The Effect of Obesity on Neutrophil Fc Receptors and Adhesion Molecules (CD16, CD11b, CD62L)

Background: There is a large body of epidemiological data associating obesity with a wide variety of clinical disease processes, including cancer and wound infections. However, defining the specific defects of neutrophils has proved difficult and often contradictory. Methods: 27 patients having gastric bypass surgery for obesity (BMI>40) were compared with 10 normal controls (BMI<26). Relative neutrophil frequencies and expression of the activation antigens CD11b (integrin adhesion molecule), CD16 (Fc receptor), and CD62L (L- selectin), were evaluated by flow cytometry. Results: The study control group had a mean age of 37 ± 7.6 yrs (range 30 to 57) with no significant health problems.Their mean BMI was 23 ± 2.5 kg/m² (range 21-26). The mean age of the sample group was 40.36 ± 13.7 yrs (range 18 to 60) with a mean BMI of 52 ± 8.2 kg/m2 (range 41 to 72).These patients had a large spectrum of diseases that afflict the morbidly obese, including hypertension (14), arthritis (10), exertional dyspnea (13), venous stasis (7), hypothyroidism (2), NIDDM (3), heart murmur (1), along with 8 smokers. The neutrophil frequency in the obese patients was comparable to the controls (control 49% vs obese 51%). Additionally, there was no apparent difference between obese and controls regarding CD11b or CD16 expression (424 vs 498 gmf) (267 vs 262 gmf). However, there was a significant reduction of CD62L (L-selectin) expression noted in the morbidly obese with respect to controls (102 vs 303 gmf, p<0.001). An increased percentage of eosinophils when compared to controls (6.7% vs 1.73%, p<0.001) was also observed. Conclusion: Discordant CD11b/CD62L levels, depressed levels of CD62L, and elevated eosinophil percentages support the hypothesis that a chronic inflammatory state exists in morbid obesity. Decreased levels of CD62L in the morbidly obese neutrophil pool possibly affect the neutrophil's ability to activate and migrate to sites of inflammation. This may play a role in the higher incidence of infectious complications seen in morbidly obese individuals.     

Dysfunctional Immune-Privilege In Morbid Obesity: Implications and Effect of Gastric Bypass Surgery

Background: Despite the epidemiological evidence linking obesity and cancer, there has never been a causal link.We believe the chronic inflammation present in obesity may predispose the obese to cancer through Fas-receptor over-expression and L-selectin under-expression in leukocytes, and elevated Fas ligand secretion in tumors affecting the morbidly obese. Methods: Leukocytes from 25 patients having gastric bypass surgery were compared to 15 normal controls preoperatively and at 1, 3, 6, and 12 months postoperatively using flow cytometry to measure CD3, CD4, CD8, CD56, CD62 (L-selectin), CD 69, and CD95 (Fas antigen) expression on T lymphocytes, B lymphocytes, natural killer cells, and neutrophils. Results: The percentage of CD95+T cells was significantly elevated from controls (69.4% vs 56%, P=0.005). This difference persisted through 1 month postoperatively. Furthermore, expression of CD95 per cell, was significantly greater in these patients than that of the controls (80.2 vs 62.6 gmf, P=0.018) preoperatively, and this continued to 1 month. Polymorphonuclear cells also displayed a similar elevation in CD95 gmf expression preoperatively (54.1 vs 40.7 gmf, P=0.023) which normalized by 3 months. Natural killer cells did not display elevated numbers of CD95 gmf preoperatively, but they did experience a significant decline by 12 months. Additionally, there was significant reduction in the number of naiveT cells [(T cells without L-selectin (CD62L)], when compared to normals preoperatively (41.8% vs 51.3%, P=0.001). There was no statistical difference between the postoperative patients and the controls by 3 months. CD69 was not different at baseline from controls in T or B cells, but there was a significant decrease by 12 months. Conclusion: The reduced expression of L-selectin combined with the elevated levels of CD95 suggests that morbid obesity predisposes patients to sites of immune privilege. This could be the mechanism for increased rates of cancer and wound infections seen in obesity. Surgically-induced weight loss eliminates these risk factors.     

