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Tacrolimus as secondary intervention vs. cyclosporine continuation in patients at risk for chronic renal allograft failure.

BACKGROUND: Chronic renal allograft failure (CRAF) is the leading cause of graft loss post-renal transplantation. This study evaluated the efficacy and safety of tacrolimus as secondary intervention in cyclosporine-treated kidney transplantation patients with impaired allograft function as indicated by elevated serum creatinine (SCr) levels. METHODS: Patients receiving cyclosporine-based immunosuppression who had an elevated SCr at least 3 months post-renal transplantation were enrolled. Treatment allocation was 2:1 to switch to tacrolimus or continue cyclosporine. This analysis was performed after 2 yr; patients will be followed for an additional 3 yr. RESULTS: There were 186 enrolled and evaluable patients. On baseline biopsy, 90% of patients had chronic allograft nephropathy. Baseline median SCr was 2.5 mg/dL in both treatment groups. For patients with graft function at month 24, SCr had decreased to 2.3 mg/dL in the tacrolimus-treated patients and increased to 2.6 mg/dL in the cyclosporine-treated patients (p = 0.01). Acute rejection occurred in 4.8% of tacrolimus-treated patients and 5.0% of cyclosporine-treated patients during follow-up. Two-year allograft survival was comparable between groups (tacrolimus 69%, cyclosporine 67%; p = 0.70). Tacrolimus-treated patients had significantly lower cholesterol and low-density lipoprotein levels and also had fewer new-onset infections. Cardiac conditions developed in significantly fewer tacrolimus-treated patients (5.6%) than cyclosporine-treated patients (24.3%; p = 0.004). Glucose levels and the incidences of new-onset diabetes and new-onset hyperglycemia did not differ between treatment groups. CONCLUSIONS: Conversion from cyclosporine to tacrolimus results in improved renal function and lipid profiles, and significantly fewer cardiovascular events with no differences in the incidence of acute rejection or new-onset hyperglycemia.

Biopsy↗

Tolerance to severe hypoxia: lessons from Mt. Everest.

Human tolerance to chronic severe hypoxia has been elucidated by two recent high altitude studies: the 1981 American Medical Research Expedition to Everest, and Operation Everest II, a 40-day low pressure chamber-simulated ascent of Everest. The severe oxygen deprivation of extreme altitudes can only be tolerated because of an enormous increase in ventilation which defends the alveolar Po2 against the reduced inspired value. Nevertheless the arterial Po2 on the Everest summit is less than 30 mmHg. The hyperventilation results in a very low arterial Pco2 which causes severe respiratory alkalosis. This has the advantage of increasing the oxygen affinity of hemoglobin and accelerating the oxygen loading by the pulmonary capillary under diffusion-limited conditions. Cardiac function is astonishingly well maintained up to extreme altitudes. The relationship between cardiac output and work rate is the same as at sea level, and there is evidence that myocardial contractility is well preserved in spite of the extreme hypoxemia. However, there is impairment of central nervous system function at high altitude which persists following return to sea level. Significant abnormalities of motor coordination persisted for more than 12 months in most members of the Everest expedition. There is evidence that the climbers who ventilate most at high altitude have the most central nervous system impairment, presumably because of the more severe cerebral vasoconstriction.

Acclimatization↗

Prevalence of overweight and smoking patients with coronary heart disease in rural China.

OBJECTIVE: To investigate the prevalence of overweight and/or smoking patients with coronary artery disease in rural China. DESIGN: A prospective survey with qualitative, open-ended questionnaires. SETTING: Tertiary referral centre. SUBJECTS: 158 hospitalised patients (71 men and 87 women) with established coronary heart disease. MAIN OUTCOME MEASURES: To determine the prevalence of overweight and/or smoking hospitalised patients who had a definitive diagnosis of coronary artery disease and to determine participants understanding of these risk factors. RESULTS: Being overweight and smoking cigarettes were found in 32.7% and 15.2% of the participants, respectively. More than 70% of the overweight participants had neither knowledge nor counselling on their weight before the study. Most smokers believed smoking was harmful to their health and cardiac condition, and had tried unsuccessfully to quit smoking. CONCLUSIONS: There was a high prevalence of overweight and/or smoking patients with coronary heart disease. A systematic approach is urgently required to educate patients and primary care physicians, and to improve the management of being overweight and smoking cigarettes.

Adult↗

Towards more effective use of decision support in clinical practice: what the guidelines for guidelines don't tell you.

