The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite

Live Lactobacillus paracasi 33 (LP33) may effectively improve the quality of life for patients with perennial allergic rhinitis. It has been demonstrated that heat-killed lactic acid bacteria (LAB) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals. The aim of this study was, therefore, to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust-mite in human subjects. A total of 90 patients were enrolled in a randomized, double blind, placebo-controlled trial and assigned to three treatment groups. Patients in groups A and B received two capsules per day of live or heat-killed LAB (5 x 10(9) colony-forming units/capsule), respectively, over a period of 30 days while those in Group C received placebo capsules. A modified questionnaire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit. The overall quality of life score decreased for groups A and B, as compared with the placebo group, in terms of both frequency (9.47 +/- 2.89, 6.30 +/- 2.19, vs. -3.47 +/- 1.53, respectively; p < 0.0001) and level of bother (5.91 +/- 3.21, 6.04 +/- 2.44, vs. -2.80 +/- 1.64, respectively; p = 0.004) after the 30-day treatment. The efficacy of the heat-killed LP33 was not inferior to the live variant. No obvious side effects were reported for either active treatment group during the study period. Our results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis, and that it may be efficacious as an alternative treatment.     

A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis

To examine whether long-term consumption of fermented milk containing a specific Lactobacillus casei may improve the health status of preschool children suffering from allergic asthma and/or rhinitis a randomized, prospective, double blind, controlled trial was conducted in 187 children 2-5 y of age. The children received for 12 mo either fermented milk (100 mL) containing Lactobacillus casei (10(8) cfu/mL) or placebo. The time free from and the number of episodes of asthma/rhinitis after starting intervention were the outcome measures. The number of fever or diarrhea episodes and the change in serum immunoglobulin were further assessed. No statistical difference between intervention and control group occurred in asthmatic children. In children with rhinitis, the annual number of rhinitis episodes was lower in the intervention group, mean difference (95% CI), -1.6 (-3.15 to -0.05); the mean duration of an episode of diarrhea was lower in the intervention group, mean difference -0.81 (-1.52 to -0.10) days. While long-term consumption of fermented milk containing Lactobacillus casei may improve the health status of children with allergic rhinitis no effect was found in asthmatic children.     

Allergic conjunctivitis in children with asthma, rhinitis and eczema in a secondary outpatient clinic

Little evidence is available on the prevalence of allergic conjunctivitis in pediatric populations. The objective of this study was to assess the cumulative prevalence of allergic conjunctivitis in children with rhinitis, asthma and eczema in a secondary pediatric outpatient clinic. Children aged 5-15 yr referred during the period of 2002-2004 in whom allergic conjunctivitis, asthma, allergic rhinitis or eczema was diagnosed were included in a retrospective survey. At referral patient characteristics, history, symptoms, signs and results of type 1 allergy tests were entered into an electronic form. Four hundred and fifty-eight children with a mean age of 9.4 yr were studied. Of 316, 324 and 149 children with rhinitis, asthma or eczema, respectively, 133 (42%), 78 (24%) and 45 (30%) had concomitant allergic conjunctivitis. One hundred and thirty-seven (30%) had allergic conjunctivitis, of whom 133 (97%) also had allergic rhinitis, 77 (56%) asthma and 45 (33%) eczema. One hundred and twenty-five (91%) of the children with allergic conjunctivitis had positive allergy tests to one or more allergens, sensitization to house dust mites being more frequent in chronic allergic conjunctivitis than in acute allergic conjunctivitis (95% vs. 53%; p < 0.01). Sensitization to grass was more frequent in children with acute allergic conjunctivitis (78% vs. 57%; p = 0.03). In a secondary pediatric outpatient clinic allergic conjunctivitis is a frequent co-morbidity to allergic rhinitis and to asthma and eczema. Allergic conjunctivitis need to be included as an important co-morbidity in future guidelines on asthma, rhinitis and eczema management.     

The influence of metoclopramide on the composition of human breast milk.

