Oral spray immunization may be an alternative to intranasal vaccine delivery to induce systemic antibodies but not nasal mucosal or cellular immunity.

Sixty-five healthy adult volunteers were immunized four times at 1-week intervals with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1) without adjuvant. The vaccine was administered as nasal spray with a newly developed device to secure intranasal delivery (OptiMist, OptiNose AS, Oslo, Norway), as regular nasal spray, nasal drops or as an oral spray. Significant IgA-antibody responses in nasal secretions were induced in volunteers immunized intranasally but not after oral spray immunization. In saliva, IgA antibodies were only marginally amplified even after oral spray immunizations. At least 73% of the volunteers belonging to any group of vaccine delivery reached serum haemagglutination inhibition titres of 40 or higher, considered protective against influenza, after only two vaccine doses. Those who had the vaccine delivered intranasally also showed evidence from in vitro secretion of granzyme B that cytotoxic T cells had been stimulated. Although immunization with the breath-actuated OptiMist device and nasal drops were superior with respect to both mucosal and systemic immune responses, oral spray immunization might still be considered for studies of mucosal adjuvants that are not yet acceptable for intranasal use.

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

AIM: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. METHODS: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. RESULTS: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR=4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan. CONCLUSION: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.

Presence of platelet antibodies in idiopathic thrombocytopenic purpura may discriminate acute from chronic disease.

UNLABELLED: This study estimated the prevalence of serum antibodies against thrombocyte glycoproteins, at disease onset (54 patients) and later on during the course of the disease (71 patients), in sera from children with idiopathic thrombocytopenic purpura (ITP). Only a minority had serum antibodies at disease onset, with a significantly higher frequency in those who developed the acute form of the disease than in those who developed the chronic form. Serum antibodies may persist after spontaneous cure of acute disease. There was no switch from immunoglobulin M (IgM) to IgG antibodies over time. CONCLUSION: The pathogenesis of the acute and chronic forms of ITP may be different.

Diagnostic assessment of haemorrhagic rash and fever.

AIMS: To establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes for haemorrhagic rashes accompanied by fever. METHODS: In a prospective study, 264 infants and children hospitalised with fever and skin haemorrhages were studied. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables distinguished between meningococcal disease and other conditions on admission: (1) skin haemorrhages of characteristic appearance; (2) universal distribution of skin haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than 2 mm; (4) poor general condition (using a standardised observation scheme); and (5) nuchal rigidity. If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

The fluctuating pattern of various genome types of respiratory syncytial virus in Copenhagen and some other locations in Denmark.

A semi-nested RT-PCR method based on a region of the F and G glycoprotein genes was established, allowing the simultaneous detection and differentiation of group A and group B isolates of respiratory syncytial virus (RSV). The PCR products were subjected to digestion with restriction endonucleases to further differentiate the isolates. Using, in addition, previously reported studies the prevalence of various genome types in the Copenhagen region over a period of 6 years was established. Furthermore, the prevalence of genome types was determined in a distant region in Denmark during the winters of 1996/97 and 1997/98, and in yet another distant region during the winter of 1997/98. It was shown that the different regions in Denmark to a large extent share the same pool of genome types of RSV. Yet, while the fluctuating patterns of the two groups and various genome types were almost identical at different hospitals in the Copenhagen region, they varied between the different regions. This suggests that epidemics in local communities primarily rely on region-specific herd immunity parameters and emerge from strains endemically circulating in these local communities. Group B strains in Copenhagen showed an overall predominance, being predominant in three of the six epidemic seasons studied, and of almost equal predominance in one season.

Nitrofurantoin versus trimethoprim prophylaxis in recurrent urinary tract infection in children. A randomized, double-blind study.

The efficiency of nitrofurantoin and trimethoprim prophylaxis in preventing recurrent urinary tract infections (UTI) was compared by means of actuarial percentage recurrence-free curves in a randomized, double blind study in 130 children (126 girls, 4 boys) aged 1 to 14 years (mean 7.5). The children received the antibiotics for 6 months. Nitrofurantoin proved to be the most efficient prophylactic drug in patients with abnormal urography and/or reflux (n = 60) as evaluated by actuarial percentage recurrence-free analysis (p = 0.0025). However, no differences was found in patients without urinary tract abnormalities. Nitrofurantoin prophylaxis altered neither the pattern of resistance nor the bacteriological constellation, while patients receiving trimethoprim prophylaxis had 76% trimethoprim resistant bacteria during prophylaxis, compared with 8% before (p less than 0.0001) and 17% after (p less than 0.0001) prophylaxis. The percentage of recurrences due to E. coli (70-80%) was unaffected by trimethoprim prophylaxis, but the proportion due to trimethoprim resistant E. coli was significantly higher during prophylaxis (65%) than before (6%, p less than 0.0001) and after (11%, p less than 0.001). The percentage of Staphylococcus epidermidis UTI was significantly higher during trimethoprim prophylaxis (27%) than before (2%, p less than 0.0003). Following prophylaxis there was no difference in the actuarial percentage recurrence-free curves of the two regimens. Side effects occurred more frequently in the nitrofurantoin group (37%) than in the trimethoprim group (21%) (p = 0.05). The majority of side effects in the nitrofurantoin group derived from gastrointestinal symptoms. In conclusion, nitrofurantoin is recommended as the first choice prophylactic treatment of children with recurrent UTI and urinary tract abnormalities.

