were observed in a Hepes-buffered bathing solution without bicarbonate (HCO3-). These results indicate that the positive inotropic action of alpha-adrenergic stimulation is mediated in part by a mechanism requiring Cl-. Furthermore, data suggest that the antagonistic effect of Clo- removal is not mediated via Cl-/HCO3- exchange.

Adrenergic alpha-Agonists↗
PubMed1994

Nitric oxide has no chronotropic effect in right atria isolated from rat heart.

This study was designed to determine if nitric oxide (NO) has direct effects on heart rate or if it is involved in the chronotropic actions of adrenergic or cholinergic stimulation. Right atria were isolated from hearts of adult male rats, bathed in Krebs-Henseleit buffer (37 degrees C), and used to monitor spontaneous rate. For comparison, ring segments of thoracic aorta were also suspended in the Krebs-Henseleit solution and used to examine vascular actions of various agents. The dose-dependent chronotropic effects of acetylcholine (10(-7)-10(-3) M) and norepinephrine (10(-8)-3 x 10(-4) M) in right atria were not affected by pretreatment with 10(-4) M N-nitro-L-arginine or 10(-3) M N-nitro-L-arginine-methyl ester, inhibitors of L-arginine-derived NO production. SIN-1 (3-morpholino-sydnonimine), an agent which releases NO in aqueous solution, elicited a dose-dependent (0.3-100 microM) vasorelaxation in aortic preparations constricted with 60 mM KCl; the ED50 value for this effect was increased by pretreatment with methylene blue (10 microM) and LY-83,583 (6-(phenylamino)-5,8- quinolinedione; 1 and 3 microM), compounds which inhibit NO-induced stimulation of guanylate cyclase. SIN-1 produced a negative chronotropic effect in right atria; however, this action was not observed at concentrations less than 300 microM and was not antagonized by methylene blue or LY-83,583. 8-Bromo cyclic GMP produced a dose-dependent (10-3000 microM) decrease in KCl-induced tension in aortic rings. In right atria, 8-bromo cyclic GMP elicited a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Radical transhiatal oesophagectomy under direct vision.

Modified transhiatal oesophagectomy is described for the resection of tumours affecting the distal third of the oesophagus. The operation confers the advantages of radical resection and the ability to undertake the procedure under direct vision. Forty patients with a median age of 67 years underwent this operation during a 36-month period and were followed for up to 42 months after surgery. The hospital mortality rate was one of 40 patients and the median postoperative stay 10 days. All but four patients left hospital within 2 weeks of operation. Eighteen of 30 patients were alive at 12 months and seven of 18 at 24 months after operation. Only two patients are known to have developed local recurrence in the tumour bed. This procedure confers the advantages of a radical approach under direct vision and incorporates the principles of near-total oesophagectomy and cervical anastomosis in the treatment of oesophageal cancer.

Adenocarcinoma↗
PubMed1994

The effect of age on halothane-induced alterations of contractility in isolated rat aorta.

Aging is implicated as a factor which increases the susceptibility to volatile anesthetic-induced depression of the cardiovascular system. However, little is known regarding mechanisms responsible for this enhanced depression. Current experiments examined the effects of 1.2 and 2.4 vol.% halothane on norepinephrine-induced contractility in endothelium-intact and -denuded aortic preparations isolated from 4-, 14-, and 24-month-old Fisher-344 rats. Prior to exposure to halothane, endothelium removal significantly enhanced the sensitivity to norepinephrine in all age groups without altering the maximum tension. Additionally, in endothelium-intact preparations, increasing age from 4 to 24 months decreased the sensitivity to norepinephrine. Exposure to 2.4 vol.% halothane caused a significant decline in the maximum tension generated in response to norepinephrine in all groups. There were no differences in the amount of depression seen with 2.4 vol.% halothane either within age groups or between endothelium-intact and -denuded preparations of the same age. Halothane at 1.2 vol.% caused a significant reduction in the amount of tension generated in the 4-month-old, endothelium-denuded group. However, all age groups with and without endothelium tended to decrease to a similar degree at 1.2 vol.% halothane, and there were no differences either within age groups or between endothelium-intact and -denuded preparations of the same age. In the 4- and 14-month-old endothelium-intact groups, both 1.2 and 2.4 vol.% halothane decreased the sensitivity to norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Squamous cell carcinoma of the eyelid.