Fasting Plasma Ghrelin Concentrations 6 Months after Gastric Bypass are not Determined by Weight Loss or Changes in Insulinemia

Background: Ghrelin is a gastric peptide with potent orexigenic effects. Circulating ghrelin concentrations are increased in obese subjects, but increase after weight loss. However, in patients undergoing Roux-en-Y gastric bypass (RYGBP), a decrease in ghrelin levels has been reported. The effect of comparable weight loss induced by either adjustable gastric banding (AGB), RYGBP or conventional dietary treatment (Conv) on ghrelinemia was studied. Methods: 24 matched obese male patients in whom similar weight loss had been achieved by either AGB (n=8), RYGBP (n=8) or Conv (n=8) were studied before and 6 months after treatment start. The independence of ghrelin concentrations from body mass index (BMI) and weight loss was further analyzed in a group of patients with total gastrectomy (TtGx, n=6). Results: Comparable weight loss after 6 months exerted significantly different effects on plasma ghrelin concentrations, depending on the procedure applied (AGB: 424.6 ± 32.8 pg/ml; RYGBP: 131.4 ± 13.5; Conv: 457.3 ± 18.7; P<0.001). Without significant differences in body weight and BMI, patients who had undergone the RYGBP exhibited a statistically significant decrease in fasting ghrelin concentrations, while the other two procedures (AGB and Conv) showed a weight loss-induced increase in ghrelin levels. Despite significant differences in BMI between RYGBP and TtGx patients after 6 months (31.9 ± 2.2 vs 22.0 ± 0.7 kg/m², respectively; P<0.05), both groups showed similar ghrelin concentrations. Conclusion: The reduction in circulating ghrelin concentrations in RYGBP patients after 6 months of surgery are not determined by an active weight loss or an improved insulin-sensitivity but rather depend on the surgically-induced bypass of the ghrelin-producing cell population of the fundus.     

Varying Blood Monocyte and Dendritic Cell Responses after Laparoscopic Versus Open Gastric Bypass Surgery

Background: Laparoscopy may activate innate immunity less than conventional open surgery. This may be important in obese patients who have pre-existing low-grade inflammation. This study examined phenotypic changes in blood monocytes (Mcs) and dendritic cells (DCs) from patients undergoing laparoscopic (L) or open (O) Roux-en-Y gastric bypass (RYGBP) surgery. Methods: 8 patients (3 male) had blood drawn before and after RYGBP, and on postoperative day (POD) 1, 3, and 28. Mc and DC quantity, phenotype, and activation status were determined by flow cytometry. Results: Mean BMI was 53 ± 4 and 46 ± 1, and length of stay was 6.3 ± 3.2 and 3.5 ± 0.6 days, in the O (n=4) versus L (n=4) groups, respectively. Postoperative WBC count was 16 ± 1 × 10³/mm³ after O and 10 ± 1 × 10³/mm³ after LRYGBP (P<0.001). This was due to a greater rise in neutrophils and decline in lymphocytes after ORYGBP (P<0.001). Total Mcs increased in both groups at POD 1, but the number of CD18+ Mcs was reduced after ORYGBP (P=0.04). Mc human leukocyte antigen (HLA)-DR expression was lower in CD16+ Mcs after ORYGBP, suggesting decreased capacity to present antigen (P=0.002). Postoperatively, total DCs decreased in both groups, but recovered (P=0.04). The proportion and activation of the tolerogenic DC2 phenotype was lower, whereas the percentage of the ldDC phenotype was higher, in the O group (P=0.006). Conclusion: RYGBP changes the quantity and phenotype of circulating blood Mcs and DCs. Although there were overall similarities in the overall response to gastric surgery between open and laparoscopic, there were some notable differences, including a greater reduction in HLA-DR expression and increased number of immature DCs in the ORYGBP group. The findings suggest that RYGBP may have varying immunologic consequences depending upon the surgical procedure employed.     