The breast milk prolactin (PRL) has been claimed to play a role in the control of electrolyte composition of the milk. Since metoclopramide has been shown to increase milk production in humans, we have made an attempt to investigate the production, the PRL and sodium concentrations in milk with (group I) and without (group II) maternal metoclopramide treatment (5 days, 30 mg/day). Both groups consisted of 11 mothers and their full-term newborn infants. The daily milk production was significantly higher in the treated group (276.4 +/- 36.6 vs 150.9 +/- 25.3 ml/day, p less than 0.01). The PRL measured by RIA was similar in the milk samples of the metoclopramide treated and control groups (80.5 +/- 17.7 vs 90.7 +/- 27.3 ng/ml). The sodium concentration in the milk of mothers taking metoclopramide was 22.1 +/- 1.6 mmol/l and 24.3 +/- 3.2 mmol/l in the control group (p = 0.59). On the 5th postnatal day the plasma PRL of the newborns of mothers treated with metoclopramide does not differ from the values of the control babies (29.8 +/- 2.6 vs 30.7 +/- 2.4 ng/ml) indicating that the amount of metoclopramide transferred into the milk has no apparent influence on the hypothalamo-hypophyseal axis of the neonate. In conclusion: the maternal metoclopramide treatment augments the milk production without having any effect on the PRL and sodium concentration of human "mature" milk.     

Neonatal nutrition with enriched human milk. EOPROTIN 60 in comparison with human albumin]

The influence of feeding fresh human milk supplemented either with EOPROTIN (n = 13) or human albumin (n = 15) on biochemical parameters and growth were studied in preterm infants with gestational ages below 32 weeks p.m. up to the 42nd day of postnatal life. In both feeding groups the intakes of protein, energy and electrolytes were similar. The serum concentrations of bile acids, alpha-amino-nitrogen and prealbumin, the renal excretion of total nitrogen, alpha-amino-nitrogen, urea and ammonia as well as the growth in weight and length were studied in all infants. The supplementation of the fresh human milk with EOPROTIN results in significant lower serum concentrations of alpha-amino-nitrogen (1.56 +/- 0.21 vs 2.03 +/- 0.27 mmol/l; p less than 0.01), higher serum concentrations of prealbumin (89.8 +/- 20.3 vs 72.7 +/- 13.3 mg/l; p less than 0.02), and lower urinary excretion of total nitrogen (7.4 +/- 0.9 vs 8.9 +/- 1.1 mmol/kg/day); if compared to the results found in the infants fed human albumin supplemented human milk. The higher nitrogen retention in the EOPROTIN than in the human albumin fed infants was associated by a significant higher growth in weight (16.6 +/- 1.4 vs 13.7 +/- 1.9 g/kg/day; p less than 0.01) as well as in length (1.02 +/- 0.08 vs 0.87 +/- 0.1 cm/week; p less than 0.01). The results indicate that the bioavailability of EOPROTIN is higher than that of human albumin. The observed differences in the nutritional response between the two human milk supplements may be based on differences in the amino acids composition which is in EOPROTIN adapted to the nutritional available part of the protein in human milk.     

Abnormal spirometry in children with persistent allergic rhinitis due to mite sensitization: the benefit of nasal corticosteroids.

Inflammatory processes affecting nasal and bronchial mucosa are similar in nature. The purpose of this study was to examine whether children with perennial allergic rhinitis, without underlying asthma, have impaired pulmonary function. We also investigated whether nasal corticosteroids and loratidine would improve the pulmonary function tests of those children with impaired lung function. Fifty subjects with moderate/severe persistent allergic rhinitis due to exclusively dust mite sensitization and no past medical history suggestive of asthma were assessed. The control group consisted of 26 matched healthy subjects. Subjects with airway obstruction, as detected by forced expiratory volume/1 s (FEV1) or forced expiratory flow from 25/% to 75% (FEF(25-75)) values <80% of those predicted, were treated with loratidine, once a day for 10 days, and daily nasal budesonide for 3 months. We found that 11 of 50 patients (22%) with perennial allergic rhinitis had impaired pulmonary function (FEF(25-75) values <80%), compared to 1/26 (3.8%) of the control group (p < or = 0.05). Reversibility was observed in 9/11 (81.8%), mean 24.7% +/- 10.3%. Within 3 months of treatment, 7/10 had FEF(25-75) > 80% of their predicted values as well as significant improvements in their FEV1 (p = 0.04), and FEV1/FVC (p = 0.04). We conclude that a substantial proportion of children with perennial allergic rhinitis have diminished FEF (25-75) values and reversible airway obstruction. Nasal corticosteroids improve the pulmonary function tests of these children with impaired lung function.     

