Mechanisms of enhanced prevalence of asthma and atopy in developed countries

Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise.     

Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44

Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.     

Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome

Blood gene expression profiling has been applied to a variety of hematological malignancies, autoimmune disorders, and infectious diseases. This study applies this approach to genetic diseases without obvious blood phenotypes. Three genetic diseases including tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome were compared with a group of healthy controls. RNA from whole blood was surveyed using Affymetrix U133A arrays. Each disease was associated with a unique gene expression pattern in blood that can be accurately distinguished by a classifier. Genes on chromosome 21 were overexpressed in Down's syndrome, and genes controlling cell cycle and proliferation were associated with tuberous sclerosis complex type 2 or neurofibromatosis type 1. A subset of genes involved in cardiac development or remodeling were overexpressed in patients with Down's syndrome and congenital heart defects. These findings suggest that blood gene expression profiling on a broader basis might be useful for genetic disease screening/diagnosis and might help elucidate mechanisms and pathways that lead to genotype-phenotype differences.     

Inspiratory time and tidal volume during intermittent positive pressure ventilation.

We measured the tidal volume achieved during intermittent positive pressure ventilation using various inspiratory times with a minimum of 0.2 seconds. Results indicate that tidal volume shows no reduction with inspiratory times down to 0.4 seconds. An inspiratory time of 0.3 seconds, however, is likely to reduce tidal volume by 8%, and at 0.2 seconds a 22% fall may be anticipated.     

Endotracheal resuscitation of preterm infants at birth.

The adequacy of initial ventilation in 21 preterm babies (25-36 weeks'' gestation), who required endotracheal intubation and positive pressure ventilation, were studied. Pressure and flow were measured at the proximal end of the endotracheal intubation tube and expiratory volume calculated from the flow trace. The results were compared with those from a group of 26 term infants who also required resuscitation. Five of 21 preterm babies (24%) had adequate tidal ventilation with the first inflation. This rose to seven of 21 (33%) by the third inflation. This was significantly less than the results in the term infants (chi 2 = 4.38 p less than 0.05). Respiratory reflex responses to resuscitation were seen in 41% of inflations in preterm and 56% of inflations in term infants. There was a significant correlation between reflex activity and adequate ventilation in the preterm group (chi 2 = 11.83, p less than 0.001) but not in the term group (chi 2 = 0.212, p = NS). No correlation was seen between initial ventilation and outcome.     

Cancer of the paranasal sinuses and nasal cavities. Part II. Results of treatment

Part I of this account of a large consecutive series of 561 patients with cancer of the paranasal sinuses and nasal cavities treated at the Royal Marsden Hospital reveals some significant clinical and radiological features. The histopathology of every case has been carefully reviewed by one pathologist. Carcinoma was found to account for almost 80 per cent of tumours. An account is given of treatment methods in present use. End-results are reported in Part II of the paper and demonstrate that patients with sinus cancer receiving combined treatment in one centre have a better prognosis than when it is given in two or more hospitals. The discussion also concentrates on the use of main treatment methods and emphasizes some advances in surgical techniques. The value of initial cytotoxic chemotherapy is unproven but may offer some further advantage in prognosis. Precise comparison with the results of other series is not possible owing to lack of agreement on classification, variable case selection and differing treatment techniques.