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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a series of 26 heart transplant recipients with renal impairment in which sirolimus was used as the basic immunosuppresive drug (without associated calcineurin inhibitors) to avoid further nephrotoxicity. Sirolimus (trough levels 10 to 12 ng/mL, average daily dose 3 mg) was used in two settings: de novo in 7 patients with significant preexistent renal impairment and as a chronic conversion in 19 stable patients with established renal failure (creatinine level >2 mg/dL). In all de novo patients (n = 7), the renal function significantly improved. Creatinine fell from 2.95 +/- 0.9 mg/dL to 1.41 +/- 0.4 mg/dL at follow-up (P = .0017). One patient died suddenly of a massive pulmonary embolism. Only one patient experienced histologic but reversible rejection. In one patient, anemia and diarrhea prompted sirolimus withdrawal. Five patients had infectious episodes: three bacterial pneumonias, one mediastinitis, and two CMV infections. In the chronic conversion group (n = 19), the improvement was mostly limited to patients with moderate renal failure (creatinine < or =2.5 mg/dL) in which creatinine fell from 2.24 +/- 0.2 to 1.9 +/- 0.27 mg/dL, P = .009). When basal creatinine was over 2.5 mg/dL, only one third of the patients improved after conversion. Two patients died: terminal renal failure and cerebrovascular accident. There were no clinical episodes of rejection. Secondary effects prompted the discontinuation of sirolimus in five patients: two definite and one possible interstitial pneumonitis and two cases of anemia). The symptoms resolved after sirolimus withdrawal. Six patients had infection: four pneumonias, one sepsis, and one cutaneous abscess. Sirolimus is an interesting alternative to calcineurin inhibitors in selected patients with renal impairment. It prevents renal failure in de novo recipients at high risk of catastrophic renal damage and ameliorates renal dysfunction in chronic patients with moderate renal dysfunction. Given the high incidence of secondary effects, the adequate dosage and the secondary effects profile needs further study.
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PMID:Sirolimus as an alternative to anticalcineurin therapy in heart transplantation: experience of a single center. 1638 15

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by thrombocytopenia, haemolytic anemia, fluctuating neurological deficits, fever, and renal impairment. This case report is about a young man who presented with acute onset right sided paralysis, dysarthria, and central facial paralysis, suggestive of cerebrovascular accident, but eventually diagnosed as TTP. In addition, the clinical presentation of TTP is discussed and some teaching points for the emergency physicians are emphasised.
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PMID:Thrombotic thrombocytopenic purpura mimicking acute ischemic stroke. 1692 Oct 72

Hypertension remains one of the primary causes of preventable death in developed countries. Universally accepted clinical practice guidelines based on well designed trials are needed to ensure standardized treatment for these patients. It has been hypothesized that agents such as calcium channel antagonists and ACE inhibitors may be more effective than beta-adrenoceptor antagonist (beta-blocker)- or diuretic-based regimens. However, until recently, there have been limited data on the efficacy of 'newer' antihypertensive regimens, particularly combination therapy, relative to standard therapeutic options. The ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm), a prospective, randomized, controlled trial in >19 250 patients with hypertension, highlights the benefit of a combined amlodipine plus perindopril regimen over an atenolol plus diuretic-based combination in terms of significant reductions (p < 0.05) in all-cause mortality, total cardiovascular events and procedures, and fatal and nonfatal stroke. The ASCOT-BPLA trial underlines the cardiovascular benefit of ACE inhibitors, specifically perindopril, beyond that provided by BP reduction, and potentially reflects a mechanistic feature of the ACE inhibitors. It also suggests that the combination of amlodipine plus perindopril may provide broad-spectrum cardiovascular protection, as well as reduce the incidence of new-onset diabetes mellitus and renal impairment, in addition to its efficacy in lowering BP. The ASCOT-BPLA trial provides evidence of the need to reconsider traditional prescribing recommendations in patients with hypertension, particularly conclusions reached in the US after the publication of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study. The recently published National Institute for Health and Clinical Excellence (NICE) guidelines in the UK emphasize the efficacy of ACE inhibitors as first-line agents for hypertensive patients <55 years of age and recommend ACE inhibitor therapy at any stage of hypertension management.
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PMID:The ASCOT trial: clarifying the role of ACE inhibition in the reduction of cardiovascular events in patients with hypertension. 1708 67

