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PubMed2001

Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain.

1. This study was designed to assess the influence of activation and blockade of the endogenous opioid system in the brain on two key proteins involved in the regulation of programmed cell death: the pro-apoptotic Fas receptor and the anti-apoptotic Bcl-2 oncoprotein. 2. The acute treatment of rats with the mu-opioid receptor agonist morphine (3-30 mg x kg(-1), i.p., 2 h) did not modify the immunodensity of Fas or Bcl-2 proteins in the cerebral cortex. Similarly, the acute treatment with low and high doses of the antagonist naloxone (1 and 100 mg x kg(-1), i.p., 2 h) did not alter Fas or Bcl-2 protein expression in brain cortex. These results discounted a tonic regulation through opioid receptors on Fas and Bcl-2 proteins in rat brain. 3. Chronic morphine (10-100 mg x kg(-1), 5 days, and 10 mg x kg(-1), 13 days) induced marked increases (47-123%) in the immunodensity of Fas receptor in the cerebral cortex. In contrast, chronic morphine (5 and 13 days) decreased the immunodensity of Bcl-2 protein (15-30%) in brain cortex. Chronic naloxone (10 mg x kg(-1), 13 days) did not alter the immunodensities of Fas and Bcl-2 proteins in the cerebral cortex. 4. The concurrent chronic treatment (13 days) of naloxone (10 mg x kg(-1)) and morphine (10 mg x kg(-1)) completely prevented the morphine-induced increase in Fas receptor and decrease in Bcl-2 protein immunoreactivities in the cerebral cortex. 5. The results indicate that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro-apoptotic Fas receptor protein and damping the expression of anti-apoptotic Bcl-2 oncoprotein.

Animals↗

PubMed2002

Opportunities for sustainable riverine management in the Queensland Murray-Darling Basin.

The RiverReach program has provided significant material, planning and educational resources to communities throughout the QMDB over the last three years. The devolved granting process has proven to be a valuable mechanism for the initiation of on-ground works and as a platform for the delivery of educational and awareness raising activities. The range of riverine management projects developed among riparian communities reflects both the socio-economic and the environmental circumstances. An increasing knowledge of riverine management issues among both the community and practitioners and a growing acceptance of the need for riverine management within the community has increased opportunities for sustainable riverine management in the region. While the range of riverine management issues is diverse, and their integration complex, the combination of all three aspects (financial assistance, technical advice, and awareness raising) has enabled significant management outcomes to be achieved.

Community-Institutional Relations↗

PubMed1983

Availability of electrophysiological approach to the selection and assessment of antiarrhythmic drugs for recurrent ventricular tachycardia.

We performed serial electrophysiological-pharmacological studies on 21 patients with recurrent sustained or non-sustained ventricular tachycardia (VT). In 8 of 11 patients with recurrent sustained VT, VT could be induced repeatedly by programmed electrical stimulation and terminated by ventricular burst pacing. In 13 of the 21 patients, repetitive ventricular response (RVR) was successfully induced. In the 8 patients with induced VT, the efficacy of several antiarrhythmic drugs intravenously administered was assessed. Procainamide prevented the initiation of VT in 57%, disopyramide in 50% and mexiletine in 40%. However, lidocaine, propranolol and verapamil could not prevent VT in any of 5, 3 and 6 patients, respectively. Verapamil in combination with quinidine prevented the initiation of VT in one case. Each of disopyramide, propranolol and verapamil increased the VT zone in 2 patients. The drugs belonging to the same group classified by their electrophysiological properties were not interchangeable in 2 patients. Their ability to terminate induced VT did not always correlate with that to prevent its initiation in 2 patients. The effects of specific drugs were rather variable and unpredictable in each patients, and especially those of combination regimens using more than 2 antiarrhythmic drugs were more unpredictable. In all patients, the induced VT was morphologically identical to the spontaneously occurring VT and its rate was ranged within 13% of that of the spontaneously VT. In 10 of 13 patients with RVR, QRS configuration of RVR was not similar to the spontaneously occurring arrhythmia. The pharmacological suppression of RVR as an index for prevention against spontaneous VT remains controversial. This study concludes that the serial electrophysiological-pharmacological study provides a rapid prediction of effectiveness of a particular regimen and combination and a rapid identification of the deleterious effects of certain drugs in patients with recurrent sustained VT.

