Noonan's and DiGeorge syndromes with monosomy 22q11

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.     

Effects of a few food diet in attention deficit disorder

Seventy-eight children, referred to a diet clinic because of hyperactive behaviour, were placed on a 'few foods' elimination diet. Fifty nine improved in behaviour during this open trial. For 19 of these children it was possible to disguise foods or additives, or both, that reliably provoked behavioural problems by mixing them with other tolerated foods and to test their effect in a placebo controlled double blind challenge protocol. The results of a crossover trial on these 19 children showed a significant effect for the provoking foods to worsen ratings of behaviour and to impair psychological test performance. This study shows that observations of change in behaviour associated with diet made by parents and other people with a role in the child's care can be reproduced using double blind methodology and objective assessments. Clinicians should give weight to the accounts of parents and consider this treatment in selected children with a suggestive medical history.     

Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.     

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.     

Thermal balance and metabolic rate during upper respiratory tract infection in infants

Sequential recordings were made in the first five months after birth of metabolic rate, environmental temperature, and body temperature during sleep at home in 17 infants, each with an older sibling. Further recordings were made whenever an older sibling developed an upper respiratory tract infection (URTI), again four to six days later, and again two weeks later, aiming to achieve recordings before, during, and after an URTI in the infant. The temperature of the room and wrapping of the infant were determined according to their usual practice by the parents. Parents added appropriate wrapping to achieve thermal neutrality based on our calculated values and the measured oxygen consumption. In five of the six infants who developed an URTI in the first three months after birth there was no change or a decrease in metabolic rate at the time of the infection; for infants older than 3 months the metabolic rate increased in three of the five episodes recorded. Peripheral skin temperature decreased at the time of URTI at all ages, though in the older infants it usually increased in parallel with rectal temperature during the latter part of the night, when pyrexia was most common. Infants thus respond to URTI by heat conservation. In the younger infants the lower metabolic rate and the further decrease in this rate with URTI means that fever is rare, and their temperature may decrease on infection. In the older infants the increase in metabolic rate (from an already higher baseline) may result in fever. These differences may contribute to the increased vulnerability of the older infants to heat stress, particularly at the time of acute viral infections.     

The multidisciplinary management of a family with epithelial ovarian cancer.

OBJECTIVE: To describe the management of a family with an inherited predisposition to ovarian and breast cancer. Particular attention is paid to the problems of contraception, screening, prophylactic surgery and hormone replacement therapy. SETTING: The multidisciplinary Grampian Familial Epithelial Ovarian Cancer Study Group. SUBJECTS: 162 members of a family extending over five generations. In the third generation, five of the 10 women died with epithelial ovarian cancer. Three women in generation IV have developed pre-menopausal breast cancer. There are now 78 family members in the fifth generation aged between 2 and 22 years. INTERVENTIONS: Counselling of female family members is started at the age of 18 years. The combined oral contraceptive pill is advocated to suppress ovulation. Gynaecological follow-up after the age of 28 includes yearly pelvic examination, transvaginal ultrasonography and serum CA125 estimation. Laparoscopy with peritoneal cytology is indicated if any part of this yearly assessment is abnormal. Prophylactic oophorectomy is advised between the ages of 35 and 40 years after the family is complete. In generation IV, 20 of the 29 women have undergone prophylactic oophorectomy. Oestrogen hormone replacement therapy with a cyclical progestogen is recommended after prophylactic oophorectomy. Breast cancer screening starts at the age of 25 and involves annual clinical breast examination augmented by mammography and breast ultrasound. CONCLUSIONS: Only by the careful questioning and recording of family history, including at least third degree relatives (cousins), will similar groups with familial ovarian/breast cancer be identified. When predisposing genes are characterized it will be possible to identify carriers within the family and concentrate clinical effort on them while offering appropriate reassurance to those with decreased risk.