Femtosecond laser-assisted selective reduction of neovascularization in rat cornea

Nonlinear multiphoton absorption induced by focusing near infrared (NIR) femtosecond (fs) laser pulses into a transparent cornea allows surgery on neovascular structures with minimal collateral damage. In this report, we introduce an fs laser-based microsurgery for selective treatment of rat corneal neovascularizations (in vivo). Contiguous tissue effects are achieved by scanning a focused laser pulse below the corneal surface with a fluence range of 2.2–8.6 J/cm². The minimal visible laser lesion (MVL) threshold determined over the corneal neovascular structures was found to be 4.3 J/cm². Histological and optical coherence tomography examinations of the anterior segment after laser irradiations show localized degeneration of neovascular structures without any unexpected change in adjacent tissues. Furthermore, an approximately 30 % reduction in corneal neovascularizations was observed after 5 days of fs laser exposure. The femtosecond laser is thus a promising tool for minimally invasive intrastromal surgery with the aid of a significantly smaller and more deterministic photodisruptive energy threshold for the interaction between the fs laser pulse and corneal neovascular structures.     

Changes In Lipid Profile after Biliopancreatic Diversion

Background: Bariatric operations have varying degrees of effectiveness and different mechanisms of action. Our objective was to evaluate the efficacy of the biliopancreatic diversion (BPD) in reduction of weight and serum lipids. Methods: A prospective study was conducted with follow-up from 12 to 72 months (average 39.4 months) of 58 patients with morbid obesity (10 men, 48 women, mean BMI 49.4 kg/m²). Their lipid levels were generally normal or slightly high. All the patients were subjected to subtotal gastrectomy and BPD with jejunoileostomy 50 cm proximal to the ileocecal valve, and they were instructed to maintain the same hypocaloric diet as before BPD. Serum lipoproteins and apolipoproteins B and A1 were measured before BPD and every 6 months during follow-up. Results: Early and very significant reduction (P<0.001) of total cholesterol (32.8%), LDL (46.3%), total cholesterol / HDL ratio (29.7%) and apolipoprotein B (37%), with more moderate decrease of triglycerides (21.3%, P=0.004), were observed. This lipid decrease was maximum at 1 year after BPD. Important and persistent weight reduction that did not correlate with changes in lipids was observed. The youngest patients and those with high basal lipid levels proved to benefit most from BPD. There were no important side-effects. Conclusion: BPD, with careful selection of patients, is a well tolerated procedure that offers excellent results in the short- and mid-term in reduction in weight and blood levels of most atherogenic lipoproteins.     

Lipoprotein‐associated phospholipase A2 levels are associated with erectile dysfunction in patients without known coronary artery disease

Endothelial dysfunction and microvascular damage play a crucial role in the pathogenesis of erectile dysfunction (ED). Lp‐PLA2 is a calcium‐independent member of the phospholipase A2 family and hydrolyses oxidised phospholipids on low‐density lipoprotein (LDL) particles that plays a pivotal role in ox‐LDL‐induced endothelial dysfunction. The purpose of the current study was to determine the association between Lp‐PLA2 levels and ED in patients without known coronary artery disease (CAD). All patients were evaluated for ED and divided into two groups: 88 patients suffering from ED for >1 year were enrolled as an experimental group and 88 patients without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score‐5. Levels of Lp‐PLA2 were measured in serum by colorimetric assay. The relationship between Lp‐PLA2 levels and ED in patients was evaluated statistically. The mean age of patients with ED group was 59.4 ± 11.32 and 55.8 ± 9.67 in the control group. Plasma Lp‐PLA2 levels were significantly higher in ED than in the control group (220.3 ± 66.90 and 174.8 ± 58.83 pg ml^?1, respectively, P < 0.001). The Lp‐PLA2 levels were negatively correlated with score of ED (r = ?0.482, P < 0.05). In logistic regression analysis, enhanced plasma Lp‐PLA2 levels result in approximately 1.2‐fold increase in ED [1.22 (1.25–2.76)]. In this study, serum Lp‐PLA2 levels were found to be associated with endothelial dysfunction predictive of ED. Serum Lp‐PLA2 level appears to be a specific predictor of ED, and it may be used in early prediction of ED in the male population.     

