Subclinical hyperthyroidism due to a thyrotropin receptor (TSHR) gene mutation (S505R)

AIM: To identify the molecular defect by which non-autoimmune subclinical hyperthyroidism was caused in a 6-mo-old infant who presented with weight loss. METHODS: Congenital non-autoimmune hyperthyroidism is caused by activating germline mutations in the thyrotropin receptor (TSHR) gene. Therefore, the TSHR gene was sequenced directly from the patient's genomic DNA. RESULTS: Molecular analysis revealed a heterozygous point mutation (S505R) in the TSHR gene as the underlying defect. CONCLUSION: A constitutively activating mutation in the TSHR gene has to be considered not only in patients with severe congenital non-autoimmune hyperthyroidism, but also in children with subclinical non-autoimmune hyperthyroidism.     

An activating mutation of the thyrotropin receptor gene in hereditary non-autoimmune hyperthyroidism

The thyroid stimulating hormone (TSH) receptor gene displays a diverse spectrum of activating and inactivating mutations. We report a germline activating mutation M463V of the TSH receptor gene in two siblings with hereditary non-autoimmune hyperthyroidism. The onset of disease in the affected members of the pedigree occurred during childhood or adolescence. The significance of diagnosing activating TSHR mutations lies in therapeutic management and genetic counseling; thyroid ablation is advocated as first line treatment.     

Sodium handling in congenitally hypothyroid neonates

Early observations emphasized the possible development of hyponatraemia in hypothyroid children and adults, but recently this has been questioned. Aim: To investigate whether hyponatraemia develops in hypothyroid status by examining sodium handling in screening-detected neonates and infants with congenital hypothyroidism (CH). Methods: Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), sodium (Na), creatinine (Cr), urinary Na, Cr, fractional sodium excretion rate (FENa) and other chemicals were measured before and after L-thyroxine (LT4) replacement therapy in 32 screening-detected CH neonates (11M, 21F) and 16 age-matched control neonates. Results: No cases of hyponatraemia were found in the 32 CH neonates. Their serum Na concentrations (139.1 ± 1.5 mmol/L, ranging from 136 to 142 mmol/L, median 139 mmol/L) were not statistically different from those of 16 control neonates (139.3 ± 1.3 mmol/L, ranging from 137 to 142 mmol/L, median 139 mmol/L,). No correlation was found between serum levels of TSH and FT4 and serum Na or FENa. No significant changes were found in serum Na concentrations in hypothyroid neonates two months after LT4 replacement therapy. The serum Na concentration (139.1 ± 0.3 mmol/L, n = 25) before treatment did not change statistically (138.9 ± 0.2 mmol/L, n = 25) two months after LT4 replacement therapy.

Conclusion: As seen in various earlier reports, hyponatraemia can occur in hypothyroid patients, but no causal relationship exists between them. When hyponatraemia is detected in hypothyroid children, it does not seem to be directly related to lack of thyroid hormones and therefore other possible causes should be sought.     

Pathology of the TSH receptor

Gain of function and loss of function mutations of the TSH receptor have been implicated in the pathogenesis of various thyroid diseases. Gain of function mutations, when somatic, are the first cause of autonomous nodules; when germline, they are responsible for hereditary non-autoimmune toxic thyroid hyperplasia and for some cases of sporadic congenital hyperthyroidism. A subset of mutations modifying the receptor selectivity have recently been found to be involved in the pathogenesis of familial gestational hyperthyroidism. These mutations are of great interest for understanding the mechanism of receptor activation. Loss of function mutations of the TSH receptor are responsible for different phenotypes ranging from asymptomatic resistance to TSH to overt congenital hypothyroidism.     

Attitudes and feelings towards menstruation and womanhood in girls at menarche

Aim: To elucidate early adolescent girls' attitudes, thoughts and feelings towards menstruation and their bodies. Methods: 309 12-y-old girls answered questionnaires. One part of the questionnaire dealt with thoughts and feelings towards menstruation. The other part dealt with thoughts and feelings towards menstruation and sex and ability to communicate on aspects of womanhood. Results: Postmenarcheal girls were less positive towards menstruation than premenarcheal girls (p=1×10^-6). Many girls (43%) did not reaffirm the statement “I like my body” and almost one quarter stated being teased for their appearance. Many of the girls claimed that they had been called “cunt” (38%) or “whore” (46%). If called “cunt” or “whore”, 17% stated that they felt alone, 76% felt anger and 50% were offended. Mothers were those with whom girls could most easily “chat” about their period. Sixty-seven per cent received information about menstruation from school nurses.

