Laparoscopic anterior cardiomyotomy plus anterior Dor fundoplication without division of lateral and posterior periesophageal anatomic structures for treatment of achalasia of the esophagus

Laparoscopic cardiomyotomy is the treatment of choice for patients with achalasia of the esophagus. Several different techniques and modifications have been reported concerning the approach (thoracoscopic or laparoscopic), type and length of the myotomy, with or without fundoplication, type of fundoplication, etc. In this prospective study, we report our simplified technique for anterior cardiomyotomy with Dor fundoplication and the results obtained using this procedure. Only the anterior wall of the esophagus was exposed without dissection of the lateral or posterior periesophageal anatomic structures for the technique. Twenty-five patients were operated by a single surgeon. The diagnosis was based on the clinical, radiologic, endoscopic, and functional esophageal tests. Achalasia was classified into 3 types: achalasia type I was diagnosed in 5 patients, type II in 6 patients, and type III in 14 patients. Manometry demonstrated a mean resting pressure of 33.5 mm Hg (range, 18 to 55), associated with incomplete relaxation. The hospital stay was 3 days; the median operative time was 115 minutes (range, 90 to 150), 2 small mucosal perforations occurred which were immediately sutured during surgery without conversion into open technique and no postoperative complications occurred. After operation, lower esophageal sphincter pressure returned to normal values and complete relaxation in all patients. In type II and III achalasia, the esophageal body diameter decreased more than 50% (P=0.001) compared with the preoperative diameter, and the internal diameter of the esophagogastric junction increased significantly (P=0.001). Only 2 patients presented occasional heartburn and 2 patients received 1 session of hydrostatic dilatation due to mild residual dysphagia. No late recurrence of dysphagia has been observed to the present time (1 to 5 y of follow-up). In conclusion, the goals of the surgery for achalasia are obtained with this simplified technique.     

A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1

Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor.     

Understanding the factors associated with differences in caesarean section rates at hospital level: the case of Latin America

As in many other regions of the world, caesarean section (CS) rates in Latin America are increasing. Studies elsewhere have shown that providing feedback to caregivers regarding their own performance relative to their peers can significantly reduce the rates. Our objectives are to calculate risk-adjusted CS rates for hospitals in Latin America and to identify factors associated with differences among risk-adjusted rates. We included 120 randomly selected institutions in eight countries of Latin America, representing 97 095 pregnancies. We used random-effects models to calculate a risk-adjusted rate for each hospital and to identify hospitals significantly higher or lower than a benchmark rate. We conducted a regression analysis to identify characteristics of hospitals associated with differences among risk-adjusted rates.
The overall CS rate was 35%, ranging from 0% to 85%. Risk-adjusted CS rates ranged from 11% to 78%. Three-quarters of hospitals had risk-adjusted rates significantly above the previously identified benchmark of 20%. Characteristics of institutions explained 48% of the variability among risk-adjusted rates, including being a private as opposed to a public institution, having some economic incentive for CS as opposed to no incentive, and having ≥50 maternity beds.
Strategies to halt further increases in CS rates and reduce rates to levels that reflect the best quality of care, are urgently needed worldwide. The involvement of local quality control departments is an essential component in achieving success. Our results can be used to identify institutions that can be targets for further interventions to reduce CS rates.     

Exercise training enhances elastin, fibrillin and nitric oxide in the aorta wall of spontaneously hypertensive rats

This work aimed to analyze the effect of low-intensity exercise training on ultrastructural and molecular aortic remodeling. Male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were allocated into four groups: sedentary WKY (SED-WKY), exercised WKY (EX-WKY, 1 h/day, 5 days/week treadmill exercise training), sedentary SHR (SED-SHR), and exercised SHR (EX-SHR). EX-SHR showed blood pressure reduction of 26% in comparison to SED-SHR after 1 month of exercise (P < 0.05). At the 20th week, BP level was not different between EX-SHRs and WKYs. Circumferential wall tension (CWT) was higher by 77% in SED-SHRs than in SED-WKYs (P < 0.001). Exercise training reduced CWT by 30% in EX- vs. SED-SHR (P < 0.001). In SED-SHRs, endothelial cells showed large and numerous cytoplasmatic vacuoles, fragmented inner elastic lamina and scarce elastin and fibrillin, while exercise training ameliorated it in EX-SHR group. The highest eNOS immunodensity was observed in EX-SHR, which was 50% higher than EX-WKY (P < 0.01) and 120% higher than SED-SHR (P < 0.0001). In conclusion, present findings indicate beneficial effects of exercise training in hypertensive rats since it increased elastin, fibrillin and eNOS content in the aortic wall.     

Low Bone Volume—A Risk Factor for Coronary Calcifications in Hemodialysis Patients

