Exercise training improves aerobic capacity, muscle strength, and quality of life in renal transplant recipients.

Renal transplant recipients (RTR) have reduced peak aerobic capacity, muscle strength, arterial function and an unfavorable cardiovascular disease risk (CVD) profile. This study compared the effects of 12 weeks of supervised endurance and strength training (EST, n = 16) versus usual care (UC, n = 15) on peak aerobic capicity, cardiovascular and skeletal muscle function, CVD risk profile, and quality of life (QOL) in RTR (55 ± 13 years). Peak aerobic capacity and exercise hemodynamics, arterial compliance, 24-h blood pressure, muscle strength, lean body mass, CVD risk score, and QOL were assessed before and after 12 weeks. The change in peak aerobic capacity (EST: 2.6 ± 3.1 vs. UC: -0.5 ± 2.5 mL/(kg·min)), cardiac output (EST: 1.7 ± 2.6 vs. UC: -0.01 ± 0.8 L/min), leg press (EST: 48.7 ± 34.1 vs. UC: -10.5 ± 37.7 kg) and leg extension strength (EST: 9.5 ± 10.3 vs. UC: 0.65 ± 5.5 kg) improved significantly after EST compared with UC. The overall change in QOL improved significantly after 12 weeks of EST compared with UC. No significant difference was found between groups for lean body mass, arterial compliance, 24-h blood pressure or CVD risk score. Supervised EST is an effective intervention to improve peak exercise aerobic capacity and cardiac output, muscle strength and QOL in clinically stable RTR.

Cardiac resynchronization therapy modulation of exercise left ventricular function and pulmonary O2 uptake in heart failure.

To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P < 0.05). During moderate-intensity exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P < 0.05), and steady-state stroke volume increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P < 0.05). LV end-diastolic volume did not change from rest to steady-state exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P < 0.05). For peak exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P < 0.05). The increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P < 0.05). These findings demonstrate the chronic CRT-mediated cardiac factors that contribute, in part, to the speeding in Vo(2) kinetics and increase in peak Vo(2) in clinically stable heart failure patients.

Investigating the European Society of Cardiology Diastology Guidelines in a practical scenario.

AIMS: Recently, the European Society of Cardiology (ESC) released a consensus statement for the diagnosis of heart failure with preserved ejection fraction (HFPEF). It state that E/e' > 15 or <8 clearly define those with or without HFPEF and that for those in the range 8-15, other parameters should be examined. METHODS AND RESULTS: We retrospectively analysed 1229 consecutive echocardiograms (57% males) for the utility of echocardiographic measures including left atrial volume index (LAVI), left ventricular mass index (LVMI), and pulmonary venous and mitral inflow Doppler. LAVI of 40 ml/m(2) provided the greatest sensitivity and specificity of 76 and 77%, respectively, with reference to E/e' for the detection of diastolic dysfunction. The ESC definition of raised LVMI yielded a sensitivity and specificity of 32 and 99%, respectively. We found that the mitral and pulmonary inflow provided little incremental information. These results remained consistent between those with normal and abnormal ejection fraction. CONCLUSIONS: There appears to be little incremental value of pulmonary and mitral Doppler measures beyond the measure of mitral E wave. An LAVI cut-off of 40 ml/m(2) maximizes both sensitivity and specificity. However, ESC guidelines of raised LVMI in patients with HFPEF would appear to heavily trade sensitivity for specificity.

Impaired pulmonary oxygen uptake kinetics and reduced peak aerobic power during small muscle mass exercise in heart transplant recipients.

We examined peak and reserve cardiovascular function and skeletal muscle oxygenation during unilateral knee extension (ULKE) exercise in five heart transplant recipients (HTR, mean +/- SE; age: 53 +/- 3 years; years posttransplant: 6 +/- 4) and five age- and body mass-matched healthy controls (CON). Pulmonary oxygen uptake (Vo(2)(p)), heart rate (HR), stroke volume (SV), cardiac output (Q), and skeletal muscle deoxygenation (HHb) kinetics were assessed during moderate-intensity ULKE exercise. Peak exercise and reserve Vo(2)(p), Q, and systemic arterial-venous oxygen difference (a-vO(2diff)) were 23-52% lower (P < 0.05) in HTR. The reduced Q and a-vO(2diff) reserves were associated with lower HR and HHb reserves, respectively. The phase II Vo(2)(p) time delay was greater (HTR: 38 +/- 2 vs. CON: 25 +/- 1 s, P < 0.05), while time constants for phase II Vo(2)(p) (HTR: 54 +/- 8 vs. CON: 31 +/- 3 s), Q (HTR: 66 +/- 8 vs. CON: 28 +/- 4 s), and HHb (HTR: 27 +/- 5 vs. CON: 13 +/- 3 s) were significantly slower in HTR. The HR half-time was slower in HTR (113 +/- 21 s) vs. CON (21 +/- 2 s, P < 0.05); however, no significant difference was found between groups for SV kinetics (HTR: 39 +/- 8 s vs. CON 31 +/- 6 s). The lower peak Vo(2)(p) and prolonged Vo(2)(p) kinetics in HTR were secondary to impairments in both cardiovascular and skeletal muscle function that result in reduced oxygen delivery and utilization by the active muscles.

