Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour

Aims:  Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene ( HMOX-1 ) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients.
Methods and results:  Tumour and corresponding healthy tissue DNA of 44 patients who underwent surgical resection of GIST were analysed by polymerase chain reaction, capillary electrophoresis and DNA sequencing. GTn polymorphism was classified into short (S) and long (L) allele. There was no difference detected in GTn genotype between tumour and healthy tissue DNA. Short GTn allele (SGTn) was significantly associated with metastatic disease, higher tumour recurrence rates and high risk GIST (consensus criteria 2001). Furthermore, SGTn allele carriers had significantly shorter disease-free and overall survival (log rank test, P  < 0.0001). On multivariate Cox regression analysis, GTn polymorphism was identified as an independent prognostic factor for survival ( P  = 0.001).
Conclusions:  HMOX-1 promoter GTn polymorphism is a potential prognostic marker and may help to allocate patients to different risk groups, customized therapy and follow-up. Haeme oxygenase-1 could represent an important candidate gene in the pathogenesis and growth of GIST.     

Role of tissue harmonic imaging in focal hepatic lesions: comparison with conventional sonography

Background: The purpose of the present study was to compare iissue harmonic imaging (THI) and conventional sonography in focal hepatic lesions. Methods: Fifty patients with focal hepatic lesions were enrolled for study. Conventional grayscale and THI was performed in all the patients and two sets of images of the lesions were recorded (one each for THI and conventional) and assessed for fluid–solid differentiation, detail and overall image quality. These images were compared with conventional sonographic images and graded better, same or worse as per the case. Lesions were confirmed by fine‐needle aspiration cytology (FNAC)/surgery/other modalities such as computed tomography (CT) or magnetic resonance imaging (MRI). Results: Out of 50 patients with focal hepatic lesions, 21 patients had metastatic lesions (two single; 19 multiple) five patients had hepatocellular carcinoma (HCC), five patients had hydatid cysts, nine had simple hepatic cyst whereas five patients had liver abscess, three had focal fatty infiltration; and lymphoma and hemangioma were seen in one patient each. The first observer ranked THI better than standard sonography in 40 patients (80%) for fluid–solid differentiation, in 38 (76%) for detail and in 39 (78%) for overall image quality. The second observer ranked THI better than standard sonography in 39 patients (78%) for fluid–solid differentiation, in 40 (80%) for detail and in 42 (84%) for overall image quality. Tissue harmonic imaging provided additional information in eight patients (16%) and resulted in treatment alteration in three patients (6%). Conclusion: Tissue harmonic imaging was significantly better than conventional sonography for fluid–solid differentiation, detail and total image quality in focal hepatic lesions, especially in obese patients and patients with poor acoustic window.     

A Review of Neuroimaging Findings in Repetitive Brain Trauma

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE.     

Synthesis of diversely substituted bis-pyrrolizidino/ thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via sequential azomethine ylide cycloaddition

Curcumin has been transformed to several diversely substituted bis-pyrrolizidino/thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via a sequential azomethine ylide cycloaddition reaction using isatins/acenaphthoquinone and proline/thioproline as the reagents. The products were separated via extensive chromatography and characterized by 1D/2D NMR and HRMS analysis.

Curcumin has been transformed to several diversely substituted bis-pyrrolizidino/thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via a sequential azomethine ylide cycloaddition reaction.     

Intrahepatic portal venopathy and related disorders of the liver

Intrahepatic portal venopathy leads to various entities that are important causes of portal hypertension. Noncirrhotic portal fibrosis (NCPF) occurs in the Indian subcontinent, whereas idiopathic portal hypertension (IPH) occurs in Japan although the pathogenesis and presentation of both are similar. NCPF presents mainly with upper gastrointestinal bleeding; IPH presents with massive splenomegaly. The liver functions are preserved. Wedged hepatic venous pressure is normal, but portal venous pressure is high indicating a presinusoidal block. Patients are best managed with endoscopic therapy or surgery, with better results than in patients with cirrhosis. Nodular regenerative hyperplasia is a histological diagnosis characterized by development of nodules in the liver due to uneven perfusion of the portal venous blood. These patients may develop portal hypertension and if they bleed would require treatment as in NCPF/IPH. Schistosomiasis produces portal hypertension by the development of fibrous tissue around the portal veins as a response to schistosome eggs. Gratifying results have been reported with praziquantel therapy. Rarely sarcoidosis and chronic biliary obstruction may also produce portal venopathy.     

Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease.

BACKGROUND: Comparative trials of ursodeoxycholic acid (UDCA), vitamin E and weight management programs among patients with nonalcoholic fatty liver disease (NAFLD) are lacking. AIM: To find an effective single agent or combination of agents for management of NAFLD. METHODS: In this retrospective study, consecutive patient with histologically confirmed NAFLD with raised ALT were included. The patients received either weight management (exercise and therapeutic lifestyle changes [TLC] diet with a target to reduce body weight 10% in 6 months) (group I) ; weight management + UDCA (300 mg BID) (group II); or weight management + UDCA + vitamin E (400 mg OD) (group III). Outcome measure was normalization of ALT. RESULTS: 42 patients (18, 12 and 12 in groups I, II and III, respectively) were included between 1996 and 2004. All patients in group III normalized their ALT levels, which was significantly higher than numbers in group I (8/18) and group II (5/12); (p=0.003). Post treatment ALT was significantly lower in group III (28.6 [9.3]) as compared to group I (59.3 [32.2]) and group II (49.0[31.8]); (p=0.01). Type of therapy received was the only factor predictive of ALT normalization. CONCLUSION: Combination regimen containing vitamin E appears to be effective in normalizing ALT among NAFLD patients.