A total of 24 patients (12 men and 12 women) with squamous cell carcinoma of the eyelid were identified from pathology records at Wills Eye Hospital from 1978 through 1987. Squamous cell carcinoma accounted for 24 of 648 (3.7%) malignant eyelid lesions submitted during the 10-year study period. The median age of patients at the time of diagnosis was 72 years (range, 55 to 96 years). Initial therapy of all tumors involved surgical excision. Four patients developed clinical recurrence of squamous cell carcinoma in a median of 7.5 months after surgery. There were no tumor recurrences when frozen section techniques were applied during the initial surgical excision. The data suggest that the risk of persistence or recurrence of tumor was increased for patients who delayed seeking medical care after the lesion was first noticed and when frozen section control was not used during surgery. None of the patients were known to have developed metastases, and there were no tumor-related deaths.

Aged↗
PubMed1994

Alpha 1a-adrenergic receptor mediated positive chronotropic effect in right atria isolated from rats.

Experiments in right atria isolated from adult male rats were designed to determine which of the alpha 1-adrenergic receptor (alpha 1-AR) subtypes are involved in the positive chronotropic effect of phenylephrine, an alpha 1-AR agonist. Chloroethylclonidine (CEC), an irreversible alpha 1b-, alpha 1c-, and alpha 1d-AR antagonist, did not alter the efficacy or potency of phenylephrine; however, CEC did elicit a concentration-dependent negative chronotropic effect and reduce the absolute maximum spontaneous rate observed in the presence of phenylephrine. WB4101, a competitive alpha 1a- and alpha 1c-AR-selective antagonist, did not alter basal spontaneous rate or the efficacy of phenylephrine, but it did produce a significant rightward shift of the phenylephrine concentration-response curve. Phenoxybenzamine, an irreversible nonselective alpha-AR antagonist, elicited a concentration-dependent negative chronotropic effect, a significant rightward shift of the phenylephrine concentration-response curve, and a reduction in the efficacy of phenylephrine. The chronotropic action of the beta-adrenergic agonist isoproterenol was not affected by CEC, WB4101, or phenoxybenzamine. These data suggest that the positive chronotropic effect of alpha 1-adrenergic agonists in rat right atria is mediated via stimulation of alpha 1a-ARs.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

WB4101- and CEC-sensitive positive inotropic actions of phenylephrine in rat cardiac muscle.

This study was designed to determine the role of the alpha 1-adrenergic receptor (AR) subtypes in the positive inotropic action of alpha 1-adrenergic agonists in rat myocardium. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 degrees C) containing 3 microM nadolol and paced at 3.3 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine (3 x 10(-7) to 3 x 10(-4) M) were obtained in the presence and absence of WB4101 (4 and 10 nM) and with and without treatment with chloroethylclonidine (CEC; 10, 100, and 300 microM). WB4101 antagonized the effect of phenylephrine in both tissues, increasing half-maximal effective concentration (EC50) values in a concentration-dependent manner. CEC pretreatment also increased EC50 values in both tissues, and 300 microM CEC reduced the maximal positive inotropic effect of phenylephrine by approximately 48 and 38% in left atrial and papillary muscle, respectively. CEC alone elicited significant increases in contractile force that were not readily reversible. These data suggest that the positive inotropic effect of alpha 1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of both WB4101- and CEC-sensitive alpha 1-ARs.

Adrenergic alpha-Antagonists↗
PubMed1994

Effects of WB4101 and chloroethylclonidine on the positive and negative inotropic actions of phenylephrine in rat cardiac muscle.

This study was designed to determine if the positive and negative inotropic actions of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in isolated left atrial and papillary muscle before and after treatment with prazosin, WB4101 (N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine), chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 microM) elicited a monophasic positive inotropic response in left atrial muscle and a triphasic inotropic action in papillary muscle (transient positive, then negative inotropic components preceding a sustained positive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagonized the transient negative inotropic component in papillary muscle. The transient positive inotropic response was not affected by CEC, WB4101 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic effect of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response in ventricular preparations is mediated via alpha-1B ARs. However, present data do not exclude the possibility that the CEC-sensitive inotropic responses elicited by phenylephrine may be mediated in part by other recently described alpha-1 subtypes. The receptors involved in the transient positive inotropic action cannot be identified by current results.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

The acute surgical admission: is mortality predictable in the elderly?