The Brisbane Cardiac Consortium Clinical Support Systems Program used multiple strategies in optimising quality of care of patients with either of two cardiac conditions. One of these strategies was the development and active implementation of decision support systems centred on evidence-based, locally agreed clinical practice guidelines. Our experience in undertaking this task highlighted numerous operational challenges for which solutions were difficult to extract from existing published literature. In the present article we provide a methodology grounded in both theory and real-world experience that may assist others in developing and implementing systems of guideline-based decision support.

Clinical Trials as Topic↗

The gap between knowledge and practice in the treatment and prevention of cardiovascular disease.

There is a gap between the current knowledge of the treatment of cardiac conditions derived from evidence-based medicine and the widespread application of this knowledge. The use of ACE inhibitors for patients with congestive heart failure, beta blockers in postmyocardial infarction patients, anticoagulation in patients with chronic atrial fibrillation, cholesterol medications for either primary or secondary prevention of coronary artery disease, and antihypertensive treatment, are of proven benefit, yet all are underutilized by cardiologists, as well as other medical practitioners. There is evidence that there are methods to improve the prescribing of medication, but further studies are required to identify the best ways of doing this. A challenge for the future will be to identify and apply the best educational programs to improve the quality and efficiency of medical care. (c) 2000 by CHF, Inc.

Journal Article↗

Seasonal variation in undiagnosed HIV infection on the general medicine and trauma services of two urban hospitals.

OBJECTIVE: To examine the seroprevalence of undiagnosed HIV and variation by season among patients admitted to the general internal medicine (GIM) and trauma services of two urban hospitals. DESIGN: A cross-sectional blinded HIV-1 seroprevalence survey. SETTING: A 725-bed academic medical center's hospital and an affiliated 324-bed tertiary care hospital. PARTICIPANTS: Residual serological specimens were obtained for unique patients aged 17 to 65 to study services in summer (June 16 to September 4, 2001) and fall to winter (November 1, 2001 to January 8, 2002). METHODS: Hospital files provided data on demographics, service type, and discharge clinical categories (fall-winter group only). HIV ELISA (enzyme-linked immunosorbent assay) tests with confirmatory Western blot were linked to subjects' de-identified files. We excluded 34 subjects with known HIV. Of the remaining unique admissions in summer (n=604) and fall-winter (n=978), 60% and 55% were tested, respectively. Predictors of undiagnosed HIV infection were examined using multivariate analysis. RESULTS: The summer cohort (n=362) had significantly lower unadjusted seroprevalence of undiagnosed HIV infection (1.4%; 95% confidence interval [CI], 0.4% to 3.2%) than the fall-winter cohort (n=539; 3.7%; 95% CI, 2.3% to 5.7%; P=.04). Overall, undiagnosed HIV was somewhat less likely in women (adjusted odds ratio [AOR], 0.45; 95% CI, 0.19 to 1.07) but more likely in black patients (AOR, 3.46; 95% CI, 0.70 to 17.06). In the fall-winter cohort, undiagnosed HIV was more likely for discharges with the following clinical categories versus those with a cardiac condition: dermatologic/breast (AOR, 14.90; 95% CI, 1.20 to 184.77), renal/urological (AOR, 22.43; 95% CI, 2.12 to 236.75), or infectious (AOR, 31.08; 95% CI, 2.40 to 402.98). CONCLUSIONS: The higher seroprevalence of undiagnosed HIV in the fall-winter admissions to GIM and trauma services supports especially targeting HIV testing in these months.

Adolescent↗

Physiological control of blood pumps using intrinsic pump parameters: a computer simulation study.

Implantable flow and pressure sensors, used to control rotary blood pumps, are unreliable in the long term. It is, therefore, desirable to develop a physiological control system that depends only on readily available measurements of the intrinsic pump parameters, such as measurements of the pump current, voltage, and speed (in revolutions per minute). A previously proposed DeltaP control method of ventricular assist devices (VADs) requires the implantation of two pressure sensors to measure the pressure difference between the left ventricle and aorta. In this article, we propose a model-based method for estimating DeltaP, which eliminates the need for implantable pressure sensors. The developed estimator consists of the extended Kalman filter in conjunction with the Golay-Savitzky filter. The performance of the combined estimator-VAD controller system was evaluated in computer simulations for a broad range of physical activities and varying cardiac conditions. The results show that there was no appreciable performance degradation of the estimator-controller system compared to the case when DeltaP is measured directly. The proposed approach effectively utilizes a VAD as both a pump and a differential pressure sensor, thus eliminating the need for dedicated implantable pressure and flow sensors. The simulation results show that different pump designs may not be equally effective at playing a dual role of a flow actuator and DeltaP sensor.

