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Biomedical subjects

B A Barron

Publications and source records attributed to B A Barron.

At least 19 recordsLinked to original sources
PubMed1995

Intrinsic cardiac enkephalins inhibit vagal bradycardia in the dog.

Met-enkephalin-Arg-Phe (MEAP) has been identified in acid extracts of canine heart tissue. The effects of synthetic MEAP on the vagal control of heart rate were investigated in anesthetized dogs. The arterial infusion of MEAP (3 nmol.min-1.kg-1) inhibited the bradycardia observed during electrical stimulation of the right vagus nerve by 72%. After the infusion was stopped, the responsiveness to vagal stimulation returned to normal, with a half-time between 2 and 3 min. The inhibition by MEAP was reversed by the high-affinity opiate antagonist diprenorphine (100 micrograms/kg). MEAP did not alter the negative chronotropic effect of the direct-acting muscarinic agonist methacholine. This observation suggested that MEAP exerted its effect at a site in the efferent vagal tract proximal to nodal muscarinic receptors. Increasing MEAP infusions (0.09-3.00 nmol.min-1.kg-1) produced a graded suppression of vagal bradycardia, with a half-maximal effect near 0.3 nmol.min-1.kg-1. Met-enkephalin (ME) produced responses very similar to those obtained with MEAP. The effects of ME were also blocked by prior administration of diprenorphine. Dose responses to ME were shifted to the right of those for MEAP, and half-maximal responses for ME were obtained at two to four times the dose required for MEAP. The data suggest that the intrinsic cardiac enkephalin MEAP can regulate vagal control of heart rate at physiologically achievable concentrations and may serve as a local regulator of the parasympathetic-myocardial interface.

Animals↗
PubMed1994

Aging, cardiac proenkephalin mRNA and enkephalin peptides in the Fisher 344 rat.

Cardiac proenkephalin (PENK) mRNA, methionine-enkephalin (ME) and leucine-enkephalin (LE) were determined from 2 days of age through senescence in Fisher 344 rats. Tissues were collected at 2 days, 2 weeks, 1, 2, 3, 7, 19, and either 22 or 27 months of age. Hearts were dissected, extracted and assayed for ME and LE by radioimmunoassay (RIA) or for PENK mRNA by Northern blot analysis with a cDNA probe. Relative left ventricular (LV) PENK mRNA was low in 2 day animals and increased slowly between 2 weeks and 3 months of age. LV PENK mRNA then rose five to six-fold between 3 and 27 months of age. LV ME measurements were high in neonatal animals, declined to a nadir during development and then rose again as the animals matured and advanced in age. The pattern for right ventricular (RV) ME was similar. Atrial ME, also high at 2 days, declined thereafter and remained low. LE measurements in LV, RV and the atria followed patterns similar to those described for ME. To evaluate for peptides contributed by cardiac nerves, 3, 7 and 22-month-old animals were acutely sympathectomized for 24 h with 6-hydroxydopamine. No decline in LV ME and LE was observed in the 6-hydroxydopamine treated animals. These data suggest several conclusions regarding myocardial enkephalinergic systems: (a) tissue enkephalin and PENK mRNA increase with advancing age, (b) tissue enkephalins may not strictly correlate with the relative abundance of PENK mRNA, and (c) most myocardial enkephalins are non-adrenergic in origin. The age-associated patterns in both PENK mRNA, ME and LE suggest that physiological, maturational or behavioral events between 3 and 7 months of age initiate the up-regulation and subsequent expansion of cardiac enkephalinergic systems.

Aging↗
PubMed1994

Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS: The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION: There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Acyclovir↗
PubMed1994

Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Administration, Topical↗
PubMed1992

Fungal keratitis from nylon line lawn trimmers.

Ocular trauma from nylon line lawn trimmers is becoming more prevalent. Previous case reports have described penetrating trauma caused by these tools. We managed three cases of fungal keratitis caused by injuries from nylon line trimmers. Fungal keratitis should be strongly considered as the cause of any corneal ulcer related to trauma from a nylon line lawn trimmer.

Accidents, Home↗
PubMed1992

Screening for opioids in dog heart.

