José Manuel Fort

Lower Zinc-α2-Glycoprotein Production by Adipose Tissue and Liver in Obese Patients Unrelated to Insulin Resistance

CONTEXT Zinc-alpha2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays. OBJECTIVE The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored. DESIGN This was a case-control study. SETTING The study was conducted at a university referral center. PATIENTS AND METHODS Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures. RESULTS Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 +/- 10.45 vs. 63.26 +/- 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = -0.65, P < 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = -0.68, P < 0.001) and VAT were detected (r = -0.64, P < 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro. CONCLUSION A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance.

Long-term results of tacrolimus in cyclosporine- and prednisone-dependent myasthenia gravis

To the Editor: Utilizing the Mood Disorder Questionnaire (MDQ), Ettinger et al.1 observed a high incidence of bipolar symptoms in patients selfreported as epileptic. Half the subjects with bipolar symptoms by MDQ claimed a previous diagnosis of bipolar disorder. The authors suggest that antiepileptic drug (AED) therapy may be effective considering the relationship between altered brain physiology and mood. I submitted a related observation to the American Psychiatric Association’s 159th annual meeting. Forty-two referred patients (24 women, mean age 37 years) with a history of bipolar I or II (Diagnostic and Statistical Manual of Mental Disorders–IV criteria) underwent a behavioral neurologic assessment including EEG.2 None of these patients received prior AED treatment. Eighteen (45%) had EEG abnormalities classified as a focal dysrhythmia grade III (Mayo Clinic classification) and 12 had dysrhythmia grade II (28%). In 21 of the 30 patients with EEG abnormalities (70%), AED therapy that included lamotrigine, levetiracetam, topiramate, or oxcarbazepine proved effective in stabilizing mood without serious adverse event in 18 (85%) over 6 to 60 months (mean 36).3 Because none of these patients had a prior history of epilepsy, a diagnosis of interictal dysthymic disorder was excluded.4 These observations confirm those of Ettinger et al.’s that physiologic assessment in behavioral disorders and behavioral assessment in epilepsy should be further investigated.Seventy-nine patients with cyclosporine- and prednisone-dependent myasthenia gravis (MG) after thymectomy received tacrolimus for a mean of 2.5 +/- 0.8 years. Prednisone was withdrawn in all but two patients. Anti-acetylcholine antibodies and MG score for disease severity decreased significantly and muscular strength increased by 39%. Complete stable remission was achieved in 5% of patients and pharmacologic remission in 87.3%. All patients resumed full activities of daily living.

Diabetes Is the Main Factor Accounting for Hypomagnesemia in Obese Subjects

Objective Type 2 diabetes (T2DM) and obesity are associated with magnesium deficiency. We aimed to determine whether the presence of type 2 diabetes and the degree of metabolic control are related to low serum magnesium levels in obese individuals. Methods A) Case-control study: 200 obese subjects [50 with T2DM (cases) and 150 without diabetes (controls)] prospectively recruited. B) Interventional study: the effect of bariatric surgery on serum magnesium levels was examined in a subset of 120 obese subjects (40 with type 2 diabetes and 80 without diabetes). Results Type 2 diabetic patients showed lower serum magnesium levels [0.75±0.07 vs. 0.81±0.06 mmol/L; mean difference −0.06 (95% CI −0.09 to −0.04); p<0.001] than non-diabetic patients. Forty-eight percent of diabetic subjects, but only 15% of non-diabetic subjects showed a serum magnesium concentration lower than 0.75 mmol/L. Significant negative correlations between magnesium and fasting plasma glucose, HbA1c, HOMA-IR, and BMI were detected. Multiple linear regression analysis showed that fasting plasma glucose and HbA1c independently predicted serum magnesium. After bariatric surgery serum magnesium increased only in those patients in whom diabetes was resolved, but remain unchanged in those who not, without difference in loss weight between groups. Changes in serum magnesium negatively correlated with changes in fasting plasma glucose and HbA1c. Absolute changes in HbA1c independently predicted magnesium changes in the multiple linear regression analysis. Conclusions Our results provide evidence that the presence of diabetes and the degree of metabolic control are essential in accounting for the lower levels of magnesium that exist in obese subjects.