Most scoring systems used to predict mortality are complex. A simple preoperative assessment, the Sickness Assessment (SA), was evaluated as a predictor of mortality in elderly patients admitted as surgical emergencies. The three parameters comprising the SA are: hypotension on admission, the presence of severe chronic disease, whether the patient was independent and self-caring. Prospectively, 487 consecutive patients of over 65 years of age admitted as surgical emergencies were studied. On admission, the SA and the APACHE II score were calculated. Hospital mortality was used as the endpoint. Of 309 patients with zero SA, 21 (7%) died. In 178 with a positive SA, 64 died (36%) (chi 2 = 64.6, P < 0.001). After laparotomy, mortality was 57% (36/67) with a positive SA, but 15% (15/103) with a zero assessment (chi 2 = 33.6, P < 0.001). When the single parameter of hypotension on admission was present, mortality was 77% (23/30). The predictive ability of the APACHE II score was not superior to SA. The SA is a simple preoperative assessment which identifies a high-risk group. It should be used in emergency surgical practice to improve outcome and avoid inappropriate surgery.

Acute Disease↗
PubMed1993

Effects of cesium on spontaneous rate in right atria isolated from diabetic rats.

Previous studies have shown that streptozotocin (STZ) induced diabetes in rats is associated with a decrease in the spontaneous rate of isolated right atria. Present experiments were designed to determine whether this model of insulin-dependent diabetes mellitus alters the chronotropic actions of cesium (Cs+). Right atrial preparations were isolated from STZ-treated and diluent-treated control rats, and bathed in Krebs-Henseleit buffer at 37 degrees C; dose-dependent (0.2-10 mM) effects of Cs+ were examined by cumulative addition. Preparations isolated from diabetic rats had a slower beating rate before exposure to Cs+, and the negative chronotropic response to this cation was diminished in these tissues. In fact, at concentrations between 2 and 10 mM Cs+, spontaneous rate did not differ between the diabetic and control groups. These data suggest that the hyperpolarization-activated current, I(f), may play a role in the slower spontaneous pacemaker rate observed in right atria isolated from STZ-induced diabetic rats.

Animals↗
PubMed1993

Modulation of cerebral arterial tone by endothelium-derived relaxing factor.

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

Animals↗
PubMed1993

Alpha 1b-adrenoceptor-mediated stimulation of Na-K pump current in adult rat ventricular myocytes.

The purpose of this study was to determine if myocardial alpha 1a-and/or alpha 1b-adrenoceptors are involved in the increase in Na-K pump current (Ip) elicited by alpha 1-adrenergic agonists. Single rat ventricular myocytes were isolated by enzymatic disaggregation. The whole cell patch-clamp technique was used to examine dose-dependent effects of phenylephrine (PE) on holding current (Ih) and to determine whether observed actions were mediated via alpha 1a-or alpha 1b-adrenergic receptors. To minimize the contribution of transsar-colemmal currents other than Ip to Ih, membrane voltage was held constant -40 mV, and cells were maintained in a Ca-free perfusate containing 1 mM Ba and 0.1 mM Cd. All experiments were conducted in the presence of 3 microM nadolol. PE elicited dose-dependent increases in Ih, with a peak effect of 0.57 +/- 0.03 pA/pF observed at 30 microM. The response to PE was dose dependently inhibited by prazosin and chloroethylclonidine and was totally eliminated by 1 mM ouabain. When used at doses selective for the alpha 1a-subtype, WB4101 failed to significantly antagonize the action of PE. These data suggest that the observed alpha 1-adrenoceptor-mediated increase in Ih in isolated rat ventricular myocytes is the result of an increase in Ip effected via stimulation of alpha 1b-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1993

The impact of streptozotocin-induced diabetes on the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetics in the rat.

We designed experiments to examine the effects of insulin-dependent diabetes mellitus on the anesthetic requirements for volatile anesthetics. A standard tail-clamp technique was used to determine minimum alveolar anesthetic concentrations for halothane, enflurane, and isoflurane in spontaneously breathing rats. Three groups of animals were used: 1) diabetic rats (12 wk after induction of diabetes with streptozotocin, 50 mg/kg, single dose, intravenously), 2) insulin-treated (7 U extended insulin zinc suspension per day, subcutaneously, beginning 5 wk after streptozotocin treatment) diabetic rats, and 3) control rats. The minimum alveolar anesthetic concentration values of the control animals were 1.16 +/- 0.02 vol% for halothane, 2.25 +/- 0.05 vol% for enflurane, and 1.42 +/- 0.04 vol% for isoflurane. Minimum alveolar anesthetic concentration was reduced by 23% for halothane (0.90 +/- 0.06 vol%), by 18% for enflurane (1.85 +/- 0.07 vol%), and by 17% for isoflurane (1.18 +/- 0.04 vol%) in diabetic rats. Insulin treatment restored the anesthetic requirement to control levels for all three anesthetics. These data from the rat model indicate that uncontrolled diabetes lowers anesthetic requirements significantly.