Exhaled breath condensate pH measurement in children with asthma, allergic rhinitis and atopic dermatitis

Recent studies have shown that the pH of exhaled breath condensate (EBC) could be predictive of asthma exacerbation. Moreover, it has been documented that both allergic rhinitis and atopic dermatitis constitute risk factors for the occurrence of asthma in a progression of disease known as atopic march. The aim of our study was to establish if condensate pH could be used as a valuable mean of monitoring of asthma in atopic children. We studied 34 atopic children with acute asthma, 70 with stable asthma, 35 children with allergic rhinitis, and 17 with atopic dermatitis. Thirty healthy children were used as controls. All children underwent skin prick tests and lung function tests. Exhaled breath condensate samples were collected with a condensing device and de-aerated with argon. The pH of EBC was measured using a pH meter. Children with acute asthma were treated with inhaled steroids and bronchodilators. We found that the pH of condensate in patients with acute asthma was lower than that of patients with stable asthma, rhinitis, and controls (7.25 vs. 7.32, p < 0.05; 7.25 vs. 7.48, p < 0.02; 7.25 vs. 7.78, p < 0.0001, respectively). Patients with stable asthma, rhinitis, and eczema had also lower pH than that of controls (7.32, 7.48, and 7.44 vs. 7.78; p < 0.0001, p < 0.006, p < 0.04, respectively). Patients with acute asthma normalized their pH after treatment (7.82 vs. 7.25; p < 0.0001). Finally, patients with acute asthma showed a positive correlation between pH and lung functional parameters (forced expiratory volume in 1 s; r = 0.39, p = 0.04). Our study shows that EBC pH measurement may be a promising marker for assessing airway inflammation and monitoring response to anti-inflammatory treatment in asthmatic children. Furthermore, we report the first evidence of airways acidification in children with allergic rhinitis and atopic dermatitis. Therefore, EBC pH assessment may be useful in the evaluation of progression of the atopic march toward the development of asthma later in life. Further studies are recommended in order to confirm this indication.     

Seasonal changes of proapoptotic soluble Fas ligand level in allergic rhinitis combined with asthma

The function of apoptosis is to eliminate unnecessary or dangerous cells. The balance between production and death is important in the control of cell numbers within physiological ranges. Cells involved in allergic reactions may have altered apoptosis. The aim of this study was to examine the seasonal changes of programmed cell death in children with pollen allergy. We measured serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL), and examined whether there was any correlation between soluble apoptosis markers and development of asthma and or rhinitis in children with pollen allergy. We examined two groups of patients with ragweed pollen allergy. The first group consisted of 17 children with 'rhinitis only'. The second group consisted of 16 children with 'asthma + rhinitis'. For seasonal analysis we pooled the two groups and termed this the 'ragweed sensitive' group (n = 33, 5-18 yr, 25 boys, eight girls). Measurements (sFas and sFasL) were taken during the ragweed pollen allergy season, while control measurements were performed during the symptom-free period. There was no difference in sFas levels measured during and after [1941 +/- 68, 1963 +/- 83 pg/ml (mean+/-s.e.m, respectively)] the pollen season in the 'ragweed sensitive' group. The sFasL level showed seasonal change, which was significantly higher (p = 0.0086) in the symptomatic period compared to the symptom-free state (99 +/- 13 and 53 +/- 16 pg/ml, respectively). There was a difference between the 'rhinitis only' and the 'asthma + rhinitis' groups in the measured parameters of apoptosis. Children having allergic rhinitis combined with asthma had a significantly (p = 0.03) higher sFas level in the symptom-free state than the 'rhinitis only' group did (2115 +/- 156 and 1820 +/- 52 pg/ml, respectively). During the allergic symptom state the sFasL level of the 'asthma + rhinitis' group was significantly higher (p = 0.025) than that of the 'rhinitis only' group (125 +/- 20 and 75 +/- 14 pg/ml, respectively). In conclusion, the increased level of sFasL during the pollen season may signal its role in the pathogenesis of allergic airway diseases. There was no seasonal change in sFas levels in the examined ragweed allergic group, however in the symptomatic period we observed a diminished level of antiapoptotic factor (sFas) and an elevated level of proapoptotic factor (sFasL) if there was a combined disease with pollen allergic asthma. We suggest that there is a deviation in the apoptotic reaction in children that may increase the seasonal allergic inflammation.     

