Ultrasonographic nomograms of the fetal fourth ventricle: additional tool for detecting abnormalities of the posterior fossa.

OBJECTIVE: To characterize normal growth of the fetal fourth ventricle on ultrasonography throughout pregnancy. METHODS: Consecutive biometric measurements and fetal organ scans were obtained from 299 patients undergoing fetal anatomic surveys between 13 and 40 weeks' gestation. Using 7- and 3.5-MHz transducers for early (13- to 17-week) and late (>17-week) examinations, respectively, we scanned the fetal head in the axial plane with special focus on the posterior fossa of the brain. The fourth ventricle was identified, and its anteroposterior diameter and width were measured. A "triangle" formula was used for calculating its circumference and area. RESULTS: The fourth ventricle was shown as a hypoechoic triangle below the level of the cerebellum. A linear regression line of the fourth ventricle was observed across gestational age, and a first-degree correlation was found between gestational age and anteroposterior diameter of the fourth ventricle (r = 0.894; P < .0001; y = -0.84 + 0.23 x gestational age), its width (r = 0.657; P < .0001; y = 3.82 + 0.14 x gestational age), its circumference (r = 0.843; P < .0001; y = 5.11 + 0.58 x gestational age), and its area (r = 0.844; P < .0001; y = -10.11 + 1.17 x gestational age). Twelve enlarged fourth ventricles were found between 14 and 16 weeks, but results of follow-up scans at 20 weeks were normal. CONCLUSIONS: An isolated enlarged fourth ventricle in the early second trimester might represent a normal variant; it should be followed, but decisions about the fate of the pregnancy should not be based solely on this finding.     

Effect of Early Versus Late Weightbearing in Conservatively Treated Acute Achilles Tendon Rupture: A Meta-Analysis

Achilles tendon ruptures can be either surgically or conservatively treated with either early functional mobilization or cast immobilization. The purpose of the present study was to conduct a meta-analysis comparing the effect of early versus late weightbearing in conservatively treated adult patients, including only randomized controlled trials (RCTs). The primary endpoint was rerupture, and the secondary endpoints were strength, quality of life during treatment, range of motion, deep venous thrombosis, return to sports, and return to work. The search for studies was conducted using PubMed, EMBASE, and the Cochrane Central Register of Controlled trials. A search was performed, and 2 reviewers independently screened the studies by title, abstract, and, finally, by reading the full text. Four studies met the inclusion criteria. The reference lists of the included studies were scanned and 1 additional RCT study was included. The critical appraisal skills program checklist was applied for study appraisal. A statistician performed the data management and analysis. No statistically significant differences were found between the 2 treatment groups concerning rerupture (p = .796), return to sports (p = .455), or return to work (p = .888). One RCT found 1 case of deep venous thrombosis in the late weightbearing group. One RCT reported significant improvement in quality of life and one reported a significantly improved range of dorsiflexion in the early weightbearing group. No statistically significant difference was found between early and late weightbearing with conservative treatment regarding the rerupture rate. The results of the other outcomes were limited by the low number of studies included in the present meta-analysis. Larger randomized studies are needed to investigate these outcomes. From the results in the present study, we would recommend early weightbearing when an Achilles tendon rupture is treated conservatively.     

Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed mechanisms of an endothelial disease

First described in 1983, antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of antiphospholipid antibodies (aPL). While thrombosis is the most well-known pathogenic mechanism in this disorder, the relevance of some other mechanisms such as arterial stenosis is being increasingly recognized. Arterial stenosis has been first described in the renal arteries in patients with APS, however intracranial and coeliac arteries can also be involved with various and treatable clinical manifestations. The underlying pathophysiology of this stenotic arterial vasculopathy is not fully understood but some recent studies revealed new insights into the molecular mechanism behind this endothelial cell activation in APS. In this review, we discuss these newly discovered mechanisms and highlight the diagnostic and therapeutic modalities of the APS related arterial stenosis.     

Pregnancy-induced severe left ventricular systolic dysfunction in a patient with hypertrophic cardiomyopathy

This paper reports the first case of hypertrophic cardiomyopathy (HCM) that developed postpartum congestive heart failure (CHF) and severe left ventricular (LV) systolic dysfunction. Review of the literature and clinical implications are discussed.     

Accelerated delay of random flaps in a rat model

Random flaps have been supplanted by more immediate and reliable reconstructive methods because the former require two or more procedures and a period of delay. This study was designed to test the hypothesis that a random flap can be elevated, delayed, and safely divided within 4 days. Ninety-two Sprague–Dawley rats were operated by elevating an 8 cm × 4 cm cranially based dorsal flap with its underlying panniculus carnosus muscle. The rats were divided into four groups, one control and three experimental, with 23 rats in each. In the control group, the flap was elevated and its caudal end divided at the same time without delay. In the experimental groups, we tested three delay procedures and all flaps had their caudal end divided 4 days after elevation. The number of flaps showing total viability compared to the flaps showing any amount of necrosis was as follows: control group 1:22, mini delay group 18:5, progressive craniocaudal elevation group 19:4, and the accelerated delay group 22:1. The extent of necrosis, expressed as mean percentage area of necrosis in each group, was as follows: control group 45.9%, in the mini delay group 2.3%, progressive craniocaudal elevation group 2.5%, and the accelerated delay group 0.1%. Delay of this random flap can be accomplished safely in 4 days. In terms of total flap survival and mean percentage necrosis, all three experimental delay procedures were effective in improving total viability and reducing the extent of necrosis significantly. We believe the observed difference in total viability and mean percentage necrosis in the accelerated delay group to be clinically significant.     

Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis

Background

Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described.

Methods

BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT), expression of TGF-β receptor type I (TGF-βRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-α induced apoptosis of proximal tubular cells.

Results

BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2.

Conclusions

The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.     

Results of percutaneous drug‐eluting stent implantation for unprotected left main coronary disease according to left ventricular systolic function

Objectives: We aimed to appraise the early and long‐term outcome after percutaneous coronary intervention (PCI) with drug‐eluting stents (DES) in patients with unprotected left main disease (ULM) and left ventricular systolic dysfunction (LVD). Background: PCI with DES has being performed with increasing frequency in subjects with ULM and LVD, but few specific data are available. Setting and Patients: We identified patients undergoing PCI with DES for ULM at our Center and distinguished those with ejection fraction (EF) >50% from those with 40% <EF ≤50% and those with EF ≤40%. The primary end‐point was the rate of major adverse cerebro‐cardiovascular events (MACCE, ie death, myocardial infarction [MI], stroke, repeat PCI or bypass surgery). Results: A total of 197 patients were included, 57.4% with EF >50%, 32.0% with 40% <EF ≤50%, and 10.6% with EF ≤40%. In‐hospital mortality was significantly higher in those with EF ≤40% (9.5% vs. 0 and 3.2%, P < 0.001). A total of 96% patients were followed for 23 ± 14 months, yielding a MACCE rate of 44.2% (41.6% in those with EF >50%, 41.6% in those with 40% <EF ≤50%, and 61.9% in those with EF ≤40%, P = 0.4). Specifically, death occurred in 2.7%, 7.9%, and 28.6% (P < 0.001), cardiac death in 1.8%, 4.8%, and 23.8% (P = 0.001), MI in 8.0%, 7.9% and 0 (P = 0.4), and TVR in 15.9%, 11.1% and 33.3% (P = 0.6). Conclusion: Systolic ventricular dysfunction is highly correlated with in‐hospital and long term death rates in patients undergoing PCI with DES for ULM disease. However it does not confer an increased risk of nonfatal adverse events or stent thrombosis. © 2009 Wiley‐Liss, Inc.     

The Neuropeptide Galanin and Variants in the GalR1 Gene are Associated with Nicotine Dependence

The neuropeptide galanin and its receptors are expressed in brain regions implicated in drug dependence. Indeed, several lines of evidence support a role for galanin in modulating the effects of drugs of abuse, including morphine, cocaine, amphetamine, and alcohol. Despite these findings, the role of galanin and its receptors in the effects of nicotine is largely underexplored. Here, using mouse models of nicotine reward and withdrawal, we show that there is a significant correlation between mecamylamine-precipitated nicotine withdrawal somatic signs and basal galanin or galanin receptor 1 (GALR1) expression in mesolimbocortical dopamine regions across the BXD battery of recombinant inbred mouse lines. The non-peptide galanin receptor agonist, galnon, also blocks nicotine rewarding effects and reverses mecamylamine-precipitated nicotine withdrawal signs in ICR mice. Additionally, we conducted a meta-analysis using smoking information from six European-American and African-American data sets. In support of our animal data, results from the association study show that variants in the GALR1 gene are associated with a protective effect in nicotine dependence (ND). Taken together, our data suggest that galanin has a protective role against progression to ND, and these effects may be mediated through GALR1.     

Alpha-7 nicotinic acetylcholine receptor agonists selectively activate limbic regions of the rat forebrain: an effect similar to antipsychotics

It is considered that activation of nicotinic alpha7 receptors (alpha7 nAChR) is useful for the treatment of cognitive disturbances in schizophrenia and Alzheimer's disease. Recently, selective alpha7 nAChR agonists have been discovered and are used to validate the alpha7 nAChR as a drug target for the treatment of cognitive disturbances in schizophrenia. One important feature shared by all known antipsychotics is their capacity to induce expression of the neuronal immediate-early gene c-fos in the limbic forebrain. Using two novel and selective alpha7 nAChR agonists, PNU-282987 and SSR180711, we investigated their ability to induce c-Fos expression in the limbic forebrain with particular emphasis on the same regions reported to be activated by antipsychotics. Both alpha7 nAChR agonists increased c-Fos dose-dependently in the prefrontal cortex and the shell of nucleus accumbens, while leaving the core of nucleus accumbens and the dorsolateral striatum unaffected. The accumbal and cortical effect of SSR180711 was blocked completely by pre-administration of the alpha7 nAChR antagonist methyllycaconitine. Also, SSR180711 displayed no c-Fos-inducing effect in alpha7 nAChR knock-out mice. In conclusion, these results show that selective pharmacologic stimulation of alpha7 nAChR function results in activation of forebrain regions similar to conventional antipsychotics.