Background and objectives: There is increasing evidence that altered bone metabolism is associated with cardiovascular calcifications in patients with stage 5 chronic kidney disease on hemodialysis (HD). This study was conducted to evaluate the association between bone volume, turnover, and coronary calcifications in HD patients.Design, setting, participants, & measurements: In a cross-sectional study, bone biopsies and multislice computed tomography were performed in 38 HD patients. Bone volume/total volume, activation frequency, and bone formation rate/bone surface were determined by histomorphometry and coronary calcifications were quantified by Agatston scores.Results: Prevalence of low bone turnover was 50% and of low bone volume was 16%. Among the studied traditional cardiovascular risk factors, only age was found to be associated with coronary calcifications. Lower bone volume was a significant risk factor for coronary calcifications during early years of HD, whereas this effect was not observed in patients with dialysis duration >6 yr. Histomorphometric parameters of bone turnover were not associated with coronary calcifications.Conclusions: Low bone volume is associated with increased coronary calcifications in patients on HD.Cardiovascular disease and stroke account for 60 to 70% of all deaths in patients with chronic kidney disease (CKD) on maintenance hemodialysis (HD) (1,2). In a study utilizing electron beam computed tomography, dialysis patients presented with higher coronary calcification scores when compared with nondialysis patients (3). In HD patients, vascular calcifications were shown to be associated with cardiovascular morbidity and mortality (4). Conspicuously, however, two prospective trials on modification of traditional cardiovascular risk factors in CKD patients could not demonstrate significant differences in cardiovascular outcomes, including death between an intensive “multiple traditional risk factor intervention” group and the standard therapy group despite significantly improved traditional risk factor control in the former (5,6). Recent evidence shows that vascular calcifications in CKD can occur early, and that deposition of calcium in the vascular wall is a complex and tightly regulated process that is akin to bone mineralization (7,8). In addition, abnormalities in bone turnover and bone volume are associated with more vascular calcifications in uremic patients (9,10).Taking this evidence into consideration, the international initiative, Kidney Disease: Improving Global Outcomes, recommends the inclusion of evaluation for extraskeletal calcifications into a new classification for “chronic kidney disease-mineral and bone disorder” (11). Although an association between low bone turnover and increased vascular calcification (measured by a semiquantitative vascular calcification score) was reported previously (9), the relationship between histomorphometric parameters of bone formation and bone volume and quantitative determinations of coronary calcifications by multislice computed tomography (MSCT) while controlling for the traditional cardiovascular risk factors of hypertension, gender, age, cholesterol, and tobacco use has not been investigated in HD patients. The study presented here aims at providing this information.     

Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus

Neurogenesis persists in certain regions of the adult brain including the subgranular zone of the hippocampal dentate gyrus wherein its regulation is essential, particularly in relation to learning, stress and modulation of mood. Lysophosphatidic acid (LPA) is an extracellular signaling phospholipid with important neural regulatory properties mediated by specific G protein-coupled receptors, LPA(1-5). LPA(1) is highly expressed in the developing neurogenic ventricular zone wherein it is required for normal embryonic neurogenesis, and, by extension may play a role in adult neurogenesis as well. By means of the analyses of a variant of the original LPA(1)-null mutant mouse, termed the Malaga variant or "maLPA(1)-null," which has recently been reported to have defective neurogenesis within the embryonic cerebral cortex, we report here a role for LPA(1) in adult hippocampal neurogenesis. Proliferation, differentiation and survival of newly formed neurons are defective in the absence of LPA(1) under normal conditions and following exposure to enriched environment and voluntary exercise. Furthermore, analysis of trophic factors in maLPA(1)-null mice demonstrated alterations in brain-derived neurotrophic factor and insulin growth factor 1 levels after enrichment and exercise. Morphological analyses of doublecortin positive cells revealed the anomalous prevalence of bipolar cells in the subgranular zone, supporting the operation of LPA(1) signaling pathways in normal proliferation, maturation and differentiation of neuronal precursors.     

Low prevalence of hypothyroidism among black and Mulatto people in a population-based study of Brazilian women

Objective African-Americans have been shown to have low prevalence of hypothyroidism. Brazil has a high ethnic admixture allowing further exploration into whether environmental factors can explain the ethnic differences. Design A survey, representative of the population of Rio de Janeiro, a large metropolitan city in Brazil. Factors studied included race, parity, income, schooling, and smoking. Population The survey was carried out in Rio de Janeiro whereby households (1500) were selected using three-stage probability sampling. A total of 1298 (86.5%) women participated in the survey (non-response: 13.5%). Measurements TSH from blood drawn at the households. Anti-thyroperoxidase (anti-TPO) antibodies and free T4 were also measured. Results Overall prevalence of hypothyroidism (TSH > 4 mUI/ml or taking medication) was 12.3%. Prevalence was 6.9% in black people, 8.8% in Mulatto people, and 16.7% among white people. The mean serum TSH of the population was 2.65 (95% confidence interval 2.33-2.97). The TSH distribution of black and Mulatto people was shifted to the left compared to white people. After adjustment for age, income, smoking and presence of anti-TPO, Black and Mulatto people were still protected from hypothyroidism. The adjusted odds ratio for black compared to white people was 0.45 (95% CI 0.30-0.68) and for Mulatto people was 0.34 (95% CI 0.18-0.63). Serum TSH levels were significantly lower in smokers than in non-smokers, but there was no association between number of cigarettes smoked and serum TSH level. Conclusions This is the first time it has been demonstrated that Mulatto people have a prevalence of hypothyroidism which lies between that of white and black people, independent of the prevalence of anti-TPO and smoking.     

Haemostatic changes related to fibrin formation and fibrinolysis during the first trimester in normal pregnancy and in recurrent miscarriage

We have studied some biophysical properties of the fibrin network during the normal state of pregnancy and in patients with recurrent miscarriage (RM), in the first trimester of pregnancy. The fibrin polymerization process, followed by turbidity, showed that the rate of fibrin monomer assembly and the final turbidity was increased in the pregnant group (normal and with history of RM) compared to non-pregnant women (normal and RM), which is consistent with the increased fibrinogen concentration during pregnancy. No changes were observed in the Darcy constant (Ks) of RM clots, pregnant or not; however, in pregnant control subjects the Ks increased (p = 0.03). The fibrin lysis rate was increased in pregnant women compared to non-pregnant, being faster in women with RM. The rheological properties of the fibrin network in the non-pregnant group (control and RM patients) were similar; in the pregnant state, the fibrin network of the control group was 1.3 times stiffer compared to the control non-pregnant women, and almost unchanged in RM patients. In this study we have found changes in the clot structure that seem to be related to normal pregnancy and an increased rate of the fibrin lysis process in the RM patients, which may have clinical relevance.