Early Changes in Postprandial Gallbladder Emptying in Morbidly Obese Patients Undergoing Roux-en-Y Gastric Bypass: Correlation with the Occurrence of Biliary Sludge and Gallstones

Gallstones have been frequently diagnosed after Roux-en-Y gastric bypass (RYGBP). Gallbladder stasis associated with duodenal exclusion may play a role in their pathogenesis. Gallbladder emptying was studied before and on the 30th and 31st postoperative days (POD) after RYGBP in 20 morbidly obese patients. Gallbladder volume after fasting and every 15 min during a 2-h period following administration of a standard liquid meal was determined by sonography. On the 31st POD, the meal was administered through the gastrostomy in order to promote its transit through the duodenum. Fasting volume (FV), maximum ejection fraction (Max EF), and residual volume (RV) were determined. Biliary sludge and calculi were investigated after 1 and 6 months, respectively. FV was 39.4 +/- 20.2 ml, 50.1 +/- 22.7 ml, and 47.9 +/- 23.4 ml, respectively, for the preoperative and two postoperative assessments (P = 0.09). RV was 7.6 +/- 8.7 ml, 25.1 +/- 20.0 ml, and 24.6 +/- 20.9 ml; and Max EF was 80.5 +/- 20.9%, 54.3 +/- 21.4%, and 50.5 +/- 29.0%, respectively, for the pre-, postoral, and postgastrostomy infusion measurements. There was only a significant difference between the preoperative value and the two postoperative values (P < 0.001). Biliary sludge was detected in 65% of the patients and 46% of them subsequently developed gallstones. Gallbladder emptying became significantly compromised after RYGBP. This impairment was unrelated to duodenal exclusion but it was associated with biliary sludge and stone formation.

Tessier No. 4 Facial Cleft: Evolution of Surgical Treatment in a Large Series of Patients

Background: Tessier no. 4 facial cleft is a rare, complex, and challenging craniofacial malformation. The present article aims to describe different clinical features evidenced in 21 cases of this malformation, discussing a 20-year experience with and evolution of its surgical treatment. Methods: Some demographic data, clinical features, and reconstructive results were evaluated retrospectively. These patients have been evaluated and treated in three specialized Brazilian craniofacial centers. Nineteen were already operated on, with a mean follow-up of 3.5 years (range, 1 to 20 years). Results: Sex distribution showed a male prevalence (2: 1). The average age of initial treatment was 5.4 years. Four cases were affected on the right side of the face, seven on the left, and 10 bilaterally. Six patients had other rare associated facial clefts, including nos. 5 (three patients), 7, 9, and 10. Cleft upper lip was evidenced in all patients, and maxillary hypoplasia was present in five and maxilla cleft in eight. Lower eyelid coloboma was seen in almost every case (19 patients); 10 of these had medial canthus dystopia. Four patients had amniotic bands in the limbs. Surgical repair was individualized to each patient. Surgical experience gained with these patients allowed the authors to develop some technical modifications, which have improved aesthetic results, camouflaging scars into natural folds and anatomical units, without compromising functional outcomes. Conclusions: The great majority of Tessier no. 4 facial clefts can be appropriately treated using local flaps. Classic techniques are extremely useful, but long-term results could be improved if the technical modifications described were adopted. (Plast. Reconstr. Surg. 122: 1505, 2008.)

Age, invasive ventilatory support and outcomes in elderly patients admitted to intensive care units

Objective: to determine the relationship between age and in-hospital mortality of elderly patients, admitted to ICU, requiring and not requiring invasive ventilatory support. Design: prospective observational cohort study conducted over a period of 11 months. Setting: medical-surgical ICU at a Brazilian university hospital. Subjects: a total of 840 patients aged 55 years and older were admitted to ICU. Methods: in-hospital death rates for patients requiring and not requiring invasive ventilatory support were compared across three successive age intervals (55-64; 65-74 and 75 or more years), adjusting for severity of illness using the Acute Physiologic Score. Results: age was strongly correlated with mortality among the invasively ventilated subgroup of patients and the multivariate adjusted odds ratios increased progressively with every age increment (OR = 1.60, 95% CI = 1.01-2.54 for 65-74 years old and OR = 2.68, 95% CI = 1.58-4.56 for >= 75 years). For the patients not submitted to invasive ventilatory support, age was not independently associated with in-hospital mortality (OR = 2.28, 95% CI = 0.99-5.25 for 65-74 years old and OR = 1.95, 95% CI = 0.82-4.62 for >= 75 years old). Conclusions: the combination of age and invasive mechanical ventilation is strongly associated with in-hospital mortality. Age should not be considered as a factor related to in-hospital mortality of elderly patients not requiring invasive ventilatory support in ICU.

