Novel PEGylated Basal Insulin LY2605541 Has a Preferential Hepatic Effect on Glucose Metabolism

The impact of the novel basal insulin LY2605541 (LY) on hepatic and nonhepatic glucose uptake (non-HGU) was evaluated. Conscious dogs underwent euglycemic clamps with tracer and hepatic balance measurements. Clamp period infusions were peripheral venous regular insulin (0.1 nmol ⋅ kg⁻¹ ⋅ h⁻¹ [control], n = 6) or LY (bolus [nmol/kg], continuous [nmol ⋅ kg⁻¹ ⋅ h⁻¹]: 0.5, 0.5 [n = 6]; 0.375, 0.375 [n = 5]; 0.25, 0.25 [n = 4]), somatostatin, and glucose, as well as intraportal glucagon (basal). During the clamp, the dogs switched from net hepatic glucose output to uptake (rates reached 2.1 ± 1.2, 0.9 ± 2.1, 8.6 ± 2.3, and 6.0 ± 1.1 µmol ⋅ kg⁻¹ ⋅ min⁻¹ within 5 h in control, LY_0.25, LY_0.375, and LY_0.5, respectively). Non-HGU in LY increased less than in control; the ratio of change from basal in non-HGU to change in net hepatic glucose balance, calculated when glucose infusion rates (GIRs) were ~20 µmol ⋅ kg^-1 ⋅ min⁻¹ in all groups, was higher in control (1.17 ± 0.38) versus LY_0.25 (0.39 ± 0.33), LY_0.375 (−0.01 ± 0.13), and LY_0.5 (−0.09 ± 0.07). Likewise, the change from baseline in glucose R_d-to-R_a ratio was greatest in control (1.4 ± 0.3 vs. 0.6 ± 0.4, 0.5 ± 0.2, and 0.6 ± 0.2 in LY_0.25, LY_0.375, and LY_0.5, respectively). In contrast to exogenously administered human insulin, LY demonstrated preferential hepatic effects, similar to endogenously secreted insulin. Therefore, the analog might reduce complications associated with current insulin therapy.     

Prevalence of celiac disease in nutritional anemia at a tertiary care center

Background

While anemia occurs in 80 % to 90 % of patients with celiac disease (CD), it may be the sole manifestation of CD. The prevalence of CD in Indian patients with nutritional anemia is not known.

Patients and Methods

Adolescent and adult patients presenting with nutritional anemia were prospectively screened for CD using IgA anti-tissue transglutaminase antibody (anti-tTG Ab) followed, if positive, by upper gastrointestinal endoscopy and duodenal biopsy.

Results

Ninety-six patients [mean?±?SD age 32.1?±?13.1 years and median duration of anemia 11 months (range 1 to 144 months)] were screened. Of these patients, 80 had iron deficiency anemia, 11 had megaloblastic anemia, and 5 had dimorphic anemia. Seventy-three patients were on hematinics and 36.4 % had received blood transfusions. Nineteen had a history of chronic diarrhea and the mean?±?SD duration of diarrhea in them was 9.7?±?35.8 months. IgA anti-tTG Ab was positive in 13 patients, of whom 12 agreed to undergo duodenal biopsy. Ten patients had villous atrophy (Marsh grade 3a in three, 3b in one, and 3c in six) and two did not. Thus, 10 patients with nutritional anemia (iron deficiency 9, vitamin B₁₂ deficiency 1) were diagnosed to have CD. On multivariate logistic regression, age, duration of symptoms, and presence of diarrhea were found to be the predictors of CD. All the patients with CD were put on gluten-free diet and with iron and vitamin supplementations and showed a significant improvement in hemoglobin concentration.

Conclusions

CD screening should be included in the work up of otherwise unexplained nutritional anemia.     

Fulminant hepatitis due to human adenovirus

Purpose

To describe the demographics, clinical manifestations, treatment and outcomes of patients with human adenovirus (HAdV) hepatitis.

Methods

A case of fulminant HAdV hepatitis in a patient with chronic lymphocytic leukemia receiving rituximab and fludarabine is described. We conducted a comprehensive review of the English-language literature through May, 2012 in search of definite cases of HAdV hepatitis.

