Safety and efficacy of hormonal therapy in menopausal kidney-allograft recipients

AIM: A higher risk of premature menopause and osteoporosis has been observed in female kidney-allograft recipients, providing particular indications for hormonal therapy. We have summarized our 10-year-experience with hormonal therapy in menopausal kidney transplant recipients. MATERIALS AND METHODS: From 1995 to 2004, hormonal therapy was administered to 54 kidney transplant recipients. At onset of therapy the ages of the women ranged from 31 to 52 years, and the period from transplantation from 3 months to 13 years. The mean time on therapy was 4.2 years. All patients received transdermal estradiol (E(2)) in combination with oral progestin. RESULTS: Total regression of climacteric symptoms was reported in 75% of patients. After 3 months of the therapy follicle stimulating hormone (FSH) and E(2) levels normalized: FSH from 129 +/- 30.1 IU/L to 38.3 +/- 26.1 IU/L and E(2) from 18.5 +/- 5.8 pg/mL to 98.6 +/- 33.2 pg/mL. No significant change was noted in serum creatinine. Eleven patients developed abnormal uterine bleeding but none had premalignant or malignant lesions of the uterus on endometrial curettage. No incidence of breast cancer was noted during mean treatment period of 5.2 years. Seventeen patients discontinued therapy for medical indications: one for profound thrombophlebitis and 16 for significant deterioration of liver function. Twelve women made their own decision to discontinue therapy. CONCLUSION: Hormonal replacement therapy was effective with no negative impact either on graft function or sex organs among kidney transplant recipients. Liver parameter monitoring seemed to be essential for safe continuation of treatment.     

Intraspinal mesenchymal chondrosarcoma in a 14-year-old patient: diagnostic and therapeutic problems in relation to the review of literature

Mesenchymal chondrosarcoma (MC) is an infrequent, highly malignant neoplasm of the soft tissues and bone. It is very rare in the pediatric age group, especially in the intraspinal location. Only 24 cases have been reported to date. The authors present a case of a 14-year-old boy with an intraspinal MC who died of the disease 50 months from the initial diagnosis and after the third local recurrence. The patient was treated with a combination of chemotherapy, radiotherapy, and surgery. The authors review the clinical presentation, diagnostics, and the efficacy of treatment of pediatric patients with MC reported in the literature from 1978 to 2010.     

Orexin A stimulates glucose uptake, lipid accumulation and adiponectin secretion from 3T3-L1 adipocytes and isolated primary rat adipocytes

Aims/hypothesis

Orexin A (OXA) modulates body weight, food intake and energy expenditure. In vitro, OXA increases PPAR?? (also known as PPARG) expression and inhibits lipolysis, suggesting direct regulation of lipid metabolism. Here, we characterise the metabolic effects and mechanisms of OXA action in adipocytes.

Methods

Isolated rat adipocytes and differentiated murine 3T3-L1 adipocytes were exposed to OXA in the presence or absence of phosphoinositide 3-kinase (PI3K) inhibitors. Ppar?? expression was silenced using small interfering RNA. Glucose uptake, GLUT4 translocation, phosphatidylinositol (3,4,5)-trisphosphate production, lipogenesis, lipolysis, and adiponectin secretion were measured. Adiponectin plasma levels were determined in rats treated with OXA for 4?weeks.

Results

OXA PI3K-dependently stimulated active glucose uptake by translocating the glucose transporter GLUT4 from cytoplasm into the plasma membrane. OXA increased cellular triacylglycerol content via PI3K. Cellular triacylglycerol accumulation resulted from increased lipogenesis as well as from a decrease of lipolysis. Adiponectin levels in chow- and high-fat diet-fed rats treated chronically with OXA were increased. OXA stimulated adiponectin expression and secretion in adipocytes. Both pharmacological blockade of peroxisome proliferator-activated receptor ?? (PPAR??) activity or silencing Ppar?? expression prevented OXA from stimulating triacylglycerol accumulation and adiponectin production.

Conclusions/interpretation

Our study demonstrates that OXA stimulates glucose uptake in adipocytes and that the evolved energy is stored as lipids. OXA increases lipogenesis, inhibits lipolysis and stimulates the secretion of adiponectin. These effects are conferred via PI3K and PPAR??2. Overall, OXA??s effects on lipids and adiponectin secretion resemble that of insulin sensitisers, suggesting a potential relevance of this peptide in metabolic disorders.     

Bioabsorbable fixation: scientific, technical, and clinical concepts

Bioabsorbable internal fixation has been clinically available for nearly 20 years and has been used for hard tissue and/or soft tissue fixation from the head to toe. During this time, there has been a rapid evolution in bioabsorbable polymers as well as in the implants and their clinical applications. There is a plethora of bioabsorbable polymers now available for clinical use, and although all are related chemically, seemingly small changes in formulation can have a dramatic effect on their biomechanical and physiological properties. This article summarizes much of the relevant scientific, technical, and clinical literature in a simple, straightforward manner to help surgeons better understand and appreciate the nuances of bioabsorbable fixation. This up-to-date review should also help researchers establish a baseline of knowledge that can provide a platform for further developments in this exciting field.     

