The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.

The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.     

National audit of incontinence surgery in the United Kingdom.

The aim of the study was to describe the experience, current trends and management of incontinence surgery for urodynamic stress incontinence (USI) in the United Kingdom. The study was a postal questionnaire survey that was sent to a cohort of surgeons known to be performing continence surgery. The subjects addressed included the considered role of the surgeon, the total number and type of operations performed in the last year, urodynamics and physiotherapy prior to incontinence surgery, operative complications, postoperative advice and follow-up (lengths and methods). The response rate was 54%. Large variations were found in all areas. The survey provides evidence of the number of incontinence operations performed, potentially important trends and differences in the practice and management of incontinence in the United Kingdom. This survey may be helpful in making guidelines and standards for audit at regional, local and individual levels as well as recommendations for strategies to enhance professional expertise in urogynaecology in the United Kingdom.     

Survivorship of cemented knee replacements

The survivorship method of analysis has been used to compare the failure rate and overall success of 1,430 cemented primary total knee arthroplasties performed at The Hospital for Special Surgery over a 15-year period. There were 224 total condylar prostheses with a polyethylene tibia, 289 of the posterior stabilised type with an all polyethylene tibia, and 917 posterior stabilised with a metal-backed tibial component. There were 12 failures in the total condylar series, giving an average annual failure rate of 0.65% and a 15-year success rate of 90.56%. The posterior stabilised prosthesis with a polyethylene tibia showed an average annual failure rate of 0.27% and a 10-year success rate of 97.34%, and this prosthesis with a metal-backed tibial component gave an annual failure rate of 0.19% and a seven-year success rate of 98.75%. The overall survival rate was not influenced by sex or age, diagnosis or the percentage of ideal body weight. No metal-backed tibial components have yet needed revision for loosening. It seems that infection will be the major cause of failure.     

Melanoma of the upper aerodigestive tract: a review of 21 cases

In this report 21 cases of primary malignant melanoma arising from the mucosa of the upper aerodigestive tract are reviewed. The patients ranged in age from 30 to 86; mean age was 67 years. There were 10 men and 11 women. All but one patient were white. Sites of involvement were: nose and paranasal sinuses, oral cavity and labial mucosa, parotid duct, and larynx. Surgery was the primary method of treatment. The 2-year survival rate was 44% (7/16) and the 5-year survival rate was 13% (2/15). Regional metastases were seen in 19% (4/21) while distant metastases was seen in 55% (11/21). The local recurrence rate was 69% (11/16). Distant metastases were usually associated with uncontrolled disease at the primary site. This fact as well as the low incidence of regional metastases lead us to conclude that better local control rather than regional lymphatic control is necessary if decreased distant metastases and increased survival are to be achieved.     

Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.     

Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines

BACKGROUND: The mechanism of progression of established renal disease remains unclear. While a low protein diet slows this progression, the role of cytokines in this process has been little investigated. METHODS: We investigated cytokine expression by Northern blot and immunohistochemistry in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low (6%) protein diet and compared them with sham operated controls. RESULTS: The rats on 6% protein diet had significantly less focal glomerulosclerosis (FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis (GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05). Both experimental groups showed three times control levels of MCP-I expression after 2 weeks. However in the 5/6 Nx 6% protein group the expression decreased at 4 weeks (1.5 times controls) and reached control levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a further marked increase after 4 weeks (5.6 times controls) and was still two-fold higher after 7 weeks. TGF-beta expression was modestly but consistently increased at all time points (120-160% of controls), with no difference between the two study groups. Neither IL-1 beta or TNF-alpha was detectable at any time. Immunohistochemistry demonstrated TGF-beta intracellularly in distal tubular cells in both experimental and control animals, while MCP-1 protein was found in the area of FGS and in the apical pole of distal tubular cells in both experimental groups. Glomerular and interstitial ED1 positive cells were significantly increased after four weeks in the 5/6 Nx 24% protein group (P < 0.05). CONCLUSIONS: A 'mechanical' injury to the kidney clearly results in an inflammatory response associated with the upregulation of MCP-1. A low protein diet modulates the expression of MCP-1 and improves the morphological sequelae seen after renal ablation.