Effect of captopril on renal function in patients with essential hypertension

The glomerular filtration rate (creatinine clearance), glomerular permeability (qualitative and quantitative proteinuria), tubular reabsorption (k-λ chains of immunoglobulins and lysozyme) and indexes of tubular cell lysis (alpha-glucosidase and gamma-glutamyltranspeptidase) were measured in the urine of 10 patients with moderate, uncomplicated essential hypertension during placebo therapy and after captopril given at increasing doses of 25, 50, 100 and 200 mg twice daily, the first three doses being given for 3 days and the last one for 4 weeks in all patients and for an additional 6 months in 5 patients. During placebo therapy, proteinuria was absent in eight patients and detectable (glomerular and selective) in two; selective proteinuria appeared in two and a decrease in selectivity was observed in two patients with previous proteinuria after 4 weeks of captopril therapy. No proteinuria was detectable in the five patients followed up for 6 months, not even in the one in whom a decrease in glomerular selectivity had occurred after 4 weeks. The glomerular filtration rate was unchanged as were lysozyme and gamma-glutamyltranspeptidase values, while light chains were always undetectable. Alpha-glucosidase showed some increase; however, increments were transient and always much lower than those observed with known tubular toxic drugs. These data show that under our experimental conditions captopril caused no evident changes in glomerular and tubular function.     

Comparison of an intravenous pulse of methylprednisolone versus oral corticosteroid in severe acute rheumatic carditis: a randomized clinical trial

OBJECTIVES: To compare the short-term prognosis of patients with severe acute rheumatic carditis when treated with an intravenous pulse of methylprednisolone in comparison with conventional treatment using oral prednisone. METHODS: We designed a randomized clinical trial in the setting of a university general hospital in Brazil. We randomly allocated 18 patients with the diagnosis of severe acute rheumatic carditis and congestive heart failure to receive an intravenous pulse as opposed to oral prednisolone. Methylprednisolone was administered in a dose of 1 g intravenously for 3 consecutive days in the first and second weeks, for two days in the third, and one day in the fourth week. Prednisone was administered in a dose of 1.5 mg/kg/day over the period of 4 weeks. RESULTS: The mean age of the patients was 11.1 +/- 3.7 years, with a median of 12 years. Patients on oral treatment showed a more pronounced decrease in the heart rate, sedimentation rate, and in the titres of C-reactive protein than those receiving intravenous therapy. At the end of treatment, a mild decrease in the left ventricular end-systolic dimension was found in those having oral treatment, compared to an increase in the group having intravenous treatment (p = 0.036). The ejection fraction showed a median increase of 5% in those undergoing oral treatment, and a median decrease of 6% in the group with intravenous therapy (p = 0.009). There were 5 therapeutic failures in those receiving intravenous therapy (56%), including 1 death. Therapeutic failures were not observed in those treated orally (p = 0.03). CONCLUSION: Intravenous treatment of methylprednisolone, as a single anti-inflammatory agent, was inferior to conventional treatment with oral prednisone in the control of severe rheumatic carditis.     

The Valsalva maneuver in Chagas disease patients without cardiopathy.

BACKGROUND: The Valsalva maneuver is a simple and reliable test of parasympathetic heart control that can also be used as a trigger of cardiac arrhythmia. Few studies are available about the Valsalva maneuver in Chagas disease patients without cardiac involvement and their results are contradictory. In a cross-sectional study, we compared Chagas disease patients without cardiac involvement and normal individuals using the Valsalva maneuver in order to study the vagal cardiac control and the occurrence of cardiac arrhythmia in the early phase of Chagas disease. METHODS: Fifty-nine patients with Chagas disease without cardiac involvement and 37 controls were submitted to a carefully standardized Valsalva maneuver. Cardiac vagal control was assessed by the Valsalva ratio and the occurrence of cardiac arrhythmia was recorded and coded. RESULTS: The two groups were comparable in terms of left ventricular ejection fraction and left ventricular end-diastolic dimension. When compared to the control group, patients with Chagas disease had significantly lower Valsalva ratios (1.81+/-0.41 versus 2.01+/-0.41, P=0.017) which were not significantly correlated with age, left ventricular function or the presence of radiological esophageal abnormalities. Atrioventricular block (mainly 2nd degree Mobitz type I) occurred exclusively in Chagas disease patients (15,6%, P=0.021) and may indicate an early involvement of the AV node. Premature ventricular contraction was more frequent in Chagas disease patients (16.9% versus 8.1%, P=0.217), although the difference was not statistically significant. CONCLUSION: The Valsalva maneuver is a useful test to detect early vagal dysfunction in Chagas disease patients without cardiac involvement.     

Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction

OBJECTIVES: The aim of this research was to assess the incidence, clinical predictors, and outcome of contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Contrast-induced nephropathy is associated with significant morbidity and mortality after PCI. Patients undergoing primary PCI may be at higher risk of CIN because of hemodynamic instability and unfeasibility of adequate prophylaxis. METHODS: In 208 consecutive AMI patients undergoing primary PCI, we measured serum creatinine concentration (Cr) at baseline and each day for the following three days. Contrast-induced nephropathy was defined as a rise in Cr >0.5 mg/dl. RESULTS: Overall, CIN occurred in 40 (19%) patients. Of the 160 patients with baseline Cr clearance >/=60 ml/min, only 21 (13%) developed CIN, whereas it occurred in 19 (40%) of those with Cr clearance <60 ml/min (p < 0.0001). In multivariate analysis, age >75 years (odds ratio [OR] 5.28, 95% confidence interval [CI] 1.98 to 14.05; p = 0.0009), anterior infarction (OR 2.17, 95% CI 0.88 to 5.34; p = 0.09), time-to-reperfusion >6 h (OR 2.51, 95% CI 1.01 to 6.16; p = 0.04), contrast agent volume >300 ml (OR 2.80, 95% CI 1.17 to 6.68; p = 0.02) and use of intraaortic balloon (OR 15.51, 95% CI 4.65 to 51.64; p < 0.0001) were independent correlates of CIN. Patients developing CIN had longer hospital stay (13 +/- 7 days vs. 8 +/- 3 days; p < 0.001), more complicated clinical course, and significantly higher mortality rate (31% vs. 0.6%; p < 0.001). CONCLUSIONS: Contrast-induced nephropathy frequently complicates primary PCI, even in patients with normal renal function. It is associated with higher in-hospital complication rate and mortality. Thus, preventive strategies are needed, particularly in high-risk patients.     