Conclusion: Wanting to be an adult and liking that their body develops seem to be associated with a more positive feeling towards menstruation. Furthermore, mothers' timing and ability to communicate attitudes towards menstruation and the body are as important as those in a girl's immediate environment.     

PCDDs, PCdfs and Co-PCBs in human breast milk samples collected in Tokyo, Japan

Aim: To observe the distribution of PCDD/Fs and Co-PCBs in samples of human breast milk collected in Japan. Methods: Using high-resolution gas chromatography, milk samples for polychlorinated dibenzo-p-dioxins (PCDDs; 14 congeners), polychlorinated dibenzofurans (PCDFs; 15 congeners) and coplanar polychlorinated biphenyls (Co-PCBs; 12 congeners) from 240 mothers residing in Tokyo were analysed. There were 120 donors each of primiparae and secundiparae, each group including 60 donors aged 25 to 29 y (“the younger group”) and 60 aged 30 to 34 y (“the older group”). Individual milk samples (about 50 ml) were obtained 30 d after delivery in 1999 and in 2000. Results: The mean toxic equivalent (TEQ) level of PCDD/Fs (the sum of PCDDs and PCDFs) was 14.9 pg TEQ/g fat, of Co-PCBs 10.6 pg TEQ/g fat, and the total sum of PCDD/Fs and Co-PCBs was 25.6 pg TEQ/g fat. The mean TEQ levels of PCDD/Fs, Co-PCBs, and total PCDD/Fs and Co-PCBs were higher in primiparae than in secundiparae. In each of these, the levels were higher in the subgroup of older mothers. In the secundiparae, the mean levels were lower in the group of mothers who had breastfed their first babies than in those who bottle-fed or partly bottle-fed their first born.

Conclusions: The concentrations of PCDD/Fs and Co-PCBs in the breast milk of Japanese women were slightly lower than those described in previous studies conducted in Japan and other countries; and the concentrations of PCDD/Fs and Co-PCBs in the breast milk were influenced mainly by the mother's age and nursing history.     

Nontuberculous mycobacterial adenitis: effectiveness of chemotherapy following incomplete excision

Background: Management of lymphadenopathy caused by nontuberculous mycobacteria (NTM) is primarily surgical. Where this cannot achieve sufficient clearance of infected nodes, chemotherapy is often given. Aim: This study compared results of surgery alone with surgery followed by chemotherapy in instances where there was incomplete surgical removal of diseased tissue. Methods: Chemotherapy comprised azithromycin 10 mg/kg and rifabutin 6 mg/kg both given once daily for 6 mo. Ninety-eight children with NTM infection were seen in the period 1990-2004. Sixty-eight cases with adenopathy where “time to healing” (discharge stopped and inflammation settled) was known were available to compare response to treatment. Results: The median (range) “time to healing” in weeks for 43 patients who had surgery alone was: incision and drainage (I&D)/curettage 6 (1-72) (n=10); excision 3 (1-28) (n=22); and from the last operation of multiple (repeat) surgery 3 (1-40) (n=11). For 25 patients who required chemotherapy in addition to surgery, the median (range) “time to healing” in weeks was I&D/curettage 10 (1-40) (n=17), excision 14 (8-20) (n=2) and multiple surgery 29 (2-88) (n=6).

Conclusion: In children with adenitis due to NTM, where surgical resection is followed by continued discharge and inflammation, chemotherapy should be considered before further surgery is undertaken.     

Alterations of neonatal thyroid function

Grüters A, Krude H, Biebermann H, Liesenkötter KP, Schöneberg T, Gudermann T. Alterations of neonatal thyroid function. Acta Pædiatr 1999; Suppl 428: 17–22. Stockholm. ISSN 0803–5326
Recent progress has been made in understanding the pathogenesis of neonatal thyroid disorders. Autosomal recessive inheritance of mutations of the thyroid peroxidase and thyroglobulin genes has been described in some patients with congenital hypothyroidism (CH) and a family history of CH. Autosomal recessive inheritance of mutations of the thyrotrophin (TSH) receptor gene has also been reported in patients with CH and thyroid hypoplasia, and autosomal dominant mutations of the PAX8 gene have been described in patients with different forms of thyroid dysgenesis. These discoveries are important for patients with CH diagnosed by neonatal screening, as these patients will have normal fertility. The molecular genetic analysis of mutations of the TSH gene in patients with familial and sporadic cases of isolated central CH, who are missed by TSH screening programmes, now enables rapid diagnosis and appropriate therapy in the neonate. In newborn infants with severe non-autoimmune hyperthyroidism, autosomal dominant gain-of-function mutations in the TSH receptor gene have been demonstrated. In these patients, molecular genetic studies are extremely helpful in therapeutic decision making, as early thyroid ablation is the only effective treatment that avoids the sequelae of long-term hyperthyroidism. Molecular genetic studies are therefore useful in the diagnostic work-up of neonatal thyroid alterations. □ Congenital hypothyroidism, molecular pathogenesis, neonatal hyperthyroidism     

