Anti-asthmatic prescription variability in children according to age.

INTRODUCTION: There is little research in the Spanish paediatric population about the consumption of anti-asthmatic agents. The aim of this study was to describe the current pattern of anti-asthmatic drug prescription in the paediatric population from a region of Spain, using the prescribed daily dose as a unit of measurement. METHODS: We analysed the requirements of R03 therapeutic subgroup (anti-asthmatic agents) in children less than 14 years of age in the Public Health System of Castilla y León from 2005 to 2010. Consumption data are presented in prescribed daily doses per thousand inhabitants per day (PDHD) and compared with defined daily doses per thousand inhabitants per day (DHD). RESULTS: 394 876 prescriptions of anti-asthmatics were given to a population of 1 580 229 persons/year. Bronchodilators, leukotriene receptor antagonists, single inhaled corticosteroids (ICS) and long-acting ß2-adrenergics associated with inhaled corticosteroids were the most commonly prescribed drugs: 7.5, 5.2, 4.9 and 2.2 PDHD, respectively. The maximum prescription of bronchodilators (15.9 PDHD/9.8 DHD) occurred in children under 12 months, with montelukast (8.9 PDHD/3.6 DHD) and single inhaled corticosteroids (7.9 PDHD/2.9 DHD) at one year of age. CONCLUSIONS: Between 2005 and 2010, children under four years received a high prescription of anti-asthmatic drugs. The use of maintenance therapy was poorly aligned with the recommendations of asthma guidelines. The PDHD was more accurate for measuring consumption than DHD, especially in younger children.

Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in coeliac disease patients.

BACKGROUND: The IL-15/NF-κB axis has an important role in coeliac disease (CD) and may represent a molecular target for immunomodulation. Ascorbate (vitamin C) is known to show inhibitory effects on NF-κB. Therefore, we studied if ascorbate supplementation to gliadin gliadin-stimulated biopsy culture could down-regulate the mucosal immune response to gliadin in CD. METHODS: Duodenal biopsy explants from treated CD patients were gliadin challenged in vitro (100 µg/ml) with and without 20mM ascorbate. An extra tissue explant in basal culture was used as internal control. Secretion levels of nitrites (3h), and IFNγ, TNFα, IFNα, IL-17, IL-13, and IL-6 (24h) were measured on the supernatants. IL-15 was assayed by western-blot on whole protein duodenal explants. RESULTS: The addition of ascorbate to in vitro culture gliadin-challenged biopsies blocked the secretion of nitrites (p=0.013), IFNγ (p=0.0207), TNFα (p=0.0099), IFNα (p=0.0375), and IL-6 (p=0.0036) compared to samples from non-ascorbate supplemented culture. Cytokine secretion was downregulated by ascorbate even to lower values than those observed in basal cultures (IFNγ: p=0.0312; TNFα: p=0.0312; IFNα: p=0.0312; and IL-6: p=0.0078). Gliadin-challenge induced IL-15 production in biopsies from treated CD patients, while the addition of ascorbate to culture medium completely inhibited IL-15 production. Moreover, the inhibition of IL-15 by ascorbate took place even in the only treated CD-patient who had basal IL-15 production. CONCLUSIONS: Ascorbate decreases the mucosal inflammatory response to gluten in an intestinal biopsy culture model, so it might have a role in future supplementary therapy in CD.

Diet and prevalence of atopic eczema in 6 to 7-year-old schoolchildren in Spain: ISAAC phase III.