Elevated circulating levels of soluble CD-40 ligand in haemodialysis patients with symptomatic coronary heart disease

Aim: The CD40–CD40L system has been implicated in the pathogenesis of atherothrombotic complications in cardiovascular disease. The aim of this study was to determine the relationship between plasma soluble CD40 ligand (sCD40L) and symptomatic coronary heart disease (CHD) in end-stage renal disease (ESRD) patients on maintenance haemodialysis (HD). Methods: This cross-sectional study included 57 HD patients, 31 of whom had symptomatic CHD. Lipid profile, markers of endothelial activation such as sCD40L, and both inflammatory and oxidative stress markers were measured and analyzed. Results: The sCD40L concentration was significantly higher in HD patients than in controls (1.34 ± 0.53 vs 0.86 ± 0.12 ng/mL, P < 0.01). Plasma concentration of sCD40L (P < 0.01), soluble vascular adhesion molecule-1 (sVCAM-1; P < 0.01) and high-sensitivity CRP (hsCRP; P < 0.01) were higher in HD patients with symptomatic CHD than in those without CHD. In addition, we also found that oxidative stress biomarkers such as nitrotyrosine (NT), malonaldehyde (MDA) and protein carbonyl (PC) were significantly elevated in patients with symptomatic CHD compared to those without. There was a strong overall positive relationship between sCD40L concentration and sVCAM-1 (r = 0.54, P < 0.001), MDA (r = 0.365, P < 0.01), NT (r = 0.293, r < 0.05) and log-transformed triglycerides (r = 0.275, P < 0.05). Conclusion: Circulating concentrations of sCD40L were elevated in HD patients with symptomatic CHD. This study suggests that CD40–CD40L may play a potentially important role in the atherosclerotic complications of HD patients.     

Obesity and the White Blood Cell Count: Changes with Sustained Weight Loss

Background: Obesity is a chronic inflammatory condition, and elevated white blood cell counts (WBC) have widely recognized associations with inflammatory conditions. The authors explored the relationship between the WBC and degree of obesity, basic anthropometry, and clinical and biochemical markers of the metabolic syndrome at baseline, and with weight loss following Lap-Band^? surgery. Methods: 477 patients with complete biochemical and clinical data at baseline and at 2 years were selected for analysis. Paired analysis assessed the change in WBC at 2 years, and stepwise linear regression assessed factors independently associated with baseline counts and any change at 2 years. Results: Mean ± SD weight loss at 2 years was 29.3 ± 16.2 kg. There were significant decreases in total WBC (−12.2%), and major components, neutrophils (11.7%) and lymphocytes (6.9%), at 2 years (P<0.001 for all). Baseline WBC, neutrophils and lymphocyte counts increased with increasing BMI and decreased with age. Insulin levels were independently positively associated with higher neutrophil counts and triglycerides with higher lymphocyte counts. Age, gender, BMI and components of the metabolic syndrome when modeled together accounted for <10% of the variance of baseline counts. Higher BMI predicted a greater fall in the neutrophil counts at 2 years. Change in BMI at 2 years was the only independent predictor of the change in both neutrophils and lymphocytes, but accounted for <10% of the variance of change. Conclusion: BMI contributes to both baseline and weight loss WBC. However, crude WBC counts are influenced in minor ways by obesity markers and have limited value as clinical markers.     

Time Course of β2-Integrin CD11b/CD18 (Mac-1, αMβ2) Upregulation on Neutrophils and Monocytes after Coronary Artery Bypass Grafting: CD11b upregulation after CABG surgery

Although upregulation of CD11b/CD18 receptor, i.e. activation of neutrophils and monocytes, during cardiopulmonary bypass is well documented, the duration of the active state after uncomplicated operation is less understood. We therefore investigated CD11b expression of phagocytes in blood samples collected 2-4, 24, 48 and 72 h after coronary artery bypass grafting. CD11b expression on neutrophils was significantly elevated at 2-4 and 24 hours after operation as compared with baseline. On monocytes, expression peaked at 24 h and returned to baseline by 72 h. Because CD11b is a sensitive marker, effects of different sampling techniques on its expression were also studied. CD11b expression was similar in samples collected with a syringe from arterial or central venous catheter or with open technique from cubital vein. On neutrophils from healthy subjects, sampling with syringe caused small (10%) but statistically significant increase of expression. We conclude that activated neutrophils disappear from circulation within hours after CABG surgery while activated monocytes may continue circulating for 2-3 days, and that CD11b sampling can be done with a syringe.     