Roux-en-Y Gastric Bypass versus a Variant of Biliopancreatic Diversion in a Non-Superobese Population: Prospective Comparison of the Efficacy and the Incidence of Metabolic Deficiencies

Background: In the non-superobese population, an agreement has not been made as to the optimal bariatric operation. The present study reports the results of a prospective comparison of Roux-en-Y gastric bypass (RYGBP) and a variant of biliopancreatic diversion (BPD) in a non-superobese population. Methods: From a cohort of 130 patients with BMI 35 to 50 kg/m², 65 patients were randomly selected to undergo RYGBP and 65 to undergo BPD. All patients underwent complete follow-up evaluation at 1, 3, 6, and 12 months postoperatively and every year thereafter. Results: Patients in both groups have completed their second postoperative year. Mean % excess weight loss (%EWL) was significantly better after BPD at all time periods (12 months, P=0.0001 and 24 months, P=0.0003), and the %EWL was >50% in all BPD patients compared to 88.7% in the RYGBP patients at 2-year follow-up. No statistically significant differences were observed between the 2 groups in early and late non-metabolic complications. Hypoalbuminemia occurred in only 1 patient (1.5%) after RYGBP and in 6 patients after BPD (9.2%). Only 1 patient from each group was hospitalized and received total parenteral nutrition. Glucose intolerance, hypercholesterolemia, hypertriglyceridemia and sleep apnea completely resolved in all patients in both groups, although mean total cholesterol level was significantly lower in BPD patients at the second year follow-up (t-test, P<0.0001). Diabetes completely resolved in all BPD patients and in 7 of the 10 diabetic RYGBP patients. Conclusion: Both RYGBP and BPD were safe and effective procedures when offered to non-superobese patients. Weight loss after BPD was consistently better than that after RYGBP, as was the resolution of diabetes and hypercholesterolemia. Because the nutritional deficiencies that occurred following this type of BPD were not severe and were not significantly different between the 2 operations, both may be offered to non-superobese patients, keeping in mind the severity and type of preoperative co-morbidities as well as the desired weight loss.     

Course of Metabolic Syndrome following the Biliopancreatic Diversion of Larrad

Background: The authors assessed the effect of Larrad's biliopancreatic diversion (BPD) on the main components of the metabolic syndrome. Patients and Methods: Plasma concentrations of glucose, insulin, total cholesterol (TC), HDL and LDL cholesterol, triglycerides, LDL/HDL and TC/HDL ratios, and blood pressure and body weight were retrospectively evaluated in 40 patients 3-6, 12, 24 and 60 months after undergoing BPD for morbid obesity with metabolic syndrome. Results: 3-6 months after BPD, glycemia and insulinemia had normalized in 97.5% of the patients and remained stable over the following 5 years. Over this period of 3-6 months to 5 years following BPD, total and LDL cholesterol levels fell by 45.2% and 53.1%, respectively. From 12 months onwards, triglyceride levels decreased appreciably, dropping by 57.4% at 5 years. HDL cholesterol concentrations failed to vary significantly or increased to normal levels in patients showing low initial values. At 5 years, high blood pressure had resolved in 75% of patients and the amount of excess weight lost was 65.5% (±14.6). No patient required reversal of the BPD due to severe gastrointestinal or metabolic complications. Conclusions: Technically adapted to the patient's weight, the Larrad BPD effectively stabilizes the main components of the metabolic syndrome. The BPD has low morbidity rate and should be considered a therapeutic option for patients who do not respond to medical treatment.     

