Preoperative changes of forced vital capacity due to body position do not correlate with postoperative respiratory function in obese subjects.

BACKGROUND: Obese patients are at risk of developing postoperative pulmonary complications. We hypothesized that preoperative changes in dynamic spirometry due to body posture would correlate with the drop of forced vital capacity (FVC) measured early after surgery. METHODS: Thirty consecutive morbidly obese patients undergoing gastric banding were investigated. All subjects were studied the day before surgery (T0) and on postoperative day one (T1). Forced Vital Capacity (FVC) was measured, together with heart rate, mean arterial pressure and respiratory rate. At T0 measurements were taken in a random fashion with subjects in upright and in supine position. Subjects were then investigated after surgery in the supine position (T1). Postoperative pain was assessed at T1 using visual analogue scale. Intraoperative variables were also collected. RESULTS: Body Mass Index (BMI) of the investigated subjects was 43.9 ± 5.7 Kg/m2 (range 33.8-60); their age was 40 ± 8 years. All dynamic spirometric data decreased significantly from upright to supine position (P<0.05) and after surgery from 3.07 L (2.77-3.71) to 1.50 (1.15-2.12) (FVC T0 supine vs. T1, P<0.05). Changes of FVC due to body position did not correlate with changes of FVC occurring after surgery (R2=0.105, P=0.081). When subjects were stratified by the median postoperative drop of FVC (45.74%), preoperative (anthropometric and spirometric data), intraoperative (ventilatory settings and hemodynamics) and postoperative (FVC and pain) parameters were similar between groups. The duration of pneumoperitoneum was correlated with the drop of FVC (R2=0.551, P<0.05). CONCLUSION: The derangement of FVC that occurs in obese subjects after gastric banding is not predictable before surgery from anthropometric or spirometric data. The duration of pneumoperitoneum significantly contributes to postoperative impairment of respiratory function.

Increased insulin receptor substrate 2 expression is associated with steatohepatitis and altered lipid metabolism in obese subjects.

OBJECTIVE: The aim of this study was to evaluate whether dysregulation of molecules involved in FOXO1-dependent insulin signaling in the liver is associated with de novo lipogenesis (DNL) and altered lipid metabolism in severely obese subjects. DESIGN: Observational retrospective study. SUBJECTS: We considered 71 obese subjects (age 20-68 years; body mass index (BMI)>40 kg m(-2) or BMI>35 kg m(-2) in the presence of metabolic complications) classified into three groups according to liver histology: normal liver (n=12), simple steatosis (n=27) and nonalcoholic steatohepatitis (NASH; n=32). Key nodes in insulin signaling and gene expression of molecules implicated in insulin-dependent glucoregulatory pathway and DNL were evaluated by quantitative real-time PCR and western blotting. RESULTS: Patients with steatosis had decreased phosphorylation of the insulin kinase AKT1, mediating insulin receptor signaling, and the transcription factor FOXO1, which was therefore more active mediating insulin resistance at transcriptional level. Despite no changes in insulin receptor substrate (IRS)1 mRNA levels, the mRNA and protein levels of the FOXO1 target IRS2 increased progressively with the severity of steatosis from normal liver to NASH. IRS2 expression was correlated with the severity of steatosis, dyslipidemia and liver damage. In patients with NASH, upregulation of IRS2 was associated with preserved activation of AKT2, mediating the stimulating effect of insulin on DNL, and overexpression of its target sterol regulatory element-binding protein 1c (SREBP1c), inducing DNL at transcriptional level. Both FOXO1 and SREBP1c overexpression converged on upregulation of glucokinase, providing substrates for DNL, in NASH patients. CONCLUSION: Differential regulation of IRS1 and IRS2 and of their downstream effectors AKT1 and AKT2 is consistent with upregulation of FOXO1 and may justify the paradoxical state of insulin resistance relative to the glucoregulatory pathway and augmented insulin sensitivity of the liporegulatory pathway typical of steatosis and the metabolic syndrome in obese patients.

Determinants of health-related quality of life in morbid obese candidates to gastric banding.

OBJECTIVE: To analyse determinants of self reported health-related quality of life (HR-QoL) in morbid obese patients candidates to laparoscopic adjustable gastric banding (LAGB). METHODS: Determinants of HR-QoL were investigated in 383 morbid obese patients (82 M and 301 F) with BMI≥40 kg/m² (BMI≥35 kg/m² if complicated obesity) and age 18-60 years. HR-QoL was determined with the SF-36 questionnaire. Determinants of the two summary measures of SF-36 (physical component and mental component) were analysed by stepwise multiple linear regression analysis with age, BMI, physical comorbidites, mental comorbidites and eating behaviour disorders as independent variables. Physical comorbities (diabetes, hypertension, hypertriglyceridemia, low HDL, sleep apnea and osteoarthritis) were coded as present or absent on the basis of simple diagnostic clinical criteria; mental comorbidities (depression) and eating behaviour disorders (binge eating, sweet eating and nibbling) on the basis of an unstructured clinical interview. RESULTS: Mean age was 38.8±10.2 years and mean BMI was 41.5±5.4 kg/m². Scores in the eight SF-36 subscales were lower in women than in men and lower than in the general Italian population. However, 18.4-43.5% of the participants had HR-QoL levels above the normative values, depending on the scale. In both genders, low scores in the mental component of the SF-36 were associated to the presence of depression and eating behaviour disorders and not to physical comorbidities or BMI levels. Low physical self-perceived well being was associated to high BMI levels in men and to depression, hypertension and hypertriglyceridemia in women. CONCLUSION: HR-QoL was poor in morbid obese candidates to LAGB, particularly in women, and was negatively affected more by mental comorbidites and eating behaviour disorders than by physical comorbidities or BMI levels.

Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease.

BACKGROUND/AIMS: The aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance. PATIENTS AND METHODS: 702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients. RESULTS: The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of approximately 70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD. CONCLUSIONS: The ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.

Metabolic parameters after BioEnterics Intragastric Balloon placement in obese patients.

BACKGROUND: BioEnterics Intragastric Balloon (BIB) is a non-invasive, temporary and relatively safe procedure shown to be effective in the short-term treatment of obesity. Nowadays, BIB does not show convincing evidence of significant long-term weight loss, as compared with conventional management, and data regarding changes in metabolic and nutritional parameters are lacking. METHODS: Forty obese patients [11 males, 29 females, age 36.65+/-10.6 yr, body mass index (BMI) 44.9+/-8.9 kg/m2] were evaluated before and 3 and 6 months after BIB placement by assessment of anthropometric and biochemical parameters as well as nutritional habits. RESULTS: Patients showed a significant reduction in weight (-13.2+/-6.5%), BMI (-13.2%), waist circumference (-6.5 cm), and percentage of fat mass (-19.5%), but not fat-free mass. A significant improvement in insulin sensitivity but not in lipid pattern was seen. After BIB insertion, a significant reduction in caloric intake was paralleled by a redistribution of nutrients; in particular, increased lipid (12.8%) and decreased carbohydrate (-11.7%) percentage, but not absolute intake was observed. CONCLUSION: These data show that BIB improves anthropometric parameters, with reduction of fat mass and preservation of fat-free mass, as well as insulin resistance, but not other metabolic features. The observed change in dietary habits, with a relative increase in lipid intake, once BIB is removed, might favor body weight regain and impact negatively on body weight composition and the other traits of the metabolic syndrome.

An unusual complication of gastric banding: recurrent small bowel obstruction caused by the connecting tube.

Laparoscopic adjustable gastric banding (LAGB) is a widely performed surgical procedure for morbid obesity. The application of this mini-invasive approach has given the benefits of shorter hospital stay, less postoperative pain and quicker functional recovery. LAGB complications are related either to the access-port, such as port-site infection or tubing disconnection, or to the band, such as band slippage, pouch dilatation, or intragastric migration. We report a case of recurrent small bowel obstruction caused by the connecting tube around a jejunal loop, in a woman who had under-gone LAGB 3 years before. The diagnosis was difficult to establish because the clinical history and examination were non-specific. A 3-dimensional CT scan was needed to explain the cause of the recurrent abdominal pain, and the small bowel loop was freed from the connecting tube at laparoscopy.

Iatrogenic injury in videolaparoscopic cholecystectomy: difficult surgical correction biliary tract.

Two cases of biliary tract serious lesions during videolaparoscopic cholecystectomy are reported. In the first case of lithiasic cholecystitis there had been a complete damage of the common biliary duct; in the second case there had been a double main biliary duct binding with removal of a biliary tract segment. In both cases a biliary confluence-jejunal anastomosis with Roux-en-Y loop was made up. In the first one the operation was difficult because of the main bile duct's fragility and modest expansion. In the second one the presence of a secondary biliary duct in gallbladder fossa not recognized, but drained outside with a common drainage placed during the operation prevented appearance of jaundice with dilatation of biliary ducts. It was heavily conditioned performing confluence-jejunal anastomosis with Roux-en-Y loop. The post-operative course was characterized by appearance of an external biliary fistula which has spontaneously disappeared. One year later, neither of the two patients had any stenosis or cholangitis problems.

The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors.

Post-thrombotic syndrome (PTS) in young women may cause impairment in the quality of life of otherwise healthy people. We aimed to evaluate the prevalence of PTS and its risk factors in young women. We evaluated 51 women with at least one previous episode of symptomatic, objectively documented deep vein thrombosis (DVT) before the age of 40. Each patient asked for symptoms had a physical examination, a color-coded Doppler ultrasonography of the superficial and deep venous system and an extensive laboratory evaluation for the congenital and acquired coagulation abnormalities predisposing to thrombosis. The median follow-up was 47 months. PTS was absent in 37%, mild in 55%, moderate in 4% and severe in 4% of patients. No correlation was found between PTS and the presence of coagulation abnormalities, triggering factors, recurrences, use of elastic stockings for one year after DVT, degree of recanalization, presence of superficial reflux. Patients with a body mass index (BMI) >22 had an adjusted ratio of 4.7 (98 CI: 1.0-23.3) of developing the PTS. Though severe and moderate PTS are rare, mild PTS is present in the majority of young women after DVT. A BMI >22 is associated to the risk of developing PTS. Attempt to control weight in women after DVT should be considered and studied to prevent PTS.

