Effect of Bariatric Surgery on Obstructive Sleep Apnea and Hypopnea Syndrome, Electrocardiogram, and Pulmonary Arterial Pressure

Background: We evaluated the impact of surgically-induced weight loss on Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS), electrocardiographic changes, pulmonary arterial pressure and daytime sleepiness in morbidly obese patients. Methods: 16 women and 13 men (n=29) underwent bariatric surgery in a 3-year period. The following tests were performed before and 1 year after surgery: nocturnal polysomnography, daytime Multiple Sleep Latency Test (MSLT), and echocardiogram. Results: Mean age was 37.9±11 years (range 20-56). Preoperative body mass index was 56.5±12.3 kg/m² and it was 39.2±8.5 kg/m² at 13.7±6.6 months follow-up. Performed surgical procedures included: vertical banded gastroplasty in 6, Roux-en-Y gastric bypass in 12, and Distal Roux-en-Y gastric bypass in 11. Weight loss induced by surgery eliminated OSAHS in 46% of obese patients with an important improvement in oxygen saturation. Neck, thorax, waist and hip circumferences decreased significantly after surgical intervention but only neck circumference correlated significantly with the apnea/hypopnea index (Spearman rho=0.63, P <0.0001). Electrocardiographic abnormalities were present in 9 patients (31%) before surgery (sinus arrhythmia, ventricular arrhythmias, and sinus arrest). The number of electrocardiographic abnormalities decreased after surgery but new abnormalities appeared in some patients. Systolic pulmonary arterial pressure significantly decreased in the group of patients in whom OSAHS disappeared after surgery. Daytime sleepiness persisted after surgery in most patients. Conclusion: Bariatric surgery effectively reduces respiratory disturbances during sleep and improves pulmonary hypertension. Electro cardiographic abnormalities change after surgery. Daytime sleepiness appeared not to be related to respiratory disturbances during sleep.     

Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance

Nonalcoholic fatty liver disease (NAFLD) and insulin resistance have recently been found to be associated with increased plasma concentrations of apolipoprotein CIII (APOC3) in humans carrying single nucleotide polymorphisms within the insulin response element of the APOC3 gene. To examine whether increased expression of APOC3 would predispose mice to NAFLD and hepatic insulin resistance, human APOC3 overexpressing (ApoC3Tg) mice were metabolically phenotyped following either a regular chow or high-fat diet (HFD). After HFD feeding, ApoC3Tg mice had increased hepatic triglyceride accumulation, which was associated with cellular ballooning and inflammatory changes. ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-? activation, and decreased insulin-stimulated Akt2 activity. Increased hepatic triglyceride content in the HFD-fed ApoC3Tg mice could be attributed to a ≈ 70% increase in hepatic triglyceride uptake and ≈ 50% reduction hepatic triglyceride secretion. CONCLUSION: These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance.     

How reliable is MRCP with an SS-FSE sequence at 3.0 T: comparison between SS-FSE BH and 3D-FSE BH ASSET sequences

PurposeThe purpose of the present study was to evaluate the visibility and the image quality of the biliary and pancreatic duct system on magnetic resonance cholangiopancreatography (MRCP) images based on two breath-hold (BH) methods using array spatial sensitivity technique: a single-shot fast spin-echo (SS-FSE) sequence and a three-dimensional single slab fast spin-echo (3D-FSE) sequence.Materials and methodsIn the present prospective comparative study, 47 patients (22 male and 25 female, mean age=50 years, age range=22–82 years) that were referred for MRCP during a 12-month period are included. All of them were referred with suspected pancreaticobiliary disease. All patients underwent MRCP with both a SS-FSE BH sequence and a 3D-FSE BH sequence. Qualitative evaluation regarding the depiction of three segments of the pancreaticobiliary tree and the frequency of artifacts was performed. Two radiologists graded each sequence of the obtained studies in a blinded fashion. Quantitative evaluation including calculation of relative signal intensity (rSI) and relative contrast (RC) ratios at seven segments of the pancreaticobiliary tree between fluid-filled ductal structures and organ parenchyma at the same ductal segments was performed. In order to evaluate the parameters' differences of the two sequences, either in qualitative or in quantitative analysis, the Wilcoxon paired signed-rank test was performed.ResultsOn quantitative evaluation, both rSI and RC ratios of all segments of the pancreaticobiliary tree at SS-FSE BH sequence were higher than those at 3D-FSE BH sequences. This finding was statistically significant (P< .01). On qualitative evaluation, the two radiologists found intrahepatic ducts and pancreatic ducts to be better visualized with SS-FSE BH than with 3D-FSE BH sequence. This finding was statistically significant (P< .02). One of them found extrahepatic ducts to be significantly better visualized with SS-FSE BH sequence. Moreover, the frequency of artifacts was lower in the SS-FSE sequence, a finding that was of statistical significance. Interobserver agreement analysis found at least substantial agreement (κ>0.60) between the two radiologists.ConclusionThe SS-FSE sequence is performed faster and significantly improves image quality; thus, it should be included into the routine MRCP sequence protocol at 3.0 T. Furthermore, we recommended SS-FSE BH MRCP examination to be applied to uncooperative patients or patients in emergency because of its short acquisition time (1 s).     

