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Biomedical subjects

M E Sullivan

Publications and source records attributed to M E Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1998

A qualitative study of Parent to Parent support for parents of children with special needs. Consortium to evaluate Parent to Parent.

OBJECTIVE: To examine qualitatively the experiences of parents participating in Parent to Parent programs. METHOD: Twenty-four parents of children with special needs, a subset of subjects in a larger quantitative study, participated in a semi-structured telephone interview to explore the impact and meaning of being matched with a trained supporting parent. RESULTS: Qualitative analysis reveals a successful match is contingent upon creation of a "reliable ally" in the supporting parent, comprised of four main components: (1) perceived sameness, (2) situational comparisons that enable learning and growth, (3) round-the-clock availability of support, and (4) mutuality of support. CONCLUSIONS: Parent to Parent support creates a community of similar others trained to listen and be supportive and provides an opportunity for matched parents to experience equality and mutuality in their relationship. Findings also identify the need for quality control in Parent to Parent programs and the importance of such programs as an adjunct to traditional professional services.

Adaptation, Psychological↗
PubMed1998

Endothelin and erectile dysfunction: a target for pharmacological intervention?

Although erectile dysfunction (ED) is not life threatening, this common problem can significantly affect the quality of life and psychological and social well-being. The Massachusetts male ageing study (1,290 men aged 40 - 70 years) showed that 52% of men reported some degree of ED (17.1% mild, 25.2% moderate, 9.6% total). In the UK, an estimated 17 - 19% of men are thought to suffer from ED. This problem is more common with advancing age and since this proportion of the population is increasing, the prevalence of ED is expected to rise. Endothelin-1 (ET-1) belongs to a family of potent vasoconstrictor peptides consisting of 21 amino acids. We review the evidence showing that ET-1 plays a role via (ET(A) and ET(B) receptors) in the regulation of cavernosal smooth muscle tone. We also consider the various risk factors that are involved in the pathogenesis of ED and how these relate to the action of ET-1. In particular, the role of diabetes, hypertension, smoking and dyslipidaemia are discussed. The pharmaceutical industry has declared an interest in the development of ET antagonists for use in the treatment of various diseases including ED. We briefly comment on experimental ET-1 antagonists that may be of therapeutic benefit in ED.

Journal Article↗
PubMed1997

Alterations in endothelin B receptor sites in cavernosal tissue of diabetic rabbits: potential relevance to the pathogenesis of erectile dysfunction.

PURPOSE: Diabetes Mellitus (DM) is a major risk factor for erectile dysfunction in both patients and animal models. The pathogenesis of this dysfunction has not been fully elucidated. However, alterations in the synthesis of a number of vasoactive compounds, such as nitric oxide (NO) and prostacyclin (PGI2), have been reported in various diabetic tissues. The interaction between NO, PGI2 and endothelin-1 (ET-1), a powerful vasoconstrictor and smooth muscle cell mitogen, is thought to be important in maintaining vascular tone and the erectile process. We investigated the density and distribution of ET-1 and endothelin receptor subtypes in cavernosal tissue and assessed any changes brought about by DM in a rabbit model. MATERIALS AND METHODS: DM was induced in New Zealand White rabbits using alloxan. Penises were excised from the diabetic rabbits three months (n = 6) and six months (n = 6) after the induction of DM. Low and high resolution autoradiography was performed using radioligands for ET-1, endothelin A (ETA) and endothelin B (ETB) receptors and were analyzed densitometrically. The results were compared with those from six age-matched healthy control rabbits for each group. Immunohistochemical localization of ET-1 immunoreactivity was also performed, together with ultrastructural evaluation of the corpus cavernosum. RESULTS: ET-1, ETA and ETB receptor binding sites were primarily localized to the smooth muscle cells of the corpus cavernosum and the endothelium lining the cavernosal spaces. A significant increase in ETB receptor binding sites was found only in cavernosal tissue six months after induction of DM, when compared with age-matched healthy controls. These receptor changes were accompanied by ultrastructural changes in the corpus cavernosum indicative of an early, atherosclerosis-like process. CONCLUSIONS: The autoradiographic and immunohistochemical findings in this study suggest that ET-1 may have a role in the pathophysiology of diabetic ED. This peptide may be released in an autocrine fashion causing cavernosal smooth muscle cell (CSMC) contraction and/or proliferation.

Animals↗
PubMed1996

Thrombelastographic evaluation of coagulation in transurethral prostatectomy.