Does Laparoscopic Gastric Bypass Result in a Healthier Body Composition? An Affirmative Answer

Background: Bariatric surgery results in sustained weight loss. While weight loss is the goal of bariatric surgery, fat loss and muscle conservation are germaine goals. This study investigated the hypothesis that body composition would significantly change after laparoscopic Roux-en-Y gastric bypass (LRYGBP). Methods: Patients undergoing LRYGBP were studied. Percent fat and percent water were calculated via bioelectrical impedance analysis (BIA). Waist and hip circumference were measured in all patients as well. Measurements were taken preoperatively, and at 1 month, 3 months, 6 months, and 1 year. Non-parametric ANOVA was utilized for statistical analysis. Results: There were 151 patients included in this study. Fat percentage (48.6 ± 10.0 vs 34.6 ± 10.8; P<0.001), total fat mass (141 ± 37 vs 67 ± 30; P<0.0001) and total water mass (108 ± 27 vs 93 ± 23; P<0.0001) decreased postoperatively at 1 year. Water percentage increased postoperatively at 1 year (37.0 ± 6.6 vs 52.5 ± 3.3; P<0.001). Waist:hip ratio improved from preoperatively to 1 year postoperatively (0.895 ± 0.115 vs 0.811 ± 0.076; P<0.001). Conclusions: Bariatric surgery results not only in fat loss but also in a change in body composition. Improved waist:hip ratio, fat percentage decreases, and water percentage increases all indicate an overall healthy body composition. While weight loss is important, improvement in body composition should be another recognized benefit of bariatric surgery.     

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.     

Weight loss after Swedish Adjustable Gastric Banding: relationships to insulin resistance and metabolic syndrome

Background:The metabolic syndrome is a cluster of cardiovascular risk factors (central obesity, hypertension,dyslipidemia, disturbance in glucose metabolism) associated with insulin-resistance. The cluster of risk factors defining the metabolic syndrome increases cardiovascular risk more than each single component. The aim of the present longitudinal study was to evaluate the relationship between weight loss and changes in insulin-resistance and in the prevalence of the metabolic syndrome 1-year after SAGB implantation. Methods: 51 premenopausal severely obese women (mean age 35.2±8.8 years, BMI 43.3±6.9) were enrolled. As a control group, 51 premenopausal nonobese women (BMI<30) were enrolled. All obese subjects underwent successful implantation of the SAGB via videolaparoscopy. In all subjects insulinresistance was estimated by HOMA index and metabolic syndrome was defined according to the criteria of the European Group for the Study of Insulin Resistance. Results: HOMA (4.2±2.0 vs 1.9±0.8, P<0.001) and the prevalence of the metabolic syndrome (58.8% vs 7.8%, P<0.001) were significantly higher in obese than non-obese women. 1 year after SAGB, BMI significantly decreased from 43.3±6.9 to 34.5±7.4 (P<0.001). HOMA index showed a significant dramatic breakdown (4.2±2.0 vs 2.4±1.0, P<0.001). The prevalence of the metabolic syndrome declined significantly (58.8% vs 21.6%, P<0.001). Conclusion: Our study shows that in severely obese women, insulin-resistance and the prevalence of the metabolic syndrome significantly decrease 1 year after SAGB. Our findings indicate that SAGB could be a useful tool to reduce the global cardiovascular risk in severely obese people and to improve their long-term prognosis.     

Gastroesophageal Reflux Disease in Morbid Obesity: The Effect of Roux-en-Y Gastric Bypass

