Gastrointestinal stromal tumor in ileal neobladder

Abstract  Gastrointestinal stromal tumor (GIST) is a recently described mesenchymal tumor that can develop in any portion of the gastrointestinal tract. The occurrence of a GIST in the urinary tract is rare, but GIST can present as tumor of the urinary tract or invade the urinary tract. This is the first reported case of GIST in the ileal neobladder, which presented as a submucosal tumor. The patient underwent an open exploration and partial resection of the neobladder pouch.     

The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole

1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800  mg sulphamethoxazole and 160  mg trimethoprim) alone or 1  h after either fluconazole (150  mg) or ketoconazole (200  mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24  h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N₄-acetyl sulphamethoxazole, or sulphamethoxazole N₁-glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points.     

Proliferation of DU145 prostate cancer cells is inhibited by suppressing insulin-like growth factor binding protein-2

BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP-2) is expressed by all human prostate cancer cell lines and dramatically increases in the serum of prostate cancer patients. However, the role of IGFBP-2 in prostatic tumorigenesis is not known. The aim of the present study was to investigate the effects of IGFBP-2 on the proliferation of DU145 human prostate cancer cells in culture. METHODS: Using cell proliferation assays, we examined the effects of exogenously administered and endogenously modulated levels of IGFBP-2 on the proliferation of DU145 cells. RESULT: Cell growth was stimulated by exogenously administered IGFBP-2, but significantly retarded (P < 0.05) by its neutralizing antibody. Overexpression of IGFBP-2 by transfection also stimulated cell growth, which was significantly (P < 0.05) inhibited in transfectants expressing antisense mRNA to IGFBP-2. Furthermore, the proliferation of IGFBP-2 overexpressing cells was significantly dampened by exogenously administered IGFBP-2 antibody. CONCLUSIONS: IGFBP-2 is an autocrine growth factor for DU145 human prostate cancer cells and cell proliferation can be significantly retarded by neutralizing or inhibiting its synthesis. These findings provide a strong rationale for targeting IGFBP-2 in the testing of novel strategies to treat prostate cancer.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

PHARMACOKINETICS OF MORPHINE FOLLOWING ADMINISTRATION BY THE BUCCAL ROUTE

The pharmacokinetics of morphine administered via the buccalroute as a controlled release formulation were assessed afterthe administration of three different doses and found to belinear in the dose range 10–30 µg. The plasma concentrationsof morphine-3-glucuronide and morphine-6-glucuronide demonstratedconsiderable inter-subject variation and conclusions could notbe drawn regarding their pharmacokinetics. These large differencesmay reflect not only variability in buccal absorption, but mayhave resulted from the preparation dissolving in saliva, followedby absorption from the gastrointestinal tract. ^* Present addresses: Sir Humphry Davy Department of Anaesthetics,Bristol Royal Infirmary Bristol Present addresses: Shackleton Department of Anaesthetics, SouthamptonGeneral Hospital Southampton     

Reliability of the acetabular teardrop as a landmark

Summary This study investigated the effect of tilt and observer reliability on radiographic measurements of the position of a prosthetic acetabular cup in seven dry bone pelves using the teardrop as a landmark. Coronal or sagittal tilt of more than five degrees was easily recognisable and there was effectively no observer variation in the measurements up to this limit. In addition, 90 out of 100 randomly selected antero-posterior pelvic radiographs from an outpatient department were not significantly rotated and 93 demonstrated a clearly defined teardrop. Measurements about the teardrop on routine radiographs are therefore sufficiently accurate to allow assessment of prosthetic position.

---

La valeur du sourcil cotyloidien comme repère d'analyse radiologique

Résumé Cette étude, conduite sur 7 bassins secs, apprécie l'effet de l'inclinaison du bassin sur la qualité de l'analyse radiographique de la position d'une cupule prothétique de hanche en utilisant le sourcil cotyloïdien comme repère. Une inclinaison du bassin dans les plans coronal et sagittal est aisément détectable et il n'existe pas de variation d'analyse entre les différents observateurs en dessous de 5° d'inclinaison. De plus, sur 100 radiographies antéro-postérieures de bassin choisies au hasard dans les dossiers de consultation, 90 avaient été réalisées sans incidence particulièrement adaptée et l'on pouvait repérer facilement le sourcil sur 93% d'entre elles. Les mesures faites sur des radios de routine sont donc suffisamment précises pour permettre l'évaluation de la position d'une prothèse à partir du sourcil cotyloïdien.