Overnight central and peripheral temperature changes in normal infants

Aim: To explore the relationship between central and peripheral temperature in normal infants after being put down to sleep. Methods: Overnight shin and rectal temperatures of 21 normal infants were continuously recorded at home for three nights at 2 wk, 6 wk, 3 mo and 5 mo of age. Parents documented the start and end of feed/nappy changes during the night. Results: An initial fall in rectal temperature was recorded on 149 out of 161 nights. This was linearly correlated with a rise in shin temperature for 106/149 (71%) nights (median R[Formula: See Text] = 0.95, lower quartile 0.92, upper quartile 0.97). It was not possible to rule out a change in thermal insulation over the shins as a confounding variable in this strong association. However, a similar inverse relationship was seen between shin and rectal temperature during 111 of 121 (92%) feed/nappy changes.

Conclusion: The fall in rectal temperature after being put down to sleep may be due to redistribution of heat rather than decreased production or heat loss. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work is required to distinguish peripheral temperature changes on falling asleep from those associated with changes in thermal insulation.     

Impact of inhaled corticosteroids on the risk of early Pseudomonas aeruginosa acquisition in cystic fibrosis

Aim: To investigate the role of inhaled corticosteroids (IC) on the risk of Pseudomonas aeruginosa acquisition before the age of 10 y in cystic fibrosis (CF) patients. Methods: For each subject the cumulative dose kg^-1 of IC received for each year of age was calculated until the end of follow-up. The age at CF diagnosis, the nutritional status (NS) and the number of respiratory exacerbations (RE) were used as surrogate measures for the severity of CF. Results: A total of 83 patients (40 M, 43 F) entered the study. Their median length of follow-up was 4.4 y, for a total of 386 person-years at risk. Twenty-three patients acquired P. aeruginosa at a median age of 4.6 y (range 0.4-9.9 y). The estimated survival without P. aeruginosa acquisition was 65% at 10 y of age. The effect of different risk factors (IC, NS, RE and age at CF diagnosis) on the probability of P. aeruginosa acquisition was evaluated: none of them was significantly associated with the risk of P. aeruginosa acquisition. In particular, patients receiving very high cumulative doses of IC (4th quartile) had a non-significantly increased risk of P. aeruginosa acquisition compared with those receiving low doses of IC (1st quartile) (hazard ratio = 1.73, 95% confidence limits 0.40-7.38).

Conclusion: This retrospective study was not able to demonstrate any role of IC in increasing the risk of P. aeruginosa acquisition. This complication seems to occur at a constant pace that is independent of CF severity and age. Prospective multi-institutional randomized studies are needed to investigate the effects of high-dose IC in CF patients.     

Immunogenicity and safety in infants of a DTwPHib full liquid vaccine

Aim: Combining paediatric vaccines is a rational solution to reduce the number of injections during a single clinical visit, to maintain parents' compliance and to extend vaccine coverage. Different diphtheria, tetanus and whole cell pertussis (DTwP)-containing combination vaccines are licensed and used world-wide. This study assessed the immunogenicity and safety in infants of a combined diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b-CRM₁₉₇ conjugate full liquid vaccine. Methods: The safety and efficacy of a combined ready-to-use liquid vaccine containing diphtheria and tetanus toxoids, cell suspension of Bordetella pertussis and H. influenzae type b-CRM₁₉₇ conjugate vaccine (DTwPHib) were assessed in infants eligible for the local Expanded Programme on Immunization (EPI) in Valencia, Spain. The comparative group received separate injections of reference vaccines DTwP + Hib. Results: Local and systemic reactions and adverse events were generally mild and similar in the two groups. DTwPHib elicited anti-PRP antibody titres ≥0.15 μg ml^-1 in 97% and DTwP + Hib in 94% of infants. Furthermore, 89% of DTwPHib and 78% of DTwP + Hib recipients attained anti-PRP antibody titres ≥1.0 μg ml^-1, signifying long-term protection. The anti-PRP geometric mean titre was significantly higher in the combined DTwPHib vaccine group (6.65 vs 3.57 μg ml^-1). In both groups, 99% of infants achieved protective (≥0.01 IU ml^-1) anti-diphtheria antibody levels and all children achieved protective (≥0.1 IU ml^-1) anti-tetanus antibody levels. DTwPHib caused a ≥2-fold increase in anti-pertactin antibody titres in 91% and a ≥4-fold increase in 82% of recipients. The corresponding proportions in the DTwP + Hib group were 95% and 90%. DTwPHib induced a ≥2-fold increase in anti-Aggl2 and 3 antibody levels in 79% and a ≥4-fold increase in 73% of recipients. The corresponding proportions among DTwP + Hib infants were 85 and 82%. Conclusion: Overall, the combined liquid vaccine DTwPHib is a safe and effective immunogenic vaccine for EPI use in infants.     

