<Emphasis Type="Italic">FABP2</Emphasis>, <Emphasis Type="Italic">LEPR223</Emphasis>, <Emphasis Type="Italic">LEP656</Emphasis>, and <Emphasis Type="Italic">FTO</Emphasis> Polymorphisms: Effect on Weight Loss 2 Years After Bariatric Surgery

Purpose

Differences in weight loss outcomes after bariatric surgery may be related to individual preoperative characteristics. The aim of this study was to evaluate the potential effect of fatty acid binding protein-2 (rs1799883), leptin receptor (LEP223, rs1137101 and LEP656, rs1805094), and fat mass and obesity-related (rs9939609) genotypes on weight loss 2 years after bariatric surgery in Brazilian patients.

Materials and Methods

Prospective observational study involving 105 patients (lost to follow-up, 25.7%). In the preoperative period, patients were clinically evaluated and a fasting blood sample for genetic analysis (by real-time DNA amplification technique) was collected. From the patient’s medical records, follow-up weight loss (3, 6, 12, 24 months) was obtained. Percentage of excess weight loss (%EWL) was examined by pairwise comparison across the polymorphisms.

Results

At baseline, the mean weight was 127.5 (23.3) kg and age 43.1 (10.9) years old. The %EWL was significant over time (p?<?0.01). Only the LEP223 genotype showed association (p?<?0.01). Up to 6 months after surgery, no differences were observed. At 12 months, a significant difference (p?=?0.03) between AA (n?=?19) and GG (n?=?34) groups was observed, with 76.5% EWL versus 52.0%, respectively. This difference remained at 24 months. Other genotypes did not present any significant association.

Conclusions

There is a different evolution of weight loss in carriers of the LEP223 after bariatric surgery. The AA genotype seems to be associated with a higher weight loss. However, this pattern was evident only at 12 months after surgery.

     

Does simvastatin stimulate bone formation <Emphasis Type="Italic">in vivo</Emphasis>?

Background  

Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS) to the known anabolic effects of PTH in an established model of ovariectomized (OVX) Swiss-Webster mice.     

Do mutations in <Emphasis Type="Italic">COL4A1</Emphasis> or <Emphasis Type="Italic">COL4A2</Emphasis> cause thin basement membrane nephropathy (TBMN)?

Thin basement membrane nephropathy (TBMN) is the commonest cause of persistent glomerular haematuria and often presents in childhood. Only 40% of affected individuals have mutations identified in the COL4A3 and COL4A4 genes, but mutations in the genes for other COL4A isoforms also result in thinned membranes in humans (COL4A5) and mice (COL4A1). This study examined whether COL4A1/COL4A2 represented a further genetic locus for TBMN. Nine families with TBMN in whom haematuria did not segregate with COL4A3/COL4A4, were examined for linkage to COL4A1/COL4A2 using five micro-satellite markers. In addition, index cases from these families plus a further 14 unrelated individuals with TBMN that was not due to COL4A3 or COL4A4 mutations (n=23) were screened for mutations in each of the 52 exons of COL4A1 and the 47 exons of COL4A2 using single stranded conformational analysis (SSCA). DNA samples that demonstrated bandshifts were sequenced. Haplotype analysis demonstrated that haematuria segregated with the COL4A1/COL4A2 locus in only two small families (2/9, 22%). No definite COL4A1 or COL4A2 mutations were identified in the 23 unrelated individuals with TBMN although novel polymorphisms were demonstrated. This study indicates that COL4A1/COL4A2 does not represent a further major genetic locus for TBMN.     

Is <Emphasis Type="Italic">Enterobius vermicularis</Emphasis> infestation associated with acute appendicitis?

Purpose

Enterobius vermicularis might be seen in specimens of patients who underwent surgery due to acute appendicitis. There is still debate as to E. vermicularis infestation causes acute appendicitis. The primary aim of this study is to determine the incidence of E. vermicularis infestation, and the secondary aim is to determine the possible role of E. vermicularis in pathogenesis of appendicitis as well as the adequacy of demographic data and laboratory values in predicting infestation preoperatively.

