KRAS mutation and microsatellite instability in endometrial adenocarcinomas showing MELF-type myometrial invasion.

BACKGROUND: Some uterine endometrioid adenocarcinomas exhibit a distinctive morphological phenotype characterised by the formation of microcystic, elongated and fragmented (MELF) glands. Immunohistochemical studies have suggested that MELF-type changes represent an epithelial-mesenchymal transition which has been associated with KRAS activation in various tumours. AIMS: To investigate the molecular characteristics of endometrial tumours showing MELF, with particular reference to the frequencies of KRAS and BRAF mutations and of microsatellite instability (MSI). METHODS: MSI, and KRAS and BRAF mutation status, were assessed in 33 low-grade endometrial adenocarcinomas showing MELF features and the results compared with 33 control cases exhibiting a 'conventional' pattern of myometrial invasion. Standard histological parameters were also reviewed. RESULTS: Tumours with a MELF pattern of myometrial invasion showed more frequent vascular invasion and focal mucinous differentiation. KRAS mutations were more frequent in MELF positive than MELF negative tumours (45% vs 30%), but this difference was not statistically significant. BRAF mutations were not identified in any of the cases. MSI was identified in 20% of cases overall but did not correlate with the MELF phenotype. CONCLUSIONS: Mutations in KRAS and BRAF genes are not directly implicated in the development of a MELF pattern of invasion in endometrial carcinoma. However, RAS-associated signalling pathways could be activated through other genetic or epigenetic mechanisms. The characterisation of such alterations may become increasingly important as novel therapies are developed that target mediators involved in tumour invasion.

Accidental asphyxia in bed in severely disabled children.

OBJECTIVE: To determine whether there are specific situations which may increase the risk of accidental asphyxia during sleep in children with physical and mental disabilities. METHODOLOGY: Review of all cases where death was attributed to accidental asphyxia caused by unsafe sleeping situations in children listed in the Department of Histopathology database over a 10-year period from March 1989 to February 1999. RESULTS: A total of 26 cases were found (M:F, 19:7; age range, 1-48 months; average age, 7.4 months). Of those cases, two involved children with significant mental and physical impairment. Case 1: A 4-year-old boy with Klippel-Trenaunay-Weber syndrome, macrocephaly and severe developmental delay, was found dead with his head hanging over a wooden board attached to the side of his bed. Case 2: A 4-year-old boy with lissencephaly and severe developmental delay was found dead wedged between a retractable mesh cot side and the side of his bed. In both cases the devices resulting in death had been put in place to prevent the boys from falling out of bed. CONCLUSIONS: Accidental asphyxia in physically and mentally impaired children may be caused by devices that have been used to prevent injury from falling out of bed. Careful assessment of the specific developmental problems that children suffer should be undertaken before their beds are modified. It may be safer for these children either to have no barrier, or to have drop-sided cots/beds that meet recognized safety standards.

Clinical and laboratory features of severe and complicated falciparum malaria the experience from Gonder Hospital.

Over a period of 6 months in 1988, 104 patients with severe and complicated falciparum malaria were admitted to the Gonder College Hospital (GCH), Gonder, Ethiopia; 85 male (81.7%) and 19 female (18.3%). The age ranged between 14 and 70 years with a mean age of 31 years. Eighty-one patients (78.3%) had moved from a nonendemic to a malariaendemic area shortly before their illness. Altered state of consciousness, hyperparasitaemia and severe anaemia were the most frequent complications found. Fifty-three patients (51.0%) died. Non-immune status and unknown duration of symptoms were significantly associated with mortality. Among those who died, comatose state on admission, hyperparasitaemia and acute renal failure were more frequently seen. Forty-six (86.8%) had developed two or more complications and 15 (28.3%) had superimposed bacterial infections. Inadequate preventive measures and treatment facilities may be two important factors accounting for the high mortality.