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.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

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.     

Mobile intraventricular cyst of the third ventricle treated with stereotactic puncture. Report of a case

A case of a pedunculated arachnoid cyst within the third ventricle is presented. The cyst was small so as not to appear as a significant expanding lesion on CT. The clinical history, however, suggested intermittent increase of the intracranial pressure. On CT there was some widening of the lateral and third ventricles, while the fourth ventricle had normal width. This finding in combination with the clinical history prompted further neuroradiologic examinations, including pneumoencephalography and ventriculography. The presence of a pedunculated mobile cystic lesion within the third ventricle was shown and its nature further elucidated by stereotactic puncture combined with contrast injection into the cyst. After emptying of the cyst, the patient has been free of symptoms during an observation time of 2 years. The diagnostic and differential diagnostic aspects are discussed and the value of traditional neuroradiologic methods emphasized.     

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.