Thalidomide treatment down-regulates SDF-1 alpha and CXCR4 expression in multiple myeloma patients

The chemokine stromal-derived factor-1 alpha (SDF-1 alpha) and its receptor CXCR4 are critically involved in directional migration and homing of plasma cells in multiple myeloma. Here, we show that the expression of SDF-1 alpha and CXCR4 was significantly down-regulated in patients treated with thalidomide (n = 10) as compared to newly diagnosed MM patients (n = 31) and MM patients treated with other drugs (n = 38). SDF-1 alpha and CXCR4 expression was also significantly decreased in a RPMI 8226 cell line treated with 10 and 20 mu mol/L of thalidomide. Our findings indicate that thalidomide therapy induces down-regulation of CXCR4 and its ligand SDF-1 alpha in multiple myeloma. (c) 2008 Elsevier Ltd. All rights reserved.

Altered adhesion molecules expression on peripheral blood mononuclear cells from patients with systemic sclerosis and clinical correlations

The aim of the study was to evaluate the expressions of adhesion molecules (AM) on peripheral blood mononuclear cells (PBMNC) from systemic sclerosis (SSc) patients. Thirty-one SSc patients (ACR) and 20 normal subjects were selected for the study. PBMNC were analyzed for LFA-1 alpha, LFA-1 beta, ICAM-3, ICAM-1, and l-selectin expressions. ICAM-3 expression was decreased while ICAM-1 was increased on SSc PBMNC, compared to controls (p = 0.04 and 0.003, respectively). A positive association was found between LFA-1 alpha (r = 0.37, p = 0.03), LFA-1 beta (r = 0.38, p = 0.002), ICAM-3 (r = 0.42, p = 0.01), and l-selectin (r = 0.38, p = 0.03) expressions and greater number of immunosuppressive drugs taken by SSc patients. Also, anti-centromeric positive SSc patients had lower expressions of LFA-1 alpha, LFA-1 beta, ICAM-3, and l-selectin. Lower expression of ICAM-3 and higher expression of ICAM-1 suggest that AMs may be involved in the pathogenesis of scleroderma.

Mutational analysis of the necdin gene in patients with congenital isolated hypogonadotropic hypogonadism

Context: Necdin activates GNRH gene expression and is fundamental for the development, migration, and axonal extension of murine GNRH neurons. In humans, necdin plays a potential role in the hypogonadotropic hypogonadism phenotype in patients with Prader-Willi syndrome. Aim: To investigate necdin gene (NDN) variants in patients with isolated hypogonadotropic hypogonadism (IHH). Patients and methods: We studied 160 Brazilian patients with IHH, which includes 92 with Kallmann syndrome and 68 with normosmic IHH. Genomic DNA was extracted and the single NDN exon was amplified and sequenced. To measure GNRH transcriptional activity, luciferase reporter plasmids containing GNRH regulatory regions were transiently transfected into GT1-7 cells in the presence and absence of overexpressed wild-type or mutant necdin. Results: A heterozygous variant of necdin, p.V318A, was identified in a 23-year-old male with Kallmann syndrome. The p.V318A was also present in affected aunt and his father and was absent in 100 Brazilian control subjects. Previous FGFR1 gene analysis revealed a missense mutation (p.P366L) in this family. Functional studies revealed a minor difference in the activation of GNRH transcription by mutant protein compared with wild type in that a significant impairment of the necdin protein activity threshold was observed. Conclusion: A rare variant of necdin (p.V318A) was described in a family with Kallmann syndrome associated with a FGFR1 mutation. Familial segregation and in vitro analysis suggested that this non-synonymous variant did not have a direct causative role in the hypogonadism phenotype. NDN mutations are not a frequent cause of congenital IHH.