Effectiveness of Biliopancreatic Diversion in the Patients with Bulimia Nervosa

Background: Bulimia nervosa (BN) is an eating disorder, characterized by consumption of huge amounts of food during discrete periods. Unlike patients with binge-eating disorder (BED), patients with BN demonstrate elements of compensatory "purging" behavior to prevent weight gain and obesity: i.e. self-induced vomiting, use of laxatives and enemas. These habits may prevent patients from attaining morbid obesity (MO), but may seriously affect life-style and become an excruciating, sometimes life-threatening condition. Methods: 6 of 108 patients (5.6%) who underwent BPD in our clinic (laparoscopic Scopinaro BPD - 1, open BPD/DS - 4, Lap. BPD/DS - 1) suffered from BN preoperatively. Their preoperative weight was 68-117 kg and BMI 27.6-41.9 kg/m². 4 of 6 patients had BMI <40 kg/m² before BPD but were MO in the past. The patient with the lowest weight had repeated gastroesophageal bleeding during self-induced vomiting. 3 of the 6 patients had previously failed intragastric balloon or Lap-Band^?. Results: All 6 patients were cured or significantly improved of bulimic symptoms soon after BPD. Weight loss was very good and never reached an undesirably low level. Patient satisfaction was high. Conclusion: Severe BN may be considered as a latent and potentially malignant MO. BPD (or BPD/DS) may be an effective solution for some patients with severe BN, as a final decision after unsuccessful organized conservative attempts. All candidates for bariatric surgery should be screened for BN, because it may influence choice of procedure in favor to BPD or BPD/DS.     

Examining the Discriminant Validity of Complex Posttraumatic Stress Disorder and Borderline Personality Disorder Symptoms: Results From a United Kingdom Population Sample

Complex posttraumatic stress disorder (CPTSD) was added to the diagnostic nomenclature in the 11th revision of the International Classification of Diseases (ICD‐11). Although considerable evidence exists supporting the construct validity of CPTSD, the distinguishability of CPTSD symptoms from those of borderline personality disorder (BPD) has been questioned. The present study examined the discriminant validity of CPTSD and BPD symptoms among a trauma‐exposed population sample from the United Kingdom (N = 546). Participants completed self‐report measures of CPTSD and BPD symptoms, and their latent structure was assessed using exploratory structural equation modeling (ESEM). A three‐factor model with latent variables reflecting PTSD, disturbances in self‐organization (DSO), and BPD symptoms provided the best fit of the data, χ²(399, N = 546) = 1,650, p < .001; CFI = .944; TLI = .930; RMSEA = .077, 90% CI [.073, .081]. We identified multiple symptoms distinctive to individual constructs (e.g., disturbed relationships and suicidality) as well as symptoms shared across the constructs (e.g., affective dysregulation). The PTSD, β = .24; DSO, β = .23; and BPD, β = .27, latent variables were positively and significantly associated with childhood interpersonal trauma. The current findings support the discriminant validity of CPTSD and BPD symptoms and highlight various phenomenological signatures of each construct as well as demonstrate how these constructs share important similarities in symptom composition and exogenous correlates.     

Biliopancreatic Diversion with Duodenal Switch Combined with Laparoscopic Adjustable Gastric Banding

Background: The authors investigated the usefulness of an approach combining biliopancreatic diversion (BPD) with duodenal switch (DS) and laparoscopic adjustable gastric banding (LAGB) in morbidly obese patients. Methods: 258 morbidly obese patients underwent bariatric surgery. 80 underwent gastric bypass (GBP), with an 80-ml pouch, a 120-150-cm common channel and a 350-cm alimentary limb (Group 1). 178 underwent BPD combined with DS-LAGB (Group 2): an 80cm common channel and a 200-cm alimentary limb were created in 68 patients (Subgroup 2a); a 120-cm common channel and a 300-cm alimentary limb were created in 110 patients (Subgroup 2b). Quality of life was assessed using the Moorehead-Ardelt Quality of Life Questionnaire (MA-QLQ). Results: At 2 years, mean BMI and %EWL were 27.8 kg/m² and 77.4 (Group 1), 25.2 kg/m² and 99.6 (Subgroup 2a), and 27.6 kg/m² and 79.3 (Subgroup 2b), respectively. 4 GBP patients regained their weight 2 years after surgery. There was 1 death, not related to surgery in Subgroup 2b. Preoperative MA-QLQ scores were similar between groups; at 2 years, MA-QLQ scores were higher in Subgroups 2a and 2b compared to Group 1 (+2.49 and +2.59 vs +0.98, respectively). Conclusion: Combination bariatric surgery is a safe, effective and durable weight loss option for the treatment of morbid obesity.     