OBJECTIVE: To assess the changes in overall coagulation status and define the degree of systemic fibrinolysis occurring in patients undergoing transurethral prostatectomy (TURP). PATIENTS AND METHODS: Thirty patients undergoing TURP, 23 for benign prostatic hyperplasia and seven for prostatic carcinoma, were studied prospectively. Serial venous blood samples were taken using the two-syringe technique. Samples were taken before, during and at intervals up to 72 h and 10-14 days after surgery. Thrombelastography (TEG) was performed on native whole blood samples. Peri-operative blood loss was assessed, until the catheter was removed, by photometric estimation of the haemoglobin content of the irrigant fluid and the measurement of clot volume. RESULTS: There was no evidence of fibrinolysis (TEG Percentage Clot Lysis Ly60 > 15%) in any patient over the whole peri-operative period. There was a significant change in the mean TEG variables towards hypercoagulation from 3 h until 10-14 days postoperatively, compared with the pre-operative values (P < 0.05). There was a significant correlation between blood loss and clot volume. CONCLUSION: These results question the role of systemic fibrinolysis in primary and secondary haemorrhage following TURP and thus the rationale of using antifibrinolytics in these patients. The persistent hypercoagulable state post-operatively indicates a possible role of hypercoagulability in clot retention.

Blood Coagulation↗
PubMed1996

Autoradiographic localization of nitric oxide synthase binding sites in normal and diabetic rat corpus cavernosum.

OBJECTIVES: To investigate density and distribution of nitric oxide synthase (NOS) binding sites in rat cavernosal tissue, and to assess any changes brought about by the onset of diabetes mellitus. METHODS: Hyperglycaemic non-ketonuric diabetes mellitus was induced in 5 rats using streptozotocin. The penises were excised from these rats 2 months after the administration of streptozotocin and stored at -70 degrees C. Longitudinal serial sections (6 microns) were cut in a cryostat and thaw mounted onto gelantinized microscope slides. Low- and high-resolution autoradiography was performed using a radioligand for NOS. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from 5 age-matched no-diabetic rats. RESULTS: NOS binding was primarily localized to the endothelium lining the cavernosal lacunar spaces. Significantly increased binding of NOS was seen in the diabetic cavernosal tissue 2 months after induction of diabetes mellitus. CONCLUSIONS: NOS binding is present on the endothelium of the rat corpus cavernosum and is increased in diabetic rats 2 months after streptozotocin administration. This increase in NOS binding may be part of the endothelial dysfunction which is reported in the corpus cavernosum of diabetic patients or rats.

Animals↗
PubMed1995

Reoperation on prosthetic heart values. Patient-specific estimates of in-hospital events.

Reoperation on prosthetic heart valves is increasingly under consideration for both clinical and prophylactic indications. To determine the correlates of hospital events, including in-hospital mortality, new persisting neurologic deficit, and length of postoperative stay, a three-institution study of 2246 consecutive prosthetic valve reoperations performed on 1984 patients between 1963 and 1992 was undertaken. The combined experience ranged from high-risk patients coming moribund to the operating room to an important number of well individuals undergoing prophylactic reoperations on potentially failing valves. The risk-unadjusted hospital mortality was 10.8%, neurologic deficit at hospital discharge 1.1%, and length of stay 10 days (median). Multivariably determined correlates of outcome included age at reoperation, degree, severity, and acuity of impairment of cardiac function, extensiveness of valvular heart disease, coexisting morbid conditions, number of previous heart operations, and concomitant procedures. The risk-adjusted hospital mortality for the first elective reoperation in a good-risk patient was 1.3% (90% confidence limits 0.3% to 4.4%), neurologic deficit 0.3% (90% confidence limits 0.02% to 1.8%), and length of postoperative stay 7 days (90% confidence limits 4 to 13), emphasizing the wide variance in outcome events. Equations were developed to permit wide application of the results of the study for quantitatively estimating the risk of outcome events based on individual preoperative patient characteristics. These estimates should be useful for informed patient consent, considerations of prophylactic valve replacement, and cost and resource use.

Adolescent↗
PubMed1995

The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum.

OBJECTIVE: To investigate the density and distribution of endothelin 1(ET-1) and endothelin receptor subtypes in rat cavernosal tissue, and to assess any changes brought about by the onset of diabetes mellitus (DM). MATERIALS AND METHODS: Hyperglycaemic non-ketotic diabetes mellitus was induced in five rats using streptozotocin (STZ). Two months later the penises were excised and stored at -70 degrees C. Longitudinal serial sections (6 microns) were cut using a cryostat and thaw- mounted onto gelatinized microscope slides. Low and high resolution autoradiographs were taken using radioligands for ET-1 and endothelin A (ETA) and endothelin B (ETB) receptors and the autoradiographs analysed densitometrically. These results were compared with those from five age-matched control rats. RESULTS: ET-1 and ETA receptor binding was primarily localized to the endothelium lining the cavernosal lacunar spaces: trabecular corporeal smooth muscle was much less intensely stained. No ETB receptor binding could be demonstrated, but increased binding of ET-1 and ETA receptors was seen in the diabetic cavernosal tissue. CONCLUSION: ET-1 and ETA receptor binding is increased in diabetic rat cavernosal tissue. A reduction in receptor linked nitric oxide (NO) release has previously been reported in diabetic rats. This finding may provide an explanation for the upregulation of ET-1 and ETA receptor binding in the diabetic rat.