Uptake by breast carcinoma of a lipidic nanoemulsion after intralesional injection into the patients: A new strategy for neoadjuvant chemotherapy

Objective. Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors and may carry drugs directed against neoplastic tissues. Use of the nanoemulsion decreases toxicity of the chemotherapeutic agents without decreasing the anticancer action. Currently, the hypothesis was tested whether the nanoemulsion concentrates in breast carcinoma tissue after locoregional injection. Methods. Three different techniques of injection of the nanoemulsion were tested in patients scheduled for surgical treatment: G1 (n=4) into the mammary tissue 5 cm away from the tumor; G2 (n=4) into the peritumoral mammary tissue; G3 (n=6) into the tumoral tissue. The nanoemulsion labeled with radioactive cholesteryl oleate was injected 12 h before surgery; plasma decay of the label was determined from blood samples collected over 24 h and the tissue fragments excised during the surgery were analyzed for radioactivity uptake. Results. Among the three nanoemulsion injection techniques, G3 showed the greatest uptake (data expressed in c.p.m/g of tissue) by the tumor (44,769 +/- 54,749) and by the lymph node (2356 +/- 2966), as well as the greatest concentration in tumor compared to normal tissue (844 +/- 1673). In G1 and G2, uptakes were, respectively, tumor: 60 +/- 71 and 843 +/- 1526; lymph node: 263 +/- 375 and 102 +/- 74; normal tissue: 139 +/- 102 and 217 +/- 413. Conclusions. Therefore, with intralesional injection of the nanoemulsion, a great concentration effect can be achieved. This injection technique may be thus a promising approach for drug-targeting in neoadjuvant chemotherapy in breast cancer treatment. (C) 2008 Published by Elsevier Inc.

Prognostic impact of diffuse large B-cell lymphoma subgroups in patients undergoing autologous SCT

A total of 53 patients aged 18-60 years with highintermediate or high-risk diffuse large B-cell lymphoma (DLBCL) were evaluated to analyze the impact of the cell of origin. Of 53 patients, 16 underwent autologous SCT (ASCT) in first remission and the rest received conventional chemotherapy. Immunohistochemistry was evaluated in 47 cases 17 were of germinal center (GC) origin and 30 were of non-GC origin. There was no survival difference between the two groups. Overall survival (OS) and disease-free survival (DFS) at 3 years were 93 and 83%, respectively, for the 14 patients who underwent ASCT. Their DFS was significantly better than that of patients who achieved CR but did not undergo ASCT. We conclude that ASCT is safe and improves the DFS of high-intermediate and high-risk DLBCL, regardless of the cell of origin. This observation should be confirmed in a larger study.

Centrilobular Fibrosis: An Underrecognized Pattern in Systemic Sclerosis

Background: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. Objectives: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). Methods: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. Results: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 +/- 16.31%; DLCO: 61.66 +/- 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). Conclusions: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach. Copyright (C) 2008 S. Karger AG, Basel

SINGLE MEASUREMENTS OF C-REACTIVE PROTEIN AND DISEASE ACTIVITY SCORES ARE NOT PREDICTORS OF CAROTID ATHEROSCLEROSIS IN RHEUMATOID ARTHRITIS PATIENTS

Background: Although inflammation has a defined role in the pathogenesis of atherosclerosis, the link between rheumatoid arthritis (RA) parameters of disease activity and atherosclerotic findings are not defined. Objective: To investigate the association between subclinical carotid atherosclerosis and clinical/laboratorial parameters of RA systemic inflammatory activity. Methods: Seventy-one RA patients were consecutively selected and compared to 53 healthy controls. Smoking, diabetes and hypertension were excluded, as well as the use of statins or fibrates. B-mode carotid ultrasound was performed in all subjects. CRP, ESR and fibrinogen were determined in both groups. Clinical assessment of RA activity included DAS 28 and SDAI. Correlation between plaques and intima-media thickness (IMT) of common carotid arteries and inflammatory parameters was evaluated. Results: Carotid plaques were more prevalent in RA patients than in controls (14.1% vs. 1.9 %, p=0.02) and marginally increased IMT was observed (0.72 +/- 0.17 vs. 0.67 +/- 0.15mm, p=0.07). RA patients with plaques had older age (p=0.001) and increased IMT (p<0.001), but low SDAI (p=0.025) compared to those without plaques. RA patients with plaques had also longer disease duration, although this difference did not reach statistical significance (p=0.06). No significant correlations were found between IMT and ESR (p=0.80), CRP (p=0.75), fibrinogen (p=0.94), HAQ (p=0.89) and DAS 28 (p=0.13). Conclusions: Carotid atherosclerosis is more frequently detected in RA but its prevalence was not correlated with isolated inflammatory markers measurement or noncumulative activity scores. These findings reinforce the need to evaluate subclinical atherosclerosis in RA patients, and to find predictors of atherosclerotic lesions.

Conversion to Sirolimus in Kidney-Pancreas and Pancreas Transplantation

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21.%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .01.8). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.