Background  Gastroesophageal reflux disease (GERD) is a common condition in obesity. The impact of Roux-en-Y gastric bypass (RYGBP) on GERD is poorly known. We studied the effect of the RYGBP on GERD in patients with morbid obesity (MO). Methods  Twenty consecutive patients with MO (BMI > 40 kg/m²) were studied before and 6 months after RYGBP. GERD symptoms were evaluated with Carlsson–Dent questionnaire (CDQ). All the patients underwent esophageal manometry and ambulatory 24-h pH-metry. Chi-square test was used to compare categorical variables, and Wilcoxon test was used for numerical variables. A p value under 0.05 was considered significant. Results  There were 16 women (80%) and 4 men (20%) with mean age 38.9 ± 6.9 years included in this study. BMI was 48.5 ± 6.2 kg/m² and 33.2 ± 4.5 kg/m² before and after RYGBP, respectively. Mean weight reduction was 42.5 ± 9.7 kg (p < 0.001). Reflux symptoms measured by CDQ and esophageal acid exposure improved significantly after RYGBP. The percentage of time of pH < 4 was 10.7 ± 6.7 before and 1.6 ± 1.2 after the surgical procedure (p < 0.001). LES basal pressure before and after the RYGBP was 18 ± 11 and 20.1 ± 5.6 mmHg (p = 0.372), and the esophageal body amplitude was 104.2 ± 47.2 and 75.1 ± 36.2 mmHg, respectively (p = 0.005). Conclusion  RYGBP improves GERD symptoms and reduces esophageal acid exposure in patients with MO.     

Is Roux-en-Y Gastric Bypass Adequate in the Super-Obese?

Background:The outcome after Roux-en-Y gastric bypass (RYGBP) in morbidly obese (MO) (body mass index [BMI] 40-50) was compared with super-obese (SO) (BMI >50) and super-super-obese (SSO) (BMI >60) patients. Methods: A prospective study was conducted in 738 consecutive patients who underwent RYGBP. 483 MO were compared with 184 SO and 70 SSO. Study endpoints included: effect on co-morbid conditions, postoperative morbidity and mortality, and long-term results. Statistical analysis utilized SPSS 11.0. Results: Percentage of males was significantly greater in the SO groups (16.5% vs 13%, P=0.01). Obesity-related conditions were significantly more frequent in the SO groups: sleep apnea (38% vs 17%, P<0.0005), gallstones (23% vs 14%, P=0.013); diabetes (29% vs 17%, P=0.002). Hospital stay was longer in the SO groups (5.7±6.1 days vs 4.6±2.6 days, P=0.024). Wound infection was more frequent in the SO groups (4.7% vs 1.4%, P=0.019). Postoperative mortality was greater in the SSO and SO groups (1.6% and 1.4%) than MO (0%) (P=0.019). Incisional hernia was more frequent in the SO groups (14.1% vs 8.6%; P=0.041). There was no significant difference in percent of excess weight loss (%EWL) between the three groups. EWL >50% at 5 years was: MO 81.5%, SO 87.5%, SSO 80%. The surgery was effective in treating the co-morbid conditions. Conclusion: RYGBP achieved significant durable weight loss and effectively treated co-morbid conditions in SO and SSO patients with acceptable postoperative morbidity and slightly greater mortality than in MO patients.     

DRG,Costs and Reimbursement following Roux-en-Y Gastric Bypass: an Economic Appraisal

Background: There is disagreement regarding hospital and physician reimbursement fees when DRG codes are used. We have found that physicians and hospitals are rewarded differently depending on the type of insurance coverage - per diem HMO (Health Maintenance Organization) vs public. Methods: 133 patients were retrospectively analyzed in a single institution. There were 59 privately-insured and 74 publicly-insured patients. Using DRG 288, hospital and surgeon reimbursement rates, complications, length of stay, blood loss and basic demographics were evaluated on all patients. Reimbursement rates were then compared to inpatient hospital costs per case for both open and laparoscopic Roux-en-Y gastric bypass (RYGBP). Statistical analysis used Student's t-test and standard deviation. Results: The 2 groups were similar in terms of age, sex and BMI. There was a large difference in physician reimbursement when comparing public to private insurance ($931±73 vs $2356±822, P<0.001). Likewise, there was a large difference in hospital reimbursement (public $11773 ± 4462 vs private $4435 ± 3106, P<0.001). The estimated costs for open gastric bypass was $3179 vs $4180 for the laparoscopic bypass. The HMO per diem rate was $1000 per day. Conclusion: There is a relative disincentive for surgeons to treat publicly-insured patients, while there is an incentive for hospitals to treat those patients. The converse is true for the privately-insured patients. This dichotomy will impede the development of new centers and place greater burden on bariatric surgeons to reduce cost by performing the open RYGBP.     

Monocyte adhesion molecule expression in interstitial inflammation in patients with renal failure.