Animals↗
PubMed1993

Electrophysiologic activity and antiarrhythmic efficacy of CK-3579, a new class III antiarrhythmic agent with beta-adrenergic blocking properties.

CK-3579 (N-[4-[2-hydroxy-3-[[2-[4-(1H-inidazol-1- yl)phenoxy]ethyl]amino]propoxy]phenyl]methanesulfonamide, HCL-[RS]), is a new class III antiarrhythmic agent with beta-adrenoceptor blocking properties shown to be effective in preventing ventricular arrhythmias in experimental animals. We examined the beta 1- and beta 2-adrenoceptor binding properties, cellular electrophysiology, and antiarrhythmic efficacy of CK-3579 and the two enantiomers CK-4000 (S) and CK-4001 (R). Both CK-3579 and CK-4000 were equipotent in displacing [3H]dihydroalprenolol from cardiac membranes (IC50 = 2.4 +/- 0.3 and 1.7 +/- 0.4 microM, respectively) and were approximately 23-59 times more selective for the heart receptor than the lung receptor. The IC50 for CK-4001 at the beta 1-adrenoceptor was 38.1 +/- 8 microM and > 100 microM at the beta 2-adrenoceptor. In isolated canine Purkinje fibers and ventricular muscle preparations, all three compounds increased action potential duration at 95% repolarization (APD95) with equal potency, having an average EC20 of approximately 1 microM in Purkinje fiber and 2 microM in ventricular muscle. No significant effects were observed on any other action potential (AP) parameters. In Purkinje fibers with APs shortened by isoproterenol, the class III activity of CK-4000 was significantly greater than that of CK-4001. CK-4000 inhibits the potassium delayed rectifier current Ik in a concentration-dependent manner in isolated feline ventricular myocytes. The IC50 for inhibition of fully activated current was 0.4 +/- 0.2 microM. Steady-state currents negative to -20 mV were unchanged by CK-4000, but the "hump" in the outward current between -20 and +30 mV was flattened.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Synthesis, cardiac electrophysiology, and beta-blocking activity of novel arylpiperazines with potential as class II/III antiarrhythmic agents.

A series of novel arylpiperazines have been prepared in an attempt to incorporate both class II (beta-receptor blocking) and class III antiarrhythmic properties in a single molecule. The key step in the preparation of the new compounds involves a regioselective heterocyclic ring formation. All but four compounds significantly prolonged action potential duration in canine cardiac Purkinje fibers (class III activity). All but one of the compounds demonstrated beta-receptor affinity in a competitive binding assay and three had beta 1-receptor selectivity. Compared to sotalol, a reference class II/III agent, arylpiperazine 7a (4-[(methylsulfonyl)amino]-N-[(4- phenylpiperazin-2-yl)methyl]benzamide) demonstrated beta 1-selectivity and was 1 order of magnitude more potent in the in vitro class III and the beta 1-receptor screens. Compound 7a was evaluated further and found to be effective in preventing programmed electrical stimulation-induced arrhythmias in conscious dogs (class III activity) and against epinephrine-induced arrhythmias in halothane anesthetized dogs (class II activity).

Action Potentials↗
PubMed1991

University-state hospital collaboration in an inpatient psychiatric rehabilitation program.

From 1981 until present the Department of Psychology of the University of Nebraska-Lincoln has collaborated with the Lincoln Regional Center, a state hospital, on an inpatient psychiatric rehabilitation project. The University provides clinical psychology services under contract, including direct clinical services and consultation on program development. The project includes a 40-bed inpatient treatment unit, which represents a clinical training and research site for University faculty and graduate students. Program evaluation data indicate the collaboration has produced a cost-effective state-of-the-art treatment program, now considered a model for psychiatric rehabilitation services across the state. The collaboration played a key role in securing two major grants, one for specialty training for clinical psychologists in schizophrenia and psychiatric rehabilitation, one for a treatment outcome study. Facilitating factors in the project include convergence of the collaborators' professional and research interests with national and state mental health policy. Obstacles include hospital administrative policies which fail to recognize or appreciate requirements for program management and accountability, and unwillingness to recognize program leadership from nonmedical professionals.

Academies and Institutes↗
PubMed1991

Cellular electrophysiological effects of the class III antiarrhythmic agents sematilide and clofilium on rabbit atrial tissues.

