Heart rate variability and cardiac failure.
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Adolescent↗
Biomedical subjects
J Nolan
Publications and source records attributed to J Nolan.
Hip replacement audit.
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Arthroplasty, Replacement, Hip↗
Recommendations for uniform reporting of data following major trauma--the Utstein Style. An International Trauma Anaesthesia and Critical Care Society (ITACCS) initiative.
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Data Collection↗
A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles.
OBJECTIVE: To compare the effects of two doses of conjugated equine estrogen (CEE) and two of esterified estrogen plus methyltestosterone (E + A) in surgically menopausal women. STUDY DESIGN: A two-year, parallel-group, double-blind study of 311 women who were randomly assigned to one of four regimens: (1) CEE, 0.625 mg/d; (2) CEE, 1.25 mg/d; (3) esterified estrogens, 0.625 mg, + methyltestosterone, 1.25 mg/d; or (4) esterified estrogens, 1.25, + methyltestosterone, 2.5 mg/d. Study parameters were symptoms, lipids, bone mineral density, side effects and safety. RESULTS: All treatments prevented loss of bone in the spine and hip. The higher E + A dose increased spine and hip BMD more than other treatments (P < .002). All treatments improved menopausal symptoms, with non-significantly greater improvements in well-being and sexual interest in the E + A groups. Similar and significant decreases in low-density lipoprotein were observed in all groups, but high-density lipoprotein and triglycerides were increased only in the unopposed estrogen groups (P < .05). Hirsutism was uncommon and similar in all groups at two years. Discontinuation rates and reasons for withdrawal from the study were similar in both groups. No clinically significant side effects or laboratory test abnormalities were seen. CONCLUSION: As compared to estrogen alone, E + A significantly improved BMD and was well tolerated in surgically menopausal women.
Administration, Oral↗
An IT awareness programme for the health sector in Ireland.
This paper describes an Awareness Programme delivered throughout Ireland which aims to increase the level of understanding of healthcare professionals as to the benefits of Information and Communications Technology (ICT) and of emerging trends in Health Informatics in Europe. The programme examines the use of ICT across the whole health sector--primary, secondary and tertiary. It has been delivered at over 30 centres to more than 1500 health professionals.
Computer Literacy↗
Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).
BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.
Aged↗
Indolequinone antitumor agents: reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro.
A series of indolequinones bearing a variety of leaving groups at the (indol-3-yl)methyl position was synthesized by functionalization of the corresponding 3-(hydroxymethyl)indolequinone, and the resulting compounds were evaluated in vitro as bioreductively activated cytotoxins. The elimination of a range of functional groups-carboxylate, phenol, and thiol-was demonstrated upon reductive activation under both chemical and quantitative radiolytic conditions. Only those compounds which eliminated such groups under both sets of conditions exhibited significant hypoxia selectivity, with anoxic:oxic toxicity ratios in the range 10-200. With the exception of the 3-hydroxymethyl derivative, radiolytic generation of semiquinone radicals and HPLC analysis indicated that efficient elimination of the leaving group occurred following one-electron reduction of the parent compound. The active species in leaving group elimination was predominantly the hydroquinone rather than the semiquinone radical. The resulting iminium derivative acted as an alkylating agent and was efficiently trapped by added thiol following chemical reduction and by either water or 2-propanol following radiolytic reduction. A chain reaction in the radical-initiated reduction of these indolequinones (not seen in a simpler benzoquinone) in the presence of a hydrogen donor (2-propanol) was observed. Compounds that were unsubstituted at C-2 were found to be up to 300 times more potent as cytotoxins than their 2-alkyl-substituted analogues in V79-379A cells, but with lower hypoxic cytotoxicity ratios.
Animals↗
1998 European guidelines on resuscitation. Simplifications should make them easier to teach and implement.
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Cardiopulmonary Resuscitation↗
Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial.
BACKGROUND: Troglitazone is a new insulin-sensitizing agent used to treat type 2 diabetes mellitus. The mechanism by which troglitazone exerts its effect on systemic glucose metabolism is unknown. OBJECTIVE: To determine the effects of 6 months of troglitazone monotherapy on glucose metabolism in patients with type 2 diabetes mellitus. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Six general clinical research centers at university hospitals. PATIENTS: 93 patients (mean age, 52 years) with type 2 diabetes mellitus (mean fasting plasma glucose level, 11.2 mmol/L) who were being treated with diet alone or who had discontinued oral antidiabetic medication therapy. INTERVENTION: Patients were randomly assigned to one of five treatment groups (100, 200, 400, or 600 mg of troglitazone daily or placebo) and had metabolic assessment before and after 6 months of treatment. MEASUREMENTS: Plasma glucose and insulin profiles during a meal tolerance test; basal hepatic glucose production and insulin-stimulated glucose disposal rate during a hyperinsulinemic-euglycemic clamp procedure. RESULTS: Troglitazone at 400 and 600 mg/d decreased both fasting (P < 0.001) and postprandial (P = 0.016) plasma glucose levels by approximately 20%. All four troglitazone dosages also decreased fasting (P = 0.012) and postprandial (P < 0.001) triglyceride levels; 600 mg of the drug per day decreased fasting free fatty acid levels (P = 0.018). Plasma insulin levels decreased in the 200-, 400-, and 600-mg/d groups (P < 0.001), and C-peptide levels decreased in all five study groups (P < 0.001). Basal hepatic glucose production was suppressed in the 600-mg/d group compared with the placebo group (P = 0.02). Troglitazone at 400 and 600 mg/d increased glucose disposal rate by approximately 45% above pretreatment levels (P = 0.003). Stepwise regression analysis showed that troglitazone therapy was the strongest predictor of a decrease in fasting (P < 0.001) or postprandial (P = 0.01) glucose levels. Fasting C-peptide level was the next strongest predictor (higher C-peptide level equaled greater glucose-lowering effect). CONCLUSION: Troglitazone monotherapy decreased fasting and postprandial glucose levels in patients with type 2 diabetes, primarily by augmenting insulin-mediated glucose disposal.
