The role of WNT signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC.     

Abolition of postprandial alkaline tide after vagotomy and its use as a screening test in the assessment of vagotomy

Assessment of completeness of vagotomy has always been an irksome and time-consuming affair. The commonly employed test of insulin-induced hypoglycaemia (Hollander) is tedious, risky and associated with practical limitations and theoretical objections, which have resulted in its being replaced by the modified sham feed technique in some centres. The postprandial alkaline tide is attributed to HCO3- release consequent to H+ secretion. Any procedure which reduces acid secretion is expected to affect the postprandial urinary pH. This study was performed to evaluate the effect of vagotomy on the postprandial alkaline tide by measuring prevagotomy and postvagotomy fasting and postprandial urinary pH. The results show that postprandial urinary pH falls after vagotomy and this method may be used to assess the completeness of vagotomy. The proposed test is convenient and may be used as a screening method in the assessment of vagotomy and other acid reducing operative procedures, if further validated, by comparison with already established tests.     

Development of tolerance to the CNS effects of aminoglutethimide in mice

Initially, there is a high incidence of CNS-depressant side-effects when the aromatase inhibitor, aminoglutethimide, is used in the treatment of patients with advanced breast cancer. Tolerance to these effects develops with continued dosing. This study examines the development of tolerance to various indices of CNS depression with the drug in mice. Single doses of aminoglutethimide induced a dose-dependent depression of spontaneous locomotor activity, rotarod performance, righting reflex and body temperature and a dose-related antileptazol activity. On repeated dosing with the drug, tolerance to these various activities occurred. The tolerance was found to be dose-dependent in the rotarod and righting reflex tests and time-dependent in the locomotor and body temperature tests. Although the results do not allow a determination of whether this clearly demonstrated phenomenon in the mouse is primarily functional or dispositional, the slow onset (14 days) for complete tolerance may be indicative of a functional mechanism.     

Abuse of phencyclidine (PCP) a laboratory experience

Emergency Room patients at Riverside General Hospital who are found by the attending physician to have depressed sensorium and altered personality are routinely subjected to urine tests for various drugs of abuse including phencyclidine (PCP). The findings of the laboratory analysis of these patients are presented in this paper. The toxicology laboratory of this hospital performs screening procedures for various drugs on urine specimens by thin layer chromatography. Drugs detected are confirmed by gas chromatography and a homogeneous enzyme immunoassay technique. In 1981, 1.6% of the urine specimens of patients in the above-mentioned category were found to be positive for PCP. This percentage increased sharply during 1982 (5.8%) and 1983 (5.6%). During 1984 and 1985 the percentage dropped to 4.2% and 4.6%. It is implied from data that the abuse of this drug in this area has leveled off. The data also indicated that PCP is predominantly used by young adults with ages ranging from 21 to 30 years. The abuse of this drug in people over 40 years of age is comparatively very small. Among users of this drug, 67.5% are men and 32.5% are women. Out of 68 women found to be abusing PCP, 5 delivered their babies in this hospital. PCP was detected in the urine specimens of each of these babies. Four out of the five infants showed withdrawal symptoms such as extreme irritability, jitteriness, hyperactivity with high pitched cries and a poor ability to take food.     

Kidney transplantation in patients travelling from the UK to India or Pakistan

Sir, I read with great interest the letter by Higgins and co-workers[1].