Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis

Background Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non‐alcoholic steatohepatitis. Aim To investigate the role of insulin sensitizers in the treatment of individuals with non‐alcoholic steatohepatitis (NASH). Methods A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 ± 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. Results With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment‐insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 ± 24.2 to 33.3 ± 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 ± 46.3 to 47.3 ± 34.5 IU/L, P < 0.001] and histological features (median non‐alcoholic fatty liver disease activity score: 5.0–3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 ± 11.1 to 30.0 ± 8.6 IU/L, P < 0.01; ALT: 66.9 ± 28.9 to 42.0 ± 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high‐sensitivity C‐reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. Conclusion Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.     

Vogt-Koyanagi-Harada Syndrome in Children: Report of a Case and Review of the Literature

This article reviews the therapeutic approaches in children with Vogt-Koyanagi-Harada (VKH) syndrome, and reports on a 9-year-old girl with progressive visual loss due to VKH syndrome in spite of treatment. In previous reports, corticosteroids were found to be the most effective agents in the treatment of VKH syndrome, while combination therapies with cyclosporine, methotrexate, or azathioprine were used with favorable results in refractory cases. In the current case, none of the treatments sufficiently stabilized the vision, but triple combination of corticosteroids, cyclosporine, and methotrexate suppressed the relapses of intraocular inflammation. Treatment of children with VKH syndrome is challenging. Various treatment modalities have been reported with various responses, but there is still no definite treatment regimen, and the treatment is usually individualized in pediatric VKH cases.     

The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease

To determine the prevalence, clinical and radiological characteristics of spondyloarthropathy (SpA) in patients with inflammatory bowel disease (IBD), to assess the association between HLA B27 and B51 and the extraintestinal symptoms and to evaluate whether IBD is associated with Behçet’s disease (BD). One hundred and sixty-two consecutive adult patients with established diagnosis of IBD as either Crohn’s disease (CD) or ulcerative colitis (UC) were evaluated. All the patients including those previously diagnosed with or without SpA had a complete rheumatologic examination and they were evaluated according to the European Spondyloarthropathy Study Group (ESSG) criteria for SpA and The International Study Group for Behçet’s disease criteria for BD. The demographic and clinical data were recorded on a standardized form. The radiographies were obtained in all the patients and computed tomography (CT) was performed in the patients with suspected pelvic radiographies and/or low back pain in the physical examination. Radiological evaluation was made according to the Modified New York criteria. HLA B27, B51 and anti-neutrophile cytoplasmic antigen (ANCA) were searched in all the patients. Of the 162 patients with IBD (mean age 41.48±11.63 years, male 60, female 102), 78 were CD and 84 were UC. The mean of the IBD duration was 54.92±50.32 months and SpA duration was 20.63±34.37 months. The prevalence of SpA and AS in IBD was 45.7 and 9.9%, respectively. Frequencies of SpA and AS, the difference between UC and CD were not significant. Spondylitis, enthesitis, peripheral arthritis, oral ulcer and uveitis were not different between UC and CD, but erythema nodosum was found significantly more common in the CD patients compared with UC patients (P=0.005). The duration of IBD and SpA was similar in both groups. As the IBD duration increased, the prevalence of SpA development decreased (rr=0.991, P=0.009). Of the IBD patients, 13.6% were asymptomatic for musculoskeletal manifestations of SpA and their sacroiliac radiographies and CTs showed grade 2 sacroiliitis. HLA B27, B51 and ANCA positivities were not different between the patients with UC and CD. HLA B27 was significantly more common in the patients with sacroiliitis, spondylitis, enthesitis, peripheral arthritis, erythema nodosum, uveitis (P<0.001) and oral ulcer (P=0.025). BD was diagnosed in none of the patients. ANCA positivity was found to be related with the presence of erythema nodosum and uveitis (P=0.001 and P=0.005). The prevalence of SpA and AS is higher in the prospectively evaluated patients with radiological studies than those in the previously published studies. There is a high prevalence of asymptomatic sacroiliitis in IBD. An early diagnosis of inflammatory arthritis in IBD patients may prevent a disability due to SpA and AS.     

The effect of edothelium on the response to propofol on bovine coronary artery rings

In this study, the effect of propofol on isolated bovine coronary artery tone was studied in artery rings precontracted with PGF_2α. Propofol, in concentrations of 10^-6-10^-5 M did not change vascular smooth muscle tone, but at high concentrations (10^-4-10^-1 M) produced relaxation in rings with intact endothelium. In rings denuded of endothelium or treated with methylene blue, propofol produced relaxation at 10^-3-10^-1 M concentrations, but there was a significant decrease in relaxation compared to endothelium intact rings. In the presence of a calcium agonist (Bay K 8644; 10^-5 M), propofol produced constriction in rings denuded of endothelium.
These results suggest that high concentrations of propofol may have vasorelaxant effect on bovine coronary artery and that these effects may be due to actions on the endothelium and mediated by calcium channels.     