Beta-glucuronidase in the diagnosis of bacterial meningitis and response to treatment

Aim: β-Glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the β-glucuronidase activity in the cell-free CSF of bacterial meningitis and its course during treatment, and compare it with other CSF parameters. Methods: The β-glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 43 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had one or two follow-up lumbar punctures. Results: The β-glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136 μmoles 4-methylumbelliferone l ^-1  h ^-1 (range 44-826) and in controls 14 (7-23). In all patients who improved, the activity was lower in the follow-up CSF samples. Six to 12 h after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 h of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had two follow-up punctures showed that the β-glucuronidase activity was the best prognostic index.

Conclusion: β-Glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.     

Upper endoscopic findings in children with active juvenile chronic arthritis

Aim: To investigate the association between gastroduodenal mucosal damage and symptoms of the digestive tract in children with juvenile chronic arthritis (JCA) Methods: This was a prospective, open, non-randomized study. Gastroscopy was performed on 45 children with active JCA in 1996-2000. Gastrointestinal symptoms before and during the treatment were noted, as was the length of antirheumatic medication, for which the data were retrospectively assessed. Plasma haemoglobin (Hb) and mean corpuscular volume (MCV) levels and erythrocyte sedimentation rate (ESR) were analysed. Mucosal biopsies were obtained for histology and Helicobacter pylori culture. All patients were taking non-steroidal anti-inflammatory drugs (NSAIDs) and 11 (24.4%) were on peroral steroids; 16 (35.6%) were receiving hydorxychloroquine, 9 salazopyrine, 5 myocrisine and 14 methotrexate. Results: Seven children (15.6%) were found to have active inflammation in their gastric and/or duodenal mucosa, two having ulcers and two being infected with H. pylori. Abnormal endoscopic findings were more common in symptomatic children (n = 24) than in children without symptoms (n = 21) (75% vs 38%, p = 0.017). There was no clear association between the Hb or MCV level and the degree of gastroduodenal inflammation (p = 0.98 and 0.7, respectively). Significantly more children (66.6% vs 33.3%) experienced abdominal pain after beginning medical therapy than before therapy (p = 0.02).

Conclusion: Endoscopic evaluation of patients with JCA and receiving NSAIDs should be considered at least in symptomatic cases.     

Extended gene analysis can increase specificity of neonatal screening for cystic fibrosis

Aim: To assess whether carriers and patients can be accurately identified by extended gene analysis for cystic fibrosis (CF) in dried blood spots. Methods: A blinded analysis was performed in 10-mm² blood spots on Guthrie cards, punched as if to remove material for the IRT test, from 10 CF patients and 10 carriers with known CF mutations. Genomic DNA was isolated. Aliquots of 1 µl dissolved DNA were used for subsequent PCRs. Analysis of the ΔF508 mutation was followed by an oligonucleotide ligation assay. Denaturing gradient gel electrophoresis of the whole CFTR gene was carried out in samples with only one identified mutation. Amplicons revealing an aberrant pattern were sequenced. Results: In all cases, the blood-spot genotype was identical to that previously determined from whole-blood analysis. Estimated time needed to complete the procedure in a series of Guthrie cards was 3-4 wk.

Conclusion: Extended gene analysis in dried blood spots can discriminate CF patients and carriers. If proven equally reliable in larger series, an approach to neonatal screening in which tests are only considered as screen positive when two CF mutations are found is possible. This can increase the specificity of the screening programme, and carrier detection can practically be avoided.     