Adolescent↗

PubMed2004

Use of medical emergency team responses to reduce hospital cardiopulmonary arrests.

BACKGROUND: Medical emergency team (MET) responses have been implemented to reduce inpatient mortality, but data on their efficacy are sparse and there have been no reports to date from US hospitals. OBJECTIVES: To determine how the incidence and outcomes of cardiac arrests have changed following increased use of MET. METHODS: Objective criteria for MET activation were created and disseminated as part of a crisis management program, after which there was a rapid and sustained increase in the use of MET. A retrospective analysis of clinical outcomes was performed to compare the incidence and mortality of cardiopulmonary arrest before and after the increased use of MET. RESULTS: A retrospective analysis of 3269 MET responses and 1220 cardiopulmonary arrests over 6.8 years showed an increase in MET responses from 13.7 to 25.8 per 1000 admissions (p<0.0001) after instituting objective activation criteria. There was a coincident 17% decrease in the incidence of cardiopulmonary arrests from 6.5 to 5.4 per 1000 admissions (p = 0.016). The proportion of fatal arrests was similar before and after the increase in use of MET. CONCLUSIONS: Increased use of MET may be associated with fewer cardiopulmonary arrests.

Clinical Protocols↗

PubMed1989

[Continuous ventricular tachyarrhythmia in patients without detectable organic heart disease: clinical and electrophysiologic findings].

In 22 of 335 consecutive patients (6.6%) referred for evaluation and treatment of sustained ventricular tachyarrhythmias, hemodynamic and angiographic findings revealed no structural heart disease. Entry arrhythmia was ventricular fibrillation in 10 patients and sustained ventricular tachycardia in 12 patients. A subgroup of four young patients presented with slow recurrent (during 51 +/- 43 months) sustained ventricular tachycardias that were reproducibly terminated by intravenous application of verapamil. Programmed ventricular stimulation replicated the clinical arrhythmia in nine patients (75%) with ventricular tachycardia. In five patients (50%) with ventricular fibrillation no sustained ventricular arrhythmia could be induced, and only with three extrastimuli in four of the remaining five patients. On hospital discharge, 14 patients received type III antiarrhythmic agents, five patients received type I agents, and one patient received verapamil. Two patients were discharged without medical therapy. During the following 24 +/- 9 months, four patients had recurrent sustained ventricular tachycardia. No patient died suddenly during follow-up. We conclude that about 6% of all patients with ventricular tachyarrhythmias have apparently normal hearts. These idiopathic tachyarrhythmias seem to have a benign course, at least when treated. Slow, verapamil-sensitive tachycardias of young people may represent a unique entity.

Adolescent↗

PubMed1987

Decline in inducibility of sustained ventricular tachycardia from two to twenty weeks after acute myocardial infarction.

To determine temporal evolution of sustained ventricular arrhythmias inducible after acute myocardial infarction (AMI), serial programmed ventricular stimulation (PVS) was performed in 27 patients 15 +/- 4 and 150 +/- 28 days after AMI. These patients did not have worsening of congestive heart failure or angina, coronary artery bypass surgery or spontaneous sustained ventricular tachycardia (VT) in the period between 2 PVS studies. During initial PVS, sustained VT or ventricular fibrillation (VF) was inducible in 17 patients (group I) and was not inducible in 10 (group II). Late PVS in group I induced sustained VT or VF in 8 patients (47%) and nonsustained VT or no VT in 9 (53%). A decrease in late inducibility of sustained VT/VF was greater for arrhythmias induced during initial PVS by triple extrastimuli and burst pacing than for those induced by double extrastimuli (88% vs 25%, p less than 0.04), but appeared to be unrelated to the morphologic characteristics or cycle length of the initially induced sustained VT or VF and to other clinical, hemodynamic or angiographic variables. During late PVS in 10 group II patients, sustained VT or VF remained noninducible in 9 (90% concordance); in 1 patient sustained VT was induced. During a mean follow-up of 14 +/- 5 months since late PVS, none of 27 patients had spontaneous sustained VT and 2 patients in group I died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

A brief history of work expectations for welfare mothers.