Evaluation of yogurt effect on acute diarrhea in 6-24-month-old hospitalized infants

Yogurt helps in treatment and prevention of diarrhea. The aim of this study was to determine the efficacy of consumption of local factory yogurt, which is made with pasteurized milk, on moderately dehydrated hospitalized infants aged 6-24 months with acute non-bloody and non-mucoid diarrhea. Eighty moderately dehydrated breast-feeding children aged between 6-24 months with acute non-bloody and non-mucoid diarrhea for fewer than four days were included in the study. Patients were randomly separated into two groups according to their treatment. Infants in the case group received at least 15 ml/kg/day of pasteurized cow milk yogurt orally plus routine hospital treatment. Infants in the control group received routine hospital treatment as in the case group. Weight gains, period of hospitalization, and reduction in diarrhea frequency during hospitalization period of the two groups were compared. Mean duration of hospitalization (days), weight gain, and reduction in diarrhea frequency were 2.7 +/- 0.91 vs 3.1 +/- 0.74 days, 435 +/- 89.20 vs 383 +/- 98.9 g, and 4.30 +/- 1.74 vs 3.60 +/- 1.23 times for case and control groups, respectively. Significant differences were observed in mean hospitalization days (p=0.035), reduction in diarrhea frequency (p=0.049) and weight gain (p=0.017). This study recommends universal use of yogurt in acute non-bloody diarrhea.     

Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants

BACKGROUND: It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth. AIMS: To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants. INFANTS AND METHODS: Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay. RESULTS: Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers. CONCLUSION: Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.     

Recombinant human erythropoietin: analysis of a policy of treatment in an hospital based population of very-low-birthweight infants]

AIM OF THE STUDY: To evaluate a policy of treatment with human recombinant erythropoietin (rhEPO) and to describe factors related to red blood cell transfusions (RBCTs) in treated neonates. STUDY: Prospective, observative study. PATIENTS AND METHODS: One-hundred and sixty-five neonates with gestational age (GA) < 30 weeks and/or birthweight < 1000g admitted between may 1998 and october 1999. Ninety were excluded (congenital malformations n = 6, deaths n = 16, referral to a general hospital before discharge n = 67, ECMO n = 1). Data about the characteristics of the population, the severity of the neonatal period, hemoglobin at birth, blood loses, treatment with rhEPO, number of red blood cells transfusions (RBCTs) and donors were recorded in all infants. RESULTS: Thirty-eight in seventy-five (51%) neonates received 112 blood transfusions. Eighty-eight were prescribed after day 15. In most of the cases (n = 68), RBCTs were done according to the protocol. In 20 cases (23%) infants were transfused during a late-onset infection. No difference was observed between the non-transfused (group I) and the transfused neonates (group II) with regards to the drug administration: first dose on day 3 +/- 2, number of injections (17 +/- 4 vs 18 +/- 1, ns). The start of oral supplementation with iron was late (12j +/- 8 vs 19j +/- 10, ns). Infants in group II had a lower birthweight (850 +/- 240 vs 1050 +/- 160 g, p < 0,01) for a similar GA (28 +/- 1SA vs 28 +/- 2SA, ns) in association with an increased number of small for date babies (p = 0.03). Antenatal stero?ds administration (89 vs 74%, ns), administration of surfactant (59 vs 81%, ns) were similar in the two groups. The Clinical Risk Index for Babies was higher in group II: 5 +/- 3 vs 2 +/- 1 (p < 0,001) as was the duration of oxygen delivery (53 +/- 44 vs 14 +/- 20 days, p < 0,01) and postnatal administration of corticostero?ds ( 38% vs 3%, p < 0.01). CONCLUSION: The quality of iron administration, RBCTs and the limitation of donors could be improved in our population. Transfusions among neonates born before 30 weeks and/or with a birthweight of less than 1000 g and treated with rhEPO are associated with intrauterine malnutrition and a worse clinical condition on admission. Early identification of at risk neonates could improve prevention of RBCTs and the efficacy of rhEPO administration to preterm infants.     

