The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

Radiotherapy for T1 glottic carcinoma: impact of anterior commissure involvement

The clinical notes of all new patients with T(1) squamous cell carcinoma of the glottis seen in one head and neck cancer unit between 1989 and 1996 were reviewed. Fifty-three patients were treated with radical radiotherapy and of these 42 (79.2 per cent) had no loco-regional recurrence, after a median follow-up of seven years. Eleven (20.8 per cent) developed local recurrence and were treated with salvage surgery. Fourteen of the 53 (26.4 per cent) tumours involved the anterior commissure and eight of these 14 (57.1 per cent) developed recurrence, whereas only three of the 19 (15.8 per cent) tumours arising from the anterior half of the fold but not involving the anterior commissure had recurrence. None of the remaining tumours recurred. This difference is statistically significant (p<0.001). Anterior commissure involvement is a predictor of poor response to radiotherapy. This may be the result of understaging as none of the cases had computed tomography (CT) scans performed. Technical radiotherapy factors may also be important, although in all cases of anterior commissure involvement steps were taken to ensure adequate radiation dose to this region.     

Double foreign bodies in the bronchus

An unusual case double foreign in the bronchus is reported for its rarity and unusual presentation.     

A comparison of the transradial and the transfemoral approach in chronic total occlusion percutaneous coronary intervention

Background: Transradial coronary intervention is a safe and effective method of percutaneous revascularization. Furthermore, the indications for transradial percutaneous coronary intervention (PCI) are expanding. However, there is limited data on the efficacy and the safety of the transradial approach for chronic total occlusion (CTO) PCI. Methods: We examined 468 patients who underwent CTO PCI between January 2003 and December 2005, and compared the radial (318 patients) and the femoral (150 patients) approach. Results: Baseline demographics, lesion location, and the vessel treated were similar in both groups. Angiographic success was 82% in radial versus 86% in femoral group, P = 0.28, similar in both groups. Total fluoroscopy time (24.49 ± 13.18 vs. 24.07 ± 14.12 min, P = 0.36), total procedure time (54.22 ± 25.35 vs. 60.23 ± 28.15 min, P = 0.23), and the use of total contrast volume (395.54 ± 180.25 vs. 406.15 ± 173.98 ml, P = 0.27) were similar in radial and femoral group, respectively. In hospital MACE [radial: 12 MI (3.8%) vs. femoral: 1 death (0.7%) and 5 MI (3.5%), P = 0.26] were similar in both groups. Access site vascular complications [radial: 11 (3.5%) vs. femoral: 17 (11.3%), P ≤ 0.001] were significantly less in radial group. Conclusions: The radial approach in CTO PCI is as fast and successful as the femoral approach with comparable in hospital MACE. However, there are far less access site complications with radial approach. © 2008 Wiley‐Liss, Inc.     

Pott's puffy tumour: an unusual presentation and management.

Pott's puffy tumour is a rare clinical entity in this era of antibiotics. It is usually seen as a complication of frontal sinusitis. This is the first report of Pott's puffy tumour presenting as a complication of maxillary sinusitis. This is also the first reported case of Pott's puffy tumour treated with debridement and gentamicin beads. We discuss the clinical presentation and successful treatment of this rare disease.     

Efficacy of laser palatoplasty: four-year results

There are few reports on the long-term results of laser-assisted uvulopalatoplasty (LAUP), with some casting doubt about its long-term efficacy. We report satisfactory results in patients with more than four years' follow-up. We conducted a retrospective study of patients who underwent LAUP at the Princess of Wales Hospital over a period of five years. Thirty-three patients underwent LAUP as a day case procedure. They had had a mean follow-up period of four years and five months. Twenty-eight of these were asked details of their pre- and postoperative levels of snoring regarding frequency, volume and disturbance to their partners. There was a 50% reduction in frequency of snoring, a 51.85% reduction in volume and a 53.7% reduction in disturbance to their partners. All these figures are statistically significant (p<0.001). Overall, 60.8% of the patients felt the surgery was successful and had reduced their snoring to acceptable levels. We conclude that LAUP is an effective treatment for snoring, even in the long term.