Methods

A retrospective investigation was conducted with all patients who underwent appendectomy due to acute appendicitis in a secondary care center. Patients with E. vermicularis were compared with 24 controls that underwent appendectomy during the same time period. Demographic data, preoperative white blood cell (WBC) count, eosinophil counts, and histopathological findings for both groups were analyzed and compared.

Results

Enterobius vermicularis was detected in the appendectomy materials in 9 of 1446 patients (0.62 %). Histopathologically, only one of nine patients had acute appendicitis while the others were diagnosed with lymphoid hyperplasia. There were no statistically significant differences between the groups except WBC count. However, the WBC count was significantly (p < 0.05) lower in the group which was detected E. vermicularis.

Conclusions

Enterobius vermicularis is rarely associated with the histopathological findings of acute appendicitis. Also eosinophil count and elevation of white blood counts are inadequate for predicting preoperative E. vermicularis.

     

Two Single Nucleotide Polymorphisms in the <Emphasis Type="Italic">CYP</Emphasis>17 and <Emphasis Type="Italic">COMT</Emphasis> Genes—Relation to Bone Mass and Longitudinal Bone Changes in Postmenopausal Women with or without Hormone Replacement Therapy

Sex steroids are important physiologic regulators of bone mass, and genes regulating sex steroid production and metabolism are obvious as candidate genes for osteoporosis susceptibility. We present data from a study of 1795 recent postmenopausal women, assigned to either hormone replacement therapy (HRT) or no treatment and followed for 5 years. The association between bone mass measurements and two single nucleotide polymorphisms, a T (A1) to C (A2) transition in the 5-UTR of the cytochrome P450c17 (CYP17) gene and a G (Val) to A (Met) transition in exon 4 of the catechol-O-methyltransferase (COMT) gene, was evaluated. Association with CYP17 genotype was modified by body mass index (BMI). In lean women, individuals homozygous for the CYP17 A2 allele were 1 cm shorter and had lower baseline BMD (bone mineral density), BMC, and CSA (cross sectional area) in the spine and femoral neck than did other women (BMD spine A2A2: 0.975 g/cm² versus 1.011 g/cm² in A1A1 + A1A2, P = 0.002). Conversely, an adverse association with A2A2 and bone loss over 5 years seemed present only in overweight women, but differences were small. Response to HRT was not dependent on CYP17 genotype. COMT genotype was not associated with bone mass at baseline, bone loss in untreated women, or response to HRT. In conclusion, the A2 allele of the CYP17 T²⁷-C polymorphism is associated with reduced bone mass and bone size in lean perimenopausal women, whereas high BMI protects against this negative association. The COMT G¹⁹⁴⁷-A polymorphism is not associated with bone parameters in this study.Presented in part as an abstract for poster presentation at the 2nd International Workshop on the Genetics of Bone Metabolism and Disease, Davos, Switzerland, February 2003     

Is the <Emphasis Type="Italic">E</Emphasis>/<Emphasis Type="Italic">V</Emphasis><Subscript>p</Subscript> index useful for evaluating prognosis in chronic heart failure with atrial fibrillation? A pilot study

Background  

The ratio of transmitral peak E wave velocity to color flow propagation velocity (E/V _p index) has proved to be a significant predictor of prognosis in cardiac diseases with sinus rhythm. However, its usefulness in patients with atrial fibrillation (AF) and heart failure has not yet been established. The aim of this study was to determine the feasibility of using the E/V _p index for the prediction of mortality and heart failure hospitalization in this group.     

Anatomically Shaped Breast Prosthesis <Emphasis Type="Italic">in Vivo</Emphasis>: A Change of Dimension?