The best known of the nation's welfare programs, Aid to Families with Dependent Children (AFDC), has from its inception reflected a tension between the desire to support children in poor, lone-parent families and the belief that parents should be held responsible for providing for themselves and their children. Against that backdrop, this article reviews the history of the AFDC program and traces the emergence of policies and programs intended to encourage employment of the parents (almost exclusively mothers) who receive benefits. The article examines in detail the Work Incentive Program (WIN) launched in 1967 and the Family Support Act of 1988, comparing these to each other and to the outlines of welfare reform signed into law in 1996. The article emphasizes the importance of sustained attention to the implementation of policy goals in concrete programs and shows that the merits of those early programs have not been fully tested because they were never funded or implemented at the scale intended. The article also outlines ways in which welfare-to-work programs can be used to assist children as well as parents, and urges that children's well-being remain the core purpose of welfare policy.

Aid to Families with Dependent Children↗

PubMed1991

Acute hypokalemia and inducibility of ventricular tachyarrhythmia in a nonischemic canine model.

Inducibility of sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) by programmed ventricular stimulation following acute hypokalemia was studied in 21 anesthetized dogs free of inducible ventricular tachyarrhythmias at baseline. The control mean serum potassium concentration of 3.65 mEq/L was decreased to 2.14 mEq/L by insulin and furosemide administration. Inducibility of arrhythmias was also assessed following isoproterenol infusion before and after induction of hypokalemia. None of the animals developed sustained VT. Only one animal developed VF following hypokalemia (p greater than 0.05). Two normokalemic animals and five hypokalemic animals developed VF following isoproterenol infusion; this difference was not significant (p greater than 0.05). In this study, hypokalemia did not predispose to the development of a substrate necessary for the genesis and maintenance of VT. The inducibility of VF following hypokalemia was not significantly enhanced and appears to be related to the "aggressive" stimulation protocol.

Acute Disease↗

PubMed1984

Programmed electrical stimulation in patients with high-grade ventricular ectopy: electrophysiologic findings and prognosis for survival.

The significance and treatment of ventricular premature beats (VPBs) in patients without sustained ventricular tachycardia (VT), sudden death, or syncope remains unclear. We undertook a prospective study of programmed electrical stimulation (up to two extrastimuli and burst pacing) in 73 patients (age 60 +/- 10 years) with high-grade VPBs who had no evidence of sustained VT, sudden death, or syncope as determined by 48 hr of monitoring in the cardiac care unit and 48 hr Holter monitoring. Fifty-six patients (76.7%) had atherosclerotic heart disease, 10 (13.7%) had cardiomyopathy or valvular heart disease, and seven (9.6%) had no evident heart disease. Thirty-seven patients (50.7%) had Lown grade IVB VPBs, 30 (41.1%) had Lown grade IVA VPBs, and six (8.2%) had Lown grade III VPBs. Programmed electrical stimulation identified two groups of subjects: group 1 comprised 20 patients (27%) in whom VT or ventricular fibrillation was induced, group 2 comprised 53 patients (73%) in whom no ventricular arrhythmia or only two to four repetitive ventricular responses were induced. There was a significant difference between the presence of atherosclerotic heart disease, old myocardial infarction, and ejection fraction of less than 40% in group 1 compared with group 2. However, there was no significant difference in the grade of VPBs between the two groups. Seventeen of 20 patients from group 1 were placed on antiarrhythmic therapy (defined by programmed electrical stimulation), whereas group 2 patients were randomly assigned to prophylactic antiarrhythmic therapy. A total of 70 patients were followed up for 30 +/- 15 months. The incidence of sustained VT and/or sudden death (31.5% vs 2%; p less than .001) was significantly higher in group 1 compared with group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

[Combination of celiprolol and amiodarone in the treatment of recurrent ventricular tachycardia].