Survival after surgery for congenital heart defects: Does reduced early mortality predict improved long‐term survival?

Aim: The objectives of this study were 1) to compare early mortality (first 30 d after surgery) and long-term survival between two cohorts of patients operated on for congenital cardiac defects, and 2) to evaluate the impact of possible changes in early mortality on long-term survival. Methods: 945 patients with congenital cardiac defects, born in 1990-1999 and operated on in the same period were examined in a retrospective cohort study. The patients were divided into three groups: “univentricular cardiac defects”, “severe cardiac defects” and “less severe cardiac defects”. The study population was divided into two cohorts: group 1 included patients born and operated on in 1990-1994; group 2 included patients born and operated on in 1995-1999. The survival patterns in the two groups were compared. Results: For all patients, except those with univentricular cardiac defects, early mortality (30 d after surgery) was reduced. Among patients with severe cardiac defects, early mortality was reduced from 18.6% in group 1 to 2.9% in group 2. Among patients with less severe cardiac defects, early mortality was reduced from 6.2% to 1.9%. The improved outcome was maintained during the following 5 y. Overall relative risk of death during follow-up was reduced to 0.31 (95% CI: 0.15-0.56) for patients with severe cardiac defects, and to 0.53 (95% CI: 0.31-0.93) for patients with less severe cardiac defects born and operated on in 1995-1999.

Conclusion: Early mortality has been substantially reduced in congenital heart defect patients, and corresponds with significantly improved long-term survival.     

Behavioural effects of phenylalanine-free amino acid tablet supplementation in intellectually disabled adults with untreated phenylketonuria

Aim: To evaluate the effects of phenylalanine (Phe)-free essential amino acid (AA) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria (PKU). Methods: Phe-free AA tablets and placebo tablets were administered to 19 untreated PKU subjects on a normal diet for 6 mo in a prospective double-blinded crossover study. The adaptive behaviour of the patients was tested prior to the study and at 6 and 12 mo after the start, using a simplified version of the Vineland Adaptive Behaviour Scale. For each sub-domain, the patients were rated either “0” (for poor performance) or “1” (for good performance). Neurological signs and symptoms and specific behavioural characteristics were recorded monthly by caretakers. Every 6 mo, neurological examination of the patients was performed, and the caretakers were interviewed. The statistical significance of the results was tested by means of the Fisher's exact and Wilcoxon tests. Results: The most significant changes were an improved concentration and the development of a meaningful smile, which were observed in 44% and 43% of the patients on AA tablet treatment, respectively, but not patients on placebo. Other important but less significant changes included increased awareness of external stimuli (63%) and less self-injury (43%), and 40% were smiling and laughing occasionally. The mean overall rating increased from an initial value of 6.3 to 10.1 in patients when on AA tablet treatment (p=0.002), and to 7.0 in patients when on placebo (p=0.068). The difference between active AA treatment and placebo was statistically significant (p=0.027).

Conclusions: This pilot study suggests that Phe-free AA tablets enriched in tyrosine and tryptophan may improve the quality of life in some intellectually disabled adults with untreated PKU.     

Disaccharidase activities in Belgian children: reference intervals and comparison with non-Belgian Caucasian children

Aim: To establish reference values for disaccharidase activities in Belgian children and to compare enzyme activities with those of non-Belgian Caucasian children. Methods: Data from Belgian children who had undergone endoscopic jejunal biopsies (1994-2000) for suspected malabsorption were reviewed. The patients were divided into three groups based on histology: (A) normal (n = 201), (B) moderate changes (n = 58) and (C) (sub)total atrophy (n = 14). The 95% reference limits for disaccharidase activities (U/g protein) were calculated for group A after exclusion of patients with a positive hydrogen breath test, a history of lactose intolerance or coeliac disease (final population: n = 151, 0.1-12 y). Values were compared with those of 34 non-Belgian Caucasian children with normal histology (28 of Mediterranean origin). Results: The reference limits (90% confidence interval) were 86 (65-111)-423 (366-494) for maltase, 9 (6-12)-91 (78-122) for lactase and 24 (18-30)-155 (120-184) for sucrase. No gender-related differences in enzyme activities were found. Lactase levels showed a slight decrease with increasing age. Disaccharidase activities of children with histologically confirmed mucosal injury were significantly lower than those of children with normal histology: median values for groups A, B and C were 208, 181 and 96, respectively, for maltase, 40, 28 and 7, respectively, for lactase and 69, 54 and 25, respectively, for sucrase. Median disaccharidase activities in biopsies with normal histology were lower in non-Belgian children, the difference being only statistically significant for lactase, 33 versus 40.