BACKGROUND: The prevalence of atopic dermatitis (AD), a chronic skin disease, has increased substantially in recent decades, and different factors have been implicated in its etiology. Although dietary habits are being investigated, few conclusive findings have been reported. Nevertheless, increased consumption of polyunsaturated fatty acids (PUFA) and a diet poor in antioxidants have been related to AD. OBJECTIVES: The objectives of this study were to investigate the association between AD, the intake of different foods, and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7. METHODS: We performed a cross-sectional study with 20 106 schoolchildren aged 6-7 years from 10 different areas of Spain. The participation rate was 76.50%. The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood questionnaire and the criteria of the Spanish Academy of Dermatology. To calculate the Mediterranean diet score, we classified food into 2 groups: Mediterranean food, including fruit, seafood, vegetables, pulses, cereals, pasta, rice, and potatoes; and non-Mediterranean food, including meat, milk, and fast food. RESULTS: Milk was negatively associated with AD. Butter and nuts also were negatively associated, although statistical significance was only reached when these foods were consumed 3 or more times a week. CONCLUSIONS: We found no association between the Mediterranean diet score and AD and a positive association between AD and obesity.

Higher constitutive IL15R alpha expression and lower IL-15 response threshold in coeliac disease patients.

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R alpha mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R alpha mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.

How the presence of rhinoconjunctivitis and the severity of asthma modify the relationship between obesity and asthma in children 6-7 years old.

BACKGROUND: The association between asthma and obesity in children, and the effect modification of allergy on this association have not been fully established. Aims The objective of the study was to know the effect modification of the severity of asthma and of the coexistence of rhinoconjunctivitis (RC) in the relationship between obesity and asthma. METHODS: A cross-sectional study of 17 145 schoolchildren 6-7 years old from eight Spanish cities who had completed information on height and weight of the ISAAC phase III questionnaire, which also included questions about asthma and RC symptoms and on various risk factors. Body mass index (BMI) was used to define obesity according to international standards. Two different logistic regressions, using current occasional asthma (COA) and current severe asthma (CSA) as dependent variables, were made stratifying for gender and for the coexistence of RC and controlling for age, older and younger siblings, exercise, mother's education, truck traffic, cat/dog during the first year of life and smoking father or mother. RESULTS: Obesity was a risk factor of CSA without RC, both for boys (1.92, CI 95% 1.13-3.25) and for girls (2.99, CI 95% 1.68-5.32). Every BMI unit increment increased by 6.7% the risk of CSA without RC in boys and by 12.4% in girls. Obesity was not a risk factor for CSA with RC. The association between COA and obesity was weaker and the coexistence of RC did not modify it greatly. CONCLUSIONS: Obese schoolchildren are more at risk of suffering from non-allergic asthma than the non-obese subjects.

[Interleukin 18 (IL-18) and other immunological parameters as markers of severity in acute pancreatitis]. / Interleucina-18 (IL-18) y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda.

OBJECTIVE: Our aim was to prospectively compare the behavior of interleukin 18 (IL-18) levels and other immunological parameters during the first week of hospitalization between acute pancreatitis patients with and without severity criteria, as well as between patients with and without late pseudocyst development. PATIENTS AND METHODS: In 36 patients with acute pancreatis we compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days 1, 2, 3 and 7 after hospitalization between mild pancreatitis, severe pancreatitis, and a "control" group (13 patients) with uncomplicated biliary colic, as well as between patients with and without pseudocyst. RESULTS: On comparing mild to severe pancreatitis, IL-18 was significantly higher only the first day in severe pancreatitis, while the other parameters were steadily higher after the second day. In patients developing pseudocyst, IL-18 was also noticeably higher the first day. CONCLUSIONS: IL-18 appears to be the earliest marker of complications and severity in acute pancreatitis at both the systemic and local level (pseudocyst).

[Geographic variation in the prevalence of asthma symptoms in Spanish children and adolescents. International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, Spain]. / Variaciones geograficas en la prevalencia de sintomas de asma en los ninos y adolescentes espanoles. International Study of Asthma and Allergies in Childhood (ISAAC) fase III Espana.