Gene expression of paired abdominal adipose AQP7 and liver AQP9 in patients with morbid obesity Relationship with glucose abnormalities

The trafficking of glycerol from adipose and hepatic tissue is mainly mediated by 2 aquaporin channel proteins: AQP7 and AQP9, respectively. In rodents, both aquaporins were found to act in a coordinated manner. The aim was to study the relationship between adipose AQP7 and hepatic AQP9 messenger RNA expression and the presence of glucose abnormalities simultaneously in morbid obesity. Adipose tissue (subcutaneous [SAT] and visceral [VAT]) and liver biopsies from the same patient were obtained during bariatric surgery in 30 (21 male and 9 female) morbidly obese subjects. Real-time quantification of AQP7 in SAT and VAT and hepatic AQP9 gene expression were performed. A 75-g oral glucose tolerance test was performed in all subjects. The homeostasis model assessment of insulin resistance and lipidic profile were also determined. Visceral adipose tissue AQP7 expression levels were significantly higher than SAT AQP7 (P = .009). Subcutaneous adipose tissue AQP7 positively correlated with both VAT AQP7 and hepatic AQP9 messenger RNA expression (r = 0.44, P = .013 and r = 0.45, P = .012, respectively). The correlation between SAT AQP7 and liver AQP9 was stronger in intolerant and type 2 diabetes mellitus subjects (r = 0.602, P = .011). We have found no differences in compartmental AQP7 adipose tissue distribution or AQP9 hepatic gene expression according to glucose tolerance classification. The present study provides, for the first time, evidence of coordinated regulation between adipose aquaglyceroporins, with a greater expression found in visceral fat, and between subcutaneous adipose AQP7 and hepatic AQP9 gene expression within the context of human morbid obesity.

The Initial Learning Curve for Robot-Assisted Sleeve Gastrectomy: A Surgeon's Experience While Introducing the Robotic Technology in a Bariatric Surgery Department.

Objective. Robot-assisted sleeve gastrectomy has the potential to treat patients with obesity and its comorbidities. To evaluate the learning curve for this procedure before undergoing Roux en-Y gastric bypass is the objective of this paper. Materials and Methods. Robot-assisted sleeve gastrectomy was attempted in 32 consecutive patients. A survey was performed in order to identify performance variables during completion of the learning curve. Total operative time (OT), docking time (DT), complications, and length of hospital stay were compared among patients divided into two cohorts according to the surgical experience. Scattergrams and continuous curves were plotted to develop a robotic sleeve gastrectomy learning curve. Results. Overall OT time decreased from 89.8 minutes in cohort 1 to 70.1 minutes in cohort 2, with less than 5% change in OT after case 19. Time from incision to docking decreased from 9.5 minutes in cohort 1 to 7.6 minutes in cohort 2. The time required to dock the robotic system also decreased. The complication rate was the same in the two cohorts. Conclusion. Our survey indicates that technique and outcomes for robot-assisted sleeve gastrectomy gradually improve with experience. We found that the learning curve for performing a sleeve gastrectomy using the da Vinci system is completed after about 20 cases.

Surgically induced weight loss by gastric bypass improves non alcoholic fatty liver disease in morbid obese patients

AIM To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients. METHODS A group of 26 morbidly obese patients aged 45 ± 2 years and with a body mass index > 40 kg/m(2) who underwent open surgical weight loss operations had paired liver biopsies, the first at surgery and the second after 16 ± 3 mo of weight loss. Biopsies were evaluated and compared in a blinded fashion. The presence of metabolic syndrome, anthropometric and biochemical variables were also assessed at baseline and at the time of the second biopsy. RESULTS Percentage of excess weight loss was 72.1% ± 6.6%. There was a reduction in prevalence of metabolic syndrome from 57.7% (15 patients) to 7.7% (2 patients) (P < 0.001). Any significance difference was observed in aspartate aminotransferase or alanine aminotransferase between pre and postsurgery. There were improvements in steatosis (P < 0.001), lobular (P < 0.001) and portal (P < 0.05) inflammation and fibrosis (P < 0.001) at the second biopsy. There were 25 (96.1%) patients with non alcoholic steatohepatitis (NASH) in their index biopsy and only four (15.3%) of the repeat biopsies fulfilled the criteria for NASH. The persistence of fibrosis (F > 1) was present in five patients at second biopsy. Steatosis and fibrosis at surgery were predictors of significant fibrosis postsurgery. CONCLUSION Restrictive mildly malabsorptive surgery provides significant weight loss, resolution of metabolic syndrome and associated abnormal liver histological features in most obese patients.

Single-port transumbilical laparoscopic cholecystectomy: A prospective randomised comparison of clinical results of 140 cases