Computer Simulation↗

Cardiac pacing and valvular surgery.

Over a 17-year period (1970-1987) 75 patients, 3% of overall valvular surgery (VS) patients have been permanently paced at the time of VS (group 1), nine have been paced long after (group 2), 12 were already paced at the time of valve replacement (group 3), and 81 had a permanent pacing lead inserted during VS without further need for permanent pacing (group 4). Based on pre-, per- and post-operative clinical and electrocardiographic data we studied these four groups (GR). Aortic disease and especially calcified aortic stenosis (CAS) are the main valvular pathologies in all GR. The survival rate in GR 1 is lower than the survival rate of our overall VS PT5 due to older average ages and more severe cardiac conditions. In five patients GR 2 a myocardial pacing lead placed during VS was used long after for permanent stimulation. Patients in GR 3 were older than in other GR at the time of VS. The mortality was high in the patients operated on between 1973 and 1978 (average survived 3.5 years after pacing/2 years after VS) thus demonstrating the benefit of myocardial protection. For GR 4 the ratio of permanent lead implantation during VS was high in the late seventies (10%), it is now around 0.5%. In cases where the evolution of peroperative conduction disturbances is doubtful, it seems to us simpler to place a myocardial lead avoiding subsequent endocardial pacing if necessary, later, especially in patients with tricuspid disease.

Aged↗

Health-related quality-of-life assessment of patients with life-threatening ventricular arrhythmias.

The purpose of this study was to determine whether treatments for life-threatening ventricular arrhythmias are associated with quality-of-life (QOL) and psychological distress. Multidimensional measures of QOL and psychological distress were used to cross-sectionally compare patients with ICDs to patients treated with antiarrhythmic drugs and patients without serious cardiac conditions. The sample consisted of 157 patients: 35 patients treated with antiarrhythmic medication only, 24 patients treated with ICD only, 25 patients treated with ICD and antiarrhythmic medication, and 73 controls. Patients completed the Medical Outcomes Study SF-36 health survey, the Brief Symptom Inventory, and background questionnaires. There were no significant differences in self-reported QOL and psychological distress between patients with or without ICD, and the occurrence of defibrillator shocks was unrelated to QOL and psychological distress. However, patients treated with antiarrhythmic drugs reported greater QOL impairment in physical functioning, vitality, emotional role limitations, and sleep, as well as greater psychological distress than patients not treated with antiarrhythmics. These limitations may be attributed to adverse effects arising from antiarrhythmic pharmacotherapy. Results of the present investigation suggest that QOL and psychological distress are maintained among ICD patients, whereas treatment with antiarrhythmic drugs are associated with a diminished QOL and greater psychological distress. These findings may assist cardiologists to select the optimal treatment for life-threatening ventricular arrhythmias that minimizes disturbances in health-related QOL and psychological distress and increases patient compliance.

Activities of Daily Living↗

Detection of Embolism with Doppler Ultrasound: A Review.

Doppler detection of venous and arterial gas emboli has been recognized since 1968. The technology has been applied using 5-MHz ultrasound to study decompression sickness and monitor cardiopulmonary bypass and intracranial surgery. Since the advent of transcranial Doppler, which requires the use of lower ultrasonic carrier frequencies to penetrate the temporal bone, the detection of particulates moving in the bloodstream has been available. Using 2 MHz, microembolic signals have been detected in a variety of clinical situations, including cardiac conditions known to have high probabilities to produce embolic stroke. The basic features of a Doppler embolic signal have been clarified, and many investigators are applying the technology to determine the clinical significance of the detected emboli and their use in diagnosis and medical and surgical treatments. The basis for automatic sizing, counting, and characterizing the emboli is under development. The applications of Doppler detection of emboli will range from diagnosis and localization of embolic sources to improvement in surgical techniques and adjustments in medical treatments. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

Journal Article↗

Influence of atropine on fractal and complexity measures of heart rate variability.