Montelukast decreased exhaled nitric oxide in children with perennial allergic rhinitis

BACKGROUND: Measurement of exhaled nitric oxide (eNO) is a simple and noninvasive method for assessment of inflammatory airway diseases. eNO is elevated in adolescent patients with perennial allergic rhinitis and related to bronchial hyperresponsiveness. The aim of this study was to investigate whether oral loratadine, montelukast, nasal budesonide or nasal sodium cromoglycate could reduce airway inflammation as indicated by decrease of eNO in children with perennial allergic rhinitis as demonstrated by eNO levels. METHODS: A randomized and investigator-blinded study was conducted in a hospital-based outpatient clinic. Children with perennial allergic rhinitis were divided into four groups and treated by loratadine, loratadine with nasal sodium cromoglycate, loratadine with oral montelukast, and loratadine with nasal budesonide, respectively. Allergic rhinitis scores, eNO and peak expiratory flow were measured before and 2, 4, 6 and 8 weeks after treatment. RESULTS: Results showed that eNO in children with perennial allergic rhinitis was reduced by nasal budesonide and oral montelukast within 2 weeks (24.56 +/- 14.42 vs 18.42 +/- 12.48, P < 0.001, in budesonide group; 27.81 +/- 13.4 vs 19.09 +/- 10.45, P < 0.001, in montelukast group), but not in the loratadine and cromoglycate groups. In contrast, loratadine or sodium cromoglycate also did not decrease eNO levels although they could decrease the symptom scores. CONCLUSIONS: It was concluded that four common treatment modalities could effectively release symptom scores, but decrease of airway inflammation as determined by decrease of eNO might be only achieved by nasal budesonide and montelukast, but not nasal sodium cromoglycate and loratadine. Children with perennial allergic rhinitis with high eNO levels may require oral montelukast or nasal budesonide treatment to prevent airway hyperresponsiveness.     

Effects of methylprednisolone pulse on cytokine levels in Kawasaki disease patients unresponsive to intravenous immunoglobulin

This study aimed to determine the effects of intravenous methylprednisolone pulse (IVMP) therapy on cytokine levels in patients with acute Kawasaki disease (KD) unresponsive to initial intravenous immunoglobulin (IVIG) therapy. Fifteen KD patients unresponsive to initial IVIG, 2 g/kg/day, were randomized to receive IVMP (n = 7), 30 mg/kg/day for 3 days or additional IVIG (n = 8), 2 g/kg/day, and plasma cytokine levels were compared. The fraction of febrile patients was significantly lower in the IVMP group than in the additional IVIG group on day 2 (0/7 vs. 3/8, p = 0.03), but not on day 4 and later (3/7 vs. 4/8, p = 1.00) because of recurrent fever. The prevalence of coronary lesions was similar between the two groups (2/7 vs. 2/8, p = 1.00). The ratios of plasma levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 to those at enrollment (defined as day 1) were significantly lower in the IVMP group on day 4 (0.50 +/- 0.27 vs. 1.01 +/- 0.46, 0.53 +/- 0.39 vs. 0.93 +/- 0.44, p = 0.02 and 0.045, respectively), but not on day 7 (0.54 +/- 0.34 vs. 0.88 +/- 0.39, 0.76 +/- 0.39 vs. 0.61 +/- 0.17, p = 0.07 and 0.83, respectively). The ratios of interleukin-2 receptor, interleukin-6, and vascular endothelial cell growth factor to those at enrollment did not differ significantly between the two groups. In conclusion, for KD patients unresponsive to initial IVIG, IVMP suppresses cytokine levels faster, but subsequently similarly, compared with additional IVIG.     

Infants of mothers with persistent nipple pain exert strong sucking vacuums

AIM: The objective of this study was to determine whether infants of mothers experiencing persistent nipple pain exerted very strong intraoral vacuums during a breastfeed. METHODS: Thirty mothers experiencing persistent pain during breastfeeding (Pain group; infants aged 49.4 +/- 35.5 days) were compared to 30 successfully breastfeeding mothers (Control group; infants aged 55.0 +/- 22.7 days). Infant intraoral vacuums were measured via a small milk-filled tube taped alongside the nipple and connected to a pressure transducer. Milk intake was measured using the test weigh method. RESULTS: Infants in the Pain group applied significantly stronger baseline (-90.8 +/- 54.5 vs. -56.4 +/- 31.4 mmHg, p = 0.004), peak (-214.3 +/- 60.5 vs. 163.2 +/- 62.4 mmHg, p = 0.002) and pause vacuums (-104.8 +/- 67.9 vs. -45.8 +/- 30.3 mmHg, p < 0.001). Despite similar active sucking times (377.5 +/- 175.2 vs. 349.4 +/- 184.0 sec, p = 0.554) the mean milk intake was significantly lower for infants of mothers with nipple pain (41.6 +/- 31.3 vs. 70.7 +/- 30.7 g, p = 0.001). CONCLUSION: Infants of breastfeeding mothers experiencing persistent nipple pain applied significantly higher vacuum to the breast during breastfeeding despite assistance with positioning and attachment from a lactation consultant. Further investigation into the cause of the abnormally high vacuums is essential to develop successful interventions for these mother-infant dyads.     