INTRODUCTION: A novel single port access (SPA) cholecystectomy approach is described in this study. We have designed a randomised comparative study in order to elucidate any possible differences between the standard treatment and this novel technique. MATERIALS AND METHODS: Between July 2009 and March 2010, 140 adult patients with gallbladder pathologies were enrolled in this multicentre study. Two surgeons (RV and UB) randomised patients to either a standard laparoscopic (SL) approach group or to an SPA cholecystectomy group. Two types of trocars were used for this study: the TriPort™ and the SILS™ Port. Outcomes including blood loss, operative time, complications, length of stay and pain were recorded. RESULTS: There were 69 patients in the SPA group and 71 patients in the SL group. The mean age of the patients was 43.2 (17-77) for the SPA group and 42.6 (19-70) for the SL group. The mean operative time was 63.9 min in the SPA group and 58.4 min in the SL group. For one patient, the SPA procedure was converted to a standard laparoscopic technique and to open approach in the SL group. Complications occurred in eight patients: Five seromas (two in the SPA group) and three hernias (one in the SPA group).The mean hospital stay was 38.5 h in the SPA group and 24.1 h in the SL group. Pain was evaluated and was 2 in the SPA and 2.9 in the SL group, according to the visual analogue scale (VAS) after 24 h (P<0.001). The degree of satisfaction was higher in the SPA group (8.3 versus 6.7). Similar results were found for the aesthetic result (8.8 versus 7.5). (P<0.001). CONCLUSION: Single-port transumbilical laparoscopic cholecystectomy can be feasible and safe. When technical difficulties arise, early conversion to a standard laparoscopic technique is advised to avoid serious complications. The SPA approach can be undertaken without the expense of additional operative time and provides patients with minimal scarring. The cosmetic results and the degree of satisfaction appear to be significant for the SPA approach.

Benefits of FK506 (tacrolimus) for residual, cyclosporin- and prednisone-resistant myasthenia gravis: one-year follow-up of an open-label study

Thirteen patients with myasthenia gravis, unresponsive to prednisone and cyclosporin after thymectomy, received KF506 (tacrolimus) for 12 months, at starting doses of 0.1 mg/kg per day b.i.d. and then adjusted to achieve plasma concentrations between 7 and 8 ng/mL. The doses of prednisone were progressively reduced and finally discontinued. Anti-acetylcholine antibodies and myasthenia gravis score for disease severity decreased significantly and muscular strength increased by 37%. All patients achieved pharmacological remission, 11 were asymptomatic and two had minimal weakness of eyelid closure. Tacrolimus was well tolerated and appears a suitable approach after unsuccessful treatment with conventional immunosuppressants in patients with disabling myasthenia.

Adiponectin Upregulates SHBG Production: Molecular Mechanisms and Potential Implications

Epidemiological studies have shown that plasma SHBG levels correlate with plasma adiponectin levels, both in men and women. There are no reports describing any molecular mechanism by which adiponectin regulates hepatic SHBG production. The aim of the present study is to explore whether adiponectin regulates SHBG production by increasing HNF-4α levels through reducing hepatic lipid content. For this purpose, in vitro studies using human HepG2 cells, as well as human liver biopsies, were performed. Our results show that adiponectin treatment increased SHBG production via AMPK activation in HepG2 cells. Adiponectin treatment decreased the mRNA and protein levels of enzymes related to hepatic lipogenesis (ACC) and increased those related to fatty acid oxidation (ACOX and CPTI). These adiponectin-induced changes in hepatic enzymes resulted in a reduction of total TG and FFA and an increase of HNF-4α. When HNF-4α expression was silenced by using siRNA, adiponectin-induced SHBG overexpression was blocked. Furthermore, adiponectin-induced upregulation of SHBG production via HNF-4α overexpression was abrogated by the inhibition of fatty acid oxidation or by the induction of lipogenesis with a 30mM glucose treatment in HepG2 cells. Finally, adiponectin levels correlated positively and significantly with both HNF-4α and SHBG mRNA levels in human liver biopsies. Our results suggest for the first time that adiponectin increases SHBG production by activating AMPK, which reduces hepatic lipid content and increases HNF-4α levels.

Single-Port Transumbilical Laparoscopic Appendectomy: A Preliminary Multicentric Comparative Study in 87 Patients with Acute Appendicitis

Introduction. Laparoscopic appendectomy (LA) has been performed in many approaches such as open, laparoscopic and recently Single Port Access (SPAA). In order to elucidate its potential advantages, we compared the two laparoscopic approaches. Methods. 87 patients were included in a multicentric study for suspected appendicitis in order to perform (SPAA) appendectomy or laparoscopic appendectomy (LA). All outcomes, including blood loss, operative time, complications, and length of stay and pain were recorded prospectively. Results. There were 46 patients in the SPAA group and 41 in the LAG with a mean operative time of 40,4 minutes in the SPAA group and 35,0 minutes in the LA group. Only one patient was converted to an open approach. We described only 2 complications. Pain was graded 2,8 in the SPAA group and 2,9 in the LA group, according to the AVS after 24 hours. Patients in the SPAA Group were more satisfied (7,5 versus 6,9) (P < 0.05). Same results were found for the cosmetic result (8,6 versus 7,4) (P < 0.05). Conclusion. Using the single port approach feasible and safe. The true benefit of the technique should be assessed by new randomised controlled trials.