Adult↗
The United Kingdom pre-hospital study of active compression-decompression resuscitation.
This prospective, controlled trial with crossover group design compares the effectiveness of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of victims of prehospital cardiac arrest. In three UK cities, victims of non-traumatic, out of hospital cardiac arrest, over the age of 8 years received either standard or ACD-CPR on arrival of ambulance personnel. Main outcome measures were return of spontaneous circulation, survival to be admitted to the intensive care unit, survival to hospital discharge, and neurological outcome. A total of 576 patients (STD-CPR, n=309; ACD-CPR, n=267) were analysed. The treatment groups were similar with respect to age, gender, proportion of witnessed arrests, initial cardiac rhythm, and call to advanced life support interval. The proportion of patients receiving bystander CPR was higher in the ACD group (37.1% vs. 28.5%; P=0.028). The interval between collapse and defibrillation was longer in the ACD group (12.3 min vs. 10.4 min; P=0.028). There was no difference between the STD-CPR and ACD-CPR groups in survival to admission to the intensive care unit (13.6% vs. 13.8%; P=0.93) or hospital discharge (4.8% vs. 6.0%; P=0.67). There was no difference between the groups with respect to the neurological outcome of those patients surviving to hospital discharge. Analysis of important subgroups also showed no benefit for ACD-CPR. We conclude that there was no improvement in outcome with ACD-CPR when used by ambulance personnel in Cardiff and Portsmouth.
Aged↗
Indolequinone bioreductive drugs: kinetic factors which influence selectivity for hypoxia.
The factors influencing the kinetics of the oxygen-sensitive reduction of indolequinones, including those bearing leaving groups in the (indol-3-yl)methyl position, have been studied. The hydroquinones derived from some representative indolequinones were found to autoxidize slowly in oxygenated solution at rates (effective rate constant with O2 approximately 40-300 M-1 s-1) that cannot compete with the reductive elimination of leaving groups. The rates of reaction between hydroquinone and O2 were even slower in the presence of approximately 4 microM superoxide dismutase (effective rate constant approximately 2-7 M-1 s-1), indicating the role of superoxide radicals in hydroquinone autoxidation. Since the release of the leaving groups from the hydroquinones is not significantly oxygen-sensitive, tumour selectivity requires specific reduction by enzymes that are overexpressed in some tumours. Conversely, the release of leaving groups from semiquinone radicals is inhibited by oxygen too efficiently unless the semiquinone reacts with targets on a timescale of milliseconds. Modification of redox properties has been explored with the aim of changing this oxygen sensitivity. The new 2-phenylindolequinones are approximately 60-100 mV higher in reduction potential than 2-alkyl derivatives but this is insufficient to decrease the rate of electron transfer from semiquinone to oxygen to a degree which might confer hypoxia-selective cytotoxicity. These results are discussed in the context of toxicity of EO9 and related compounds towards hypoxic rather than anoxic cells.
Antineoplastic Agents↗
Autonomic assessment of cardiovascular disease.
Autonomic dysfunction plays a major role in the pathophysiology of many medical conditions, particularly cardiovascular disorders and diabetes mellitus. This article describes some of the methods used to assess cardiovascular autonomic function, and concentrates on the techniques that have a current or potential clinical application.
Autonomic Nervous System↗
2-Cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: structure-activity in vitro and efficacy in vivo.