BACKGROUND: Patients with renal failure have an increased susceptibility to infections. We therefore studied the recruitment of monocytes and their expression of adhesion molecules CD11b and CD62L at the site of interstitial inflammation in patients with renal failure. Furthermore, we studied if the capacity of monocytes to up-regulate CD11b in interstitial inflammation was determined by the interstitial concentration of chemotactic factors. METHODS: Three intensities of interstitial inflammation (0, intermediate and intense) were established in skin blister chambers. Leukocyte count, CD11b/CD62L expression, monocyte chemotactic protein-1 (MCP-1) and blister activity in terms of CD11b mobilization were determined. RESULTS: The CD62L expression on monocytes was lower in the peripheral circulation in patients with renal failure compared with healthy subjects (P<0.005 and P<0.001). At the site of interstitial inflammation patients had a higher expression of CD62L (intermediate, P<0.05; intense, P<0.005). Furthermore, monocytes from patients had an impaired capacity to mobilize CD11b both in the peripheral circulation (P<0.005) and at the intermediate and intense sites of interstitial inflammation (P<0.005 and P<0.001, respectively) compared with cells collected from healthy subjects. We incubated monocytes in blister exudates, in order to explore whether this phenomenon is caused by cellular factors and/or to the interstitial concentration of chemotactic mediators. The expression of CD11b on monocytes from healthy blood donors incubated in blister exudates from either patients or healthy subjects in vitro was similar. The interstitial concentration of MCP-1 at the site of intermediate inflammation was significantly lower in patients with renal failure compared with the corresponding blister exudate collected from healthy subjects (P<0.05), but no differences were observed at the site of intense inflammation. Furthermore, neutralizing the action of MCP-1 in blister exudates with monoclonal antibodies did not have any impact on monocyte CD11b expression following incubation in blister exudates. CONCLUSION: These studies indicate that the impaired capacity of monocytes to mobilize CD11b at the site of inflammation in patients with renal failure is more dependent on constitutive cellular factors than the concentration of CD11b mobilizing factors in the interstitium.     

Changes in Resting Energy Expenditure and Body Composition after Weight Loss following Roux-en-Y Gastric Bypass

Background The objective of this study was to evaluate changes in resting energy expenditure (REE), body composition and metabolic parameters, and to investigate predictors of the results in seriously obese patients after Roux-en-Y gastric bypass (RYGBP). Methods 31 patients (BMI 44.4 ± 4.8 kg/m2; 27 female, 4 male; 37.3 ± 11.1 y) were evaluated at baseline and 6 months after RYGBP. Weight, REE, waist circumference (WC), fat mass (FM) and fat-free mass (FFM), physical activity, food intake, fasting glucose (GLU), insulin (INS), HOMA-IR and lipid concentrations were measured. Results At 6 months, percentage of weight loss (%WL) was 29.0 ± 4.4% and percentage of excess weight loss was (%EWL) 59.7 ± 12.3%. FM loss corresponded to 77.1 ± 12.2% of the weight loss. REE decreased from 33.4 ± 4.1 to 30.1 ± 2.6 kcal/kg FFM (P < 0.05). Significant decreases (P < 0.001) were observed in GLU, INS, HOMA-IR, LDL-cholesterol and triglycerides. %EWL was correlated with baseline INS (r = 0.44; P = 0.014), baseline HOMA (r = 0.43; P = 0.017), change in %FM (r = 0.67; P < 0.001) and change in WC (r = 0.5; P < 0.01). Decrease in REE/FFM (%) was positively correlated with baseline REE/FFM% (r = 0.51; P < 0.005) and change in %FM (r = 0.69; P < 0.001). Initial REE/FFM, baseline energy balance and FM change explain 90% of REE/FFM decrease. Conclusion RYGBP was an effective procedure to induce significant weight loss, fat mass loss and improvement in metabolic parameters in the short term. Metabolic adaptation was not related to FFM wasting but to a higher baseline REE. Fasting hyperinsulinemia was the best single predictor of weight loss after RYGBP. Supported by a grant from University of Chile (DID–SAL 01/04–2).     