Dog hearts divided into right and left atria, right and left ventricles and intraventricular septum were homogenized in acid for extraction. Total opioids, and specific peptides (methionine-enkephalin, methionine-enkephalin-arg6-gly7-leu8) were determined by radioreceptor and radioimmunoassay, respectively. Catecholamines were quantitated amperometrically following HPLC. The effects of anesthetic agents (pentobarbital, alpha-chloralose), hemorrhage and ganglionic blockade (hexamethonium and atropine) were evaluated. Total opioids, enkephalins and epinephrine were distributed uniformly throughout the myocardium, while norepinephrine was preferentially concentrated in the atria. Immunoreactive methionine-enkephalin accounted for only 1 to 2% of the total cardiac opioids estimated by radioreceptor assay. Hemorrhage lowered methionine-enkephalin content throughout the myocardium with no significant effect on total opioids or catecholamines. Ganglionic blockade increased total opioid, methionine-enkephalin-arg6-gly7-leu8 and catecholamine content without altering methionine-enkephalin content. HPLC of left ventricular extracts demonstrated that 50% of met-enkephalin-immunoreactivity eluted at retention times equal to synthetic metenkephalin. In summary, there appears to be substantive opioid concentrations within canine myocardium which respond to physiological and pharmacological interventions. These cardiac opioid responses do not parallel changes observed for catecholamines under the same conditions.

Amino Acid Sequence↗
PubMed1992

Effects of a coronary alpha 1-constriction on transmural left ventricular flow and contractile function.

Modulation of myocardial contractile function and perfusion by alpha 1-adrenergic receptors were examined in anesthetized dogs during left stellate ganglion stimulation. In 11 dogs, stellate stimulation significantly increased heart rate, mean arterial pressure, left ventricular systolic pressure, maximal rate of left ventricular pressure generation, segmental shortening and rate of shortening in anterior and posterior ventricular regions, and myocardial oxygen extraction. Myocardial lactate extraction decreased. The selective alpha 1-adrenergic antagonist prazosin (0.5 mg) injected into the circumflex artery during stellate stimulation caused significant additional increases in maximal rate of left ventricular pressure generation by 19 +/- 5% and in rate of shortening in posterior subendocardium by 20 +/- 6%. No changes were observed in posterior subepicardial or anterior subendocardial segmental contractile function. Myocardial oxygen and lactate extractions returned to their control values following prazosin injection. Regional left ventricular perfusion was measured using tracer microspheres in five additional dogs. Stellate stimulation increased subepicardial and subendocardial perfusion by 30%. Prazosin increased both subepicardial and subendocardial perfusion by an additional 36%. Stellate stimulation increased norepinephrine concentration in the coronary sinus, but no further increase was noted after blockage of alpha 1-receptors by prazosin. Thus, during sympathetic stimulation, an alpha 1-vasoconstriction existed uniformly across the left ventricular wall. However, blockade of this vasoconstriction was associated with an increase in contractile function only in the deeper muscle layers.

Adrenergic alpha-Antagonists↗
PubMed1992

Dynorphin, naloxone, and overflow of norepinephrine during cardiac nerve stimulation in dogs.

The effects of dynorphin-(1-9) and naloxone on norepinephrine (NE) overflow and myocardial contractility were determined during left cardiac nerve stimulation in the anesthetized dog. Stimulation-induced increases in NE overflow from the left ventricle were monitored during control conditions, during infusion of dynorphin-(1-9), during dynorphin plus naloxone, and after naloxone alone. Four electrical stimulations were applied for 1 min at 20-min intervals. Repeated left cardiac nerve stimulations (control group) reduced stimulated NE overflow 50-60% by 1 h. If stimulations were only conducted at 0 and 1 h, the decline in NE overflow was not observed. Intracoronary dynorphin (2 nmol.min-1.kg-1, 20 min) lowered the stimulation-induced increase in NE overflow further and reduced first time derivative of left ventricular pressure (dP/dt) and myocardial O2 consumption responses. Naloxone (100 micrograms/kg) prevented all of the dynorphin-mediated effects. When given alone, naloxone increased both NE overflow and left ventricular dP/dt during stimulation and prevented or significantly delayed the gradual decline in overflow observed in stimulated controls. A postjunctional effect of dynorphin was evaluated by comparing contractile responses to the intracoronary infusion of NE before and during dynorphin. Dynorphin did not alter contractile function at rest or during NE infusion. In summary, dynorphin-(1-9) depresses nerve stimulation-induced, cardiac NE overflow, and myocardial contractility in a naloxone-reversible fashion. Alone, naloxone appears to regulate stimulated NE overflow through a qualitatively different mechanism. Endogenous opioids may normally moderate myocardial function during cardiac nerve stimulation by regulating junctional NE concentrations through a combination of effects on NE release and/or its subsequent reuptake.

