We recently identified activating mutations of fibroblast growth factor receptor 3 (FGFR3) in bladder carcinoma. In this study we assessed the incidence of FGFR3 mutations in a series of 132 bladder carcinomas: 20 carcinoma in situ (CIS), 50 pTa, 19 pT1, and 43 pT2-4. All 48 mutations identified were identical to the germinal activating mutations that cause thanatophoric dysplasia, a lethal form of dwarfism. The S249C mutation, found in 33 of the 48 mutated tumors, was the most common. The frequency of mutations was higher in pTa tumors (37 of 50, 74%) than in CIS (0 of 20, 0%; P < 0.0001), pT1 (4 of 19, 21%; P < 0.0001) and pT2-4 tumors (7 of 43, 16%; P < 0.0001). Bladder cancer is the fourth most common malignancy in men and the ninth most common in women in the Western world. In these countries, more than 90% of bladder tumors are urothelial carcinomas. At the time of initial diagnosis, approximately 80% of urothelial carcinomas are confined to the epithelium (pTa, CIS) or lamina propria (pT1), whereas the remaining 20% invade the muscularis propria (pT2, pT3, pT4). pTa lesions, the most common form of bladder carcinoma, are papillary tumors. Carcinoma in situ (CIS) are flat, cytologically highgrade carcinomas. Primary isolated CIS is a very rare entity, CIS being more commonly associated with other malignant bladder lesions. 1 Clinical evidence and molecular studies suggest that there are two pathways in bladder carcinogenesis responsible for generating two types of urothelium-confined tumors (pTa and CIS) with very different behavior. 1-6 pTa tumors are associated with a high rate of recurrence (50 -75%) but a low probability (Ͻ5%) of progression to lamina propria-invasive (pT1) and muscleinvasive (pT2-4) tumors. CIS may be the most common precursor of invasive bladder cancer because CIS shows a strong tendency to progress (40 -50%), and because most muscle-invasive lesions arise with no history of a pTa precursor lesion. This clinical evidence is supported by various molecular studies showing that CIS and invasive tumors have many genetic alterations in common, such as specific chromosomal deletions and a high frequency of p53 mutations. 2,7 In our search for new markers of carcinoma progression, we recently reported specific missense mutations in a gene encoding a growth factor receptor, fibroblast

In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.

In a selected transplant population with biopsy-proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to MMF seems to be safe and allows a significant improvement of renal function.

Because recent large studies have demonstrated that mycophenolate mofetil (MMF) is superior to azathioprine (AZA) as a posttransplant immunosuppressant, it has been speculated that MMF could have a cyclosporin (CsA)-sparing effect in renal transplant recipients with chronic allograft dysfunction. Between April 1996 and October 1998, 31 patients with chronic allograft dysfunction were assigned to have conversion from AZA to MMF with concomitant CsA withdrawal. Patient and graft outcomes were analysed. Mean follow-up time after MMF conversion was 27 * 11 months. Serum creatinine concentration (sCt) significantly decreased after conversion and remained stable at the end of followup (227 * 3 1 pmol/l vs. 185 It 50 pmol/l; P < 0.0005). Mean variation in sCt was -24% after conversion, whereas it was +20% in the year before conversion ( P < 0.001). There was a significant inverse relationship between proteinuria at baseline and improvement in renal function (r = -0.35; P = 0.01). Proteinuria increased during follow-up (0.79 It 0.6 vs.

Among the extraintestinal complications of Crohn's disease, neuropathy seems to be rare, and is only exceptionally reported in the literature. The authors present the report of a patient followed over a 12-year period who developed polyneuropathy with a parallel course to Crohn's disease. There was no evidence of any other underlying condition. On one occasion, the patient developed a cutaneous vasculitis with fibrinoid deposits in the vessels. The search for circulating immune complexes was positive. The authors demonstrated increased intestinal permeability using the 51chromium-labeled ethylenediaminetetra-acetate (51Cr-EDTA) test. Ultrastructural study of a biopsy of the superficial peroneal nerve disclosed a marked denervation process. Therapeutic plasmapheresis were performed, improving the neurologic symptoms. Vasculitis with circulating immune complexes is suggested as a possible mechanism in view of the occurrence of cutaneous vasculitis, increased intestinal permeability, and plasma exchange efficiency.

The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.

Pregnant Wistar females were treated with gentamicin (G), netilmicin (N) or amikacin (A) during two periods of pregnancy covering organogenesis and the beginning of nephrogenesis. Deliveries occurred normally. We studied functional effects--influence of sex, litter size, diuresis, creatinine clearance, G-kidney concentration, and kidney morphological alterations--in rat neonates on day 1 of life. After G and N, the creatinine clearance of the neonates was decreased according to the dosage given to the mother. Whatever the aminoglycoside, kidneys presented proximal tubular alterations (close to those observed in adults) at protonic microscopy and, with electron microscopy, some modifications of distal tubules and of mature and immature glomeruli. It is concluded that the developing kidney can be altered after treating pregnant mothers with aminoglycosides. This model of in utero-induced nephrotoxicity is dose-dependent. Mature and/or immature structures could be affected. The toxicity of the investigated antibiotics could be asserted as G greater than or equal to N greater than A.

The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.