The combination of beta-blockers and amiodarone has been shown to be affective in the treatment of refractory chronic ventricular tachycardia. However, the possible induction of excessive sinus bradycardia can constitute a limitation to the use of this treatment. Celiprolol is a cardioselective beta-blocker with a partial beta-2 agonist activity and an alpha-2 blocking activity, with a minimal depressant effect on heart rate. It therefore seemed useful to evaluate this drug in combination with amiodarone in patients with chronic ventricular tachycardia refractory to amiodarone alone. Twelve men with age of 57 +/- 16 years (9 with a history of myocardial infarction) received 200 mg of celiprolol per day associated with an average of 2 grams of amiodarone per week. Failure of oral amiodarone alone was confirmed by "reloading" (1,200 mg per day for 4 days) in 11 patients. The mean left ventricular ejection fraction was 36 +/- 19%, and was < or = 30% in 5 patients. Three patients were classified as stage 3-4 of the NYHA functional classification. Episodes of tachycardia were paroxysmal in 10 patients and diurnal in 10 cases. The effects of treatment were evaluated by clinical examination, continuous electrocardiographic monitoring, stress test and endocavitary electrophysiological investigation. No patient developed cardiac decompensation or collapse during beta-blocker treatment. In one case, the dose of celiprolol had to be decreased to 100 mg per day because of hypotension. No proarrhythmic effect was observed. The sinus rate remained unchanged after addition of celiprolol to amiodarone (57 +/- 3 bpm before versus 56 +/- 4 bpm after). On the stress test, the exercise capacity was maintained and no tachyarrhythmia was induced. Right ventricular refractory periods were not modified by celiprolol (mean effective period 289 +/- 20 ms before versus 294 +/- 20 ms after). Following a hospital stay of 17 +/- 7 days, the beta-blocker was discontinued in 5 patients because of persistence of permanent tachycardia in 1 case, and because of inducibility of a tachycardia with the same frequency as before treatment in the other 4 cases. No sudden death or haemodynamically unstable recurrence of ventricular tachycardia were observed during follow-up over a period of 38 +/- 24 months (range: 2-55) of the 7 patients in whom treatment was considered to be effective. Only one patient presented a temporary and reversible deterioration of heart failure. The absence of excessive bradycardia was also observed during follow-up. In one patient, celiprolol was replaced by another antiarrhythmic due to the recrudescence of inducibility to programmed stimulation. Three patients developed a spontaneous recurrence of sustained monomorphie ventricular tachycardia, which was well tolerated. In conclusion, these results suggest that celiprolol in combination with amiodarone in the treatment of refractory chronic ventricular tachycardia is a valuable therapeutic option because of its good inotropic and particularly chronotropic safety. However, the efficacy of treatment must be evaluated by a stress test and by endocavitary electrophysiological investigation including programmed ventricular stimulation in every case.

Adrenergic beta-Antagonists↗

PubMed1981

Prevention of chronic canine ventricular tachyarrhythmias with bretylium tosylate.

The ability of chronic bretylium tosylate treatment to prevent the induction of ventricular tachycardia was assessed in the conscious dog subjected to serial programmed ventricular stimulation on days 3-6 after acute myocardial infarction. In 34 untreated control dogs, programmed ventricular stimulation produced nonsustained ventricular tachycardia in 11 dogs (32%), sustained ventricular tachycardia in 10 (29%), and ventricular fibrillation in 10 (29%) on the third and fourth day after occlusion and reperfusion of the left anterior descending coronary artery. Bretylium tosylate, 5 mg/kg i.v., was given every 12 hours to a separate group of seven dogs after the induction of ischemic myocardial injury. Programmed ventricular stimulation on the third and fourth days after the induction of myocardial ischemic injury failed to elicit ventricular arrhythmias. Induction of arrhythmias by programmed electrical stimulation could be induced in each of the seven dogs; however, 36 hours after discontinuing bretylium tosylate, two dogs (29%) had non-sustained ventricular tachycardia and five (71%) had sustained ventricular tachycardia. When retested at 60 hours after withdrawal of bretylium tosylate, five (71%) had sustained ventricular tachycardia and two (28%) developed ventricular fibrillation. Readministration of bretylium tosylate (5 mg/kg, i.v.) to four of the five surviving dogs prevented the induction of ventricular arrhythmias in response to programmed ventricular stimulation. The results of these investigations suggest that bretylium tosylate may be effective in preventing the onset of reentrant ventricular rhythms after myocardial ischemic damage, and therefore may be of value in preventing sudden coronary death.