The influence of occlusal loading location on stresses transferred to implant-supported prostheses and supporting bone: A three-dimensional finite element study

STATEMENT OF PROBLEM: Information about the influence of occlusal loading by location on the stress distribution in an implant-supported fixed partial denture and supporting bone tissue is limited. PURPOSE: The purpose of this study was to investigate the effect of loading at 1 to 3 different locations on the occlusal surface of a tooth on the stress distributions in an implant-supported mandibular fixed partial denture (FPD) and surrounding bone, using 3-dimensional finite element analysis. MATERIAL AND METHODS: A 3-dimensional finite element model of a mandibular section of bone (Type 2) with missing second premolar and its superstructures were used in this study. A 1-piece 4.1 x 10-mm screw-shape ITI dental implant system (solid implant) was modeled for this study. Cobalt-Chromium (Wiron 99) was used as the crown framework material and porcelain was used for occlusal surface.The implant and its superstructure were simulated in a Pro/Engineer 2000i program. Total loads at 300 N were applied at the following locations: 1) tip of buccal cusp (300 N); 2) tip of buccal cusp (150 N) and distal fossa (150 N); or 3) tip of buccal cusp (100 N), distal fossa (100 N), and mesial fossa (100 N). RESULTS: The results demonstrated that vertical loading at 1 location resulted in high stress values within the bone and implant. Close stress levels were observed within the bone for loading at 2 locations and 3 locations; the former created the most extreme stresses and the latter the most even stresses within the bone. With loading at 2 or 3 locations, stresses were concentrated on the framework and occlusal surface of the FPD, and low stresses were distributed to the bone. CONCLUSION: For the loading conditions investigated, the optimal combination of vertical loading was found to be loading at 2 or 3 locations which decreased the stresses within the bone. In this situation, von Mises stresses were concentrated on the framework and occlusal surface of the FPD.     

A prospective comparison of the selective observation and routine exploration methods for penetrating abdominal stab wounds with organ or omentum evisceration

BACKGROUND: Both routine laparotomy and selective observation methods have been used in the treatment of penetrating abdominal stab wounds with organ or omentum evisceration. There still are some conflicts about these treatment methods. METHODS: Between 1998 and 2003, 61 patients treated in the authors' emergency clinic because of penetrating abdominal stab wounds with organ or omentum evisceration were evaluated prospectively. Excepting those with absolute indications for mandatory laparotomy, these patients were treated by either routine laparotomy or selective observation methods. Their prognosis, rates of unnecessary laparotomy, length of hospital stay, and complications were compared using Fisher's exact test and Student's t test. RESULTS: Nine patients underwent mandatory laparotomy and were therefore excluded from the study. The overall incidence of the patients who had no significant abdominal pathology was 54.1% (33/61). The overall incidence of significant injuries among the asymptomatic patients was 36.5% (19/52). Routine laparotomy was performed for 21 patients, who experienced unnecessary laparotomy and complication rates of 33.33% and 19%, respectively. The mean length of hospital stay in this group was 137.38 +/- 53.25 hours. Of 31 patients, 24 who had been treated by selective observation methods were discharged without laparotomy. The unnecessary laparotomy and complication rates for this group were 6.45% (28.6% for the patients treated surgically) and 3.2%, respectively, whereas the mean length of hospital stay for this group was 81.22 +/- 42.46 hours. There were statistically significant differences in terms of unnecessary laparotomy rates and mean lengths of hospital stay, but no difference in terms of complication rates. CONCLUSION: The selective observation method is safe and superior to routine laparotomy for the treatment of penetrating abdominal stab wounds with omentum evisceration.     

Ursodeoxycholic acid treatment in isolated chronic graft-vs.-host disease of the liver

OBJECTIVES: Data regarding the long-term treatment of ursodeoxycholic acid (UDCA) in individuals of chronic graft-vs.-host disease (cGVHD) of the liver are limited. The aims of this prospective study were to determine whether, (i) UDCA treatment is useful as a long-term treatment for individuals with limited cGVHD of the liver following allogeneic hematopoietic cell transplantation, and (ii) the tolerability of UDCA treatment in such individuals. METHODS: Fifteen consecutive patients with de novo isolated cGVHD of the liver were included. All individuals were treated with UDCA at a dose of 13 mg/kg/d for 1 yr. Clinical evaluation and laboratory testing were assessed at 30-d intervals during UDCA therapy and every 30 d after discontinuation of UDCA for a total of 3 months. RESULTS: At the end of the treatment, 60% of patients with cGVHD of the liver had normal liver tests, the remaining 40% of patients demonstrated improvement in their abnormal liver tests (partial responders), whereas none of the patients had worsening of the liver tests. When compared with baseline, there was a significant decrease in the serum aminotransferases, alkaline phosphatase and gamma-glutamyl transpeptidase levels after completion of the UDCA treatment at 12 months (p < 0.01). No significant increase in serum liver enzyme tests was observed at the third month after the completion of therapy. Pruritus in seven of nine patients resolved after UDCA treatment. All patients completed their assigned treatment with no major adverse event. CONCLUSION: Long-term UDCA therapy appears to be effective, safe and tolerable in individuals with cGVHD presenting with isolated liver involvement.