A series of 2-cycloalkyl- and 2-alkyl-3-(hydroxymethyl)-1-methylindoloquinones and corresponding carbamates have been synthesized and substituted in the 5-position with a variety of substituted and unsubstituted aziridines. Cytotoxicity against hypoxic cells in vitro was dependent upon the presence of a 5-aziridinyl or a substituted aziridinyl substituent for 3-hydroxymethyl analogues. The activity of 5-methoxy derivatives was dependent upon the presence of a 3-(carbamoyloxy)methyl substituent. Increasing the steric bulk at the 2-position reduced the compounds' effectiveness against hypoxic cells. A 2-cyclopropyl substituent was up to 2 orders of magnitude more effective than a 2-isopropyl substituent, suggesting possible radical ring-opening reactions contributing to toxicity. Nonfused 2-cyclopropylmitosenes were more effective than related fused cyclopropamitosenes reported previously. The reduction potentials of the quinone/semiquinone one-electron couples were in the range -286 to -380 mV. The semiquinone radicals reacted with oxygen with rate constants 2-8 x 10(8) dm3 mol-1 s-1. The involvement of the two-electron reduced hydroquinone in the mediation of cytotoxicity is implicated. The most effective compounds in vitro were the 2-cyclopropyl and 5-(2-methylaziridinyl) derivatives, and of these, 5-(aziridin-1-yl)-2-cyclopropyl-3-(hydroxymethyl)-1-methylindole-4 ,7-dione (21) and 3-(hydroxymethyl)-5-(2-methylaziridin-1-yl)-1,2-dimethylindole+ ++-4,7-dione (54) were evaluated in vivo. Both compounds showed antitumor activity both as single agents and in combination with radiation, with some substantial improvements over EO9 (3) at maximum tolerated doses and as single agents against the RIF-1 tumor model and comparable efficacy in the KHT tumor model.
Animals↗
Preservation of autonomic function following successful reperfusion with streptokinase within 12 hours of the onset of acute myocardial infarction.
Successful reperfusion following thrombolysis results in increased heart rate variability in the first 24 hours after administration. Preservation of autonomic function may contribute to improved prognosis when coronary artery patency is restored with intravenous thrombolysis.
Autonomic Nervous System↗
Feasibility and applicability of coronary stent implantation with the direct brachial approach: results of a single-center study.
Implantation of stents in selected patients improves outcome after coronary angioplasty. Newer antiplatelet regimes limit access site complications associated with stenting by the percutaneous femoral approach, but a substantial proportion of patients will require anticoagulant therapy for concomitant disease or will have peripheral vascular disease that prevents access from the leg. We investigated procedural success rates and outcome in consecutive patients undergoing elective stent implantation in our institution. In 73 patients who were receiving anticoagulation therapy and were stented by a direct approach to the left brachial artery, 98.6% of stents were successfully deployed, with a major vascular access site complication rate of 1.4%. Equipment consumption, procedural success rate, and fluoroscopy time were similar in patients stented by the direct brachial or percutaneous femoral approach. Where the percutaneous femoral approach is precluded or patients are anticoagulated, stent procedures can be successfully performed by the direct brachial approach with a low rate of access site complications, even when large-caliber guiding catheters are required.
Adult↗
The correction of autonomic dysfunction in cirrhosis by captopril.
BACKGROUND/AIMS: Vagal dysfunction is reported in about 70% of patients with cirrhosis, irrespective of aetiology, as detected by cardiovascular reflex tests. We have previously shown that RR-variability on 24-h ECG is a more sensitive marker of vagal dysfunction in cirrhosis. Angiotensin II inhibits vagal function in animals, and it is elevated in cirrhosis and may be the cause of the vagal dysfunction. Our aim was to observe the effect of captopril on vagal dysfunction in cirrhosis. METHODS: Eight patients with cirrhosis (biopsy proven, male two, female six, mean age 54.25) had 24-h ECG RR-variability performed. They then received captopril 25 mg t.d.s. for 48 h. The 24-h ECG was repeated on therapy. RESULTS: Mean blood pressure remained unchanged: baseline 89.8 +/- 4.8 mmHg (mean +/- sem) versus 91.8 +/- 5.9 mmHg, p = not significant. Median baseline RR-variability was 791 (range 18-5344) counts/24 h and increased in all but one patient, with captopril, to 1548 (56-4824) p = 0.008. Three increased into the normal range. CONCLUSION: The vagal dysfunction of cirrhosis is caused by neuromodulation by angiotensin II and is not due to a neuropathy.
Adult↗
Late, intermittent obstruction of a mitral prosthesis by chordal remnants.
A 59 year old male was admitted 10 weeks following insertion of a Medtronic Hall mitral prosthesis. He suffered recurrent episodes of electromechanical dissociation (EMD). Transthoracic echocardiography demonstrated that during the times of haemodynamic compromise, the mitral prosthesis was intermittently obstructed. Emergency surgical intervention revealed that chordae tendineae had prolapsed through the lesser orifice, obstructing the valve mechanism. The mitral remnants were excised, and as the valve functioned normally, it was not replaced. Postoperatively, the patient made an uneventful recovery. This case illustrates the Doppler echocardiographic features associated with extrinsic obstruction of a mitral prosthesis, and demonstrates that this unusual complication can be responsible for late valve dysfunction.
Chordae Tendineae↗
Maryland Emergency Medical Services and Shock Trauma Centre.
The author spent one year working as an attending Anaesthesiologist at the Shock Trauma Center in Baltimore. The Maryland trauma system is, in the author's opinion, one of the best in the United States and this article will outline the Maryland EMS (Emergency Medical Service) but with specific emphasis on the Shock Trauma Center in Baltimore.
Anesthesiology↗