Animals↗

PubMed1992

Risk assessment in nonischemic ventricular arrhythmia by left and right ventriculography.

Ventricular fibrillation and sudden death are rare phenomena in nonischemic ventricular arrhythmia, particularly in arrhythmogenic right ventricular cardiomyopathy. In most instances electrophysiologic studies help to assess the risk of sudden death, but sometimes programmed ventricular stimulation is unsuccessful. Among 48 patients with ventricular fibrillation (n = 9) and sustained (n = 25) and nonsustained (n = 19) ventricular tachycardia, invasive and noninvasive diagnostic tests (coronary angiography, biventricular angiography, programmed ventricular stimulation, and echocardiography) were performed to obtain more information about the underlying heart disease. In 43 patients (90%) arrhythmogenic right ventricular cardiomyopathy was diagnosed with segmental hypokinesia (n = 31) and diffuse hypokinesia (n = 12) of the right ventricle. In patients with documented ventricular fibrillation, the right ventricular ejection fraction was lower (30.8% vs 47.8% and 45.9%, respectively) and multisegmental contraction impairment of the right ventricle was significantly more frequent (p less than 0.001). Additional left ventricular abnormalities and right ventricular dilatation were not significant parameters for identifying high-risk patients. In addition to programmed ventricular stimulation, quantitative analysis of the results of right and left ventricular angiography contributes to risk assessment in patients with nonischemic ventricular arrhythmia.

Adult↗

PubMed1990

[Effect of cibenzoline on atrial vulnerability and value of electrophysiological methods in the treatment of paroxysmal atrial fibrillation].

The effects of intravenous cibenzoline (1,5 mg/kg) on atrial vulnerability and electrophysiology were assessed in 25 patients with documented paroxysmal atrial fibrillation, in whom sustained (greater than 30 s) atrial fibrillation/-flutter was induced by programmed atrial stimulation. In seven patients atrial fibrillation persisted despite the application of cibenzoline; in eight patients induction of atrial fibrillation was not prevented. In 10 patients the induction of sustained atrial fibrillation was prevented by cibenzoline. Intraatrial conduction time and shortest ventricular cycle length during atrial fibrillation were increased by cibenzoline (p less than or equal to 0.01). The effective refractory period of the right atrium was not significantly affected. Eight patients with frequent episodes of paroxysmal atrial fibrillation received oral cibenzoline (320 mg/day) for control of paroxysmal atrial fibrillation irrespective of the efficacy of intravenous cibenzoline. Prevention of stimulation-induced atrial fibrillation predicted successful treatment of paroxysmal AF. In conclusion, cibenzoline might be effective in the treatment of atrial tachyarrhythmias. Programmed atrial stimulation seems to be helpful in the prediction of the efficacy of an antiarrhythmic treatment of paroxysmal atrial fibrillation.

Adult↗

PubMed1999

Symptomatic Ventricular Tachycardia.

The approach to patients with symptomatic ventricular tachycardia (VT) depends on the presence and type of structural heart disease. In patients with underlying heart disease and ventricular fibrillation or sustained symptomatic VT with hemodynamic compromise, the implantable cardioverter-defibrillator (ICD) is superior to antiarrhythmic drugs for the improvement of overall survival. These patients should receive an ICD unless contraindications are present. For patients with sustained VT and a structurally normal heart (idiopathic VT), radiofrequency catheter ablation is a reasonable option. If patients are symptomatic, nonsustained VT should be treated with beta-adrenergic blocking agents or antiarrhythmic drugs, which should be selected on the basis of the underlying cardiovascular substrate. In patients with coronary artery disease, depressed left ventricular function, and nonsustained VT, we recommend the use of programmed electrical stimulation for additional risk stratification. If a sustained ventricular arrhythmia is induced, an ICD should be implanted.

Journal Article↗

PubMed1999

Remediation of attention deficits in head injury.