Auditory function after continuous infusion of gentamicin to high-risk newborns.

Audiometry was performed at four years of age in 69 of 105 surviving children who had received continuous intravenous infusion of gentamicin during neonatal intensive care. A hearing loss of 20 dB was found in 2 of them (3%), corresponding to that shown in other studies of survivors following neonatal intensive care. Free field audiometry performed in another 7 children and questionnaires returned from 13 of the remaining 29 gave no suspicion of hearing loss. Thus there is no indication that continuous 24 hours intravenous infusion of gentamicin causes more hearing impairment than intermittent intravenous or intramuscular administration.

A case of the ring 20 syndrome.

A 4-year-old child with a ring 20 chromosome mosaicism, low grade developmental delay, and seizures is described.

Cerebrospinal fluid glutamine in intracranial hemorrhage in the newborn.

Cerebrospinal fluid concentration of glutamine was measured in 43 premature and mature babies suffering from intracranial hemorrhage. Compared with a control group of 38 infants we found elevated levels in all infants with intraparenchymal and subarachnoid hemorrhages. Two out of ten children with subependymal hemorrhages and approximately half of the children with intraventricular hemorrhages also had elevated levels. Elevated levels of cerebrospinal fluid glutamine persisted for up to three weeks and maximum levels were reached two days to two weeks after birth. The analysis of cerebrospinal fluid glutamine concentration might be useful in the early diagnosis of intraparenchymal and subarachnoid hemorrhage in the newborn infant.

Congenital chylothorax: management by ligature of the thoracic duct.

Congenital chylothorax in a male infant persisted for 10 weeks despite repeated thoracocenteses and dietary regimens which included total parenteral nutrition for 37 days and a peroral semielementary diet with medium-chain triglyceride content for 19 days. Thoracotomy disclosed a small leak in the thoracic duct. The duct was ligated above and below the leak, as attempted repair was unsuccessful. There was no recurrence of pleural effusion after the operation and no distal lymphoedema was observed.

Relation between ionised calcium and pH in infants with acute acid-base disturbances.

Plasma ionised calcium, [Ca2+], and pH were negatively correlated in 21 infants with disturbed acid-base homeostasis. The slopes of the individual regression lines indicated a mean decrease in [Ca2+] of 42% per pH increase. (Mean delta log[Ca2+]/delta pH = -0.184, SEM = 0.050, p less than 0.001). The value was not significantly different from the relation between [Ca2+] and pH in vitro, when whole blood or plasma was equilibrated with CO2-air mixtures. pH and [Ca2+] must be measured and considered together to allow a proper interpretation of the result.

Heart rate and ventilatory frequency as dimension-dependent variables.

Heart rate (HR) and ventilatory frequency (f) were determined at rest in 79 boys and 91 girls aged 0.07-20 years and with a range in heights from 54-198 cm to establish the relationship between decrease in HR and f during early life with increase in body dimensions. From theoretical considerations it is assumed that frequencies such as HR and f are proportional to a characteristic linear dimension of the subjects in minus first power (approximately equal to rho-1). In the present material resting HR and f decreased with increasing height of the subjects according to the equations HR = 6,408 . height-0.9015 (r = 0.8983) and f = 5,969 . height-1.1691 (r = 0.8471). These results suggest that the decrease in resting HR and f during childhood and adolescence corresponds well with increase in body dimensions. A similar equation was developed for HRmax within the range of heights from 149-198 cm. Only a slight dependency on height was observed (HRmax = rho-0.1642, r = 0.3796).

Acute haematogenous osteomyelitis and septic arthritis in childhood. A 10-year review and follow-up.

Seventy-three children, who were admitted to hospital during the period 1965-1976 with osteomyelitis or septic arthritis, were included in a retrospective study as well as a clinical and radiological follow-up. Ten cases of osteomyelitis occurred during the neonatal period and about half of the cases of osteomyelitis and septic arthritis occurred before the age of 2 years. Staph. aureus was the dominating pathogen isolated and half of the strains were penicillin-resistant. The group of children with osteomyelitis who were given early treatment, i.e. within 1 week, against penicillin-resistant Staph, aureus had a higher clinical cure rate after 1 month (0.01 < P < 0.025) compared with the rest of the children. Five children developed recurrent or chronic osteomyelitis. An early follow-up in 69 children 1-11 years after the disease showed that none had any complaints or invalidity. However, one patient with neonatal septic arthritis presented severe dysplasia and subluxation of the hip and four children with osteomyelitis had severe, but asymptomatic, radiological changes.