Relative effects of GAL+ and GALlow/- porcine hematopoietic cells on primate platelet aggregation and endothelial cell activation: implications for the induction of mixed hematopoietic chimerism in the pig-to-primate model

Abstract: Background: The induction of porcine hematopoietic cell chimerism in preconditioned baboons has been hampered by the development of thrombotic microangiopathy. As pigs that lack expression of Galα1,3 Gal (Gal) may become available in the near future, we have explored the effects of porcine hematopoietic cells that express low or no Gal (Gal^low/?) on baboon platelet aggregation and on human umbilical vein endothelial cell (HUVEC) activation. Methods: Porcine mobilized peripheral blood progenitor cells (PBPC; Gal⁺) and bone marrow mononuclear cells (BM; Gal⁺ or Gal^low/?) were investigated for their potential to (i) induce aggregation of baboon platelets, and (ii) to activate endothelial cells as measured by increased expression of vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1 (ICAM‐1), and E‐selectin on HUVEC. α‐Galactosidase‐treated PBPC were also investigated for their effect on platelet aggregation. Results: Gal⁺ PBPC and Gal⁺ BM cells (10⁷) induced aggregation of baboon platelets by 42 and 31%, respectively, whereas Gal^low/? BM cells did not induce any platelet aggregation. α‐Galactosidase‐treated PBPC induced less platelet aggregation than untreated PBPC. Gal⁺ PBPC and Gal⁺ BM cells (10⁷) increased expression of VCAM‐1, ICAM‐1 and E‐selectin on HUVEC, whereas Gal^low/? BM cells did not. Conclusions: In contrast to Gal⁺ PBPC or BM, Gal^low/? BM cells do not induce aggregation of baboon platelets or activate HUVEC. The induction of tolerance through mixed hematopoietic cell chimerism may be facilitated when α‐galactosyltransferase‐knockout pigs become available.     

Smaller low-density lipoprotein size as a possible risk factor for the prevalence of coronary artery diseases in haemodialysis patients: associations of cholesteryl ester transfer protein and the hepatic lipase gene polymorphism with low-density lipoprotein size

Aim: Smaller low‐density lipoprotein (LDL) size has recently been reported as a non‐traditional lipid risk factor for coronary artery disease (CAD). Cholesteryl ester transfer protein (CETP) and the C/T hepatic lipase (HL) gene polymorphism may promote LDL size reduction via the CETP‐mediated exchange of CE for triglyceride (TG) and subsequent HL‐mediated TG hydrolysis in LDL. However, little is known about LDL size status and its relationship with CAD prevalence in haemodialysis (HD) patients who are at high risk for atherosclerosis. Methods: CETP levels, HL genotypes and LDL size were determined, and the determinants of LDL size and its association with CAD prevalence in HD patients (n = 236) aged over 30 years were investigated. Results: The HD patients had a similar LDL size to the healthy subjects. In the HD group, high‐density lipoprotein cholesterol was an independent positive determinant of LDL size, while log₁₀ (TG) was an independent negative determinant in the high (≥2.1 µg/mL) but not low (<2.1 µg/mL) CETP group. In the patients with hypertriglyceridemia, the high CETP group had a significantly smaller LDL size than the low CETP group. Among the patients with above‐median TG levels, the CC genotype and CETP were independent negative determinants of LDL size. In the whole group and the high CETP group, the patients with CAD had a significantly smaller LDL size than those without CAD. Finally, DM and smaller LDL size were identified as independent risk factors for CAD prevalence. Conclusion: These suggest that a smaller LDL size, which is associated with higher levels of TG and CETP and the HL/CC genotype, may serve as a risk factor for CAD in HD patients.     