OBJECTIVE: To analyze geographic variations in the prevalence of symptoms related to asthma in Spanish children and adolescents. POPULATION AND METHODS: In 2001 and 2002, the Spanish arm of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 collected information on 28 445 children in the age bracket of 6-7 years in 10 metropolitan areas (A Coruña, Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona, San Sebastián, and Valencia) and on 31 257 adolescents in the bracket 13-14 years in 11 areas (the previously named areas plus Valladolid). An asthma symptom questionnaire was filled in by parents or the adolescents themselves. Differences in symptoms between geographic areas were analyzed by fitting a logistic regression model. The relationship between symptoms and age was analyzed by linear correlation. RESULTS: The prevalence of recent wheezing (last 12 months) ranged from 7.1% to 12.9% among 6-7-year-olds and from 7.1% to 15.3% among the 13-14-year-olds. The greatest risk of recent wheezing was observed for children in A Coruña (odds ratio [OR] =1.96 in comparison with the area of lowest prevalence; 95% confidence interval [CI], 1.65-2.33) and Bilbao (OR=1.83; 95% CI, 1.54-2.18) and for adolescents in A Coruña (OR=2.38; 95% CI, 2.04-2.79) and Asturias (OR=2.37; 95% CI, 2.03-2.77). A strong correlation (r=0.72) was observed between the prevalence of recent wheezing and age in each of the geographic areas. CONCLUSIONS: Considerable geographic variation in the prevalence of asthma symptoms can be seen in Spain even among young children. Symptoms are more frequent in children and adolescents who live on the Spain s northern Atlantic coast.

[Risk factors for atopic dermatitis and familial prevalence in Spain (ELIHO study)]. / Factores de riesgo y prevalencia familiar de la dermatitis atópica en España (estudio ELIHO).

INTRODUCTION: Atopic dermatitis (AD) is a cutaneous disease of unknown etiology. It shows a clear genetic predisposition with probable environmental modulation. This study evaluated risk factors associated with diagnosis and flares of AD in Spanish children. PATIENTS AND METHODS: We performed an observational, multicenter, retrospective case-control study that included 4243 children aged less than 14 years old with AD and 978 controls matched for age and sex. Family history of disease and environmental variables were collected in both groups and clinical history of AD was recorded in the case group. RESULTS: Significant risk factors for AD were: a family history of the disease and concomitant cutaneous infections. The prevalence of AD in first degree relatives was 39 % and that in second degree relatives was 19 % (higher in maternal than paternal lines). The mean age of children with AD was 4.2 (SD 3.4) years and the mean age at diagnosis was 1.5 (SD 2.2) years, with a mean of 2.9 (SD 2.6) flares during the previous year. Cold weather (Cantabrian and Continental Iberian Peninsula areas) was related to a greater number of flares. Children with AD had a greater number of concomitant cutaneous diseases and infections than children in the control group. CONCLUSIONS: AD is mainly a genetic disease, with climatic factors involved in severity modulation, and with important immunological alterations. In contrast, this study found no domestic environmental factors that were associated with disease onset.

[Time trends and geographical variations in the prevalence of symptoms of allergic rhinitis in 6-7-year-old children from eight areas of Spain according to the ISAAC]. / Tendencia temporal y variaciones geográficas de la prevalencia de síntomas de rinitis alérgica en escolares de 6-7 años de ocho áreas españolas, según el ISAAC.

BACKGROUND: Phase III of the International Study of Asthma and other Allergies in Childhood (ISAAC) was carried out in schoolchildren aged 6-7 years from eight areas of Spain to estimate time trends and geographic variations in the prevalence of symptoms of allergic rhinitis (AR). MATERIAL AND METHOD: A standard and validated questionnaire was used following ISAAC methodology and was completed by the schoolchildren's parents. The prevalence of symptoms of AR in Phase I (1993-1994) and Phase III (2001-2002) was compared. Eight centers participated: Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona and Valencia. Poisson regression was used in the analysis. RESULTS: A total of 25,113 schoolchildren were studied with a median participation of 81.7 %. In all centers, AR symptoms tended to increase, with a prevalence ratio of rhinoconjunctivitis in the previous year of 1.61 (95 % confidence interval: 1.48-1.76) when both phases, adjusted by gender, center, and seasonal variation, were compared. The prevalence of AR symptoms was higher in boys than in girls. Wide variations in the prevalence of AR were observed across centers with a higher prevalence in Asturias, Madrid, Cartagena and Bilbao. Lower prevalences were reported in Barcelona, Castellón and Pamplona. CONCLUSIONS: There seems to have been a general increase in AR symptoms. Substantial variations between centers suggested that there may be local differences in risk factors. Intense research will be required for satisfactory preventive actions.