Glycaemic control and hypoglycaemia in children, adolescents and young adults with unstable type 1 diabetes mellitus treated with insulin glargine or intermediate-acting insulin

In this open study of clinical practice, 142 paediatric patients with type 1 diabetes mellitus (>1 year duration), stratified by age, received prandial insulin (regular or lispro) and either once daily insulin glargine (GLAR; n=74), titrated to target fasting blood glucose (FBG) levels 4.4-7.8 mmol/l, or NPH/semilente insulin (NPH insulin, administered once, twice or three times daily; n=68), titrated to target FBG 4.4-8.9 mmol/l. Both groups were treated for 20 +/- 10 months. HbA(1c) significantly increased in GLAR (7.3 +/- 1.0% to 7.6 +/- 1.1%; p = 0.003) and NPH/semilente insulin (7.7 +/- 1.6% to 8.3 +/- 1.5%; p = 0.0001) treated patients. The incidence of symptomatic hypoglycaemia was comparable between GLAR versus NPH/semilente insulin at endpoint (2.19 vs. 1.94 episodes/week); however, the overall incidence of severe hypoglycaemia was significantly lower with GLAR versus NPH/semilente insulin (0.14 vs. 0.73 events/patient-year; p = 0.002). The daily insulin dose was similar between the treatment groups; however, perceived quality of life (QoL) was better with GLAR. GLAR is associated with equivalent glycaemic control, less severe hypoglycaemia and improved QoL compared with NPH/semilente insulin.     

Utilization and outcomes of neonatal cardiac extracorporeal life support: 1996-2000.

OBJECTIVES: Extracorporeal life support for neonatal respiratory failure has decreased, but utilization and outcome of cardiac extracorporeal life support are not well characterized. Among neonates born 1996-2000, our objects were to evaluate changes in utilization and outcome of cardiac extracorporeal life support and characterize correlates of survival. DESIGN: Retrospective analysis of Extracorporeal Life Support Organization Registry data. SETTING: Intensive care units participating in the ELSO registry. PATIENTS: Patients placed on extracorporeal life support for center-specified "cardiac support" at 15 days was associated with improved survival among hypoplastic left heart syndrome patients (p = .03), and survivors had fewer mean extracorporeal life support hours (89.3 +/- 52.3 vs. 147.5 +/- 129.7, p = .015). Logistic regression showed that only greater number of hours on extracorporeal life support was independently associated with nonsurvival. CONCLUSIONS: Neonatal cardiac extracorporeal life support use increased substantially from 1996 to 2000, with survival to discharge or transfer in more than one third of patients. Hypoplastic left heart syndrome was not associated with nonsurvival. Fewer hours on extracorporeal life support, diagnoses of persistent pulmonary hypertension of the neonate and transposition of the great arteries, and extracorporeal life support at <3 days were associated with survival.     

Diltiazem retards the metabolism of oral prednisone with effects on T‐cell markers

The area under the time-plasma concentration curve (AUC) was measured for prednisolone (the major active metabolite of prednisone) after ingestion of 15 mg of prednisone (phase 1) and again after 3 d of oral diltiazem (180 mg/d) followed by the same dose of oral prednisone (phase 2) in eight normal adult patients. Diltiazem increased the prednisolone AUC by 21% (range 3-38%), from 1297 +/- 157 ng/h/mL to 1560 +/- 169 ng/h/mL (p = 0.001). This effect was associated with a greater decrease from baseline in CD3+ lymphocyte number at 4 h after prednisone ingestion (596 +/- 175 vs. 516 +/- 140, p = 0.05), a larger percentage decrease of circulating CD3+ lymphocytes at 8 h (43 +/- 19% vs. 53 +/- 19%, p = 0.04), and a decrease in the number of CD3+ CD8+ T cells at 4 h post-prednisone ingestion (279 +/- 81 vs. 236 +/- 51, p = 0.04). Diltiazem retards prednisolone metabolism and when used chronically with prednisone could conceivably, in some patients, enhance its immunologic and other clinical effects. Potentiation of prednisone side-effects by diltiazem may be of special interest in pediatric patients, and possible diltiazem-prednisone interactions merit study in this population.     