Increased atherogenicity of low-density lipoprotein in heavy proteinuria

Background: Heavy proteinuria is associated with marked abnormalities of lipoprotein metabolism and increased risk of atherogenesis. It is possible that qualitative as well as quantitative changes occur in lipoproteins to contribute to increased cardiovascular risk; for example, it is known that LDL exhibits heterogeneity, with small, dense LDL III particles being more atherogenic. Methods: We investigated LDL subfractions (measured by density gradient ultracentrifugation), VLDL subfractions, and post-heparin lipases in 12 patients with primary glomerular disease and 24-h albuminuria >2.5 g. These were compared to 23 age- and sex-matched controls. Results: Total LDL concentrations were similar in proteinuric patients and controls; however, there was a shift in subfraction distribution. The larger LDL I and LDL II particles were lower in the proteinuric group (29±24 vs 62±26 mg/dl P=0.011 and 121±80 vs 197±74 mg/dl P=0.028), whereas the concentration of atherogenic LDL III (small dense) was higher (135±64 vs 75±71 mg/dl P=0.0016). The concentration of total VLDL and both its subfractions were increased in the patients with proteinuria. Post-heparin hepatic and lipoprotein lipase levels were similar to normal. Conclusions: These findings suggest that the atherogenicity of LDL is increased in patients with heavy proteinuria because of the redistribution towards smaller denser particles. Since small, dense LDL has a lower affinity for the LDL receptor, the altered nature of the lipoprotein in proteinuria may decrease its clearance by the receptor-mediated pathway and contribute to the reduced clearance of LDL observed in this population. This may contribute to progression of renal failure or the accelerated vascular disease found in patients with heavy proteinuria.     

Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells

Background: Currently the mechanisms of glomerular lipid accumulation are not completely understood. The present study characterizes the mechanisms of lipid uptake by glomerular cells. Since renal diseases are frequently associated with an accumulation of apoE-containing triglyceride-rich lipoproteins, we were interested to investigate whether glomerular epithelial or mesangial cells possess VLDL receptors besides the well established LDL receptors. Methods: Uptake kinetics of ¹²⁵I-labelled very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) in human glomerular epithelial and mesangial cells were compared to lipid uptake in cells with established receptor status, i.e. human skin fibroblasts and HepG2 cells. Results: Glomerular epithelial cells, mesangial cells, and skin fibroblasts as well as hepatocytes express VLDL receptor mRNA, indicating that they exhibit VLDL receptors. LDL uptake in glomerular epithelial cells, mesangial cells and skin fibroblasts occurred with a lower specificity than in HepG2 cells (-25%). No differences were found for the specificity of LDL uptake. VLDL uptake in HepG2 cells was inhibited more effectively with VLDL than with LDL. In skin fibroblasts, glomerular epithelial and mesangial cells, VLDL and LDL were equally effective inhibitors of VLDL uptake. The degradation-uptake ratio of VLDL in glomerular cells was elevated 50% compared to HepG2 cells, suggesting highly efficient intracellular lipoprotein turnover in these cells. Conclusion: We conclude that glomerular epithelial and mesangial cells as well as skin fibroblasts and HepG2 exhibit VLDL receptors additionally to their LDL receptors, even though the regulation of VLDL receptor in HepG2 cells seems to differ from the regulation in glomerular epithelial and mesangial cells. The high degradation-uptake-ratio in these renal cells suggests the presence of an effective clearance pathway which might serve as protection against lipoprotein accumulation.     

Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries

Purpose: The effect of near-wall blood flow velocity and plasma filtration velocity across the arterial wall on luminal surface concentration of low-density lipoproteins (LDL) and the uptake of tritium-cholesterol were investigated.Methods: A numeric analysis of LDL transport in steady flow, over the range of physiologically relevant flow rates, predicted a surface concentration of LDL of 4% to 16% greater than that in the bulk flow. The LDL surface concentration increased linearly with filtration velocity and inversely with wall shear rate.Results: These were validated experimentally in canine carotid arteries. When the transmural pressure was increased from 100 to 200 mm Hg, the filtration velocity increased from 5.13 × 10 ^-6 cm/sec to 8.41 × 10 ^-6 cm/sec, whereas the normalized uptake rate of tritium-cholesterol increased from 3.58 × 10 ^-4 cm/hour to 7.36 × 10 ^-4 cm/hour.Conclusion: These results indicate that lipids accumulate at the luminal surface in areas where blood flow velocity and wall shear stress are low and where the permeability of the endothelial layer is enhanced. Moreover, the rate of lipid infiltration into the blood vessel walls is affected by the luminal surface concentration. These findings are consistent with chronic hypertension and elevated blood cholesterol concentrations being major risk factors for atherosclerosis. (J VASC S URG 1995;21:135-45.)     

Low-dose photodynamic therapy increases endothelial cell proliferation and VEGF expression in nude mice brain

We tested whether low-dose photodynamic therapy (PDT) induces an angiogenic response in the normal brain of nude mice (n=20). Normal brains of nude mice were subjected to PDT at low doses (Photofrin: 2 mg/kg; optical: 2 J/cm² and 4 J/cm²). BrdU (50 mg/kg) was injected (intraperitoneally, i.p.) daily from PDT treatment to sacrifice (1 and 2 weeks after PDT). Laser scanning confocal microscopy, immunohistochemistry, and immunofluorescence staining were performed to assay angiogenic response. Morphological results show no significant tissue damage induced by PDT and two- and three-dimensional image analyses revealed no significant difference in vascular structure between the areas of exposure to PDT and contralateral areas in all mice. However, the number of BrdU immunoreactive cells were significantly increased in the areas of PDT treatment compared with contralateral hemisphere in both groups, and the number of BrdU-positive cells increased in a PDT-dose-dependent manner. Furthermore, immunohistochemical data indicate that PDT at these low doses significantly induces the expression of the vascular endothelial growth factor (VEGF) in PDT-treated regions in the 1-week group, but not in the 2-week group. These data indicate that low-dose PDT results in increased VEGF expression and endothelial cell proliferation in normal brains.     

A 15-Year Evaluation of Biliopancreatic Diversion According to the Bariatric Analysis Reporting Outcome System (BAROS)

Background: Biliopancreatic diversion (BPD) is the most effective bariatric procedure in terms of weight loss. However, analysis of the quality of life (QoL) has never been reported. The BAROS, giving a score to each operated patient on weight loss, improvement in medical conditions, QoL, complications and reoperations, has proven to be a standard reference for evaluating bariatric surgery outcomes. Methods: In order to apply the BAROS to BPD, we sent a questionnaire to 1,800 BPD patients who had been operated between 1984 and 1998.The responserate was 51.2%. Out of 1,709 questionnaires which actually reached their destination, we had 858 fully compiled returned. There were 615 women. 596 patients had had an ad hoc stomach (AHS) BPD, and 262 had had an ad hoc stomach ad hoc alimentary limb (AHS-AHAL) BPD. Results: According to the scoring key, 3.5% were classified as a failure, 11% were fair results, 22.8% good, 39.5% very good , and 23.2% excellent results. Considering AHS BPD and AHS-AHAL BPD separately,while the mean excess weight percent loss was 70.5±23 and 64.7±17 respectively, the failure rate was 6% in the first group and 2% in the AHAL group, while 11% and 6% of cases respectively were fair results, 24% and 20% good, 36% and 47% very good, 23% and 25% excellent results. Conclusion: The BAROS evaluation of BPD highlights the importance of its flexibility: the new policy of adapting the procedure to individual characteristics caused a drop in the failure rate and an increase in good, very good and excellent results.     

