From the outside-in: Epidermal targeting as a paradigm for atopic disease therapy

Atopic dermatitis(AD) is a chronic inflammatory skin disorder which can precede asthma and allergic rhinitis in a disease trajectory known as the atopic march. The pathophysiology of AD includes cutaneous inflammation, disrupted epidermal barrier function, xerosis and propensity to secondary infections. AD had previously been thought to arise from the systemic atopic immune response and therapies are therefore directed towards ameliorating Th2-mediated inflammation. However in recent years the focus has shifted towards primary defects in the skin barrier as an initiating event in AD. Links between loss-of-function variants in the gene encoding filaggrin and disrupted activity of epidermal serine proteases and AD have been reported. Based on these observations, a mechanism has been described by which epidermal barrier dysfunction may lead to inflammation and allergic sensitization. Exogenous and endogenous stressors can further exacerbate inherited barrier abnormalities to promote disease activity. Pathways underlying progression of the atopic march remain unclear, but recent findings implicate thymic stromal lymphopoietin as a factor linking AD to subsequent airway inflammation in asthma. This new appreciation of the epidermis in the development of AD should lead to deployment of more specific strategies to restore barrier function in atopic patients and potentially halt the atopic march.     

Percutaneous cecostomy: controlled transperitoneal approach

The authors present two cases of percutaneous cecostomy performed with a modified approach previously described for percutaneous gastrostomy and cholecystostomy. T-fastener devices were used to affix the cecum to the anterior abdominal wall; thus, the potential problem of fecal spillage was prevented. In both cases, adequate fecal drainage was provided without complication.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Methotrexate-induced erythema multiforme

The folic acid antagonist, methotrexate, has many applications in the treatment of neoplastic disease. While methotrexate produces several well-recognized toxic effects, cutaneous reactions are rare. A patient who developed classical erythema multiforme while receiving low-dose methotrexate as treatment of nonmetastatic gestational trophoblastic neoplasia is presented. Erythema multiforme has been associated with a variety of pharmacologic agents. It typically presents as a pruritic papular dermatitis of the extensor surfaces of the extremities and may require multiple skin biopsies to establish the diagnosis. Spontaneous reversal usually occurs with discontinuation of therapy. Patients developing erythema multiforme related to antineoplastic agents should be switched to an alternate regimen.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.     

Does age at the start of breast feeding influence infantile diarrhoea morbidity? A case–control study in periurban Guinea–Bissau

Colostrum protects the newborn from intestinal infection by its content of secretory immunoglobulin A and other immediately acting factors. It may also induce maturation of the child's gastrointestinal immune defences, thus contributing to the protection against diarrhoeal disease later in infancy. To test this hypothesis, a case–control study on breast feeding and diarrhoea was carried out in a periurban community in Guinea–Bissau. The child's age at the start of breast feeding was ascertained soon after birth ( n = 279). Subsequent cases of acute diarrhoea ( n = 66) were identified at 3–monthly examinations, and four concurrent controls were randomly selected among attendants. Three separate estimates of association showed that the cases tended to have started breast feeding later after birth than the diarrhoea–free controls, but no single test was statistically significant. Early breast feeding might have consequences for diarrhoeal morbidity after the neonatal period.     

Incorporation of linoleic and arachidonic acids into ovine placental phospholipids in vitro

The incorporation of [1-14C]-linoleic acid and [1-14C]-arachidonic acid into the lipids of ovine placental homogenate was studied. Both fatty acids were incorporated mainly into the phospholipid fraction with much lower levels being found in the diacylglycerols and triacylglycerols, particularly when the substrate was [1-14C]-arachidonic acid. Within the phospholipid fraction, both substrates were incorporated largely into phosphatidic acid although significant levels of incorporation were found in the phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol fractions. The incorporation of [1-14C]-arachidonic acid into phosphatidylcholine was lower and into phosphatidylethanolamine and phosphatidylinositol was higher than those levels found when the substrate used was [1-14C]-linoleic acid. While some of the trienoic and tetraenoic, but not pentaenoic, desaturation products of [1-14C]-linoleic acid were detected in phosphatidylcholine and phosphatidylethanolamine, the highest levels of incorporation of these metabolites were into phosphatidic acid. Similarly, the pentaenoic products of [1-14C]-arachidonic acid were found mainly in phosphatidic acid although significantly higher levels were observed in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol. The results suggest that in ovine placental tissue polyunsaturated fatty acids, whether supplied pre-formed or made available by desaturation and elongation processes, could potentially be incorporated into phospholipids by the de novo route via phosphatidic acid.