[Paediatric prescribing of anti-asthmatics in primary care in Castilla-León. Geographical variability]. / Prescripción pediátrica de fármacos antiasmáticos en atención primaria en Castilla y León. Variabilidad geográfica.

INTRODUCTION AND OBJECTIVES: Asthma is one of the most prevalent chronic diseases with effective treatment in paediatrics. The aim of this study is to describe the paediatric prescribing of anti-asthmatics in Castilla-León, analyzing its geographic variability and temporal evolution. MATERIAL AND METHODS: An analysis was made of prescriptions dispensed in pharmacies of R03 therapeutic subgroup (anti-asthmatic agents), and the active ingredients mepyramine and ketotifen, prescribed in children less than 14 years of age in the Castilla-León health service from 2005 to 2010 in Primary Care. Data is presented in prescribed daily doses per thousand inhabitants per day (PDHD) for each active ingredient being calculated raw rates and age-adjusted to the variables health area, type of health zone and year of study. RESULTS: A total of 462,354 prescriptions of anti-asthmatic agents were dispensed to a population of 1,580,229 persons/year. There was wide variation between areas in the type and intensity of anti-asthmatic agents used, partly explained by differences in the prevalence of asthma. Montelukast predominated as controller drug in most of them (PDHD 3.1 to 7.7), being similar the consumption intensity in the three types of health zones (PDHD 4.7 to 4.8). The annual variability was low. CONCLUSIONS: The study describes the paediatric prescribing pattern of anti-asthmatic agents in Castilla-León between 2005-2010. It shows wide geographical variation, as well as inadequacies regarding current recommendations of asthma treatment.

Decreased interleukin-12 levels in umbilical cord blood in children who developed acute bronchiolitis.

Respiratory syncytial virus (RSV) infection is common in young children, but only a few develop severe bronchiolitis. The relationship between bronchiolitis, asthma, and atopy has been debated for a long time, but the pathogenesis of wheezing remains unclear. A Th1 and Th2-type lymphocyte imbalance seems to be involved in asthma and atopic disease. Serum interleukin-12 (IL-12), IL-10, and soluble CD30 (sCD30) levels were measured by enzyme-linked immunosorbent assay (ELISA) in 23 cord blood samples kept frozen since birth: 11 from normal term newborns who several months later were admitted to the hospital with bronchiolitis, and 12 from newborns who did not develop the disease (controls). The study was also performed on 28 additional children (1-16 months old) suffering an episode of acute bronchiolitis. IL-12 was clearly increased in all cases at birth, but newborns who later developed bronchiolitis showed low IL-12 levels in cord blood compared to newborns who did not develop the disease (median 295 vs. 507 pg/mL; P = 0.001). sCD30 levels were also decreased in the first group (15 vs. 26 U/mL; P = 0.007). During episodes of bronchiolitis, a clear rise of IL-12, IL-10, and sCD30 was observed. None of the factors studied in the acute phase showed statistical differences in children who were later readmitted to the hospital due to repeated wheezing crises. Children who develop acute bronchiolitis with wheezing may have an immunological imbalance that is expressed at the time of delivery by a lower concentration of serum IL-12.

Susceptibility genes for asthma and allergy: hits and questions.