Fabry disease is an X-linked, hereditary, lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A, which results in the accumulation of the neutral glycosphingolipid globotriaosylceramide (Gb3) in the walls of small blood vessels, nerves, dorsal root ganglia, renal glomerular and tubular epithelial cells, and cardiomyocytes. It is a complex, multisystem disorder that is characterized clinically by chronic pain and acroparesthesia, gastrointestinal disturbances, characteristic skin lesions (angiokeratomata), progressive renal impairment, cardiomyopathy, and stroke. Enzyme replacement therapy (ERT) with intravenous infusions of recombinant human alpha-galactosidase A consistently decreases Gb3 levels in plasma and clears lysosomal inclusions from vascular endothelial cells. The effects of ERT on other tissues are not as obvious, suggesting that treatment must be initiated early in the course of the disease to be optimally effective or that some complications of the disease are not responsive to enzymes delivered intravenously.
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PMID:Narrative review: Fabry disease. 1737 87

Fibromuscular dysplasia typically occurs in young women and most commonly presents with hypertension, transient ischemic attack, stroke, or an asymptomatic cervical bruit. The disease is nonatherosclerotic and noninflammatory and most often affects the renal and carotid arteries, although almost any artery can be involved. On angiography, affected blood vessels characteristically resemble a string of beads in the most common type of fibromuscular dysplasia, medial fibroplasia. Patients with renal artery stenosis and hypertension or renal impairment should be treated with percutaneous transluminal angioplasty without a stent. Patients with fibromuscular dysplasia of the internal carotid artery should also be treated with angioplasty if they develop focal neurologic symptoms such as a transient ischemic attack or stroke.
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PMID:Recognizing and managing fibromuscular dysplasia. 1743 76

Fabry disease is an inborn error of glycosphingolipid catabolism resulting from a deficiency of lysosomal enzyme alpha-galactosidase A. The major clinical manifestations of the disease, such as stroke, cardiac dysfunction, and renal impairment, are thought to be caused by vasculopathy due to progressive accumulation of globotriaosylceramide in vascular endothelial cells. The pathogenesis of the vasculopathy has not been elucidated. Since in vitro studies using primary endothelial cells are hampered by the limited lifespan of these cells, the availability of cultured endothelial cells with an extended lifespan is critical for the study of the vasculopathy of Fabry disease. We therefore generated an endothelial cell line from a Fabry hemizygote by introduction of human telomerase reverse transcriptase gene. The cell line has markedly extended lifespan compared to parental primary cells. The cells stably express many key markers of endothelial cells such as von Willebrand factor, CD31, CD34, and endothelial nitric oxide synthase (eNOS) and retain functional characteristics such as uptake of acetylated low-density lipoprotein, responsiveness to angiogenic growth factors, up-regulation of eNOS production upon extracellular stimuli, and formation of tube-like structures on Matrigel basement membrane matrix. The cells show significantly reduced activity of alpha-galactosidase A compared with primary endothelial cells from normal individuals and accumulate globotriaosylceramide in lysosomes. This cell line will provide a useful in vitro model of Fabry disease and will facilitate systematic studies to investigate pathogenic mechanisms and explore new therapeutic approaches for Fabry disease.
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PMID:Establishment and characterization of Fabry disease endothelial cells with an extended lifespan. 1764 84

Patients with diabetes and chronic kidney disease (CKD) are at particularly high risk for cardiovascular disease (CVD). This post hoc analysis from the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) investigated the relationship between CKD and incident CVD in a population of patients with diabetes and documented macrovascular disease, as well as the effects of pioglitazone treatment on recurrent CVD. CKD, defined as an estimated GFR <60 ml/min per 1.73m(2), was present in 597 (11.6%) of 5154 patients. More patients with CKD reached the primary composite end point (all-cause mortality, myocardial infarction (MI), stroke, acute coronary syndrome, coronary/carotid arterial intervention, leg revascularization, or amputation above the ankle) than patients without CKD (27.5 versus 19.6%; P < 0.0001). Patients with CKD were also more likely to reach a secondary composite end point (all-cause mortality, MI, and stroke). Patients who had CKD and were treated with pioglitazone were less likely to reach the secondary end point (hazard ratio 0.66; 95% confidence interval 0.45 to 0.98), but this association was not observed among those with better renal function. In addition, there was a greater decline in estimated GFR with pioglitazone (between-group difference 0.8 ml/min per 1.73 m(2)/yr) than with placebo. In conclusion, CKD is an independent risk factor for cardiovascular events and death among patients with diabetes and preexisting macrovascular disease. Patients who had CKD and were treated with pioglitazone were less likely to reach a composite end point of all-cause death, MI, and stroke, independent of the severity of renal impairment.
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PMID:Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease. 2758 Nov 6

