Novel mutation in the ligand-binding domain of the androgen receptor gene (l790p) associated with complete androgen insensitivity syndrome.

Mutations in the X-linked androgen receptor (AR) gene cause androgen insensitivity syndrome (AIS), resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity (CAIS) produces a female external phenotype, whereas cases with partial androgen insensitivity (PAIS) have various ambiguities of the genitalia. Mild androgen insensitivity (MAIS) is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone (T) and dihydrotestosterone (DHT) synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.     

Autologous in vivo adipose tissue engineering in hyaluronan-based gels--a pilot study

BACKGROUND: There is a major clinical need for strategies for adequately reconstructing the soft tissue defects found after deep burns, tumor resection, or trauma. A promising solution is adipose tissue engineering with preadipocytes, stem-cell derived precursors of the adipose tissue, implanted within biomaterials. This pilot study evaluated hyaluronan gels mixed with autologous undifferentiated preadipocytes in a pig model for their potency to generate new fat. MATERIALS AND METHODS: Preadipocytes were isolated from intra-abdominal pig fat by collagenase digestion, plated on fibronectin-coated culture dishes in Dulbecco's modified Eagle medium/Ham's F12 (Biochrom, Berlin, Germany) combined with 10% pig serum, expanded, and mixed with hyaluronan gel. Two types of gels with varying degrees of amidation of the carboxyl groups were tested (HYADD3, HYADD4). Cell-loaded gels and unseeded controls were injected subcutaneously into the ears of three pigs, explanted at 6 wk, and analyzed histologically. RESULTS: Both cell-loaded specimens were detected macroscopically. They demonstrated a slight volume effect with limited stability after 6 wk. Unloaded HYADD3 and HYADD4 controls could not be identified at the time of explantation. Histology of HYADD3 revealed islets of mature adipocytes and vessels embedded in fat tissue surrounded by gel. In contrast, no fat formation was found in HYADD4 gels when implanted in the ear. CONCLUSIONS: Histological findings demonstrate that HYADD3 is a promising gel for generating adipose tissue. Even though HYADD3 might be a potential material for the reconstruction of small tissue defects, the question remains as to whether the adipose tissue within the gel is attributable to preadipocyte maturation or ingrowth from neighboring tissue.     

Activation of Coagulation and Fibrinolysis during Coronary Surgery: On-pump versus Off-pump Techniques

Background : The authors studied the changes in selected hemostatic variables in patients undergoing coronary surgery with on-pump coronary artery bypass grafting (CABG) or off-pump coronary artery bypass surgery (OPCAB) techniques.

Methods : Platelet counts and plasma concentrations of antithrombin, fibrinogen, D dimer, [alpha]2 antiplasmin, and plasminogen were measured preoperatively, 5 min after administration of heparin, 10 min after arrival in the intensive care unit, and 24 h after surgery in patients scheduled to undergo OPCAB (n = 15) or CABG (n = 15). To correct for dilution, hemostatic variables and platelet counts were adjusted for the changes in immunoglobulin G plasma concentrations and hematocrit, respectively.

Results : Adjusting for dilution, antithrombin and fibrinogen concentrations decreased to a similar extent in patients undergoing OPCAB or CABG (pooled means and 95% confidence limits of the mean: 95.5% of baseline, 93-98%, P = 0.002, and 91.7% of baseline, 88-95%, P = 0.0001), respectively, whereas [alpha]2-antiplasmin concentrations were unchanged. Only CABG was associated with a reduction in platelet counts (76% of baseline, 66-85%, P = 0.0001), plasminogen concentrations (96% of baseline, 91-99%, P = 0.011), and increased D-dimer formation (476%, 309-741%, P = 0.004). Twenty-four hours after surgery, platelet counts were still lower in patients undergoing CABG (P = 0.049), but all the investigated variables adjusted for dilution were similar in the two groups.     

Purified collagen I oriented membrane for tendon repair: An ex vivo morphological study

Injured tendons have limited repair ability after full‐thickness lesions. Tendon regeneration properties and adverse reactions were assessed ex vivo in an experimental animal model using a new collagen I membrane. The multilamellar membrane obtained from purified equine Achilles tendon is characterized by oriented collagen I fibers and has been shown to sustain cell growth and orientation in vitro. The central third of the patellar tendon (PT) of 10 New Zealand White rabbits was sectioned and grafted with the collagen membrane; the contralateral PT was cut longitudinally (sham‐operated controls). Animals were euthanized 1 or 6 months after surgery, and tendons were subjected to histological and Synchrotron Radiation‐based Computed Microtomography (SRµCT) examination and 3D structure analysis. Histological and SRµCT findings showed satisfactory graft integration with native tendon. Histological examination also showed ongoing angiogenesis. Adverse side‐effects (inflammation, rejection, calcification) were not observed. The multilamellar collagen I membrane can be considered as an effective tool for tendon defect repair and tendon augmentation. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 738–745, 2013     

Urinary β-1-galactosyl-0-hydroxylysine (GH) as a marker of collagen turnover of bone

Summary β-1-galactosyl-0-hydroxylysine (GH) was measured in the urine of 59 women and 48 men, aged 30–79 years, by High Performance Liquid Chromatography (HPLC) of the dansylated derivative. Vertebral mineral density, measured by quantitative computed tomography (QCT), and urinary GH were inversely correlated (r=−0.74;P<0.001). High rate of bone mineral loss is associated with a high urinary GH excretion. Measurement of GH in urine provides a simple and noninvasive method for the evaluation of the extent of bone resorption in large groups of subjects and appears to be more specific than urinary hydroxyproline excretion.     

The cornea in Sjogren's syndrome: an in vivo confocal study

PURPOSE: To analyze the in vivo morphology of corneal cells and nerves in dry eye associated with primary (SSI) and secondary (SSII) Sj?gren's syndrome and to study its relationship with the clinical evaluation. METHODS: Thirty-five patients with SS and 20 age- and gender-matched control subjects were studied. Confocal microscopy was used to investigate corneal thickness, epithelial and stromal cellular density, and subbasal plexus morphology. RESULTS: Corneal central thickness was 514.74 +/- 19.85 microm in the SS group and 550 +/- 21.46 microm in the control group (P < 0.0001, t-test); stromal central thickness was 456.62 +/- 18.05 microm in the SS group and 487.35 +/- 20.40 microm in the control group (P < 0.0001). The density of the superficial epithelial cells in the SSI and SSII groups was 965.40 +/- 96.00 and 999.80 +/- 115.67 cells/mm(2), respectively, and 1488.55 +/- 133.74 cells/mm(2) in the control group (P < 0.001, ANOVA). The number of subbasal nerves was 3.34 +/- 0.76 in the SS group and 5.10 +/- 0.79 in the control group (P < 0.0001, t-test). The average grade of nerve tortuosity was 2.62 +/- 0.94 in the SS group and 1.20 +/- 0.70 in the control group (P < 0.0001). Statistically significant correlations were found between clinical data and confocal microscopy data. CONCLUSIONS: Corneal thickness, cells, and nerves show morphologic changes in patients with dry eye associated with SS. The in vivo confocal study of these alterations may be important in better understanding the complexity of the ocular surface morphofunctional unit and the potentials of therapeutic approaches for the control of the phlogistic process and neuroprotection.     

Caval replacement strategy in pediatric retroperitoneal tumors encasing the vena cava: a single-center experience and review of literature

Background

Complete encasement of the inferior vena cava by retroperitoneal tumors is rare. Although replacement of the vena cava has been considered for various conditions in adults, it is rarely used in children except for challenging resections and as a last chance approach – often aiming more at debulking than cure.