Allergy and asthma are closely related conditions which result from a complex interaction between several genetic and environmental factors. On the basis of familial linkage analysis data from different populations, some chromosomal regions containing a series of susceptibility loci have been identified. To date, genome-wide search studies have reported a group of chromosomal regions which include most likely several candidate genes for asthma and allergy. Some of these genes are excellent candidates, as they are known to modulate the immune response and airways inflammation processes. So, by focusing efforts on the analysis of those chromosomal regions, the characterization of the potentially important genes can be achieved. This will undoubtedly provide a clue for a better understanding of those pathologic components involved in the onset and development of asthma and allergic disorders.

Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients.

Tumor necrosis factor (TNF) is a potent proinflammatory cytokine involved in asthma and atopy. Increased TNF-alpha levels have been found in airway biopsies and bronchoalveolar lavage fluids from asthmatic patients. Constitutional variations in the TNF-alpha secretion levels in vitro are associated with molecular polymorphisms located within and around the TNF loci. Our study objective was to investigate the association between atopy and two described di-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'-promoter region of the TNFA gene (TNFA*1 and TNFA*2 alleles) and an Ncol restriction fragment length polymorphism (RFLP) in the first intron of the TNFB gene (TNFB*1 and TNFB*2 alleles). The genetic study was performed in 65 unrelated atopic patients and 60 healthy controls. The regions of interest were amplified from genomic DNA using specific primers and polymerase chain reaction. SSP-PCR analysis for TNFA -308 polymorphism genotyping and endonuclease digestion analysis for the TNFB Ncol RFLP were used. The frequency of the TNFA*2 allele was significantly higher in atopic subjects compared to the control group (38.5% vs. 10.5%; chi2 = 32.06; p <0.0001). The TNFA*2 allele is associated with a higher risk for the development of atopy (risk ratio = 9.44; EF = 0.65; chi2 = 30.06 p <0.0005). On the other hand, no significant association between the TNFB alleles and atopy was found. In conclusion, the TNFA*2 allele could be also a genetic risk marker for the predisposition to atopy in our population, as has been reported in other studies. Either the TNFA gene itself or a linked gene on chromosome region 6p21, which has yet to be identified, is a candidate gene for susceptibility to atopy.

Study of HLA-DQA1 alleles in celiac children.

The familial incidence of celiac disease (CD) confirms its genetic basis, although acquired factors are also involved. Many authors have reported a linkage between celiac disease and HLA antigens, but there are differences which depend on geographical areas, and nowadays the study must be done at the genetic level. Thirty-eight celiac children and 52 normal controls were included in this study. All individuals were chosen from the Castilla and Leon area. We used the reverse ¿dot block¿ technique, using sequence-specific oligonucleotide DNA probes (Cetus, USA) to determine the HLA-DQA1 alleles in DNA samples previously amplified by PCR (polymerase chain reaction). The different frequency of alleles in patients and controls was assessed by 3 statistical tests: chi square (chi(2)), relative risk (RR) and etiologic fraction (EF). A very high frequency of DQA1*0201 (chi(2):p <0.0001) and DQA1*0501 (chi(2): p <0.0001) alleles was observed in patients; all but one (97%) had the DQA1*0501 allele vs. 40% of controls (RR: 37.00; EF: 0.955). The DQA1*0201 allele also had a high prevalence in celiacs (58%)(RR: 1.375: EF:0.438). The DQA1*01 allele was only found in 10.5% of patients compared to 79% of controls (chi(2): p <0.0001) and the DQA1*03 allele was also decreased in celiacs. There was only one celiac girl without the DQA1*0501 allele. She had no other clinical or serological differences, as compared to the other patients. In the study of allele subtypes, among the DQA1*01 allele, 50% of patients were positive for DQA1*101 and the remaining 50% had DQA1*0102, but none of the individuals were positive for DQA1*0103. Among normal controls, 32 individuals (61.5%) expressed the DQA1*0102 subtype, 15 (28.9%) the DQA1*0101 subtype and 5 (9.6%) the DQA1*0103 subtype. All positive cases for DQA1-*05 belong to the DQA1* 0501 subtype, in both celiac and control groups. There were 10 possible combinations of HLA-DQA1 genes, but we found a very unequal distribution in both celiacs and controls. Only 4 genotypes were found in patients (DQA1*01/1*0501, DQA1* 0201/1*0501, DQA1*03/1*0501 and DQA1*0501/1*0501) and 8 in controls. The DQA1*0201/1*-0501 genotype was the most discordant, being positive in 55.3% of patients vs. 3.8% of controls (chi2:p < 0.001; RR: 1.235; EF:0.534). None of the 90 individuals studied expressed the DQA1*0311*03 genotype. The DQA1*0201/1*03 genotype was not shown by any control and by only 1 celiac patient. It is noteworthy that the DQA1*0201/1*0501 genotype was more frequent than the homozygous genotype DQA1*0501/1*0501. Our results do not suggest a dosage effect for the DQA1*0501 allele. The determination of the HLA-DQA1 gene is a helpful tool for the screening of individuals with a high risk of being celiacs.