An unusual presentation of a Gastrointestinal stromal tumour (GIST).

BACKGROUND: Gastrointestinal stromal tumours (GIST) are rare tumours, now more frequently identified with the new imaging modalities like computerised tomography (CT) and magnetic resonance imaging (MRI). We report a rare presentation of a GIST with an unusual diagnostic workup in a multidisciplinary setting leading to a definitive diagnosis and treatment. CASE PRESENTATION: A 55-year-old lady was admitted under the general surgeons, with 3-day history of abdominal pain, three-week history of loss of appetite and weight. The patient was sequentially investigated with ultrasonography, computerised tomography and finally selective angiogram in a multidisciplinary setting. The selective angiogram showed a GIST with intratumour bleed, leading to successful surgical excision and being recurrence free at 22 month follow up. CONCLUSION: Clinical presentation of these tumours can be varied and gastrointestinal bleeding is the commonest mode described in the literature. The clinician needs to be aware of much more rare presentations of the GIST including an intra tumour bleed. A structured multidisciplinary approach would lead to successful diagnosis and treatment.

Long-term survival is possible after stenting for malignant ureteric obstruction in colorectal cancer.

INTRODUCTION: Ureteric obstruction is a potentially terminal event in patients with irresectable or recurrent colorectal cancer. Urinary tract obstruction is easily relieved by either two stage antegrade stenting or one stage retrograde stenting. However, there is little in the literature about outcomes after this procedure and it is unclear which, if any, patients should be offered this intervention. PATIENTS AND METHODS: This was a retrospective review of a prospectively collected database of patients diagnosed with colorectal cancer. This database comprised 1428 cases (operative and non-operative) diagnosed at a single institution. This was cross-checked with databases for patients undergoing nephrostomy and/or antegrade stenting and by clinical coding for those patients having retrograde stenting between January 1996 and October 2004. RESULTS: Thirteen patients were identified (median age, 69 years: range, 35-85 years; 9 male). The aetiology of obstruction was recurrent tumour in 6 patients and irresectable tumour in the remaining 7 patients. Two patients were discussed at a urology multidisciplinary meeting before stenting and a further two were discussed with colorectal surgeons. One patient received a palliative cystectomy and ileal conduit for a vesicovaginal fistula followed by radiotherapy. Four patients received chemotherapy after stenting. Overall median survival was 210 days (range, 13-927 days). CONCLUSIONS: Long-term survival is possible in selected patients with recurrent or irresectable colorectal cancer and malignant ureteric obstruction. This appears to be more likely in those patients in whom other treatments, particularly chemotherapy, are available.

The clinical significance of a common, functional, X-linked angiotensin II type 2-receptor gene polymorphism (-1332 G/A) in a cohort of 509 families with premature coronary artery disease.

AIMS: To assess, in families with premature coronary artery disease (CAD), the possible association, with linkage, of the X-linked AT2 receptor (-1332 G/A) gene polymorphism and premature CAD. METHODS AND RESULTS: We investigated 509 families with a history of premature CAD that consisted of one sibling affected with premature CAD and two unaffected siblings. Genotyping of subjects was performed using a restriction enzyme digestion of an initial 310 bp polymerase chain reaction fragment that included the AT2 (-1332 G/A) locus. The mean age of the 611 individuals affected by premature CAD at the time of event was 49.5 +/- 8.1 years. Conditional logistic regression analysis confirmed a significant predictive value of premature CAD for the covariates of hypertension, diabetes, dyslipidaemia, history of smoking, and male gender. The genetic data were analysed for these families using the X-linked sibling transmission/deletion test (XS-TDT) statistics program. In hemizygous men we observed evidence for association in the presence of linkage, for the AT2 (-1332 G/A) locus and premature CAD (P-exact value = 0.024) and also a trend towards association, in the presence of linkage, for this polymorphism and hypertension (P-exact value = 0.08). CONCLUSIONS: We have observed evidence of association between the presence of linkage for the X-linked AT2 (-1332 G/A) polymorphism and premature CAD in hemizygous males.

Premature coronary artery disease shows no evidence of linkage to loci encoding for tissue inhibitors of matrix metalloproteinases.

Tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3) are naturally occurring inhibitors of matrix metalloproteinases (MMPs). It has been proposed that MMPs have a role in weakening the fibrous cap and subsequent plaque rupture. We hypothesized that TIMP polymorphisms could predispose to premature coronary artery disease. As a first step, we examined the relevant loci using a linkage approach. Sibling pairs recruited for the British Heart Foundation (BHF) Family Heart Study with premature coronary artery disease were examined. Two to three microsatellite markers were examined per TIMP gene. These markers were either intragenic or very close to the locus encoding for the gene. Products were analyzed by capillary gel electrophoresis. Single and multipoint linkage analysis based on the likelihood ratio test was performed using SPLINK and Mapmaker/Sibs software; 417 families were genotyped consisting of 385 sibling pairs, 27 trios, and five sets of four siblings. We were unable to detect linkage of premature coronary artery disease to loci encoding for TIMP1-3. Polymorphisms of the tissue inhibitors of MMP genes do not predispose to premature coronary artery disease in an epidemiologically significant way.