A resorbable rivet system for pediatric craniofacial surgery: biomechanical testing and clinical experience

The use of a new method of bone fixation for pediatric craniofacial surgery was evaluated by both biomechanical tests and clinical use. A "pull-back" rivet composed of 82% poly-L-lactic acid and 18% polyglycolic acid (LactoSorb) for use with resorbable plates was developed to obviate the traditional hand-tapping technique used for the placement of resorbable screws. In in vitro testing, the average failure load of the rivets in uniaxial pullout was nearly 50 kg and approximately 75 kg in shear. Approximately two thirds of their initial strength was retained by 6 weeks. In clinical testing, 10 patients undergoing cranial vault reconstruction were treated by 1.5-mm resorbable plates secured by rivets. Although postoperative clinical outcomes were unaffected, good engagement of the devices with secure plate fixation was obtained in only about 70% of the rivets fired.Although the novel approach of a pull-back rivet was encouraging in both design and in vitro testing, its clinical use is impaired by the sensitivity of the device to the thickness of the bone into which it is placed, as well as its larger diameter compared with resorbable screws.     

Assay of bone morphogenetic protein-2, -4, and -7 in human demineralized bone matrix

Demineralized bone matrix (DBM) is a widely used bone graft material that derives its osteoinductive potential from matrix-associated bone morphogenetic proteins (BMPs). Prior investigations have shown that the osteoinductive potential can vary widely, with influence from both donor and processing sources. Although it is plausible that donor variance in the BMP profile can be an important consideration, the few published studies available have given inconsistent and incomplete information about this. The goal was to (1) characterize the variance of BMP-2, BMP-4, and BMP-7 in fully demineralized DBM derived from 20 appropriately screened (Food and Drug Administration and the American Association of Tissue Banks criteria) donors (male and female, 17-65 years) and (2) using literature review, infer the potential for this to be an important source of variability in graft function. BMPs were extracted with 4 M guanidine hydrochloride, and levels of BMP-2, BMP-4, and BMP-7 were measured using enzyme-linked immunosorbent assay. Measured levels were as follows: BMP-2 = 21.4 +/- 12.0 ng/g DBM, BMP-4 = 5.45 +/- 2.04 ng/g DBM, and BMP-7 = 84.1 +/- 34.4 ng/g DBM, which were significantly different (P < 0.05). There was a positive linear correlation between BMP-2 and BMP-7 (P = 0.0227). DBM derived from female donors had significantly greater concentrations of BMP-2 and BMP-7 than did that derived from male donors (P = 0.0257 and 0.0245, respectively). There was no significant correlation between donor age and the levels of any of the measured BMPs. The magnitude of variance of BMP profile appears to reasonably well correspond to the variance in osteoinductive potential cited by others, suggesting the possibility of using this as a method of donor screening.     

The effect of high temperature intraoperative molding on bioabsorbable PLLA-PGA craniofacial fixation

Bioabsorbable internal fixation has become an established part of the surgeons' armamentarium. There are several unique aspects of bioabsorbable polymers that can enhance their versatility. One of these is the application of heat to adapt the implant. Hot-tip cautery has been used for years to cut and otherwise customize bioabsorbable implants intraoperatively. As the tips of these devices can reach temperatures of over 1,000 degrees C, there is the potential that such practice can modify the degradation properties of these polymers. This study was performed to better understand the extent to which this potential exists. Screw heads of an 82:18 poly-L-lactic acid and poly-glycolic acid copolymer were modified by repeated passage of a hot-tip cautery wire, deforming the hex geometry to that of a ball. There was no significant difference between the glass transition temperature (approximately 59 degrees C) and inherent viscosity (approximately 1.45 dL/g) of treated and untreated screw heads, indicating no overall change in these properties throughout the mass of the screw head. Additionally, these properties were measured and comparisons made between the treated screw heads and untreated plates made of the same polymer during 28-day exposure to an in vitro bath (pH 7.4, 37 degrees C). The glass transition temperature and inherent viscosity exhibited declines during this period, with no significant differences between the two groups. Collectively, these results suggest that hot-tip cautery results in no substantial changes in the degradation characteristics of this polymer.     

Structure of a Fe4O6-Heteraadamantane-Type Hexacation Stabilized by Chelating Organophosphine Oxide Ligands

Metal-containing heteraadamantanes are compounds of interest due to their spectroscopic and magnetic properties, which make them promising materials for non-linear optics and semiconductors. Herein we report the comprehensive structural characterization of a new coordination compound of the formula [(µ-OH′)₂(µ-OH″)₄(O = P(Ph₂)CH₂CH₂(Ph₂)P = O)₄{Fe(t-BuOH)}₄](PF₆)₄(Cl)₂ with the chelating ligand Ph₂P(O)-CH₂CH₂-P(O)Ph₂. The compound crystallizes as a polynuclear metal complex with the adamantane-like core [Fe₄O₆] in the space group I-43d of a cubic system. The single-crystal XRD analysis showed that the crystal contains one symmetrically independent octahedrally coordinated Fe atom in the oxidation state +3. The adamantine-like scaffold of the Fe complex is formed by hydroxy bridging oxygen atoms only. Hirshfeld surface analysis of the bridging oxygen atoms revealed two types of µ-OH groups, which differ in the degree of exposure and participation in long-range interactions. Additionally, the Hirshfeld surface analysis supported by the enrichment ratio calculations demonstrated the high propensity of the title complex to form C-H^…Cl, C-H^…F and C-H^…O interactions.