Neurological sequelae in children surviving mechanical ventilation in the neonatal period

The incidence of mental defect, visual and hearing disability, major neurological handicap, and such minor neurological handicap as can be detected on examination at 2--9 years without formal intelligence testing, is presented among survivors of neonatal mechanical ventilation at Hammersmith Hospital between the years 1966--1973 inclusive. 77(21%) of 367 children survived, over three-quarters of them being born elsewhere. 3 died before the age of 6 months, 2 suddenly and unexpectedly at home, the third accidentally. 1 child was lost to follow up. 11 (15%) of the remaining 73 children had neurological sequelae as defined. In two-thirds this was moderate to severe. Spastic diplegia may no longer be the commonest form of cerebral palsy among those of low birthweight, particularly those surviving severe neonatal illness.     

Non-infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis

Forty two infants below the age of 2 years presenting with chronic non-infective diarrhoea and shown to have histologically proved colitis were investigated over a five year period. Allergic colitis was the most common cause of colitis, accounting for 62% of the cases. Other colitides diagnosed included: non-specific colitis, autoimmune enterocolitis, and ulcerative colitis accounting for 10% each; severe combined immunodeficiency 7%, and Crohn's disease 3%. A positive family history and a personal history of atopy were obtained in 48% and 29% of the cases respectively. Serum immunoglobulin A, IgG2, and IgG4 were very low in over 50% of the entire cohort of infants with colitis; 66% of those with severe combined immunodeficiency, autoimmune enterocolitis, and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying increase in CD8 in two thirds of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. Thus infants with proved non-infective colitis as a group show a high prevalence of IgA, IgG2, and IgG4 deficiency. It is likely that this minor deficiency of mucosa associated immunoglobulin production has a role in the pathogenesis of the colitic process.     

Length of stay in the hospital emergency department]

We evaluated the overall time spent by patients in the emergency department as well as the time employed in the different steps of emergency care and their relationship to patient's diagnosis. Data from 2421 patients, randomly selected, amongst those who attended hospital's emergency department units between november 22-28th 1990 were collected data in a specially designed form. The mean time required for examination was 13 minutes and this procedure was carried out, in average, 18 minutes after admission. The mean length of stay in emergency area was 127 minutes with a significant increase in those cases rated as "true" emergencies.     

UNDESCENDED TESTIS: A STUDY OF 50 CASES

Fifty consecutive cases of undescended testis treated at a service hospital over a period of 3 years from January 1993 to December 1995 were studied. Only 2 patients (4%) were below the age of 2 years and 25 (50%) were past the age of 15 years. Two cases presented with seminoma in intraobdominal testis. Ultrasonography was found unreliable in localizing the impalpable testis. Subdartos pouch orchiopexy (Winsburry-White) was the definitive procedure adopted in 21 out of the 25 orchiopexies performed and the results were good. Orchidectomy seems the best option of treatment in post-pubertal patients with unilateral symptomatic maldescent.KEY WORDS: Cryptorchism, Testis, Orchiopexy, Orchidectomy, Testis undescended     

Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients

The genetic basis of myotonic dystrophy (DM) is the expansion of an unstable CTG repeat in the 34 UTR of the DM protein kinase gene on chromosome 19. One of the principal features of the DM mutation is an extraordinarily high level of somatic mosaicism, due to an extremely high degree of somatic instability both within and between different tissues. This instability appears to be biased towards further expansion and continuous throughout the life of an individual, features that could be associated with the progressive nature of the disease. Although increasing measured allele size between patients clearly correlates with an increased severity of symptoms and an earlier age of onset, this correlation is not precise and measured allele length cannot be used as an accurate predictor of age of onset. In order to further characterize the dynamics of DM CTG repeat somatic instability, we have studied repeat length changes over time in 111 myotonic dystrophy patients with varying clinical severity and CTG repeat size over time intervals of 1-7 years. We have found a direct progression of the size heterogeneity over time related to initial CTG repeat size and the time interval and always biased towards further expansion. Attempts to mathematically model the dynamics have proved only partially successful suggesting that individual specific genetic and/or environmental factors also play a role in somatic mosaicism.      

Bcl-2 overexpression results in reciprocal downregulation of Bcl-X(L) and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis

Testicular germ cell tumours are hypersentive to chemotherapy and cell lines derived from these tumours are chemosensitive in vitro. We have previously shown that these cell lines express undetectable levels of the suppressor of apoptosis Bcl-2 and relatively high levels of the apoptosis inducer Bax (Chresta et al., 1996). To determine whether the absence of Bcl-2 in these cell lines makes them highly susceptible to drug-induced apoptosis, Bcl-2 was expressed ectopically in the 833K testicular germ cell tumour cell line. Stable overexpressing clones were isolated and three clones were studied further. Surprisingly, Bcl-2 overexpressing cells were sensitized to chemotherapy-induced apoptosis compared to the parental and vector control cells. Analysis of potential mechanisms of sensitization revealed there was a reciprocal downregulation of the endogenously expressed Bcl-X(L) in the Bcl-2 overexpressing clones. Downregulation of Bcl-X(L) to the same extent using antisense oligonucleotides enhanced etoposide-induced apoptosis by twofold. Our results indicate that Bcl-2 and Bcl-X(L) have different abilities to protect against chemotherapy-induced apoptosis in testicular germ cell tumours. In contrast to findings in some tumour cell types, Bcl-2 did not act as a gatekeeper to prevent entry of p53 to the nucleus.