The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the aetiology of Hodgkin's disease. To determine the role of EBV in childhood Hodgkin's disease in different geographical areas, immunohistochemical staining and in situ hybridisation were used to analyse latent membrane protein 1 (LMP 1) and small nuclear non-transcribed RNAs (EBER-1) respectively. Testing for EBV within the Reed-Sternberg and Hodgkin's cells was carried out in childhood Hodgkin's disease from 10 different countries. The proportion of LMP 1 positive cases varied significantly, being 50% of cases from the United Kingdom (38/75), South Africa (9/18), Egypt (7/14), and Jordan (8/16), 60% from the United Arab Emirates (6/10), 70% from Australia (11/16), 81% from Costa Rica (34/42), 88% from Iran (7/8), 90% from Greece (20/22), and 100% of the 56 cases from Kenya. A sensitive polymerase chain reaction based EBV strain typing technique was established using archival tissues. EBV strain type 1 was shown to be predominant in childhood Hodgkin's disease from the United Kingdom, South Africa, Australia, and Greece. Type 2 was predominant in Egypt. EBV strain types 1 and 2 were both detected in some cases of childhood Hodgkin's disease in the United Kingdom, Costa Rica, and Kenya. The high incidence of EBV and the presence especially in developing countries of dual infection with both strain types 1 and 2 may reflect socioeconomic conditions leading to malnutrition induced immunological impairment. The possibility of HIV infection also needs to be explored.     

Renovascular and growth effects of childhood sarcoid

A boy developed early onset sarcoidosis, an extremely rare mimic of juvenile chronic arthritis. Renal granulomas caused severe hypertension and renal impairment, which was controlled by azathioprine and steroids. Severe uveitis caused visual impairment. Impaired growth and delayed puberty, not previously described in childhood sarcoidosis, required growth hormone and testosterone treatment.     

Clinical significance of cough and wheeze in the diagnosis of asthma

OBJECTIVES: (1) To determine the prevalence of cough, wheeze, and breathlessness, both as single symptoms and in combination, in primary schoolchildren and their relation to doctor diagnosed asthma. (2) To identify in areas with different levels of dust pollution whether questionnaire reported 'cough alone' (without wheeze or breathlessness) had similar risk factors to the questionnaire reported triad of 'cough, wheeze, and breathlessness'. SUBJECTS AND METHODS: Two cross sectional community surveys of primary schoolchildren (5-11 years) were performed in 1991 and 1993. Parent completed questionnaires related to socioeconomic and respiratory factors were distributed through 15 schools in three areas of Merseyside, one of which had a relatively high level of dust pollution. Data were analysed to determine the prevalence of different respiratory symptom patterns. Univariate and multiple logistic regressions were used to investigate the associations between respiratory symptom profiles and potential risk factors. RESULTS: The proportions of completed questionnaires that were returned were similarly high in both surveys, 92% in 1991 (1872 of 2035) and 87% in 1993 (3746 of 4288). The proportions of children with different respiratory symptom patterns were similar in the two surveys: in 1991, asymptomatic children 70.1% (1109 of 1583), those with cough alone 8.9% (141 of 1583), and children with the symptom triad of cough, wheeze, and breathlessness 8.3% (132 of 1583); the figures for 1993 were 69.5% (2144 of 3083), 9.2% (284 of 3083), and 7.3% (224 of 3083) respectively. The prevalence of doctor diagnosed asthma increased from 17.4% in 1991 to 22.1% in 1993. The symptom of cough alone was associated with going to school in an area of increased air pollution. The symptom triad of cough, wheeze, and breathlessness was associated with reported allergies, familial history of atopy and preterm birth. In 1991, of children with the symptom of cough alone one in eight were diagnosed asthmatic; twice as many doctors made the diagnosis on this basis in 1993. CONCLUSION: The respiratory symptom of cough alone and cough, wheeze, and breathlessness represent clinical responses to different specific risk factors. Cough alone was associated with the environmental factors of school in the dust exposed zone and dampness in the home, whereas cough, wheeze, and breathlessness related to allergic history and preterm birth, and may be the best surrogate of asthma. Diagnosis of asthma on the basis of cough alone partly explains the increased prevalence of doctor diagnosed asthma, especially in dust polluted areas.     

Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological 'nesidioblastosis' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child's tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.     

Congenital misalignment of pulmonary vessels: an unusual syndrome associated with PPHN

We report a case of misalignment of pulmonary vessels and review the clinical features of all 13 cases reported to date. All were term infants dying from severe persistent pulmonary hypertension of the newborn. We have identified a triad of features that will alert neonatal clinicians to the possibility of this diagnosis: association with other non-lethal congenital malformations; delayed onset of presentation (especially after 12 h); and severe hypoxaemia refractory to conventional therapy. We recommend that any autopsy on newborn infants include a specific search for misalignment of pulmonary vessels to outline the pathophysiology and clinical significance of this disorder.     

Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity

Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n= 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/ day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (±SD) reticulocyte count (4.8 ±1.2 versus 2.7±1.4%; P <0.01), mean packed red cell volume (PCV) (0.38 ± 0.03 versus 0.34 ± 0.04, p < 0.05) and mean haemoglobin concentration (12.6 ± 1.1 versus 11.5± 1.2 g/100 ml; p< 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed. Anaemia, erythropoietin, iron, prematurity, protein     

Nutritional care and candidates for small bowel transplantation

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.     

Liver transplantation for hepatic cirrhosis in cystic fibrosis

Five children with cystic fibrosis complicated by hepatic cirrhosis received liver grafts. They all had portal hypertension with varices and three had variceal bleeding; respiratory function was only moderately impaired, but four were colonised with pseudomonas and one with aspergillus. Liver transplantation was well tolerated and there was no increase in respiratory or other early postoperative complications. Four of the children were fully well from 14 to 35 months after transplantation; the most recently transplanted had problems from a biliary stricture. In spite of the need for immunosuppression there was no increase in infection and respiratory function improved or remained stable. Once the children were stabilised after transplantation their nutrition and general health were greatly improved.     

Psychologic implications of surgical-orthodontic treatment in patients with anterior open bite

Two hundred eighty-two patients who received surgical-orthodontic treatment to correct anterior open bite were retrospectively evaluated by interview and questionnaires to determine the motivation and expectations before treatment, experience during treatment, psychosocial impact, functional and esthetic results, and satisfaction. All patients underwent a Le Fort I osteotomy, and 126 patients also received a bilateral sagittal split advancement osteotomy. The mean follow-up was 6 years. The most important reasons for treatment, as cited by the patients, were biting and chewing problems (28%), dissatisfaction with facial appearance (26%), and symptoms of temporomandibular joint (TMJ) dysfunction (21%). Patients with anterior open bite had a critical attitude toward facial appearance; therefore, esthetic aspects should be taken seriously. The expectations on chewing ability, phonetics, nasal passage, and facial appearance were met by the treatment; however, expectations on TMJ function, interincisal relationship, and biting ability were not completely fulfilled. There was a subjective improvement of TMJ sounds in 27% and a worsening in 14% of the patients. Dysesthesia of the infraorbital nerve was noticed in 4% of patients and of the mental or inferior alveolar nerve in 23% of the patients. Chewing and biting abilities improved in 53% and 73%, respectively. Facial appearance, self-confidence, and social interaction had improved. Patients had expected more information before and psychologic support after treatment. Despite the relapse of open bite in 20% of the patients, 75% were satisfied with the dental and 85% with the facial appearance.