BACKGROUND: Measurement of short-term fractal-like correlation properties of heart rate dynamics has been shown to be a useful prognostic indicator of adverse events in cardiac patients. Complexity measurements of heart rate variability (HRV) have already provided important information in many cardiac conditions. However, data on the physiological background of these newer nonlinear measures of HRV are limited. METHODS: Nine healthy subjects (aged from 22 to 35 years, 6 males, 3 females) had an electrocardiographic (ECG) recording during controlled breathing in supine position. HRV was analyzed for 5 min periods before and after intravenous injection of 0.6 mg of atropine using conventional HRV measures and newer nonlinear HRV measures including the short-term scaling exponent (alpha(1)) and approximate entropy (ApEn). RESULTS: The short-term scaling exponent alpha(1) increased significantly after atropine injection (1.01 +/- 0.23 vs 1.43 +/- 0.19, P = 0.001). There was no significant difference between ApEn values before and after atropine injection (0.87 +/- 0.17 vs 0.70 +/- 0.31, respectively, P = 0.27). At baseline before atropine administration, alpha(1) had a significant negative correlation with SDNN, RMSSD, and HF (r = -0.70, -0.76, -0.67, respectively, P < 0.05 for all), and a significant positive correlation with heart rate (r = 0.76, P < 0.05). After atropine injection, alpha(1) did not have significant correlation with any of the HRV parameters or heart rate. There were no significant correlations between ApEn and any of the HRV measures or heart rate either before or after atropine administration. CONCLUSIONS: Vagal tone has an important influence on the values of the short-term scaling exponent alpha(1). However, vagal modulation is not a major determinant of the values of ApEn.

Adult↗

Informed consent and hypoplastic left heart syndrome.

UNLABELLED: We present an ethical analysis from the perspective of shared decision-making and informed consent of a change in clinical management of infants born with hypoplastic left heart syndrome (HLHS). We reported a change in treatment of HLHS at the University of Alberta away from comfort care to life-saving surgery (LST) between 1987 and 1998. In a second review (1996-2001), 49/62 infants received LST, with 81% survival from the NICU and 58% at 35 mo. Eleven infants died preoperatively of non-cardiac conditions and two received elective comfort care. Sixteen infants had 18-mo Bayley Mental Development Index, mean score 84+/-19, but five scored <70. Although we continue to present the comfort care option to parents, since 2001 LST use for HLHS at our center is almost universal despite serious complications. CONCLUSION: We conclude that these findings are inconsistent with an open, shared decision-making model of informed consent and we suggest that comfort care should remain an ethically valid choice until the rate of serious long-term complications of LST decreases.

Bioethics↗

Vasostatins exert negative inotropism in the working heart of the frog.

An in vitro isolated working frog heart (Rana esculenta) was used to study the effects of exogenous CGA(1-76) (vasostatin 1), CGA(1-113) (vasostatin 2), and the synthetic CGA(7-57) on cardiac performance. Under basal cardiac conditions, the dose-response curves of the three peptides from 10(-8) to 10(-7) M showed a significant calcium-dependent negative inotropism that involved neither the endocardial endothelium nor the adrenergic and muscarinic receptors. In addition, the CgA fragments clearly counteracted the typical positive inotropism of isoprenaline (10(-<9) M). Taken together, these results provide the first evidence for a cardio-suppressive role for the vasostatins.

Animals↗

Cardiac murmurs: echocardiography in the assessment of patients requiring antibiotic prophylaxis for dental treatment.

BACKGROUND: Traditionally patients who indicate that they have a heart murmur or who indicate that they have had rheumatic fever are given antibiotic prophylaxis for dental treatment. This is commonly done without further assessment of the patient's actual endocarditis risk. Echocardiography is a non-invasive method of assessing cardiac valve function and haemodynamics. METHODS: Consecutive patients who were referred to a private practice oral and maxillofacial surgeon for dentoalveolar surgery and indicated that they had a cardiac problem and usually had antibiotic prophylaxis, were evaluated. Those with a clear indication for prophylaxis, for example had prosthetic heart valves or previous infective endocarditis, received antibiotic prophylaxis. Where there was uncertainty, they were referred for an echocardiogram, and if abnormal, a formal cardiology review. RESULTS: Three hundred and seventy patients out of approximately 20 000 (1.85 per cent) indicated that they had a cardiac murmur and usually received antibiotic prophylaxis for dental treatment between 1 February 1997 and 1 February 2005. Two hundred and sixty-two (71 per cent) were female and 108 (29 per cent) were male; age range 0.7 to 98 years, average 37.6 years. Two hundred and seventy (72 per cent) had normal hearts with no indication for antibiotic prophylaxis. Of the 100 (28 per cent) patients with abnormal findings, they were on average older; 49.5 years, range 0.7 to 87 years. Of these, 50 (14 per cent) met current indications for antibiotic prophylaxis. CONCLUSION: Patients who present for dental treatment indicating that they require antibiotic prophylaxis for cardiac condition need to be fully evaluated. In this study only 50 of 370 patients (14 per cent) required antibiotic prophylaxis. The remaining 320 (86 per cent) would have no benefit but a risk of adverse reaction to the antibiotic.

