Asymmetric Dimethylarginine (ADMA) and Progression of Nephropathy in Patients with Type 2 Diabetes

Diabetic nephropathy is the leading cause of kidney failure all over the world. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. ADMA is in part eliminated via urinary excretion. It is found to be elevated in end stage renal disease. Identification of the plasma concentrations of ADMA in patients with different stages of diabetic nephropathy compared with healthy age-matched control subjects for estimation of the role of ADMA as a marker of progression of kidney disease in diabetic patients. Seventy-five diabetic patients were divided into five groups: Group I: patients with normoalbuminuria (urinary albumin excretion UAE < 30 mg/d), Group II: patients with microalbuminuria (UAE: 30–300 mg/d), Group III: patients with macroalbuminuria (UAE > 300 mg/d), Group IV: patients one month after renal transplantation and Group V: patients on haemodialysis. Patients were compared to 15 healthy control subjects matched for age and sex. All subjects subjected to thorough clinical examination and laboratory investigations including: serum albumin, urea, creatinine, fasting and postprandial blood glucose, UAE, urinary albumin/creatinine ratio and serum ADMA level. All patients groups had significantly higher levels of ADMA when compared to control group P < 0.01. The levels of ADMA were positively correlated with disease progression and degree of proteinuria. ADMA can be used as a marker of progression of kidney disease among diabetic patients.     

The radial forearm free flap: a review of microsurgical options

The radial forearm free flap, highly regarded in head and neck reconstructive surgery, is known to be one of the most reliable and versatile flaps. The microsurgery is usually easy to perform due to large vessels and a long pedicle; the double superficial and deep venous networks allow many microsurgical options. The sensory nerve coaptation, still debated for weight-bearing foot reconstruction and its sensory restoration, has recently undergone technical refinements. The authors review the microsurgical options for microvascular anastomosis and for sensory restoration.     

Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor

INTRODUCTION: HDAC inhibitors (HDACIs) have the potential to restore gene expression and display antitumor effects in vitro. As single agents, HDACIs have clinical activity in lymphoma. In myeloid leukemias, combinations of DNA methylation inhibitors and HDACIs are promising. Other combinations are being studied in solid tumors. AREAS COVERED: This article covers basic information and an update on preclinical and clinical experience with the oral isotype-selective HDACI MGCD0103 (mocetinostat) in hematological malignancies and solid tumors. It also examines data concerning MGCD0103 from recent conferences and articles through to November 2010, including new data regarding responses in lymphoma and toxicities. EXPERT OPINION: MGCD0103 is well-tolerated and exhibits favorable pharmacokinetic and pharmacodynamic profiles, demonstrating target inhibition and clinical responses. It induces cell death and autophagy, synergizes with proteasomal inhibitors and affects non-histone targets, such as microtubules. In 2008, new patient enrollment in trials was temporarily suspended due to potential cardiac complications. This restriction was lifted in 2009 as no correlation between MGCD0103 exposure and pericardial effusions was found. New patient enrollment in MGCD0103 clinical trials requires the exclusion of patients diagnosed with significant cardiac abnormalities prior to enrollment. Clinical and pharmacodynamic data support a three-times-weekly administration at a 90 mg fixed dose. MGCD0103 displays promising antitumor activity in several hematological diseases.     

First report of a novel extended-spectrum beta-lactamase KOXY-2 producing Klebsiella oxytoca that hydrolyses cefotaxime and ceftazidime

Klebsiella oxytoca strains MU946294N and MB193997E were isolated from patients in Scotland. Strain MU946294N was resistant to pencillins, monbactams and cephalosporins. Isolate MB193997E displayed a β-lactam resistance phenotype consistent with chromosomal β-lactamase overproduction. No bla(TEM), bla(SHV) or bla(CTX-M) genes could be amplified in either strain; however, amplification by PCR was found with primers for the bla(OXY-2) gene. This β-lactamase gene in MU946294N differed by one mutation from the all other bla(OXY) genes previously reported, with an amino acid substitution Alanine237 Threonine enhancing the binding of cefotaxime. Strain MB193997E showed mutations at positions 255 and 283, neither of which affect function. Based on rpoB and gyrA characterization, both strains were assigned to the KoII phylogenic group but they were completely dissimilar from each other by PFGE. This study is the first to report the substitution of Alanine to Threonine at position 237 in a OXY- 2 β-lactamase and this enhances resistance to cefotaxime.     

Multifocal tuberculous dactylitis: a case report

INTRODUCTION: Tuberculous dactylitis (TD) is a rare disorder. It is the source of a diagnostic hardship as it is difficult to distinguish from other lesions. We report an unusual case with multiple affected sites both in hands and the right big toe. CASE REPORT: A 42-year-old female initially presented with two painful tumefactions affecting the left third finger and the right middle finger. These tumefactions had been present for two months. Conventional radiography and computed tomography of the hand revealed soft tissue swelling with bone expansion and cortical destruction in the proximal, middle and distal phalanx of the third finger, the proximal phalanx of the middle finger in the left hand, the proximal and middle phalanx of the middle finger of the right hand. Bone scintigraphy showed additionally infraradiologic localisation in the proximal phalanx of the first right toe. Pathology examination of a biopsy specimen revealed granulomatous osteitis with caseous necrosis. Antituberculosis treatment led to initial clinical remission followed by a recurrence and lesion spreading due to bacteria resistance. The second line treatment with Rifampicine, Ciprofloxacine, Ethambutol and Clarithromycine induced favorable outcome. CONCLUSION: Tuberculosis dactylitis is well tolerated for a long time leading to a late diagnosis which may favour its spreading. Antituberculosis treatment is effective but the functional outcome depends on early diagnosis.     

Parallel transport in diffeomorphisms distinguishes the time-dependent pattern of hippocampal surface deformation due to healthy aging and the dementia of the Alzheimer's type

Hippocampal surface structure was assessed at twice 2 years apart in 26 nondemented subjects (CDR 0), in 18 subjects with early dementia of Alzheimer type (DAT, CDR 0.5), and in 9 subjects who converted from the nondemented (CDR 0) to the demented (CDR 0.5) state using magnetic resonance (MR) imaging. We used parallel transport in diffeomorphisms under the large deformation diffeomorphic metric mapping framework to translate within-subject deformation of the hippocampal surface as represented in the MR images between the two time points in a global template coordinate system. We then performed hypothesis testing on the longitudinal variation of hippocampal shape in the global template. Both subjects with early DAT and converters showed greater rates of hippocampal deformation across time than nondemented controls within every subfield of the hippocampus. In a random field analysis, inward surface deformation across time occurred in a non-uniform manner across the hippocampal surface in subjects with early DAT relative to the nondemented controls. Also, compared to the controls, the lateral aspect of the left hippocampal tail showed inward surface deformation in the converters. Using surface deformation patterns as features in a linear discriminant analysis, we were able to respectively distinguish converters and patients with early DAT from healthy nondemented controls at classification rates of 0.77 and 0.87, which were obtained in the same training set using the leave-one-out cross validation approach.