Centrilobular histopathologic changes in liver transplant biopsies

We evaluated centrilobular histologic changes seen on post-orthotopic liver transplantation (OLT) biopsies to refine the pathologic diagnosis by systematic study of morphologic and clinical data with possible identification of prognostic criteria. A total of 110 biopsies with zone 3 pathology from 59 patients were reviewed and correlated with clinical findings. Within the first 6 months post-OLT (group I), 39 of 47 patients had combinations of centrilobular hepatocytic dropout, ballooning, and cholestasis on single or multiple biopsies attributed to perioperative ischemic/perfusion injury; 12 of 39 patients with all 3 features present had increased incidence of biliary complications and sepsis and decreased 1-year patient and graft survival; 17 of 39 patients with 2 of the 3 features had increased biliary complications but not decreased 1-year survival; and the remaining 8 of 47 patients had central venulitis associated with acute cellular rejection. After 6 months post-OLT (group II), 14 patients, including 2 from group I, had biopsies with centrilobular pathology; 8 of 14 had central venulitis related to rejection (acute, 4; chronic, 4), and fibrosis was seen in 8 (rejection, 6; cardiac problems, 2). In conclusion, combinations of centrilobular hepatocytic ballooning, dropout, and cholestasis are seen in association with reversible or irreversible ischemic/perfusion damage in the early post-OLT period. The presence of all 3 features is associated with a poor outcome. Central venulitis as a feature of acute/chronic rejection is seen at any time post-OLT and is not a predictor of poor graft/patient survival.     

The Pharmacokinetics of Recombinant Human Relaxin in Nonpregnant Women After Intravenous,Intravaginal, and Intracervical Administration

The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv) bolus administration and the absorption of rhRlx after intracervical or intravaginal administration were determined in nonpregnant women. The study was conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a minimum 7-day washout period, these women were dosed intracervically (n = 10) or intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3% methylcellulose gel. Part II was a double-blind, randomized, three-way crossover study in 26 women. At 1-month intervals, each woman received one of three intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3% methylcellulose gel. The serum concentrations of relaxin following iv administration were described as the sum of three exponentials. The mean (±SD) initial, intermediate, and terminal half-lives were 0.09 ± 0.04, 0.72 ± 0.11, and 4.6 ± 1.2 hr, respectively. Most of the area under the curve was associated with the intermediate half-life. The weight-normalized clearance was 170 ± 50 mL/hr/kg. The observed peak concentration was 98 ± 29 ng/mL, and the weight-normalized initial volume of distribution was 78 ± 40 mL/kg, which is approximately equivalent to the serum volume. If central compartment elimination was assumed, the volume of distribution at steady state (V _ss/W) was 280 ± 100 mL/kg, which is approximately equivalent to extracellular fluid volume. V _ss/W could be as large as 1300 ± 400 mL/kg without this assumption. After intravaginal administration of the placebo gel, endogenous relaxin concentrations were evident (i.e., 20 pg/mL) in 9 of the 26 women (maximum concentrations, 23–234 pg/mL). A similar proportion of women (approximately 35–40%) exhibited measurable serum concentrations of relaxin following intravaginal rhRlx treatment; this proportion increased to 90% following intracervical rhRlx treatment. For both routes of administration, the maximum serum concentrations of relaxin were usually within the range of values observed for endogenous relaxin, suggesting that the absorption of rhRlx was minimal.     

Evaluation of Serum microRNA Let-7c and Let-7d as Predictive Biomarkers for Metastatic Pancreatic Cancer