To determine whether serum 25(OH)D and/or PTH levels in older patients with hip fracture (HF) could predict short-term clinical outcomes, we conducted a prospective observational study of 287 consecutive HF patients (mean age 81.9 + or - 7.5 [SD] years, 72% females). The prevalence of vitamin D inadequacy (25[OH]D < 80 nmol/l) was 97.1%, that of vitamin D deficiency (25[OH]D < 50 nmol/l) was 79.8%, and that of elevated PTH level (>6.8 pmol/l) was 35.5%. After adjustment for age and sex, PTH was significantly associated with in-hospital mortality (OR = 1.12, 95% CI 10.5-1.20, P < 0.001), myocardial injury (OR = 1.05, 95% CI 1.03-1.15, P = 0.002), prolonged length of stay (LOS > or = 20 days; OR = 1.05, 95% CI 1.01-1.06, P = 0.044), and being discharged to institutional care (OR = 1.07, 95% CI 1.01-1.18, P = 0.48). Secondary hyperparathyroidism (SHPT), but not vitamin D deficiency, was associated with older age, a higher prevalence of trochanteric fracture, coronary artery disease, hypertension, previous stroke, renal impairment, increased levels of serum osteocalcin, bone-specific alkaline phosphatase, and adiponectin as well as a significantly higher in-hospital mortality (11.8 vs. 0.54%, P = 0.001), perioperative myocardial injury (32.7 vs. 22.5%, P = 0.043), LOS > or = 20 days (40.2 vs. 26.9%, P = 0.017), and being discharged to institutional care (29.5 vs. 14.6%, P = 0.019). In multivariate regression analyses, SHPT was strongly associated with in-hospital mortality and LOS > or = 20 days. We conclude that elevated PTH (but not vitamin D deficiency per se) is a strong independent predictor of poor outcomes in older patients.
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PMID:Elevated serum PTH is independently associated with poor outcomes in older patients with hip fracture and vitamin D inadequacy. 1976 73

Several newer anticoagulants are under clinical development. Recently two of them, Dabigatran etexilate/Pradaxa. and Rivaroxaban/Xarelto obtained marketing authorization in Europe and Canada for the prevention of thromboembolic events following major orthopedic surgery such as total hip and knee replacement. The results of Phase III clinical studies in thromboprophylaxis in major orthopedic surgery are highlighted and discussed in detail. Ongoing Phase II and III clinical trials assess their efficacy in the secondary prevention and treatment of deep vein thrombosis and pulmonary embolism, and in the long-term prevention of stroke in patients with non-valvular atrial fibrillation and in combination with aspirin and clopidogrel in patients with acute coronary syndromes. Many other small antithrombotic molecules including a new generation of low molecular weight heparins, are currently in different stages of clinical development. In addition to being administered orally, the newer anticoagulant agents have a more balanced benefit/risk ratio and wider therapeutic window. They have a rapid onset of action, a predictable anticoagulant effect that does not require routine laboratory monitoring. They have minor food and drug interactions, including those with cytochrome P450 and P.gp. They are highly specific and targeted to a single coagulation factor, and could carry similar or less hemorrhagic risks compared to the older anticoagulant agents. Finally, they may be used in a broader variety of patients, especially the medically ill patients with advanced cancer, and the elderly without any dosage adjustment, regardless of the patient age, gender, body weight, or in patients with mild renal impairment. Their use in the general world will hopefully confirm the promising results of clinical trials.
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PMID:Newer anticoagulants in 2009. 1983 70

Activation of the renin-angiotensin-aldosterone system (RAAS) results in vasoconstriction, muscular (vascular and cardiac) hypertrophy and fibrosis. Established arterial stiffness and cardiac dysfunction are key factors contributing to subsequent cardiovascular and renal complications. Blockade of RAAS has been shown to be beneficial in patients with hypertension, acute myocardial infarction, chronic systolic heart failure, stroke and diabetic renal disease. An aggressive approach for more extensive RAAS blockade with combination of two commonly used RAAS blockers [ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)] yielded conflicting results in different patient populations. Combination therapy is also associated with more side effects, in particular hypotension, hyperkalaemia and renal impairment. Recently published ONTARGET study showed ACEI/ARB combination therapy was associated with more adverse effects without any increase in benefit. The Canadian Hypertension Education Program responded with a new warning: 'Do not use ACEI and ARB in combination'. However, the European Society of Cardiology in their updated heart failure treatment guidelines still recommended ACEI/ARB combo as a viable option. This apparent inconsistency among guidelines generates debate as to which approach of RAAS inhibition is the best. The current paper reviews the latest evidence of isolated ACEI or ARB use and their combination in cardiovascular diseases, and makes recommendations for their prescriptions in specific patient populations.
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PMID:Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. 2059 Jun 19


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