Background In addition to the already existing round cohesive gel-filled breast prostheses, anatomically shaped breast prostheses were introduced in 1990 to provide a more natural shape to the augmented or reconstructed breast. To date, however, it is unclear whether the anatomic configuration of the prostheses is maintained after subpectoral implantation. Recently, a three-dimensional (3D) magnetic resonance imaging (MRI) technique became available, offering a precise visualization of the prosthesis in vivo. Using this 3D MRI technique, this study aimed to compare the shape of commercially available round and anatomically shaped silicone gel-filled breast prostheses before and after implantation. Methods Using 3D MRI, 6 conventionally round and 12 symmetrically shaped silicone gel-filled prostheses were scanned in vitro. Scans were made in vivo 6 weeks after subpectoral implantation of these prostheses in nine patients. The in vivo 3D images were compared with the in vitro 3D images. Results Overall, a 3.5% decrease in projection was found on the in vivo images, as compared with the in vitro images. On the craniocaudally oriented images, a slight lateral shift of the cohesive gel was observed in the majority of the prostheses. Inamed Style 510 prostheses showed the best in vivo preservation of their configuration. Conclusions The results show that both the round and the anatomically shaped silicone prostheses in vivo largely maintain their original in vitro configuration after subpectoral implantation. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Acute Mesenteric Ischaemia—<Emphasis Type="Italic">An Indian Perspective</Emphasis>

In Western countries, acute mesenteric ischaemia is commonly due to arterial occlusion and occurs in patients who are usually in their seventh decade. A venous cause for intestinal gangrene has been reported in only about 10 %. We examined whether this was so in India and compared the clinical features of patients with mesenteric arterial and venous ischaemia and relate these to their ultimate prognosis. We studied retrospectively, the records of all patients admitted or referred to the department with a diagnosis of acute mesenteric ischaemia between January 1997 and October 2012, noting their demographic details and mode of presentation, the results of preoperative imaging and blood investigations, the extent of bowel ischaemia, and the length of bowel that was resected at operation and their outcome. There were 117 patients, 85 males and 32 females whose median age was 53 years. Mesenteric venous thrombosis was seen in 56 patients (48 %) and mesenteric arterial occlusion in 61 (52 %). Forty six patients died (39 %); 15 with venous occlusion (27 %) and 31 with arterial occlusion (51 %). Compared to patients with arterial occlusion, the patients with venous obstruction were younger, had a longer duration of symptoms, were less frequently hypotensive at presentation, had higher platelet counts, had a shorter length of bowel resected, had fewer colonic resections and had a lower mortality. Other predictors of mortality on multivariate analysis were a longer duration of symptoms, lower serum albumin and higher creatinine levels at presentation and a shorter length of residual bowel. In India, acute mesenteric ischaemia in tertiary care centres is due to venous thrombosis in almost half of the patients who are at least a decade younger than those in the West. Significant predictors of mortality include low serum albumin and raised creatinine levels, a shorter residual bowel length and an arterial cause for mesenteric ischaemia.     

Developmental dysplasia of the hip in cerebral palsy<Emphasis Type="Bold">–</Emphasis>surgical treatment

Developmental dysplasia of the hip (DDH) in cerebral palsy (CP) is very rare, and very little clinical data is available. We have analysed the results of open reduction of the hip (Howorth), acetabuloplasty (Salter, Pemberton), pelvic osteotomy (Chiari) and femoral osteotomy in the treatment of the DDH in CP patients. Radiographic assessment was based on the Severin grading classification system and measurements of migration percentage (MP) before and after surgery. Clinical results were analysed using the Ponsetti classification system in ambulatory patients. A total of 45 hips in 31 patients were treated surgically. The average age of the patients was 5.2 years (range: 2-16 years). The average follow-up was 9.6 years (range: 3-28 years). Analysis of the radiographic results according to Severin placed 35 hips (77.8%) in groups 1 and 2 and ten hips (22.2%) in groups 3 and higher. The average preoperative MP value was 78.7% and the average postoperative MP was 15.2%. Redislocation occurred in three hips. Clinical results were disappointing: based on Ponsetti assessment 14 hips (36.8%) were classified in the first three groups and 24 hips (63.2%) in the last three groups. This analysis suggests that these surgical procedures could be applied in treating DDH in CP.     

Promoter methylation status of <Emphasis Type="BoldItalic">hMLH1</Emphasis>, <Emphasis Type="BoldItalic">hMSH2</Emphasis>, and <Emphasis Type="BoldItalic">MGMT</Emphasis> genes in colorectal cancer associated with adenoma–carcinoma sequence

Purpose  

Epigenetic silencing of the DNA mismatch repair genes has been poorly described in colorectal carcinomas showing the classic adenoma–carcinoma pathway of carcinogenesis. The aim of this study was to investigate the methylation status of MutL homolog 1 (hMLH1), MutS homolog 2 (hMSH2), and O-6-methylguanine-DNA methyltransferase (MGMT) in a series of colorectal carcinomas that contain both adenomas and carcinomas.     