Laparoscopic Bariatric Surgery in Super-obese Patients (BMI>50) is Safe and Effective: A Review of 332 Patients

Background: Bariatric surgery in super-obese patients (BMI >50 kg/m²) can be challenging because of difficulties in exposure of visceral fat, retracting the fatty liver, and strong torque applied to instruments, as well as existing co-morbidities. Methods: A retrospective review of super-obese patients who underwent laparoscopic adjustable gastric banding (LAGB n=192), Roux-en-Y gastric bypass (RYGBP n=97), and biliopancreatic diversion with/without duodenal switch (BPD n= 43), was performed. 30day peri-operative morbidity and mortality were evaluated to determine relative safety of the 3 operations. Results: From October 2000 through June 2004, 331 super-obese patients underwent laparoscopic bariatric surgery, with mean BMI 55.3 kg/m². Patients were aged 42 years (13-72), and 75% were female. When categorized by opertaion (LAGB, RYGBP, BPD), the mean age, BMI and gender were comparable. 6 patients were converted to open (1.8%). LAGB had a 0.5%, RYGBP 2.1% and BPD 7.0% conversion rate (P=0.02, all groups). Median operative time was 60 min for LAGB, 130 min for RYGBP and 255 min for BPD (P<0.001, all groups). Median length of stay was 24 hours for LAGB, 72 hours for RYGBP, and 96 hours for BPD (P <0.001). Mean %EWL for the LAGB was 35.3±12.6, 45.8±19.4, and 49.5±18.6 with follow-up of 87%, 76% and 72% at 1, 2 and 3 years, respectively. Mean %EWL for the RYGBP was 57.7±15.4, 54.7±21.2, and 56.8±21.1 with follow-up of 76%, 33% and 54% at 1, 2 and 3 years, respectively. Mean %EWL for the BPD was 60.6±15.9, 69.4±13.0 and 77.4±11.9 with follow-up of 79%, 43% and 47% at 1, 2 and 3 years, respectively. The difference in %EWL was significant at all time intervals between the LAGB and BPD (P<0.004). However, there was no significant difference in %EWL between LAGB and RYGBP at 2 and 3 years. Overall perioperative morbidity occurred in 27 patients (8.1%). LAGB had 4.7% morbidity rate, RYGBP 11.3%, and BPD 16.3% (P=0.02, all groups). There were no deaths. Conclusion: Laparoscopic bariatric surgery is safe in super-obese patients. LAGB, the least invasive procedure, resulted in the lowest operative times, the lowest conversion rate, the shortest hospital stay and the lowest morbidity in this high-risk cohort of patients. Rates of all parameters studied increased with increasing procedural complexity. However, the difference in %EWL between RYGBP and LAGB at 2 and 3 years was not statistically significant.     

Normalization of Insulin Sensitivity in the Obese Patient after Stable Weight Reduction with Bilio-Pancreatic Diversion

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven eX-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (O)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCi ratio with respect to the normal controls (O vs N: 0.01164 ± 0.00039 vs 0.02392 ± 0.0039, p < 0.05). IVGTT, AUCs: significant differences were found in each case: N vs X: 0.0591 ± 0.0075 vs 0.1402 ± 0.0399, p < 0.05; N vs O: 0.0591 ± 0.0075 vs 0.0223 ± 0.0031, p < 0.01; X vs O: 0.1402 ± 0.0399 vs 0.0223 ± 0.0031, p < 0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 ± 0.00288 vs 0.00905 ± 0.00135 per min, p < 0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs O: 12.04 × 10⁻⁵ ± 2.61 × 10⁻⁵ vs 3.29 × 10⁻⁵ ± 0.61 × 10⁻⁵, p < 0.066; X vs O: 16.42 × 10⁻⁵ ± 4.23 × 10⁻⁵ vs 3.29 × 10⁻⁵ ± 0.61 × 10⁻⁵ per min per pM, p < 0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.     

