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.     

<Emphasis Type="Italic">Roux-en-Y</Emphasis> Bypass Gastroplasty: Markers of Oxidative Stress 6 Months After Surgery

Background  

This study examined the effect of weight loss on energy intake, vitamin C, E, β-carotene (diet/blood), reduced glutathione (GSH), C-reactive protein (CRP), thiobarbituric acid reactive substances (TBARS), catalase, and myeloperoxidase, in patients with Roux-en-Y bypass gastroplasty.     

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.

     

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.     

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.     

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.     

<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.     

Die Bedeutung der <Emphasis Type="Italic">spa</Emphasis>-Typisierung für Shuntprotheseninfektionen

Background

In January 2014 an internal audit was performed at the department of surgery, division of vascular surgery of the Medical University Graz, Austria, to assess the short-term and long-term outcomes of prosthetic shunt implantations between December 1998 and December 2013. An explantation rate of 10.8?% due to graft infections was detected and the majority of cases were associated with Staphylococcus aureus.

Objectives

The aim of this study was to clarify whether a problem with nosocomial infections exists.

Patients and methods

Between December 1998 and December 2014 a total of 490 prosthetic shunt grafts were implanted. After exclusion of 54 cases, 436 shunts remained for statistical analysis. Genetic analysis of S. aureus protein A (spa typing) was carried out on three new cases with involvement of S. aureus in 2014. The impact of various factors, e.g. sex, institute for dialysis, age, type of prosthesis, implantation surgeon and position of the shunt on the shunt graft infection rate was statistically analyzed.

Results

A total of 14.0?% (61 out of 436) prostheses had to be explanted of which 12.4?% (54/436) were due to infections. In the cases due to infections, bacteria were found in blood and/or wound cultures in 77.8?% (42/54) whereby S. aureus was present in 76.2?% (32/42) of these cases and there was a sensitivity to methicillin in all cases. The infection rate was not significantly dependent on any of the investigated factors; however, the factor institute for dialysis had a remarkable p?value of 0.060 with infection rates ranging from 8.5 to 18.2?%, depending on the institution. The results showed that three different S. aureus spa types were found: t015, t359, t6265. As these patients had three different sources of S. aureus a nosocomial problem is very unlikely.

Conclusion

The results showed that spa genetic typing is a suitable technique for distinguishing between nosocomial and community-acquired sources for prosthetic shunt graft infections.

     

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.     

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     

Enhanced Recovery After Surgery: Can We Rely on the Key Factors or Do We Need the <Emphasis Type="Italic">Bel Ensemble</Emphasis>?

Background

The success of enhanced recovery (ERAS) pathways depends on the actual application of the intended protocol (adherence), but its full implementation remains challenging. In order to potentially streamline the pathway, it is indispensable to know the impact of individual items and the entire protocol on clinical outcomes.

Methods

Retrospective analysis including all consecutive colorectal ERAS patients since implementation (May 2011) until February 2014; demographics, adherence and outcomes were retrieved from a prospectively maintained database. Primary outcome was the impact of individual item and of the entire protocol on complications (overall and major) and length of hospital stay. Statistical analysis included logistic multivariate regression and adjustment for confounding factors.

Results

There were 328 patients with complete data sets analyzed. A minimally invasive approach [odd ratio (OR) 0.62; confidence interval (CI) 0.4–0.9] was significantly associated with less overall complications. In contrast, the use of prophylactic nasogastric tubes (OR 3.18; CI 1.4–7.4), prophylactic abdominal and pelvic drains (OR 1.96; 1.2–3.2) and intraoperative thoracic epidural analgesia (OR 1.76; CI 1.3–2.4) were associated with more overall complications. Minimal invasive approach was further associated with reduced hospital stay (OR 0.5; CI 0.4–0.7) and less major complications (OR 0.58; CI 0.4–0.8). Higher adherence to the entire ERAS protocol was associated with significantly less complications (P < 0.001) and shorter hospital stay (P < 0.001).

Conclusions

Minimally invasive surgery was the single most important component of the ERAS pathway while nasogastric tubes, drains and epidurals should be avoided. Overall, increasing adherence with the protocol was associated with better outcomes and should be the goal.

     

Role of <Emphasis Type="Italic">p53</Emphasis> and <Emphasis Type="BoldItalic">β-catenin</Emphasis> Mutations in Conjunction with CK19 Expression on Early Tumor Recurrence and Prognosis of Hepatocellular Carcinoma

Background  

Cytokeratin 19 (CK19), a molecular marker of hepatic progenitor cells and cholangiocytes, is expressed in hepatocellular carcinomas (HCC), but not in normal hepatocytes. However, role of CK19 in HCC progression, especially when interacted with p53 and β-catenin mutations, remained largely unknown.