Inverse association between Chlamydia pneumoniae respiratory tract infection and initiation of asthma or allergic rhinitis in children

To evaluate the role of Chlamydia pneumoniae respiratory tract infection on pediatric asthma, allergic rhinitis or atopic eczema initiation, children of three age groups (n=1211) were prospectively studied for a C. pneumoniae infection using throat swabs and polymerase chain reaction (PCR) with enzyme immunoassay (EIA) detection. Infected children (study group, SG) were examined monthly until the agent could not be detected, quantifying persistent infection. They were compared with randomly selected, non-infected children without asthma matched for age, gender and origin (control group, CG) regarding lung function and inflammatory parameters as well as initiation of allergic diseases judged by family doctor diagnosis after, in median, 22 months. At the first follow-up examination, SG children revealed a higher leukotriene B4 (median 36 pg/ml vs. 19, p=0.04) and 8-isoprostane (median 15 pg/ml vs. 12, p=0.04) in breath condensate characterizing neutrophil, agent-related inflammation and oxidative stress in the lower airways. Cysteinyl leukotrienes, important in acute allergic inflammation, were without difference. Local, anti C. pneumoniae secretory immunoglobulin A antibodies were higher in children after C. pneumoniae infection (optical density median 0.7 vs. 0.4, p=0.001) confirming PCR-EIA results. At the final examination, there was no difference in pathological lung function tests, parameters of exhaled breath condensate or eosinophilia of the nasal mucosa. Incidence of asthma (0/55 vs. 5/54, p=0.03) and allergic rhinitis [3/53 vs. 10/52, p=0.04, odds ratio and 95% confidence interval-OR 0.25 (0.06;0.98)] as well as prevalence of asthma [1/56 vs. 9/58, p=0.02, OR 0.1 (0.01;0.81)] and allergic rhinitis [6/56 vs. 16/58, p=0.03, OR 0.32 (0.11;0.88)] were lower in the SG children. There was no association in atopic eczema. Three children with persistent infection revealed a slightly higher incidence in allergic rhinitis without significance than those with single C. pneumoniae detection (1/3 vs. 2/50), however, not to the CG. In conclusion a C. pneumoniae upper respiratory tract infection may be regarded as a protective factor for childhood asthma or allergic rhinitis in a population of kindergarten and school-age children.     

吸人糖皮质激素与口服孟鲁司特治疗咳嗽变异型哮喘的疗效比较及随访研究

目的 比较吸入糖皮质激素(ICS)和口服白三烯调节剂(LTM)对儿童咳嗽变异型哮喘(CVA)的疗效,探讨儿童CVA的最佳治疗方案,并探讨CVA发展为典型哮喘的相关危险因素.方法 将84例年龄(3.9±1.2)岁(2～6岁)的CVA患儿随机分为ICS组(42例)和LTM组(42例).ICS组患儿通过定量气雾剂+储雾罐规律吸人二丙酸倍氯米松200 μg/d维持治疗,LTM组患儿每晚口服孟鲁司特5 mg维持治疗,治疗时间6个月,停用试验药物治疗后继续随访18个月.结果 ICS组平均止咳天数为(14±9)d,LTM组平均止咳天数为(13±9)d,两组问比较差异无统计学意义(Z=1.12,P=0.25).在24个月的研究观察期间,ICS组出现喘息的比率(7.1%)明显低于LTM组(33.3%)(x2=8.92,P=0.003).喘息组患儿湿疹和变应性鼻炎的患病率分别为47.1%和58.8%,明显高于无喘息组(分别为19.4%和31.3%)(x2分别为4.16和4.40,P均＜0.05).多因素逐步回归分析结果显示,湿疹和变应性鼻炎是CVA发展为典型哮喘的危险因素,OR值分别为7.668和3.855(P分别为0.002和0.049),而规律吸入ICS是有效的保护因素,其OR值为0.128(P=0.008).结论 CVA患者可转化为典型哮喘,接受ICS治疗的患儿出现喘息的比率低于接受LTM治疗的患儿,湿疹和过敏性鼻炎是CVA发展为典型哮喘的危险因素.