Lanreotide Autogel® for Acromegaly

Since their introduction into clinical practice, somatostatin analogs have been the pharmacological therapy of choice for the treatment of acromegaly. The first preparations of somatostatin analogs available for clinical use were administered subcutaneously two or three times daily, which was not optimal with respect to patient compliance. The introduction of long-acting formulations of somatostatin analogs has overcome this inconvenience. Lanreotide Autogel, a new viscous, supersaturated, aqueous solution of lanreotide, is available in a prefilled syringe and administered by deep subcutaneous injection every 28 days. Lanreotide Autogel has different pharmacokinetic properties from the earlier lanreotide slow-release (SR) formulation, which may account for its better tolerability. Furthermore, lanreotide Autogel is at least as efficacious as the other somatostatin analogs in lowering growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in the majority and in restoring safe GH and age-normalized IGF-1 levels in about 50-60% of patients with acromegaly. In conclusion, lanreotide Autogel is a valuable new addition to the acromegaly treatment armamentarium. Patients receiving intramuscular lanreotide SR injections every 7-14 days can be switched to an appropriate dose of deep subcutaneous lanreotide Autogel every 28 days, without any impact on safety or loss of efficacy.     

Reawakened interest in type III iodothyronine deiodinase in critical illness and injury

Thyroid hormones influence gene expression in virtually all vertebrate tissues. Precise regulation of the active endogenous ligand, 3,5,3'-triiodothyronine (T(3)), is achieved by the sequential removal of iodine moieties from the thyroid hormone molecule. Type III iodothyronine deiodinase (D3) is the major inactivating enzyme terminating the action of T(3) and preventing activation of the prohormone, thyroxine (T(4)). Recent studies have revealed the induction of high D3 activity in diverse animal models of tissue injury including starvation, cryolesion, cardiac hypertrophy, infarction, and chronic inflammation. By analyzing serum and tissues taken from hospitalized patients at the time of death, investigators have also documented the robust induction of D3 activity in several human tissues that normally have none, including the liver and skeletal muscle, and shown clinically relevant consequences to systemic thyroid status. These studies reveal a novel role of D3 in the tissue response to injury and in the derangement of thyroid hormone homeostasis commonly observed during critical illness.     

Continuous veno-venous hemofiltration for the treatment of contrast-induced acute renal failure after percutaneous coronary interventions.

Acute renal failure (ARF) requiring hemodialysis after percutaneous coronary interventions (PCI) is a serious complication with poor prognosis. Hemodialysis-induced hypotension may have deleterious cardiovascular effects, especially in high-risk patients. Ultrafiltrate removal and simultaneous fluid replacement with a solution similar to plasma for high-volume controlled hydration can be obtained with hemodynamic stability by continuous veno-venous hemofiltration (CVVH). We prospectively assessed the safety and effectiveness of percutaneous CVVH (Y-shaped double-lumen catheter, circuit originating from and terminating in the femoral vein) in 33 consecutive patients (23 men and 10 women; mean age, 69 +/- 9 years) who, after PCI, developed oligo-anuric ARF, associated in 20 of them with congestive heart failure. All patients received a concomitant infusion of furosemide (500-1000 mg/day) and dopamine (2 microg/kg/min). During CVVH, the average fluid volume replacement and body fluid net reduction were 1000 +/- 247 and 75 +/- 48 ml/hr, respectively. Treatment with CVVH continued for 4.7 +/- 2.7 days and corrected fluid overload in all cases. No patient experienced systemic hypotension or hypovolemia. Diuresis recovered in 32 (97%) patients, who showed a parallel improvement of renal function parameters. One patient required chronic dialysis. In-hospital and 1-year mortality was 9.1% and 27.3%, respectively. In conclusion, our data indicate that CVVH is a safe and effective therapy of radiocontrast-induced ARF following PCI. It temporarily replaces renal function without deleterious cardiovascular effects, allowing the kidney to recover from the nephrotoxic injury. However, despite promising early results, large randomized trials are required to define the role of CVVH in ARF after PCI.     

The 'Open-Artery Hypothesis': new clinical and pathophysiologic insights

The open-artery hypothesis states that myocardial reperfusion, even if late for myocardial salvage, provides benefits and prevents adverse cardiac remodeling. While observational data in humans regarding the deleterious impact of a permanent infarct-related artery occlusion and the benefits of spontaneous reperfusion are quite consistent, the reports regarding late revascularization are inconclusive in order to prove such a hypothesis. The observational studies tend to have selection biases, while randomized trials to date are too small to be conclusive. Moreover, the pathophysiological mechanisms underlying presumed benefits of reperfusion are still unclear. However, although the open-artery hypothesis remains unproven, the current evidence suggesting benefits calls for additional studies. Limitations of ischemic left ventricular dilatation and myopathy could markedly reduce cardiovascular morbidity and mortality after acute myocardial infarction.