[Blood lead in a population of children with iron deficiency]. / Estudio de la plumbemia en la población infantil con ferropenia.

BACKGROUND: Analysis of blood lead levels in relation to the state of iron metabolism was carried out in children. METHODS: A transversal study of blood lead levels was designed in 89 iron deficient children (serum ferritin < 15 micrograms/l) (group F). Fifty seven of the children did not have anemia (sub-group FS) and 32 had anemia (sub-group AF) with ages ranging between 6 months and 14 years, and 41 children of the same age with normal iron metabolism (group C). A longitudinal study was also carried out by the determination of blood lead levels prior and after iron therapy in 18 of the iron deficient children. RESULTS: A significant difference was seen between the mean of blood lead levels in iron deficient children (group F), 9.41 micrograms/dl and normal children (group C), 6.88 micrograms/dl (p < 0.01). The mean of blood lead levels of the sub-group FS was 7.79 micrograms/dl and the sub-group AF, 12.30 micrograms/dl (p < 0.01). The prevalence of lead poisoning (blood lead levels > 20 micrograms/dl) was 8% in group F (2% in sub-group FS, 19% in sub-group AF) and 0 in group C (p < 0.01). A significant decrease was found in the longitudinal study in the mean of blood lead levels following iron therapy from 14.12 micrograms/dl to 7.51 micrograms/dl (p < 0.05). CONCLUSIONS: The iron deficient state may constitute a predisposing factor of lead poisoning in childhood.

[Meningococcal sepsis in pediatrics. Parameters associated with poor outcome]. / Sepsis meningocócica en pediatría. Parámetros asociados a mala evolución.

BACKGROUND: Mortality due to meningococcal sepsis continues to be extremely high. Patients with a poor prognosis require aggressive therapy and should be identified early. OBJECTIVE: To investigate the clinical and biological factors associated with poor outcome. PATIENTS AND METHOD: Seventy-one children aged 2 months to 13 years with meningococcal sepsis were studied. Inclusion criteria were meningococcus isolation in cultures or characteristic clinical features with purpuric exanthema. METHODS: A correlational descriptive study was performed. In all patients we evaluated the Pediatric Risk of Mortality (PRISM), the Glasgow Scale for Meningococcal Sepsis (GSMS), polymorphonuclear (PMN) count and prolactin (PRL), leptin (LPT) and C-reactive protein (CRP) levels. RESULTS: Fourteen children (19.7 %) died. Death was associated with multiple organ dysfunction syndrome (MODS) (p = 0.0001), high GSMS and PRISM scores (p = 0.0001) and to a lesser extent with shock (p = 0.01). In patients who died, the determinations showing greatest alteration at admission were PRL levels (p = 0.0009) and PMN count (p = 0.0005). CRP levels were not associated with differences in mortality but were high in patients with shock (p = 0.008). Children with high body weight percentiles were at greater risk of death and showed higher levels of PRL, PCT (p = 0.006) and LPT (p = 0.006), without differences in GSMS or PRISM scores. Age did not influence mortality or PRL levels but did influence GMSM and PRISM scores and PMN and CRP levels. These differences disappeared after the age of 2-3 years. In patients with MODS or shock, the only differences found were reduced PMN count (p = 0.0001) and elevated PRL levels (p = 0.0001). CONCLUSIONS: In meningococcal sepsis, death is more frequent in children with high body weight percentiles. Moreover, these children present elevated PRL and LPT levels, although whether these variables act independently remains to be elucidated.