Results

Eighty-nine cases were reviewed. Forty-three (48 %) were liver transplant recipients, 19 (21 %) were bone marrow transplant recipients, 11 (12 %) had received chemotherapy, five (6 %) had severe combined immunodeficiency, four (4 %) were HIV infected, two had heart transplantation, and two were kidney transplant recipients. Ninety percent (46/51) of patients presented within 6 months following transplantation. Fever was the most common initial symptom. Abdominal CT scan revealed hypodense lesions in eight of nine patients. Diagnosis was made by liver biopsy in 43 (48 %), and on autopsy in 46 (52 %). The HAdV was isolated at other sites in 54 cases. Only 24 of 89 patients (27 %) survived: 16 whose immunosuppression was reduced, six with liver re-transplantation, and two who received cidofovir and intravenous immunoglobulin.

Conclusion

HAdV hepatitis can manifest as a fulminant illness in immunocompromised hosts. Definitive diagnosis requires liver biopsy. Early consideration of a viral etiology, reduction in immunosuppression, and liver transplantation can be potentially life-saving.     

Lymphoepithelial cysts and cystic lymphangiomas: Underrecognized benign cystic lesions of the pancreas

AIM: To identify their diagnostic and prognostic clinical characteristics in a large series.METHODS: Retrospective review of clinicopathologic and imaging characteristics of patients diagnosed with lymphoepithelial cysts and cystic lymphangiomas of the pancreas at Massachusetts General Hospital.RESULTS: Twelve patients were identified between 1/1/1997 and 8/1/2007. Their median age was 55.5 years(range 19-78 years), and 6 were females. The le-sion was incidentally discovered in half of the patients.Contrast enhanced computed tomography demonstrat-ed that the cysts had thin walls, without calcifications, pancreatic duct dilation or pancreatic parenchyma inva-sion. Endoscopic ultrasound with fine needle aspiration(EUS/FNA) confirmed the diagnosis of a lymphoepithe-lial cyst in 3 patients, one of whom was spared an op-eration and continues to do well after 6 years. Eleven patients had a resection: 3 pancreaticoduodenecto-mies, 7 distal pancreatectomies, and 1 enucleation. The median size of the cysts was 3 cm(range 2-20 cm). At a median follow-up of 57 mo no recurrences or other pancreas-related conditions occurred.CONCLUSION: Lymphoepithelial cysts and cystic lymphangiomas of the pancreas can be diagnosed with a combination of contrast-enhanced computed tomog-raphy scans and EUS/FNA. If the lesion is asymptom-atic, an operation might be avoided.     

How Important is the Tunnel Position in Outcomes Post-ACL Reconstruction: A 3D CT-Based Study

BackgroundDrilling the femoral and tibial tunnels at their anatomical locations are critical for good outcomes and involve seeing the footprints well. We intended to compare two techniques of drilling the tunnels and the patient-reported outcomes and knee stability of patients undergoing single bundle ACL reconstruction using 3D CT to evaluate if the tunnels were anatomical or not.Materials and MethodsSixty single bundle ACL reconstructions were analyzed, 30 each with Technique A and B. Pre-operative and after a minimum 27 month follow-up Lysholm, IKDC, Tegner score, hop test, and Lachman test were noted. 3D CT was done to classify femoral tunnels positions as being well placed, slightly or grossly misplaced and tibial tunnels as optimal or suboptimal and compared.ResultsSixty ACL reconstructions had full follow-up with a mean follow-up of 34 months. There was no significant difference between tunnel positions between the two techniques. Well-placed femoral tunnel had better Lysholm score (62.2 ± 16.2 v/s 48.5 ± 17.2, p 0.002) and IKDC score (62.5 ± 14.3 v/s 52.7 ± 15.1, p 0.012).). Those who had their surgeries within 3 months of their injury had better hop test (4.4 ± 0.9 v/s 3.9 ± 1, p 0.034) and IKDC scores (62.5 ± 15.8 v/s 33.2 ± 13.8, p 0.026) as compared to those that had surgery done after 3 monthsConclusionTibial tunnel positions were optimal in most cases and did not differ between the two techniques. Well-placed femoral tunnels and surgeries done within 3 months of the injury produced best results.