Adolescent↗

Postischemic recovery and oxidative stress are independent of nitric-oxide synthases modulation in isolated rat heart.

During myocardial ischemia and reperfusion, nitric oxide ((.)NO) was shown to exert either beneficial or detrimental effects. Uncoupled (.)NO synthases (NOS) can generate superoxide anion under suboptimal concentrations of substrate and cofactors. The aim of our study was to investigate the role of NOS modulation on 1) the evolution of functional parameters and 2) the amount of free radicals released during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 30 min of total ischemia, followed by 30 min of reperfusion in the presence of N(G)-nitro-D- or L-arginine methyl ester (NAME, 100 microM) or of D- or L-arginine (3 mM). Functional parameters were recorded and coronary effluents were analyzed with electron spin resonance to identify and quantify the amount of alpha-phenyl-N-tert-butylnitrone spin adducts produced during reperfusion. The antioxidant capacities of the compounds were determined with the oxygen radical absorbance capacity test. L-NAME-treated hearts showed a reduction of coronary flow and contractile performance, although neither L-NAME nor L-arginine improved the recovery of coronary flow, left end diastolic ventricular pressure, rate pressure product, and duration of reperfusion arrhythmia, compared with their D-specific enantiomers. A large and long-lasting release of alkyl/alkoxyl radicals was detected upon reperfusion, but no differences of free radical release were observed between D- and L-NAME or D- and L-arginine treatment. These results may indicate that, in our experimental conditions, cardiac NOS might not be a major factor implicated in the oxidative burst that follows a global myocardial ischemia.

Animals↗

A cohort study of neurodevelopmental outcome in children with DiGeorge syndrome following cardiac surgery.

AIMS: To examine whether the learning difficulties seen in a proportion of children with DGS are secondary to cardiac pathology and treatment, or a feature of the DGS phenotype. METHODS: Cohort study of all patients with DGS and coexisting cardiac lesions within a region. Ten children with 22q11 deletion were assigned two controls each, matched for age, sex, cardiac lesion, and preoperative hemodynamic status but without DGS. The neurodevelopmental status was evaluated with the Ruth Griffiths test for babies and young children. RESULTS: Children with the 22q11 deletion showed a wide range of developmental quotient (DQ; mean 71, 95% CI 47 to 95) and subscale scores, but these as a group were significantly lower than those of the control group (DQ 113, 95% CI 108 to 118). Four of the DGS children had DQs below 60. Hypocalcaemia, prolonged postoperative ventilation, and abnormal neurology perioperatively were associated with a low DQ. CONCLUSIONS: A proportion of children with DGS have a very poor developmental outcome following cardiac surgery. This outcome is not attributable to the cardiac condition and its treatment alone, but represents either a pre-existing component of the syndrome or an interaction between the syndrome and its treatment.

Case-Control Studies↗

Plasma digoxin concentration in children with heart failure.

A dosage schedule for digoxin medication is presented which has proved effective and safe in children of different ages with heart failure due to a variety of cardiac conditions. The plasma digoxin concentrations during maintenance therapy, using this schedule, agree closely with previously reported therapeutic adult plasma concentrations, though the results do not exclude the efficiency and safety of higher doses. A twice-daily dosage regimen is suggested.

Body Weight↗

Which patients are likely to die in an accident and emergency department?

Four hundred and eighty-eight deaths occurring in an accident and emergency department over five years were analysed. Their causes were categorised as medical, surgical, or traumatic. Medical causes accounted for 87% of the deaths, of which 60% were from cardiac conditions. Blood loss was an important factor in over half the deaths from surgical and traumatic causes. Lives might have been saved by considering infectious disease in patients with medical conditions and by undertaking more rapid blood transfusion, earlier chest drainage, and lateral cervical spine x rays in appropriate surgical or traumatic cases. The admission to casualty departments of people with terminal neoplasms should be discouraged. The management of medical emergencies should be emphasised when training accident and emergency department staff.

Adolescent↗