Animals↗
PubMed1992

Early diagnosis of infectious keratitis with in vivo real time confocal microscopy.

The tandem scanning confocal microscope (TSM) was adapted for in vivo examination of the cornea in rabbits with experimental bacterial and fungal keratitis. Compared to slit lamp biomicroscopy, the TSM provides superior lateral and axial resolution and serial optical sectioning capability, which may be useful for identification of corneal pathogens in the early stages of infection. We used the TSM to examine normal rabbit eyes infected with bacteria (Bacillus cereus) and a filamentous fungus (Aspergillus). We also examined a human cornea removed by penetrating keratoplasty after a clinical diagnosis of amoebic keratitis. In the early stages of bacterial infection, slit lamp examination revealed a nonspecific minimal stromal haze and limbal injection indistinguishable from sterile ulcers and epithelial defects. With the TSM, bacteria were visible as highly refractile bodies in the epithelium and superficial stroma. Branching fungal hyphae were also easily identified by the TSM, as were Acanthamoeba cysts and parasites in the subepithelial stroma. Our results indicate that this technique may provide a new modality for quickly and accurately identifying the agent of corneal infection, thereby facilitating prompt and appropriate treatment.

Acanthamoeba Keratitis↗
PubMed1991

Surgical technique for managing rhegmatogenous retinal detachment following prosthokeratoplasty.

The authors report the successful repair of a retinal detachment following Cardona prosthokeratoplasty. The surgical technique included pars plana vitrectomy, endolaser photocoagulation, peripheral cryopexy, scleral buckling, and the use of a liquid perfluorocarbon derivative, perfluorophenanthrene, to achieve and maintain reattachment. Perfluorophenanthrene was removed 3 weeks postoperatively. Postoperative visual acuity stabilized at functional levels. No ocular complications, adverse reactions, or redetachment were observed.

Adolescent↗
PubMed1991

Enkephalin lowers vascular resistance in dog hindlimb via a peripheral nonlimb site.

The intravenous administration of methionine enkephalin in anesthetized dogs produces an abrupt decline in mean arterial pressure, left ventricular pressure, and the maximal rate of left ventricular pressure development. All of these changes are prevented by receptor blockade with the opiate antagonist, naloxone. To evaluate peripheral vascular contributions to these responses, experiments were conducted in a constant pressure-isolated perfused hindlimb. In this model, the sharp decline in mean arterial pressure associated with enkephalin injection (5 micrograms/kg iv) coincided with an equally sharp decline in vascular resistance (rise in blood flow) in the hindlimb. Both were blocked by naloxone pretreatment (1 mg/kg). When equal doses of enkephalin were administered directly into the femoral inflow (external iliac artery), both arterial pressure and hindlimb flow responses were all but eliminated. This observation ruled out significant direct vascular interactions in the response and indicated a site of action outside the hindlimb. Additional catheters were placed in the bracheocephalic artery and descending aorta to permit the comparison of arterial injections conducted, respectively, into the cerebral or abdominal circulations. Injections introduced into the descending aorta consistently produced the greatest response, followed by injections (in descending order of effectiveness) into the jugular, the brachiocephalic, and external iliac. The response in the hindlimb vasculature was initiated at a site somewhere between the diaphragm and terminal aorta. The vascular response to enkephalin was subsequently eliminated by blocking ganglionic transmission with the nicotinic antagonist mecamylamine. These observations suggest that the opioids probably interrupt local vasomotor traffic via opiate receptors in regional sympathetic ganglia or in the spinal cord.

Animals↗
PubMed1991

Design and organization of the herpetic eye disease study (HEDS).