Conclusion: The reference values for Belgian children are well in line with other reported values from Caucasian children. Although enzyme activities are lower in children with histologically confirmed mucosal damage, they do not allow differentiation between histology groups. Lower lactase values were found in non-Belgian children.     

Longitudinal growth and height velocity of Japanese children with Down's syndrome

Aim: To determine the natural growth pattern of Japanese children with Down's syndrome. Methods: Longitudinal height data of 85 patients (43 males, 42 females) from birth to final height were analyzed. Based on these data, semi-longitudinal standard growth curves and height velocity curves for Down's syndrome were drawn. Results: The means ± SD of final height of males and females with Down's syndrome were 153.2 ± 5.6 and 141.9 ± 4.2 cm, respectively. They were -3.0 SD and -2.8 SD for Japanese standards. Mean peak height velocities were 8.9 and 7.5 cm y[Formula: See Text], and the ages at peak height velocity were 11.6 and 10.2 y for males and females, respectively.

Conclusion: The mean height of patients with Down's syndrome was around -2 SD for normal children before puberty. Their pubertal growth spurt starts about 1 y earlier and their peak height velocity was about 1.3-1.4 cm shorter than for normal children.     

Retrospective evaluation of long-term efficacy and safety of splenectomy in chronic idiopathic thrombocytopenic purpura in children

Aim: To review the long-term efficacy and safety of splenectomy in children with chronic idiopathic thrombocytopenic purpura (cITP). Patients and methods: Data from 33 splenectomized children were retrospectively analysed (median follow up period: 18.8 y from the removal of the spleen). The median age of children at splenectomy was 12 y and the median ITP duration 3.3 y. Indications for splenectomy were: persistent severe thrombocytopenia with extensive purpura, epistaxis and/or gum bleeds, menorrhagia (n = 5) and severe or recurrent haemorrhage from various sites (n = 11). Results: Eighty-five per cent of the patients showed an excellent (n = 26) or partial response to splenectomy. Five children (15%), all females, failed to respond. Of the responders, 25% experienced a transient recurrence of thrombocytopenia within 6 mo to 4 y from splenectomy. The mortality rate due to severe sepsis was 3%. However, the majority of the splenectomized patients have not so far suffered any severe or mild bacterial infection, despite incomplete vaccination and/or antibiotic prophylaxis.

Conclusion: Splenectomy remains the only effective therapeutic modality for children with cITP, although it is associated with transient recurrence and rarely with post-splenectomy sepsis, which could be fatal. Nonetheless, splenectomy should be the last treatment option for the cITP patient, after all available therapeutic modalities have been exhausted and the child still remains profoundly thrombocytopenic and symptomatic.     

Efficacy of three treatment schedules in severe meconium aspiration syndrome

Aim: To compare three different schedules in severe meconium aspiration syndrome (MAS) treatment: standard, bronchoalveolar lavage (BAL) with diluted surfactant, and diluted surfactant BAL plus a single early dexamethasone dose. Methods: Twenty-four full-term newborns with severe MAS (needing mechanical ventilation and with oxygenation index ≥15) were divided into three groups: group I (historical control group; n = 6) treated with standard therapy; group II (n = 7) treated in the first hours of life with one BAL using diluted surfactant (beractant 5 mg/mL) in a volume of 15 mL/kg in four aliquots; and group III (n = 11) treated with one diluted surfactant BAL and a previous single dose of intravenous dexamethasone (0.5 mg/kg) Results: At 12 h, groups II and III showed a significant improvement in oxygenation index (OI) compared with group I (14.7% and 27.0% vs -19.6% respectively; p = 0.012). Group III also showed a significantly lower OI than group I at 24 h (63.6% vs -27.9%) and at 48 h (87.1% vs 49.6%). Group III, in comparison to group I, showed a lower FiO ₂ requirement at 12 h (0.66 vs 1), at 24 h (0.4 vs 0.87) and at 48 h (0.35 vs 0.67), and a decrease in the number of days of inhaled nitric oxide administration, mechanical ventilation, oxygen therapy and hospitalisation period. All patients from groups II and III survived and none developed pneumothorax or respiratory infections.

Conclusion: Diluted surfactant BAL in the first hours of life combined with an intravenous single dose of dexamethasone may be an effective treatment for severe MAS.