The Decrease in Plasma Ghrelin Concentrations following Bariatric Surgery Depends on the Functional Integrity of the Fundus

Background: Gastric bypass surgery, which involves the production of a reduced stomach pouch,has been shown to markedly suppress circulating ghrelin concentrations. Since bypassing the ghrelin-producing cell population may be relevant to the disruption of fundic-derived factors participating in food intake signaling, the effect of weight loss induced by either adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD) was studied. Methods: 16 matched obese patients [35.0 + 2.4 years; initial body weight 124.8 ± 5.7 kg; body mass index (BMI) 47.1 ± 2.2 kg/m²] in whom similar weight loss had been achieved by either AGB (n=7), RYGBP (n=6) or BPD (n=3) were studied. Blood was obtained for biochemical and hormonal analyses. Body composition was assessed by air-displacement-plethysmography. Results: Comparable weight loss (AGB: 26.1 ± 5.1 kg; RYGBP: 32.1 ± 5.0; BPD: 31.7 ± 6.1; P=NS) and decrease in percentage body fat (AGB: 10.0 ± 1.5%; RYGBP: 14.2 ± 2.8; BPD: 10.3 ± 1.0; P=NS) induced by bariatric surgery exerted significantly different (P=0.004) effects on plasma ghrelin concentrations, depending on the surgical procedure applied (AGB: 480 ± 78 pg/ml; RYGBP: 117 ± 34; BPD: 406 ± 86). Without significant differences in BMI, body fat, glucose, triglycerides, cholesterol, insulin and leptin levels, patients who had undergone the RYGBP exhibited statistically significant diminished circulating fasting plasma ghrelin concentrations compared with the other two bariatric techniques which conserve direct contact of the fundus with ingested food (P=0.003 vs AGB and P=0.020 vs BPD). Conclusion: Fasting circulating ghrelin concentrations in patients undergoing diverse bariatric operations depend on the degree of dysfunctionality of the fundus.     

Effects of atorvastatin versus probucol on low-density lipoprotein subtype distribution and renal function in hyperlipidemic patients with nondiabetic nephropathy

Objectives: Small dense low-density lipoprotein (LDL) plays an important role in glomerular injury through conversion to an oxidatively modified form of LDL. However, few studies have evaluated the effects of antilipidemic agents on the LDL particle size and renal function in hyperlipidemic patients with nondiabetic nephropathy. Methods: This study was a randomized crossover trial comparing the effects of atorvastatin (10 mg/day) and probucol (500 mg/day) administered for 24 weeks in 31 patients (urinary albumin excretion 0.3–2.0 g/day and creatinine clearance >30 mL/min/1.73 m). Lipid parameters, mean LDL particle diameter, creatinine clearance, and urinary albumin to creatinine excretion ratio were measured before and during treatment periods. Main findings: Atorvastatin and probucol significantly reduced the serum total cholesterol and LDL cholesterol concentrations. When stratified by mean baseline LDL particle size at 25.5 nm, atorvastatin increased (p < 0.05) LDL particle size from 24.6 ± 0.5 to 25.2 ± 0.9 nm only in the <25.5 nm (pattern B) group, whereas probucol decreased (p < 0.05) LDL size from 24.8 ± 0.9 to 24.2 ± 0.9 nm in the pattern B group and from 25.9 ± 0.5 to 24.6 ± 0.8 nm in the ≥25.5 nm (pattern A) group. No significant differences in urinary albumin/creatinine excretion ratio and creatinine clearance were observed in both groups during treatment. Conclusions: Only atorvastatin improved the LDL-subtype distribution in hyperlipidemic patients with nondiabetic nephropathy, although both agents exhibited no renoprotective action, suggesting that the effects on LDL-subtype distribution do not directly lead to renoprotection.     

Reduced Plasma Zinc Levels,Lipid Peroxidation,and Inflammation Biomarkers Levels in Hemodialysis Patients: Implications to Cardiovascular Mortality

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(–)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m²) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m²) and followed for 24 months to investigate the risks for CV mortality. LDL(–) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 μg/dL) and high-LDL(–) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4μ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = –0.49; p = 0.0001) and LDL(–) (r = –0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.