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.     

Characteristics of patients with congenital clasped thumb: a prospective study of 40 patients with the results of treatment

Purpose  Congenital clasped thumb is a deformity that is associated with heterogeneous congenital anomalies and it has been addressed in many congenital syndromes. The aim of this study was to diagnose and evaluate cases of clasped thumb as regards the associated congenital anomalies and syndromes, and evaluation of the results of treatment of such cases. Methods  A prospective study on 40 patients with 73 clasped thumbs was done. All the patients’ data regarding their personal, family, pregnancy and developmental histories were recorded. All the patients were exposed to thorough clinical and radiological examination and genetic assessment. The cases were classified using the Tsuyuguchi et al. (J Hand Surg [Am] 10:613–618, 1985) classification into three types. Conservative treatment was adopted in ten hands, and surgical treatment was performed for 28 hands in 17 patients, with an average follow-up of 26 months. Results  Positive consanguinity was recorded in 57.5% of cases. Associated anomalies were recorded in 77.5% of cases. Type I was the most common one, followed by type III and then type II. Conservative treatment is effective in type I cases when presented early, and all patients were satisfied with the results of surgical treatment. Conclusions  We reported associated anomalies which are to our knowledge have not mentioned before in the literature which include; congenital blindness, radial deviation of the index finger and ventricular septal defect. We found that 68% of the patients had associated syndromes, and this has not been mentioned before. In this study, we found that there were no difference between type II and type III clasped thumb as regards the pathological findings, severity, the operative procedures, the treatment protocol and the operative results. Properly planned treatment gives satisfactory results.     

Carcinoma of thyroid--clinical presentation and outcome.

The clinical, biochemical and pathological features of 31 patients with thyroid carcinoma managed at Hospital Universiti Sains Málaysia, Kubang Kerian from 1985 to 1989 were analyzed. There were 25 females and 6 males. The types of carcinoma were: papillary-17 cases; follicular-10 cases; medullary-2 cases and anaplastic-2 cases. For papillary carcinoma the mean age of the patients was 52.9 years. For follicular carcinoma the mean age was 48.3 years, for medullary carcinoma, 48.5 years and for anaplastic, 74.5 years. All patients had pre-existing goitre except for 2 and most presented with advanced disease. The mean duration of symptoms for papillary carcinoma was 3.7 years, follicular carcinoma 1.6 years, medullary carcinoma 13.5 years and anaplastic carcinoma 6 months. 12 patients presented with goitre of increasing size; 9 had compression symptoms; 4 presented with cervical lymph node enlargement and 6 presented with bony pains of whom 2 had paraplegia. None of the patients were ever thyrotoxic or hypothyroid. Treatment in general was unsatisfactory because of patients' non-acceptance of surgery and/or radioactive iodine.     

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.