Functional outcome of a U-shaped ileocystoplasty (the Camey I procedure) in cancer of the bladder. Apropos of 14 cases

The authors studied postoperatively fourteen men who underwent urinary diversion with a Camey ileal bladder for bladder cancer in association with radical cystoprostatectomy, from March 1986 to June 1988. Mean follow-up was 19.5 +/- 9 months. Three patients died (21.4%), two other patients are alive with metastases. Ureteral reflux and upper tract dilatation occurred in 14.3 and 28.6% of the renal units, respectively. Daytime continence was achieved in 92.9% of the patients (13 patients), frequently 6 months after the operation. Nocturnal incontinence was almost universal (1 patient circumvented this problem by getting up to void every three hours during the night). Thirteen patients had urodynamic testing after the operation. Mean capacity of the ileal bladder was 344 ml with mean intraluminal pressure of 24 cm water. Mean urethral closing pressure was 49 cm water. Voiding was accomplished by abdominal straining concomitant with external sphincter relaxation. Post-void residual was less than 50 ml, except in one patient. The authors discuss these results and compare them to those of other studies.     

Role of eicosanoids in PAF-induced increases of the vascular permeability in rat airways.

1. Platelet activating factor (PAF; 1.0 and 5.0 micrograms kg-1) injected in the tail vein of unanaesthetized rats dose-dependently increased the vascular permeability of the trachea, upper and lower bronchi (up to 400%) as measured by the extravasation of Evans blue dye. The permeability of the parenchyma was not affected by PAF treatment. 2. Pretreatment of the animals with an intravenous injection of the PAF antagonist BN-52021 (10 mg kg-1) abolished almost totally the vascular permeability changes elicited by PAF injection (5.0 micrograms kg-1). 3. Pretreatment of the animals with intravenous injections of inhibitors of thromboxane formation, indomethacin (10 mg kg-1) and compound OKY-046 (10 mg kg-1), and thromboxane antagonist, compound L-655,240 (5 mg kg-1), partially reduced PAF effects in the airways (from 28 to 69%). The thromboxane mimic U-44069 (5.0 micrograms kg-1) did not modify the vascular permeability of rat airways. The effect of a low dose of PAF (0.1 microgram kg-1) on the vascular permeability of the trachea and bronchi (but not of the parenchyma) was potentiated by compound U-44069 (5.0 micrograms kg-1) or noradrenaline (400 ng kg-1) whereas the effect of a high dose of PAF (5.0 micrograms kg-1) was not affected. 4. Neither the peptidoleukotriene antagonist MK-571 (10 mg kg-1) nor the 5-lipoxygenase inhibitor, L-663,536 (10 mg kg-1) given before the injection of PAF (5.0 micrograms kg-1) affected the protein extravasation in rat lung tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phosphoramidon blocks big-endothelin-1 but not endothelin-1 enhancement of vascular permeability in the rat.

1. Changes in vascular permeability following intravenous injections of human big-endothelin-1 (big-ET-1) and endothelin-1 (ET-1) were measured by extravasation of Evans blue dye (EB, 20 mg kg-1) in selected tissues. 2. A low dose of big-ET-1 (40 pmol kg-1) failed to alter vascular permeability but a dose of 400 pmol kg-1 increased EB extravasation in the trachea, upper and lower bronchi, and lung parenchyma by 55 to 69% (P < 0.05). Vascular permeability was also enhanced in the liver, spleen, kidney, heart, and diaphragm by 20, 14, 41, 25, and 67%, respectively (P < 0.05). 3. Upon injection of ET-1 (400 pmol kg-1), EB extravasation increased in the upper and lower bronchi, lung parenchyma, liver, pancreas, kidney, heart, and diaphragm. 4. Administration of ET-1 and big-ET-1 was not associated with significant systemic responses. 5. Pretreatment with phosphoramidon (PA) blocked the response to big-ET-1 in all tissues examined but this inhibitor failed to alter the response to ET-1. 6. We conclude from these results that the dose-dependent increase in vascular permeability induced by big-ET-1 in various tissues follows its conversion to ET-1 by the endothelin converting enzyme, a PA-sensitive process.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.