Factors affecting hematopoietic progenitor cell mobilization: An analysis of 307 patients

We reviewed the data of 307 patients treated with autologous bone marrow transplantation with the aim to identify factors associated with poor hematopoietic stern cell (HSC) mobilization after administration of cyclophosphamide and granulocyte-colony stimulating factor. Success in mobilization was defined when >= 2.0 x 10(6) CD34+ cells/kg weight could be collected with <= 3 leukapheresis procedures. Success was observed in 260 patients (84.7%) and nonsuccess in 47 patients (15.3%). According to the stepwise regression model: diagnosis, chemotherapy load, treatment with mitoxantrone and platelet count before mobilization were found to be independent predictive factors for HSC mobilization. These results could help in the previous recognition of patients at risk for non response to mobilization and allow to plan an alternative protocol for this group of patients. (C) 2008 Elsevier Ltd. All rights reserved.

Dietary salt restriction increases plasma lipoprotein and inflammatory marker concentrations in hypertensive patients

Background: Dietary salt restriction has been reported to adversely modify the plasma lipoprotein profile in hypertensive and in normotensive subjects. We investigated the effects of the low sodium intake (LSI) on the plasma lipoprotein profile and on inflammation and thrombosis biomarkers during the fasting and postprandial periods. Methods: Non-obese, non-treated hypertensive adults (n=41) were fed strictly controlled diets. An initial week on a control diet (CID, Na=160 mmol/day) was followed by 3 weeks on LSI (Na=60mmol/day). At admission and on the last day of each period, the 24-h ambulatory blood pressure was monitored and blood was drawn after an overnight fasting period and after a fat-rich test meal. Results: The dietary adherence was confirmed by 24-h urinary sodium excretion. Fasting triglyceride (TG), chylomicron-cholesterol, hsC-reactive protein (CRP), tumor necrosis factor-a (TNF-alpha). interleukin-6 (IL-6) concentrations, renin activity, aldosterone, insulin, and homeostasis model assessment insulin resistance (HOMA-IR) Values were higher, but non-esterified fatty acids (NEFA) were lower on LSI than on CD. For LSI, areas under the curve (AUC) of TG, chylomicron-cholesterol, apoB and the cholesterol/apoB ratio were increased, whereas AUC-NEFA was lowered. LSI did not modify body weight, hematocrit, fasting plasma cholesterol, glucose, adiponectin, leptin, fibrinogen and factor VII (FVII), and AUC of lipoprotein lipase and of lipoprotein remnants. Conclusion: LSI induced alterations in the plasma lipoproteins and in inflammatory markers that are common features of the metabolic syndrome. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Anti-Lipoprotein Lipase Antibodies in Patients with Hypertriglyceridemia without Associated Autoimmune Disease

Background: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken. Objectives: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease. Methods: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of comorbidities, fasting lipid profile and anti-LPL antibodies. Results: Mean patient age was 55 +/- 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 +/- 3.6 kg/m(2); 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 +/- 111 mg/dl. High-density lipoprotein was 42.6 +/- 15.4 mg/dl, low-density lipoprotein 110.7 +/- 42.4 mg/dl and very low-density lipoprotein 48 +/- 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels. Conclusions: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.

Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: Postprandial effect on circulating gut peptides, glucose and insulin

Gut hormones Ighrelin, peptide YY (PYY) and ghrcagon-like peptide-1 (GLP-1)] are an important group of hormones that target appetite control. They are released from endocrine L cells of the small bowel in proportion to the volume, components and calories in a meal. In the current study, 20 g of gelatin (flavored and sweetened) were given to obese patients (n=12) and lean subjects (n=10). Subsequently, plasma samples were collected at-30-minute intervals rip to 180 minutes and glucose, insulin, PYY, GLP-1 and ghrelin were assayed using specific and sensitive immunofluorometric and radioimmunoassays. As expected, obese patients had normal serum glucose levels, higher serum insulin, and lower plasma concentration of ghrelin at all times compared to lean subjects. GLP-1 plasma levels were significantly elevated at 60 minutes, peaking at 120 minutes in obese patients and lean subjects. As a consequence, there was a significant rise in serum insulin levels with a significantly higher peak level at 60 min (obese) and 30 min (lean). There were no significant changes in PYY plasma concentrations and no correlation was found between body mass index and concentrations of ghrelin, PYY and GLP-1 in the group of obese patients. In conclusion, a single gelatin meal induces a rise in plasma GLP-1 followed by an increase in serum levels of insulin. These findings may be applied to maximize satiety in obese patients as a means of improving adherence to calorie-controlled diets as well as provide better control of diabetic patients.