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.     

Dissociation between the effects of theophylline and caffeine on premature airway smooth muscles

Xanthine derivatives relax adult airway smooth muscle (ASM). To determine whether caffeine and theophylline relax preterm ASM contracted by acetylcholine, 27 tracheal rings obtained from seven preterm lambs (120-135 d gestation) were studied. ASM was contracted using 10(-5) M acetylcholine (control) after the muscle was stretched to the length at which maximum active tension was developed isometrically. Concentration-effect curves for each xanthine were obtained by cumulative addition of the drug. Theophylline produced a significant decrease (p less than 0.001) in active tension at each dose, whereas caffeine significantly increased (p less than 0.001) active tension at 10(-4) and 10(-3) M concentrations. Addition of caffeine and theophylline to previously uncontracted ASM did not alter tension. Thus, it appears that, in contrast to their effect on adult ASM, the xanthine derivatives caffeine and theophylline have differential effects on prestimulated ASM in preterm lambs. These findings raise important questions about various aspects of the current therapeutic use of caffeine and theophylline.     

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.     

Cytological and cytoarchitectural changes in the feline cerebral cortex during experimental infantile hydrocephalus

While many reports have documented the effects of hydrocephalus on the ependyma and periventricular white matter, primarily in adult animal models, little is known about alterations specific to neurons. The present study has evaluated qualitatively the effects of hydrocephalus on the neurons and vasculature of the cerebral cortex in a neonatal animal model. The cisterna magna of 4 to 11-day-old kittens was injected with a solution of 25% kaolin to induce hydrocephalus. Ultrasonographic evidence of hydrocephalus was noted within 3-5 days of injection. Hydrocephalus progressed until day 18-25 postinjection when the animals were sacrificed. The cytologic and cytoarchitectural changes within the cortical mantle of affected animals were compared with control age-matched counterparts who had undergone intracisternal saline injections. Areas 4 (primary motor), 22 (association) and 17 (primary visual sensory) were examined light microscopically. Neurons from hydrocephalic brains exhibited 3 types of pathological response. Pyknotic somata were shrunken, disoriented and so hyperchromatic that neither nuclei or nucleoli could be delineated. Reactive somata were also shrunken and hyperchromatic, but nuclei and nucleoli could still be observed. Many neurons contained an abundance of vacuoles, giving their somata a flocculent appearance; these cells were termed 'spongy' neurons. Both normal and pathological neurons were smaller and disoriented, with a considerable decrease in neurons noted in areas 22 and 17 from severely hydrocephalic animals. The deeper cortical layers were more affected than the more superficial laminae in that more reactive and pyknotic neurons were present in layers V and VI. As the ventriculomegaly became more severe, changes could be observed in neurons within layers II and III. Furthermore, the cerebral vasculature exhibited a decrease in the number of vessels and a preponderance of profiles oriented parallel to the meningeal surface. The severity of these effects followed a rostral to caudal gradient, such that the occipital cortex demonstrated the most damage. These results suggest that both the motor deficits and the subtle cognitive deficiencies seen with hydrocephalus may be attributed to perturbation of neuronal and vascular elements in the cerebral cortex.     

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.     

The infant's eustachian tube lumen: the pharyngeal part

A study of Eustachian tube measurements in infants and children is presented. The study included 33 Eustachian tubes from normal temporal bones and 10 Eustachian tubes from temporal bones harbouring acute otitis media. The temporal bones underwent histologic serial sectioning. The lumen of the Eustachian tube's first portion, i.e. the pharyngeal part, was measured with the aid of a grid mounted on a microscope. These measurements show: A. The Eustachian tube lumen grows and enlarges to a small extent with age. B. Each age group presents a considerable variation in the range of area of the lumen comparable with the natural biological distribution. C. No statistical difference was found between the size of the pharyngeal portion of the lumen of the Eustachian tube from temporal bones which had acute otitis media and those coming from non-pathological ears. This comparison took into consideration age and physiological distribution. These findings are similar to our earlier findings regarding the isthmic region.