[Agenesis of vas deferens and cystic fibrosis]. / Agenesia de conductos deferentes y fibrosis quística.

Congenital bilateral absence of vasa deferens appears in 6% of obstructive azoospermia, and 60-70% of these patients also have cystic fibrosis mutations. Unilateral aplasia or agenesia of vasa deferens occurs in less than 1% male individuals and some studies have found that up to 43% cases show mutations in the cystic fibrosis gen. We contribute four case reports of bilateral agenesia who were seen for infertility, all of which showed presence of mutation. In none of the two cases of unilateral agenesia, who consulted for vasectomy, a mutation in the cystic fibrosis gen was found. Patients with bilateral agenesia and their partners should be screened for cystic fibrosis, prior to spermatic microaspiration and assisted fecundation.

[Clinical manifestations, diagnosis and treatment of Haemophilus influenzae infection]. / Manifestaciones clínicas, diagnóstico y tratamiento de la infección por Haemophilus influenzae.

Haemophilus influenzae is a small, nonmotile, non-spore-forming bacterium, and a strict parasite of humans found principally in the upper respiratory tract. The production of capsule is of major significance to clinicians since it is an important virulence factor. We described six antigenically distinct capsular types, designated a-f. Spread from one individual to another occurs by airborne droplets or by direct contagion with secretions. Haemophilus influenzae produces at least two factors that inhibit the ciliary activity of human epithelial cells in vitro. One of this has been shown to be lipopolysaccharide and the other factor is of low molecular weight, most likely a heat-stable glycopeptide. Type b strains are distinguished by the production of capsular polysaccharide composed of repeating units of ribosyl-ribitol phosphate, account for greater than 95 percent of systemic infections in children. Two contrasting patterns of Haemophilus influenzae disease can be identified. The first and the most serious in its consequences is invasive infection such as meningitis, septic arthritis, epiglottitis, and cellulitis in which bacteremia is a prominent feature; these infections are usually caused by type b strains and occur in young children. The second category includes less serious but numerically more common infections, that occur as a result of contiguous spread of Haemophilus influenzae within the respiratory tract; e.g. otitis media, sinusitis. These latter infections are usually, but not invariably, caused by unencapsulated strains. A provisional diagnosis of meningitis, epiglottitis, facial cellulitis, or septic arthritis will usually be prompted by the history and clinical findings. Confirmation requires microbiologic studies. Cultures of blood, CSF and other normally sterile fluids are diagnostic and therefore under the appropriate circumstances mandatory. Whenever feasible, specimens obtained for culture should also the gram-strained. Detection of capsular antigen in serum, CSF or concentrated urine using immunoelectrophoresis, latex agglutination or enzyme linked immunosorbent assay may be diagnosed and can be found in up to 90 percent of culture proved cases of meningitis. Without treatment, infection due to Haemophilus influenzae can be rapidly fatal, particularly by meningitis and epiglottitis. There is currently a trend to use certain parenteral third generation cephalosporins as initial therapy when lifethreatening Haemophilus influenzae infection is known or suspected in children beyond the neonatal period, commonly used agents included cefotaxime or ceftriaxone. Antibiotic therapy is only one facet of the management of the child with Haemophilus influenzae infection, and critical attention must also be given to supportive therapy. In the ambulatory setting, ampicillin or amoxicillin for 10 days is often satisfactory for the less severe Haemophilus influenzae infections. Cephalosporins are often chosen for treatment of adults, with pneumonia when Haemophilus influenzae is documented.