Anesthesia, Inhalation↗
PubMed1993

Fibroblast growth factor receptor-1, interleukin-1 receptor, and glucocorticoid receptor messenger RNA production in the human lacrimal gland.

PURPOSE: To determine whether messenger RNA coding for fibroblast growth factor receptor-1, interleukin-1 receptor, and glucocorticoid receptor messenger RNA are produced in human lacrimal tissue. METHODS: Total cellular RNA was isolated from three specimens of normal human lacrimal tissue and complementary DNA was synthesized. The polymerase chain reaction and sequence-specific primers were used to amplify the sequences of interest from the complementary DNA. Hot blotting and sequence-specific probes were used to demonstrate that the expected amplification products were specific. RESULTS: Data demonstrated that fibroblast growth factor receptor-1, interleukin-1 receptor, and glucocorticoid receptor messenger RNA are produced in human lacrimal tissue. CONCLUSIONS: These results and the previous identification of basic fibroblast growth factor in the lacrimal gland suggest that basic fibroblast growth factor has autocrine or paracrine functions in lacrimal tissue. More study is needed to determine whether the corresponding proteins are produced and, if so, what functions are regulated by fibroblast growth factor receptor-1, interleukin-1 receptor, and glucocorticoid receptor in the lacrimal gland.

Base Sequence↗
PubMed1992

Aging: inotropic effects of Bay K-8644 and nifedipine on rat cardiac muscle.

Inotropic effects of Bay K-8644, nifedipine, isoproterenol and extracellular calcium (Ca2+o) were examined in right ventricular strips, papillary muscle and left atria isolated from 4, 14 and 25 month old, male F344 rats. Under the experimental conditions used (37 degrees C, 1.4 mM Ca2+o and 4 Hz), control developed tension (expressed per mg wet weight) increased with age in right ventricular strips and papillary muscle, but decreased in left atria. The maximal positive inotropic response to Bay K-8644 was diminished with age in right ventricular strips and papillary muscle (but not left atria), while the negative inotropic action of nifedipine was not affected in any of the three tissues. Age decreased the inotropic efficacy of isoproterenol in right ventricular strips and papillary muscle (not left atria), had no effect on the efficacy of Ca2+o in right ventricular strips and left atria, but diminished the maximum response to Ca2+o in papillary muscle. Kd and B(max) values for [3H]nitrendipine binding were not significantly different in the three age groups. These data suggest: (1) that age-related changes in basal contractility and inotropic responsiveness differ in atrial and ventricular muscle; and (2) that these changes may result from alterations in excitation-contraction coupling which are not mediated by changes in Ca2+ channel density.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Digoxin cardiotoxicity in aging anesthetized F344 rats.

It is generally accepted that the sensitivity to toxic effects of digitalis increases with advancing age; however, the relative contribution of pharmacokinetics and pharmacodynamics to this aging-related change is presently unknown. The current study was designed to determine if senescence affects digitalis tolerance in an animal model and if observed changes are mediated by altered cardiac or autonomic nervous system responsiveness. Male, F344 rats of three age groups (4, 14 and 25 months) were anesthetized and infused intravenously with digoxin at a rate of 880 micrograms/kg per min. Two separate anesthetic regimens were employed: (a) an age-adjusted dose of urethane in spontaneously breathing animals (AR1); and (b) a non-age-adjusted dose of alpha-chloralose plus urethane in mechanically ventilated rats (AR2). Heart rate, EKG and arterial blood pressure were monitored continuously; baroreceptor reflex function was estimated before and 10 min following the start of digoxin infusion by examining the response to bilateral carotid occlusion. The infusion time required for digoxin-induced AV-dissociation was significantly reduced by senescence in rats anesthetized by AR1. However, doses of digoxin required to elicit ventricular extrasystoles and death were not significantly different among age groups in this anesthetized model and serum digoxin levels did not differ at the time of cardiac arrest. Similarly, AR2 animals showed a significant aging-related decrease in the time to AV-dissociation. However, in contrast to AR1, animals in AR2 displayed an aging-associated increase in the doses of digoxin required to produce ventricular arrhythmias and cardiac arrest. Thus, results suggest that aging in the F344 rat may, by pharmacodynamic mechanisms, promote the sensitivity to digoxin-induced AV-dissociation but not to ventricular arrhythmias or cardiac arrest.

Aging↗