The Herpetic Eye Disease Study (HEDS) includes three double-masked, placebo-controlled clinical trials for potentially blinding herpes simplex virus (HSV) eye infections. One study compares a tapering dosage of topical prednisolone or placebo eye drops for HSV stromal keratitis (HEDS-SKN). Two other trials compare oral acyclovir to placebo capsules for HSV stromal keratitis (HEDS-SKS) or iridocyclitis (HEDS-IRT) in patients on a tapering dosage of topical prednisolone drops. All medications are administered for 10 weeks. Outcome is judged by time to recurrent disease or treatment failure. This paper presents the design, estimated sample size and recruitment as of July 25, 1990.

Acyclovir↗
PubMed1990

Naloxone enhances cardiac contractile responses to epinephrine without altering epinephrine uptake from plasma.

Naloxone potentiates the inotropic effect of selected beta-agonists in the canine isolated heart. This could be accomplished by elevating circulating catecholamines through a reduction in their disposal or by the facilitation of events at or subsequent to the cardiac beta-receptor. To evaluate the first hypothesis, epinephrine was infused intravenously into a blood-perfused isolated heart-lung preparation. Catecholamines were determined and myocardial and pulmonary epinephrine uptakes were calculated. Naloxone enhanced the inotropic effect (peak +dP/dt) during epinephrine infusion. Coronary blood flow and coronary venous epinephrine concentrations were also elevated after naloxone. Calculated myocardial and pulmonary uptake of epinephrine were, however, unaltered by naloxone. The increased coronary sinus epinephrine after naloxone was evaluated further in experiments redesigned to eliminate the influence of changing coronary blood flow. Epinephrine was infused into the left common coronary and coronary blood flow as maintained constant, 100% above the resting flow rate. Naloxone enhanced the contractile response to epinephrine without altering coronary artery or coronary sinus epinephrine concentrations or myocardial epinephrine uptake. By comparison, corticosterone, an extra-neuronal uptake inhibitor, also potentiated the inotropic effect of infused epinephrine under identical conditions. However, corticosterone was accompanied by a significant increase in coronary sinus epinephrine concentration and a decrease in myocardial epinephrine uptake. We therefore concluded that the ability of naloxone to enhance the inotropic effect of epinephrine is not mediate through an increase in plasma epinephrine concentration secondary to a decrease in the disposal of circulating catecholamines.

Animals↗
PubMed1990

Mooren's ulcer treated with a periosteal graft.

We report a case of recurrent Mooren's ulcer treated with an autogenous periosteal graft. The eye responded well to this therapy. Final visual acuity was 20/40 with spectacle correction of +2.00 + 2.50 X 165.

Aged↗
PubMed1989

Role of sympathoadrenomedullary system in cardiovascular response to stress in rats.

Sympathetic nerve and/or adrenal medulla contributions to stress-induced cardiovascular responses were investigated by factoring out their influence using adrenal demedullation (DMED) and/or chemical sympathectomy with guanethidine (GUAN). Rats divided into 4 groups [sham-operated/saline (SHAM/SAL), SHAM/GUAN, DMED/SAL and DMED/GUAN] were injected i.p. over 4 weeks with either saline or GUAN (25 mg/kg/day). At the end of this treatment period, blood pressure (BP) and heart rate (HR) were monitored via carotid catheter prior to and during restraint in conscious rats. Treatments did not alter basal BP or HR when compared to controls. Restraint increased HR (delta 72 bpm) and systolic, diastolic and mean BP (delta approximately 20 mm Hg) in control animals. Restraint-induced HR change was significantly greater in DMED/SAL animals (delta 88 bpm), but less in SHAM/GUAN animals (delta 40 bpm) than in controls. DMED/GUAN was not different from SHAM/GUAN alone in altering HR response to stress, supporting the greater influence of sympathetic nerves over adrenal medulla in controlling HR. Chronic GUAN abolished normal pressor responses to restraint stress. DMED increased diastolic blood pressure response to stress. However, in DMED/GUAN rats, not only did stress fail to increase blood pressure but rather stress produced hypotension (delta - 34 mm Hg MAP), demonstrating the role of adrenal medulla in maintaining BP during stress. Differential effects of the various treatments on diastolic and systolic pressure suggest that the treatments had effects on peripheral vasculature. These results demonstrate that sympathetic nerves and adrenal medulla have important influences on cardiovascular function during stress and that in the absence of either, the other system may partially compensate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