Background:First-line treatments for metastatic pancreatic cancer are chemotherapy regimens consisting of 5-fluorouracil or gemcitabine; however, there are no biomarkers to help determine which patients might benefit from which treatment regimens. We aimed to show that microRNAs let-7c and 7d can be used as independent predictive biomarkers for metastatic pancreatic cancer.Methods:A total of 55 patients who had first-line chemotherapy with FOLFIRINOX or gemcitabine + capecitabine were included. Patients were divided into groups based on let-7c and let-7d levels and chemotherapy treatment as let-7c-7d high FOLFIRINOX, let-7c-7d high gemcitabine + capecitabine, let-7c-7d low FOLFIRINOX, and let-7c-7d low gemcitabine + capecitabine. Blood samples were taken from patients before chemotherapy for microRNA let-7c and 7d analysis. MicroRNA isolation was performed using a miRNeasy Serum/Plasma Kit and identified using spectrophotometric measurements. After isolation, microRNA was converted to cDNA using a microRNA cDNA Synthesis Kit with poly (A) polymerase tailing. The expression of microRNA was examined using quantitative real-time polymerase chain reaction.Results:The overall survival of patients who received FOLFIRINOX treatment with a high let-7c-7d level was statistically significantly longer than those who received gemcitabine + capecitabine with a high let-7c-7d level. In addition, patients with low let-7c expression receiving FOLFIRINOX progressed significantly 2.104 times earlier than patients with high let-7c expression receiving FOLFIRINOX.Conclusion:The serum MicroRNA let-7c level was found to be an independent predictive biomarker in the FOLFIRINOX treatment group.     

Effects of a home-based exercise program on quality of life, fatigue, and depression in patients with ankylosing spondylitis

The aim of this trial was to investigate the effects of a 12-week home-based exercise program (HEP) on quality of life (QOL) and fatigue in patients with Ankylosing Spondylitis (AS). Forty-three patients with AS were included in this study. Group 1 was given a HEP; Group 2 served as the control group. The functional capacity (Bath Ankylosing Spondylitis Functional Index), disease activity (Bath Ankylosing Spondylitis Disease Assessment Index), fatigue (Multidimensional Assessment of Fatigue Scale), depression (Beck Depression Inventory scores), and QOL (Short Form 36) of all participants were evaluated. There were significant improvements for all the parameters in two groups after the treatment. The improvements for all the parameters were better in the exercise group than in the control group. Home-based exercise programs are very effective in improving QOL and reducing fatigue. Because of these advantages, HEP should be advised for the management program in AS in addition to medical treatments. This study was presented at the 21st National Physical Medicine and Rehabilitation Congress, Antalya, Turkey, 24–29 September 2007.     

Cyclic Fatigue Resistance of Reciproc Blue and Reciproc Files in an S-shaped Canal

Introduction

This study evaluated the cyclic fatigue resistance (CFR) of Reciproc (R25 and R40; VDW, Munich, Germany) and Reciproc Blue (R25 and R40, VDW) instruments used in an artificial S-shaped canal.

Takayasu arteritis in children

OBJECTIVE: To retrospectively evaluate the clinical features, angiographic findings, and outcomes of children with Takayasu arteritis (TA) in Turkey. METHODS: Clinical, laboratory, and angiographic findings and outcomes of 19 children with TA were evaluated with a retrospective chart review. The criteria for inclusion were those proposed by the American College of Rheumatology. RESULTS: Mean followup period was 35.89 +/- 40.75 months (range 1-168, median 30). There were 14 girls and 5 boys. The mean age at diagnosis was 12.84 +/- 2.69 years (range 8-17, median 13). The most common complaints on admission were headache (84%), abdominal pain (37%), claudication of extremities (32%), fever (26%), and weight loss (10%). One patient presented with visual loss. Examination on admission revealed hypertension (89%), absent pulses (58%), and bruits (42%). Angiography revealed type I in 13 patients (aortic arch, descending thoracic, and abdominal aorta), type II in 4 (descending thoracic aorta and abdominal aorta), and type IV in 2 (diffuse aortic and pulmonary artery). The most commonly involved vessels were the renal, subclavian, and carotid arteries. All patients received corticosteroid therapy, and further immunosuppressive therapy was added in 15 patients. Fourteen of the 17 hypertensive patients had renal artery stenosis and 9 underwent surgery or interventional therapy. Thoraco-abdominal bypass graft was performed in 2 patients who had abdominal aortic stenosis. CONCLUSION: Hypertension is the most common clinical feature at presentation. Corticosteroid and immunosuppressive therapy was effective in the control of disease activity. Angioplasty or bypass grafting was successfully performed when needed.