[Treatment of acute symptoms of hemorrhoid disease with high-dose oral O-(beta-hydroxyethyl)-rutosides]. / Trattamento dei sintomi acuti della malattia emorroidaria con O-(beta-idrossietil)-rutosidea ad alte dosi per via orale.

The pharmacological treatment is widely used in the therapy of haemorrhoids. An efficient treatment is particularly useful in case of haemorrhoids of 2nd, 3rd and 4th degree, when phlogosis, oedema and pain are present. Forty patients were treated with either O-(beta-hydroxyethyl)-rutosides (4 g/day orally) or placebo in a double blind randomized comparative trial. The groups of treatment were homogeneous. O-(beta-hydroxyethyl)-rutosides induced a statistically significant reduction of pain and bleeding; placebo did not induce any significant improvement. Tolerability was good and similar for both treatments. It has never been necessary to stop treatment for side effects. The results obtained in this study confirm the usefulness on administering an oral treatment, and not only a local treatment, to patients with acute symptoms of haemorrhoids, both in case of intermittent treatment and in case it is used to prepare quickly the patient for surgery.

Effectiveness of defibrotide for prophylaxis of deep venous thrombosis after general surgery: a double-blind, placebo-controlled clinical trial.

The prophylactic activity of defibrotide, a new extractive antithrombotic-thrombolytic agent of mammalian origin, was assessed by detection of deep venous thrombosis (DVT) in patients who underwent general elective surgery. 120 patients (aged 25-85 years, mean 55.6) were randomly assigned to defibrotide (60 patients) or to placebo (60 patients). The two groups were homogeneous for age, sex and risk factors for DVT. The active drug was given intravenously 200 mg four times a day, starting the day before the operation and then for the following 7 days. To detect DVT, 125I-fibrinogen was used, by conventional methods. Defibrotide reduced the frequency of DVT to 4/60 (7%) from 16/60 (27%) in the placebo group. The difference was highly significant (p less than 0.01). Neither side effects nor anticoagulant activity were observed. On the basis of this evidence, defibrotide may be considered an effective and well-tolerated drug for prevention of DVT.

Fibrinolytic shut-down after surgery: impairment of the balance between tissue-type plasminogen activator and its specific inhibitor.

In nine patients with non-malignant diseases undergoing major upper abdominal surgery, the mechanism of the postoperative fibrinolytic shut-down was investigated because of its potential significance for postoperative deep vein thrombosis by employing new and specific methods for assessing and stimulating the fibrinolytic system. The shut-down was found to result from an impairment of the balance between tissue-type plasminogen activator, t-PA, and its recently discovered fast-acting inhibitor. In this balance, the t-PA antigen concentrations both in resting conditions and after stimulation evoked by desamino-D-arginine vasopressin (DDAVP) were found to be unchanged by surgery. However, there was a significant postoperative increase in t-PA inhibitor levels. The release of t-PA under the stimulus of DDAVP infusion overcame the postoperative shut-down of t-PA activity. However, DDAVP infusion was associated with potentially unfavourable increases in the Factor VIII/von Willebrand factor complex. The discovery of increased t-PA inhibitor in the postoperative period opens new possibilities for a rational approach to reduce or abolish the postoperative fibrinolytic shut-down.

An improved method for measuring red blood cell filterability.

A new simple method for measuring red blood cell (RBC) filterability by weighing the amount of RBC filtered through micropore membranes is described. Red cell filterability by weighing (RCFW) is determined on washed RBC resuspended in phosphate-buffered saline (PBS) at low (5%) hematocrit. The filtration step is performed using gravity alone and the amount of the filtered suspension is referred to the filtration of PBS alone through the same membrane. The new method shows a reproducibility better than that of the widely used Dormandy technique, with a lower coefficient of variation (5.3 vs. 7.2%) and a higher sensitivity to artificially hardened RBC.

Effects of buflomedil in a group of patients with chronic peripheral arterial diseases. Clinical and hemorheological evaluation.

Fifty-three patients suffering from chronic arterial diseases of the lower limbs were treated with buflomedil, a vasoactive drug with vasodilating and hemorheological action on the microcirculation. The patients suffered from pain on walking or pain at rest; they were given 300 mg buflomedil orally twice a day for a period of about 2 months. The walking distance before pain onset was checked in all patients before and after the trial. Blood and plasma viscosity, haematocrit and fibrinogen and a Doppler velocimetry were also recorded. A significant improvement of the walking distance before pain onset was observed in nearly all patients, and in most patients the morphology of the velocity waves improved, too. No clear correlation between the positive clinical results and the hemorheological parameters studied could be observed.