Head injury is associated with psychological sequelae which impair the patient's psychosocial functioning. Information processing, attention and memory deficits are seen in head injuries of all severity. We attempted to improve deficits of focused, sustained and divided attention. The principle of overlapping sources of attention resource pools was utilised in devising the remediation programme. Tasks used simple inexpensive materials. Four head injured young adult males with post concussion syndrome underwent the retraining program for one month. The patients had deficits of focused, sustained and divided attention parallel processing, serial processing, visual scanning, verbal learning and memory and working memory. After the retraining programme the deficits of attention improved in the four patients. Serial processing improved in two patients. Parallel processing and neuropsychological deficits did not improve in any patient. The symptom intensity reduced markedly and behavioural functioning improved in three of the four patients. The results supported an association between improving attention and reduction of symptom intensity. Attention remediation shows promise as a cost effective, time efficient and simple technique to improve the psychological and psychosocial functioning of the head injured patient.

Adult↗

PubMed2006

Assessing delayed effects of a multi-site system intervention for homeless persons with serious mental illness.

ACCESS demonstration sites were followed for an additional two years beyond the scheduled four-year evaluation to assess whether any delayed effects had occurred in system and project integration. For system integration, findings indicate that there was a sharp increase between Wave 3 (1998) and Wave 4 (2000), but experimental and comparison sites had identical trends. For project integration, experimental sites at Wave 4 sustained the high level of integration achieved at Wave 3, but the comparison sites achieved the same level as the experimental sites at Wave 4, through an abrupt increase in their scores. The absence of delayed effects is likely due to diffusion of the interventions to comparison sites both in the latter stages of the demonstration and immediately afterwards. Further, aggressive lobbying on the part of ACCESS program managers to generate local and state support to sustain their services following the termination of federal funding, had an integrating effect thereby creating linkages among comparison site agencies. Implications of these findings for policy and further research are highlighted.

Efficiency, Organizational↗

PubMed1993

Serial electropharmacologic studies in patients with ischemic heart disease and sustained ventricular tachyarrhythmias: when is drug testing sufficient?

Serial testing of antiarrhythmic drugs by programmed electrical stimulation can be costly in time, expense and risk. The purpose of this study was to evaluate the results of serial electropharmacologic tests for similarities that might obviate the need for protracted drug testing. Serial electropharmacologic testing was performed in 283 patients with coronary artery disease and clinical sustained ventricular tachycardia (VT) or fibrillation (VF). Drug tests were defined as concordant if sustained VT or VF could be consistently induced, or failed to be consistently induced during all such trials in a given patient. The following drugs were included for testing: procainamide, quinidine and disopyramide (class IA); phenytoin, mexiletine and tocainide (class IB); and flecainide and encainide (class IC). All patients were serially tested with > or = 2 (mean and median, 3) antiarrhythmic agents regardless of results from drug-free testing or initial acute drug testing. Overall, the results of serial drug trials directed by programmed stimulation were concordant in more than two thirds of patients. Concordance was comparably high whether patients were serially tested with drugs within the same antiarrhythmic class, or with drugs from differing classes, and was not related to patients' clinical or electrophysiologic characteristics. Protracted serial electropharmacologic testing does not appear necessary for predicting successful or unsuccessful antiarrhythmic drug therapy in survivors of clinical VT or VF. Single drug testing can identify most patients whose arrhythmia will or will not respond to medications.

Action Potentials↗

PubMed2005

Effects of a family intervention on the quality of life of women with recurrent breast cancer and their family caregivers.

BACKGROUND: The purpose of this study was to determine if patients with advanced breast cancer and their family caregivers, who participated in a family based intervention, report better quality of life and other psychosocial outcomes than dyads who received standard care alone. METHODS: Using a randomized clinical trial, 134 patients and their family caregivers were assigned to usual care (control) or to usual care plus the family intervention (experimental condition). Dyads were assessed at baseline, three- and six-months later. The intervention consisted of five sessions and addressed family involvement, optimistic attitude, coping effectiveness, uncertainty reduction, and symptom management. RESULTS: Patients in the family intervention reported significantly less hopelessness and less negative appraisal of illness than controls; their family caregivers reported significantly less negative appraisal of caregiving. Intervention effects were evident at three-months, but were not sustained at six-months. No difference was found in the quality of life of dyads in experimental or control conditions. CONCLUSIONS: Although the family intervention had positive effects initially, these effects were not sustained over time. Future studies need to consider program dose and duration of effect, outcome measures that are more sensitive to change, and realistic end-points for patients with advanced cancer.

Adaptation, Psychological↗