Immobilization of aminothiols on poly(oxyalkylene phosphates). Formation of poly(oxyethylene phosphates)/cysteamine complexes and their radioprotective efficiency

The necessity to apply near-toxic amounts of radioprotective drugs to achieve adequate protection during radiation treatments represents a major problem in human medicine. One of the promising strategies to suppress the toxicity of these drugs involves their incorporation into biocompatible polymers. In this study cysteamine (Cy) was attached to poly(oxyethylene phosphate), POEP, via an ionic bond. Radioprotection of E. coli B cells by this substance and its acute toxicity on male C57 BL mice were measured. The toxicity of Cy immobilized within the poly(oxyethylene phosphate) was significantly lower in comparison to pure Cy while its radioprotective efficiency remained high at half the maximum tolerable dose. The high radioprotective efficiency of the Cy/POEP complexes was further confirmed on mice at different polymer molecular weight characteristics, drug immobilization degrees, application times, and doses. It was found that POEP with molecular weight 4700 Da and containing 24% repeating units with attached Cy has the highest protection potential combined with a depot effect.     

Propofol phosphate,a water-soluble propofol prodrug: in vivo evaluation

After a single IV injection of the water-soluble propofol prodrug propofol phosphate (PP) in mice, rats, rabbits, and pigs, propofol was produced rapidly (1-15 min), inducing dose-dependent sedative effects. In mice, the hypnotic dose (HD(50)), lethal dose (LD(50)), and safety index (defined as a ratio: LD(50)/HD(50)) were 165.4 mg/kg, 600.6 mg/kg, and 3.6, respectively. Propofol was produced with half-lives of 5.3 +/- 0.6 min in rats, 2.1 +/- 0.6 min in rabbits, and 4.4 +/- 2.4 min in pigs. The maximal concentration was dose and species dependent. The elimination half-life was 24 +/- 12 min in rats, 21 +/- 16 min in rabbits, and 225 +/- 56 min in pigs. Propofol generated from PP produced pharmacological effects similar to those described in the literature. We found a correlation between PP dose and duration of sedation with propofol concentrations larger than 1.0 microg/mL, which produced somnolence and sedation in rats and pigs. Adequate sedation and, at large enough doses, anesthetic-level sedation were produced after the administration of PP. Overall, PP, the water-soluble prodrug of propofol, seems to be a viable development candidate for sedative and anesthetic applications. IMPLICATIONS: Propofol phosphate, a water-soluble prodrug of the widely used IV anesthetic propofol, was developed and evaluated in mice, rats, rabbits, and pigs after IV injection. The results of the study clearly demonstrate the feasibility of the prodrug approach to achieve sedative and anesthetic levels of propofol in laboratory animals; this warrants further evaluation in humans.     

New possibilities in the treatment of Meniere's disease

The results of the treatment of Meniere's disease by intratympanic instillation of gentamicin in 32 patients over a 24-months period were analyzed. The receded vestibular function was found in 96.8% patients, whereas in the remaining 3.2% pronounced vestibular hypofunction was observed. One month after the treatment vertiginous attacks disappeared in all the patients. However, three months after the treatment infrequent episodes of mild degree vertigo and mild unsteadiness that did not require additional intratympanic gentamicin application appeared in 15% of the patients with Meniere's disease. The vertiginous attacks ceased or were pronouncedly reduced in 85% of the patients. The unstable vestibular hypofunction was successfully converted into stabilized, centrally compensated areflexia. Intratympanic gentamicin exerted better results than the other invasive therapies for intractable Meniere's disease.     

bcl-2 Expression in Endometrial Hyperplasia and Carcinoma

The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death. bcl-2 overexpression was originally described in follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. In this study we used immunohistochemistry to examine bcl-2 protein expression in endometrial hyperplasia and carcinoma. bcl-2 protein was observed in 4/4 cases of complex hyperplasia, 1/4 cases of complex atypical hyperplasia, and 10/29 cases of carcinoma. The staining observed in the cases of complex atypical hyperplasia and carcinoma was focal and less intense than the reactivity of normal proliferative endometrium. We conclude that bcl-2 protein is seldom overexpressed in complex atypical hyperplasia or carcinoma of the endometrium. Rather, in many cases of endometrial carcinoma bcl-2 expression appears to be decreased.     

Arrhythmic cardiomyopathy. Case report

An 11 year-old boy was admitted with incessant sinus node reentrant tachycardia and secondary dilated arrhythmic cardiomyopathy, treated by radiofrequency ablation. Two years later he was admitted with incessant automatic atrial tachycardia and arrhythmic cardiomyopathy; a second catheter ablation procedure failed, but the third one, performed four month later, was successfully and resulted in a restoration of a normal sinus rhythm and a complete regression of arrhythmic cardiomyopathy.     

HLA class II and class I polymorphism in Venezuelan patients with myasthenia gravis

Oligotyping performed among ethnically mixed Venezuelan patients with myasthenia gravis (MG) and controls has revealed positive associations of HLA class I A*31, B*08, B*39, B*40, C*15, C*17, and class II DRB1*09 and negative associations of DQB1*06 and DQA1*02 with the disease. Sequential removal of human leukocyte antigen B (HLA-B) alleles when relative predispositional effects (RPEs) were looked for demonstrated that B*08 is the allele group with the largest contribution in the overall MG patients followed by B*39 and B*40. Several specificities (A*31, B*08, C*17, DRB1*03, DQA1*05, and DQB1*02) indicated increased frequencies among patients with thymic hyperplasia versus patients without hyperplasia or controls. Tests to identify alleles with the strongest association to MG in our patients detected DRB1*13 and B*38 as possible predisposing secondarily associated alleles in patients with hyperplasia. The associations observed disappear after Bonferoni correction of probability values and have been described in patients of Caucasian and/or Oriental ethnic background. Thus, our results reflect the heterogeneity of our population and of the patients tested and suggest a limited influence of several HLA genes in this heterogeneous disease or that these might be only markers of nearby non-HLA genes responsible for the susceptibility or resistance effect.