New combined anteversion technique in hybrid THA: cup-first procedure with CT-based navigation

European Journal of Orthopaedic Surgery & Traumatology - Combined anteversion (CA) technique (stem-first procedure) is generally accepted as the optimal technique to attain an appropriate CA...     

Association study of gender identity disorder and sex hormone-related genes

To investigate the biological mechanism of gender identity disorder (GID), five candidate sex hormone-related genes, encoding androgen receptor (AR), estrogen receptors α (ERα) and β (ERβ), aromatase (CYP19), and progesterone receptor (PGR) were analyzed by a case–control association study. Subjects were 242 transsexuals (74 male-to-female patients (MTF) and 168 female-to-male patients (FTM)), and 275 healthy age- and geographical origin-matched controls (106 males and 169 females). The distributions of CAG repeat numbers in exon 1 of AR, TA repeat numbers in the promoter region of ERα, CA repeat numbers in intron 5 of ERβ, TTTA repeat numbers in intron 4 of CYP19, and six polymorphisms (rs2008112, rs508653, V660L, H770H, rs572698 and PROGINS) of PGR were analyzed. No significant difference in allelic or genotypic distribution of any gene examined was found between MTFs and control males or between FTMs and control females. The present findings do not provide any evidence that genetic variants of sex hormone-related genes confer individual susceptibility to MTF or FTM transsexualism.     

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P

Background:

Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients.

Methods:

ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR–restriction fragment length polymorphism (RFLP) and PCR–SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method.

Results:

B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACF<SSA/P<cancer. The most commonly methylated genes in SSA/P were PQLC1, HDHD3, RASL10B, FLI1, GJA3, and SLC26A2. Some of these genes were methylated in ACF, whereas all genes were methylated in cancers. Immunohistochemistry revealed their silenced expression. Microsatellite instability and MLH1 methylation were observed only in cancer. The prevalence and number of ACF were significantly higher in SSA/P patients than in normal subjects. A significant correlation was seen between the numbers of SSA/P and ACF in SSA/P patients.

Conclusions:

Our results suggest that ACF are precursor lesions of the SSA/P-cancer sequence in patients with SSA/P, where ACF arise by B-RAF mutation and methylation of some of the six identified genes and develop into SSA/Ps through accumulated methylation of these genes.     

Parkinson's disease and myasthenia gravis: adverse effect of trihexyphenidyl on neuromuscular transmission

A 55-year-old man with idiopathic Parkinson's disease developed myasthenia gravis shortly after taking trihexyphenidyl. The myasthenic weakness waxed and waned with rise and fall in serum levels of trihexyphenidyl, without marked change of anti-acetylcholine receptor antibody titer.     

A case of gastric cancer in which long-term administration of 5'-deoxy-5-fluorouridine proved effective

A patient diagnosed with Borrmann type 4 gastric cancer (mucinous adenocarcinoma), who had refused surgery, was treated by oral administration of 1200 mg/day 5'-deoxy-5-fluorouridine for about 23 weeks. This resulted in substantial improvement of her condition, i.e. the tumour almost completely disappeared, distensibility improved between the central region of the corpus ventriculi and the angulus, and only small protrusions remained on the anterior and posterior walls and the pars pylorica of the lesser curvature. Mild anorexia and diarrhoea were noted as adverse reactions although these symptoms subsided by reducing the dose or temporarily stopping treatment, thereby allowing long-term treatment. Long-term use of 5'-deoxy-5-fluorouridine proved temporarily effective in this patient. The patient died about 3 years and 7 months after starting therapy. Examination showed that the cancer had been mainly in the stomach and that it had metastasized to the colon and pancreas. The liver was free of metastasis.     

Ten-year NEDO BVAD development program: moving forward to the clinical arena

Since 1995, the Baylor Group has been developing a totally implantable NEDO BVAD system. This 10-year program was completed in March 2005, and preparation for clinical trials is underway. This article summarizes the entire 10-year NEDO program and describes the strategy for clinical trials. The project aimed to achieve: (1) dual centrifugal pumps with the ability of full biventricular support, (2) a compact system implantable into small adults, (3) a totally implantable system with transcutaneous energy transmission system (TETS), (4) a durable system with a lifetime of over 5 years, and (5) a system free of thrombus and with minimal hemolysis. The final goals are to complete preclinical system evaluations and commence the clinical trials in the near future. In vitro studies have demonstrated a pump capacity of over 8.5 l/min and an Index of Hemolysis of <0.004 g/100 l. The pump-bearing life expectancy was over 5 years. To date, eight pumps endured in vivo studies of over 3 months without complications, including thromboembolic events. The in vitro endurance studies of eight pumps are longer than 1 year. There were no mechanical malfunctions or pump failure. A stepwise clinical trial is being planned: Step1, a wearable BVAD/VAD will be clinically studied; Step 2, the BVAD/VAD will be implanted intracorporeally without TETS; and, Step 3, a totally implantable system will be clinically evaluated. The NEDO BVAD system has completed preclinical testing. Clinical trial preparation is underway.