The Effect of <Emphasis Type="Italic">N</Emphasis>ω-Nitro-<Emphasis Type="SmallCaps">l</Emphasis>-Arginine Methyl Ester and <Emphasis Type="SmallCaps">l</Emphasis>-Arginine on Lung Injury Induced by Abdominal Aortic Occlusion–Reperfusion

Purpose

The aim of this study was to examine the effects of Nω-nitro-l-arginine methyl ester (l-NAME) and l-arginine on lung injury after aortic ischemia–reperfusion (IR).

Methods

Twenty-four Wistar-Albino rats were randomized into four groups (n = 6) as follows: Control (sham laparotomy), Aortic IR (30?min ischemia and 120?min reperfusion), l-Arginine (intraperitoneal 100?mg?kg<συπ>?1 live weight)+aortic IR, and l-NAME (intraperitoneal 10?mg?kg<συπ>?1 live weight)+aortic IR. In the lung specimens, the tissue levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) were measured and a histological examination was done.

Results

Aortic IR increased MDA, VEGF, and NO. l-Arginine further significantly increased MDA and NO, and decreased VEGF (P < 0.05 vs aortic IR). l-NAME significantly decreased MDA and NO (P < 0.05 vs l-arginine+aortic IR) and increased VEGF (P < 0.05 vs other groups). A histological examination showed the aortic IR to significantly increase (P < 0.05 vs control) while l-arginine also further increased (P > 0.05 vs aortic IR), whereas l-NAME caused a significant decrease in pulmonary leukocyte infiltration (P < 0.05 vs aortic IR).

Conclusions

Our results indicate that l-arginine aggravates the lung injury induced by aortic IR, while l-NAME attenuates it.

     

Enhanced Tumor Necrosis Factor-<Emphasis Type="Italic">α</Emphasis> Expression in Small Sized Abdominal Aortic Aneurysms

Abstract Circulating levels of tumor necrosis factor α (TNF-α) are elevated in the patients with abdominal aortic aneurysm (AAA). We investigated TNF-α expression and cellular infiltration in the walls of AAAs of different sizes. Twenty-seven surgical specimens of AAAs were categorized according to the maximum aneurysm diameter into a small size group (less than 50 mm in diameter, n = 8; S group), a medium-sized group (50 to 59 mm in diameter, n = 11; M group), and a large size group (larger than 59 mm in diameter, n = 8; L group). The level of TNF-α and interleukin-1β(IL-1β) in the aneurysm wall was measured by ELISA. Immunohistochemical staining was performed to observe the TNF-α expression and the infiltration of macrophages and lymphocytes in aneurysm walls. Enzyme-linked immunosorbent assay showed that the level of TNF-α in the S group (5.47 ± 3.48 pg/mg protein) was significantly higher (p < 0.05) than that in the M group (2.70 ± 1.33 pg/mg protein) or the L group (1.82 ± 1.21 pg/mg protein). No significant difference in IL-1β was observed between the S, M, and L groups. Immunohistochemical analysis also showed that TNF-α was expressed strongly in the S group but was negative or weakly positive in the M and L groups. Furthermore, the expression of TNF-α was seen mainly where the aneurysm wall showed atheromatous change and macrophage infiltration. These results indicated that the expression of TNF-α in the aneurysm wall was enhanced in small AAAs, and this enhancement might be related to the infiltration of macrophages.     

<Emphasis Type="Italic">C. difficile</Emphasis> Colitis—Predictors of Fatal Outcome

Purpose  

Clostridium difficile colitis (CDC) has a clinical spectrum ranging from mild diarrhea to fulminant, potentially fatal colitis. The pathophysiology for this variation remains poorly understood. A total abdominal colectomy may be lifesaving if performed before the point of no return. Identification of negative prognostic factors is desperately needed for optimization of the clinical and operative management.