Sematilide (N-[2-(diethylamino)ethyl]-4- [(methylsulfonyl)amino]benzamide HCl) is a new class III antiarrhythmic agent that has been shown to be effective in preventing reentrant ventricular arrhythmias in experimental animals and humans. In this study, we examined the in vitro effects of sematilide (1-100 microM) on isolated sinoatrial (SA) node, atrioventricular (AV) node, and atrial muscle. These results were then compared to another class III agent, clofilium (1-30 microM). In SA nodal tissue, sematilide increased the action potential duration (APD) and spontaneous cycle length (SCL) in a concentration-dependent manner (EC20% = 15 +/- 3 and 54 +/- 13 microM, respectively). In addition, there was a slight reduction in maximum diastolic potential at 100 microM. Clofilium had similar class III effects, but was approximately 3 to 18 times more potent (EC20% = 6 +/- 2 and 3 +/- 1 microM for the APD and SCL, respectively). Neither agent had a significant effect on the slope of phase 4 nor on other action potential parameters. Results in AV nodal preparations were similar. Both sematilide and clofilium increased the APD and SCL in a concentration-dependent manner, with clofilium being approximately four to six times more potent than sematilide (EC20% for the APD and SCL for sematilide = 12 +/- 4 and 12 +/- 8 microM, respectively, and for clofilium = 2 +/- 1 and 3 +/- 2 microM, respectively). No significant effects were observed on other action potential parameters. Sematilide and clofilium increased the APD and effective refractory period (ERP) in atrial trabeculae in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Synthesis and cardiac electrophysiological activity of aryl-substituted derivatives of the class III antiarrhythmic agent sematilide. Potential class I/III agents.

Twelve novel derivatives of the selective class III antiarrhythmic agent sematilide were prepared in an attempt to incorporate both class I and class III electrophysiological properties into a single molecule. Electrophysiological activity was determined by standard microelectrode techniques in canine cardiac Purkinje fibers. Initial assessment of class I efficacy was carried out in a ouabain-induced arrhythmia model in guinea pigs. All of the compounds prolonged action potential duration in Purkinje fibers (class III activity), and three were active against ouabain-induced arrhythmias (class I activity). Selected compounds were evaluated further in dogs for efficacy against arrhythmias occurring 24 h following coronary ligation (automatic arrhythmias) and induced by using programmed electrical stimulation techniques (reentrant arrhythmias). The most effective compounds from the series are 3g and -j, which were effective in both canine models. Molecular modeling and structure-activity relationships are discussed.

Action Potentials↗
PubMed1990

Synthesis of novel (aryloxy)propanolamines and related compounds possessing both class II and class III antiarrhythmic activity.

Several (aryloxy)propanolamines and related compounds (i.e. 5-13, 16-18, 20-24, 27-33, 35, 37-39, 41, and 42) were synthesized and investigated for their class III electrophysiological activity and class II (beta-blocking) effects with use of in vitro and in vivo models. Structure-activity relationships are discussed for a series of 30 compounds. A number of these compounds prolonged the action potential duration at 95% repolarization of isolated canine cardiac Purkinje fibers by 20% (C20APD95) at concentrations of less than 1.0 microM, with no significant effects on cardiac conduction. beta-Adrenergic receptor binding studies showed that some of these compounds were 2-20 times more potent for cardiac beta 1 receptors than for beta 2 receptors. In particular, compounds 32, 41, 1, and especially (S)-1 were found to be orally active class III agents in anesthetized mongrel dogs (1 or 3 mg/kg, id) and efficacious at suppressing programmed electrical stimulation induced arrhythmias in halothane-anesthetized dogs. The profile of these compounds was similar to that found for sotalol. Compound (S)-1, which was more potent than sotalol in the PES study and equieffective in the halothane/epinephrine dog model, is being investigated further as a combined class III/II antiarrhythmic agent.

Action Potentials↗
PubMed1990

Hemodynamic effects of Gd-DTPA administered via rapid bolus or slow infusion: a study in dogs.

The hemodynamic effects of rapid (10 sec) versus slow (1 min) IV injection of Gd-DTPA were compared in normal, pentobarbital-anesthetized mongrel dogs. Hypertonic mannitol and isotonic saline were used as equiosmotic and equivolumetric controls. Two dose levels of Gd-DTPA were administered: 0.1 mmol/kg and 0.5 mmol/kg, corresponding to dose volumes of 0.2 and 1.0 ml/kg, respectively. The rapid injection of a high dose (0.5 mmol/kg) produced a transient decrease in arterial blood pressure (21 mm Hg, p less than .001), which returned to control values within 1 min after the injection. Slow IV infusion at this high dose had no statistically significant hemodynamic effects. There were no statistically significant effects of the lower dose (0.1 mmol/kg) administered as a bolus or by infusion, nor of the saline or osmotic control solutions. These results suggest that acute hemodynamic effects of Gd-DTPA are not observed at clinically relevant doses and the vasodilation observed at a higher dose may result from a direct action of the contrast agent.

Analysis of Variance↗