Pre- and Post-prandial Plasma Ghrelin Levels Do Not Correlate with Satiety or Failure to Achieve a Successful Outcome after Roux-en-Y Gastric Bypass

Background: We tested the hypothesis that the amount of weight lost after Roux-en-Y gastric bypass (RYGBP) correlates with plasma ghrelin levels. Methods: 36 morbidly obese patients were studied 3 years after RYGBP (6 men, 30 women) with mean initial BMI 51 kg/m² and 8 healthy controls (2 men, 6 women) with mean BMI 25 kg/m². Subjects consumed a light breakfast, and the first blood sample was drawn at 1200 hrs immediately before lunch and the second sample at 1400 hrs. Satiety was assessed using a Visual Analog Scale (VAS). Patients were stratified as success (current BMI <35) or failures (current BMI ≥35). Results: Plasma ghrelin levels were significantly lower in patients after RYGBP (269 ± 66 pcg/ml) compared with lean controls (616 ± 112 pcg/ml, P<0.001). Ghrelin levels pre or post meals were not different between patients who had a successful weight loss (preoperative BMI 47, current BMI 29, 72% EWL) or those who achieved a less then ideal weight loss (preoperative BMI 48, current BMI 41, 29% EWL). There was no correlation between any of the VAS scores and plasma ghrelin. There was a strong inverse correlation between pre-prandial ghrelin levels and the preoperative or current BMI. Conclusion: Failure to lose weight after RYGBP does not correlate with pre- or post-prandial ghrelin plasma levels. Ghrelin levels were inversely proportional to BMI and did not correlate with satiety. These data do not support a role for higher plasma ghrelin levels for inadequate weight loss after RYGBP.     

Expression of glucocorticoid receptors in mononuclear cells in nephrotic syndrome

Coulter flow cytometry was used to determine glucocorticoid receptors (GCR) in the peripheral blood cells of patients with nephrotic syndrome. The expression of GCR in the lymphocytes (CD3/GCR) and monocytes (CD14/GCR) of peripheral blood of 23 (age 4.9±2.7 years) children with steroid-sensitive nephrotic syndrome was assessed before treatment (proteinuria >50 mg/kg per 24 h), after 4–6 weeks of prednisone treatment, without proteinuria, and in remission, without proteinuria and without any treatment. Before treatment the expression of CD3/GCR was 61.8±18.3% and CD14/GCR 43.6.8±20.3%; this did not differ from the results of the normal control group (P>0.05). However, after treatment GCR expression in lymphocytes was 50% (P<0.001) and in monocytes about 20% lower (P<0.05). In remission, the GCR expression increased and did not differ from the results before treatment (P>0.05). A positive correlation between the serum cortisol concentration and the expression of CD3/GCR was found (r=0.504, P=0.02). In summary, we report that in children with steroid-sensitive nephrotic syndrome, prednisone treatment causes the temporary decrease of the expression of GCR in lymphocytes. A positive correlation between GCR expression and serum cortisol was found. A decrease in GCR expression in monocytes did not correlate with cortisol concentration.     

Gastro-Esophageal Reflux and Esophageal Motility Disorders in Morbidly Obese Patients before and after Bariatric Surgery

Background Obesity is a predisposing factor to gastro- esophageal reflux disease (GERD), but esophageal function remains poorly studied in morbidly obese patients and could be modified by bariatric surgery. Methods Every morbidly obese patient (BMI ≥40 kg/m² or ≥35 in association with co-morbidity) was prospectively included with an evaluation of GERD symptoms, endoscopy, 24-hour pH monitoring and esophageal manometry before and after adjustable gastric banding (AGB) or Roux-en-Y gastric bypass (RYGBP). Results Before surgery, 100 patients were included (84 F, age 38.4 ± 10.9 years, BMI 45.1 ± 6.02 kg/m2), of whom 73% reported GERD symptoms. Endoscopy evidenced hiatus hernia in 39.4% and esophagitis in 6.4%. The DeMeester score was pathological in 53.3%; 69% of patients had lower esophageal sphincter (LES) pressure <15 mmHg and 7 had esophageal dyskinesia. BMI was significantly related to the DeMeester score (P = 0.018) but not to LES tone or esophageal dyskinesia. Postoperative data were available in 27 patients (AGB n = 12/60, RYGBP n = 15/36). The DeMeester score (normal <14.72) was significantly decreased after RYGBP (24.8 ± 13.7 before vs 5.8 ± 4.9 after; P < 0.001) but tended to increase after AGB (11.5 ± 5.1 before vs 51.7 ± 70.7 after; P = 0.09), with severe dyskinesia in 2 cases. Conclusion: GERD and LES incompetence are highly prevalent in morbidly obese patients. Preliminary postoperative data show different effects of RYGBP and AGB on esophageal function, with worsening of pH-metric data with occasional severe dyskinesia after AGB.     

