Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In patients with chronic congestive heart failure (CHF), aldosterone production may occur despite the administration of angiotensin-converting enzyme (ACE) inhibitors. This phenomenon has been termed aldosterone "escape"; its relation to the severity of the disease is unknown. We sought to assess whether aldosterone escape might be related to disease severity or functional impairment in patients with CHF. One hundred forty-one consecutive patients with CHF who received ACE inhibitors (> 6 months) underwent an evaluation of neurohormonal activation and body composition, an echo-Doppler examination, and a cardiopulmonary exercise test. Aldosterone escape was defined as plasma levels of aldosterone above the normal range in our laboratory (> 0.42 nmol/L). Fourteen patients (10%) had aldosterone escape. There were no differences between patients with and without aldosterone escape with regard to age, New York Heart Association class, neurohormonal activation, ACE inhibitor dose, hemodynamics, or skeletal muscle bulk. In contrast, mean peak oxygen consumption (14.2 +/- 3.5 vs 17.3 +/- 4.9 ml/min/kg, p < 0.05) and the slope of the relation between ventilation and carbon dioxide production (41 +/- 7 vs 36 +/- 6, p <0.05) were significantly worse in patients with aldosterone escape compared with those without it. Thus, aldosterone escape is associated with reduced exercise capacity in patients with CHF. This factor does not seem to be linked with hemodynamic mechanisms or with a reduced skeletal muscle bulk.     

Orthopedic surgery and mobility goals for children with cerebral palsy GMFCS level IV: what are we setting out to achieve?

Background

Multilevel orthopedic surgery is considered to be the gold standard treatment for ambulatory children with cerebral palsy (CP), classified at levels I, II, or III according to the Gross Motor Function Classification System (GMFCS). Hip enlocation and stability are the main goals of orthopedic intervention in the GMFCS level IV subgroup and are well researched; however, there is no evidence to date to support or challenge the effectiveness of orthopedic treatment to preserve functional mobility in this patient group. The aim of this study was to evaluate the results of orthopedic surgery to maintain or restore standing transfers and supported walking in children with CP at GMFCS level IV.

Methods

Twenty-two children with CP GMFCS level IV who underwent orthopedic surgery to improve mobility between the years 2004 and 2008 were included in this study. A retrospective chart review was performed and a satisfaction questionnaire sent to all patients. The primary outcome measure was the attainment and maintenance of mobility goals 2 years post-surgery. The secondary outcome measures were family/patient satisfaction, Functional Mobility Scale (FMS), and complications.

Results

The two goals identified by the patients and carers were standing transfers and supported walking. At the 2-year post-surgery assessment, 14 children (63.6 %) did not reach their pre-determined goals. In the questionnaire, 21.4 % of the families reported that surgery was not beneficial. The FMS score remained unchanged in 95.4 % of the patients. Fourteen patients (63.6 %) had at least one complication that prolonged their post-operative rehabilitation (e.g., neuropraxia).

Conclusion

This study suggests that orthopedic surgery in children with CP at GMFCS level IV is unlikely to maintain or restore mobility. Furthermore, it carries a significant risk of complications.

Level of evidence

Case series, Level IV.     

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.     

Rapid bolus injection of gadopentetate dimeglumine: absence of side effects in normal volunteers

The safety and tolerance of gadopentetate dimeglumine 0.1 mmol/kg when injected at a bolus rate (10 ml/15 sec; four times the recommended rate) was studied in 12 normal men between the ages of 20 and 36 years. Each of the subjects received a single injection of either gadopentetate dimeglumine (0.2 ml/kg) or a placebo (normal saline, 0.2 ml/kg), followed by a 7-day washout and a single injection of the alternative treatment (six subjects per sequence). Measurement parameters included blood pressure, pulse rate, ECG, cardiographic rhythm strips, hematology and blood chemistry evaluations, physical examinations, and adverse drug experiences. Variations of greater than or equal to +/- 15 mm Hg in diastolic blood pressure and greater than or equal to +/- 15 beats per min in heart rate were observed in some subjects after injection of either gadopentetate dimeglumine or the placebo, but no clinically significant changes from baseline were observed for any parameter. Post-gadopentetate dimeglumine results were not significantly different statistically from post-placebo results. No adverse experiences were reported for any subject. It is concluded that gadopentetate dimeglumine is safe and well tolerated when administered to normal men at a rapid injection rate of 10 ml/15 sec.     

In Vitro and In Vivo Human Herpesvirus 8 Infection of Placenta

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women.     

The endovanilloid/endocannabinoid system: a new potential target for osteoporosis therapy

Human osteoclasts express functional TRPV1 channels, CB1/CB2 cannabinoid receptors and endocannabinoid/endovanilloid synthetic/catabolic enzymes. Pharmacologic manipulation of this system can modulate osteoclast activity. Here, through multidisciplinary approaches, we demonstrate that enzymes and receptors of the endocannabinoid/endovanilloid system are differently expressed in osteoclasts from menopausal women without or with osteoporosis. We report that in osteoclasts from osteoporotic patients, TRPV1 channels are upregulated and, if persistently stimulated with resiniferatoxin, become clustered to the plasma membrane while inducing a massive over-expression of CB2 receptors. By providing new evidence for a critical functional cross-talk between CB2 and TRPV1 receptors in osteoporosis, we speculate that TRPV1 desensitization, or its enhanced trafficking, together with TRPV1 agonist-induced CB2 receptor overexpression, might be critical to minimize calcium entry in osteoclasts, which could be in turn responsible of cell over-activation and higher bone resorption. Our data pave the way to the use of TRPV1 agonist together with CB2 agonists or CB1 antagonists in osteoporosis.