Randomized Controlled Pilot Study of 2 Weeks' Treatment With High Cutoff Membrane for Hemodialysis Patients With Elevated C‐Reactive Protein

Chronic inflammation in hemodialysis (HD) patients is associated with cardiovascular complications and mortality. Circulating immune active proteins in the molecular range 15–45 kD that cannot be efficiently cleared by high‐flux (HF) dialysis may be causally involved. We intended to test the feasibility of using a high cutoff (HCO) dialyzer in chronic HD patients and its influence on inflammation and monocyte activation. The Gambro HCO1100 dialyzer was compared to a conventional HF membrane in a randomized double‐blind crossover trial in 19 chronic HD patients selected for the presence of elevated serum C‐reactive protein levels. Patients were treated for six consecutive dialysis sessions (2 weeks) with each membrane. Safety analysis recorded adverse events and albumin losses through the protein‐leaking membranes. Efficacy analysis observed reductions in the number of proinflammatory (CD14+CD16+) monocyte subpopulations in circulating blood. Treatment with the HCO membrane was well tolerated, although the number of adverse events was slightly higher. Despite significant serum albumin loss (from 34.1 ± 2.7 to 29.6 ± 3.0 g/L; P < 0.01), there was no need to supplement albumin, and rising activity of cholinesterase during HCO treatment indicated compensation by enhanced hepatic synthesis. The HCO membrane cleared high amounts of proinflammatory cytokines, but did not reduce predialysis inflammatory monocytes and markers. Although the time of HD session was extended, the study was hampered by a lower Kt/V in the HCO compared to the HF period. Treatment of chronic HD patients with this HCO dialyzer for 2 weeks is tolerable in terms of albumin loss and able to clear proinflammatory cytokines; however, this was not sufficient to decrease monocyte activation. Therefore, a more selective, less albumin‐leaking membrane is desirable to allow prolonged high‐efficient dialysis with more effective cytokine clearance.     

The Impact of Bariatric Surgery on the Veterans Administration Healthcare System: A Cost Analysis

Background: The economic burden of caring for veterans with clinically severe obesity and its comorbidities is straining the Veterans Administration (VA) healthcare system. The authors determined the cost of Roux-en-Y Gastric Bypass (RYGBP) in the VA's single-payor healthcare system. Methods:The records of all 25 patients who underwent RYGBP from May 1999 to October 2001 were reviewed. All obesity-related health-care costs including hospitalizations as well as outpatient visits, medications and home health devices were calculated for 12 months before and after the RYGBP. Results: Age was 52±2 yr and preoperative BMI was 52±2 kg/m²; ASA score was III (21 patients) and II (4 patients). Mean follow-up was 18 months.Total cost of care for these patients preoperatively was $10,778±2,460/patient (outpatient visits=$5,476±682, hospital admissions=$12,221±6,062, and home health devices=$1,383±349). Postoperative length of stay was 8±0.5 days. Cost of the gastric bypass was $8,976±497/pt (OR fixed cost=$1,900/patient + ICU and ward=$7,076±497/patient). For the first postoperative year, 6 patients had 12 admissions, but routine outpatient visits were significantly reduced from 55±6 to 18±2 postoperatively (P<0.001).The cost of all care excluding peri-operative charges for 1 year after gastric bypass was $2,840±622/patient (P=0.005 vs preop). Conclusions: Operative treatment of clinically severe obesity reduces obesity-related expenditures and utilization of healthcare resources. The cost of undertaking RYGBP at the VA is offset by reduction of health-care costs within the first year after surgery. These data support allocation of resources to support existing bariatric surgery programs throughout the VA system.