The American English version of the validated French Flare Assessment in RA Questionnaire (FLARE-RA).

OBJECTIVE: To evaluate use of a British English version of the validated French FLARE-RA questionnaire among American English speaking patients. In addition, to create a culturally adapted American English (AmE) FLARE-RA questionnaire and to examine its attributes of patient-reported RA flare status. METHODS: Using standardized cultural adaptation guidelines, we cognitively debriefed 25 American English speaking rheumatoid arthritis (RA) outpatients and created AmE-FLARE-RA with their input. One hundred three additional RA patients were recruited. Patients completed the Routine Assessment of Patient Index Data 3 (RAPID3), patient global visual analogue scale (VAS), AmE-FLARE-RA, and self-reports of flare. Physician global VAS, physician-assessed flare, swollen and tender joint count (TJC), and clinical disease activity index (CDAI) were documented. AmE-FLARE-RA and disease activity measures were compared between patient-reported and physician-reported flare categories. RESULTS: Patients were female (89%), with mean (SD) age 51.1 (± 15.3) years and mean disease duration (SD) 11.9 (± 10.1) years, with 26% in remission/low disease activity. Total AmE-FLARE-RA scores, RAPID3, CDAI, and patient global VAS were significantly higher for both patient-reported flares and physician-reported flares compared with non-flaring patients by self- or physician report (p < 0.05). Total AmE-FLARE-RA scores correlated significantly with RAPID3 (corr = 0.50, p < 0.0001) and with CDAI (corr = 0.45, p < 0.0001). Across "no flares," "one flare," and "several flare" groups, there was a non-significant increase in AmE-FLARE-RA scores (p = 0.07). CONCLUSION: The British English FLARE-RA was successfully adapted for AmE-speaking RA patients. AmE-FLARE-RA significantly correlated with RAPID3 and CDAI and distinguished between patient-reported and physician-reported flares, making it useful to detect flares in American RA patients.Key Points• The American English FLARE-RA (AmE-FLARE-RA) questionnaire is the result of cognitive debriefing with American RA patients using the British English version of the validated French FLARE-RA and incorporates patient-recommended language modifications..• Patients self-reporting flares had significantly higher AmE-FLARE-RA scores, compared with those without flares at the time of visit. AmE-FLARE-RA scores correlate with RAPID3 and CDAI.• There was a non-statistically significant trend using the AmE-FLARE-RA scores when examining patients with no flare, one flare, or several flares.• AmE-FLARE-RA total scores are uniformly elevated (~ 6.0 on a 0-10 scale), regardless of discordance between patient and MD assessment of flare at time of visit (~ 30%).

Gender differences in the relationship between body mass index (BMI) changes and the prevalence and severity of wheezing and asthma in the first year of life.

BACKGROUND: Rapid weight gain has been recently associated with asthma at school age, but its influence in respiratory symptoms during infancy is still unknown. METHODS: Answers from 6541 parents living in six different cities of Brazil to the International Study of Wheezing in Infants (EISL) questionnaire were analysed. Data from reported weight and height at birth and at one year were used to calculate BMI. Rapid body mass index (BMI) gain was defined by the difference in BMI superior to 1.0z and excessive by the difference superior to 2.0z. RESULTS: Rapid BMI gain was found in 45.8% infants and excessive in 24.4%. Boys showed a significantly higher BMI gain than girls. Girls with rapid BMI gain showed a significantly higher prevalence of hospitalisation for wheezing (8.8% vs. 6.4%; aOR: 1.4, 95%CI: 1.1-1.8), severe wheezing (18.1% vs. 15.0%; aOR: 1.3, 95%CI: 1.0-1.5) and medical diagnosis of asthma (7.5% vs. 5.7%; aOR: 1.3, 95%CI: 1.0-1.7). Girls with excessive BMI gain also had a significantly higher prevalence of hospitalisation for wheezing (9.8% vs. 6.7%; aOR: 1.5, 95%CI: 1.1-2.0) and severe wheezing (18.9% vs. 15.5%; aOR: 1.3, 95%CI: 1.0-1.6). No significant association was found among boys. CONCLUSIONS: The majority of the evaluated infants showed BMI gain above expected in the first year of life. Although more commonly found in boys, rapid and excessive BMI gain in the first year of life was significantly related to more severe patterns of wheezing in infancy among girls.

[Value of nasal nitric oxide in the diagnosis of primary ciliary dyskinesia]. / Valor del óxido nítrico nasal en el diagnóstico de la discinesia ciliar primaria.

OBJECTIVE: The aim of this study is to report nasal nitric oxide (nNO) values in children with primary ciliary dyskinesia (PCD) and to compare them with nNO values in healthy children, asthmatic children, children with cystic fibrosis and children with post infectious bronchiectasis. PATIENTS AND METHODS: We determined nNO values in 9 children with PCD, 36 asthmatic children, 31 children with cystic fibrosis, 8 children with post infectious bronchiectasis and 37 healthy children. We compared nNO values between these different conditions and calculated sensitivity and specificity of nNO to diagnose PCD. RESULTS: All children with PCD - except one (nNO 348 ppb) - had nNO values below 112 ppb, mean 88 ppb (95%CI 9.6-166). The nNO mean was 898 ppb (95%CI 801-995) in healthy children, 1023 ppb (95%CI 911-1137) in asthmatic children, 438 ppb (95%CI 367-508) in cystic fibrosis children and 361 ppb (95%CI 252-470) in children with post infectious bronchiectasis. The mean concentration of nNO was lower (P<0.05) in PCD patients, compared to the other groups. The measurement of nasal NO in our study population showed, at a cut-off level of < or =112 ppb, a sensitivity of 88.9% and a specificity of 99.1% in the diagnosis of PCD [ROC 0.98 (95%CI 0.94-0.99); P<0.0001; probability ratio 95.1]. CONCLUSIONS: The measurement of nasal NO appears to be a useful tool for screening children for PCD, in which a cut-off level of < or =112 ppb suggests the disease, although nNO above 112 ppb does not exclude PCD.

PTPN22 C1858T polymorphism and the outcome of hepatitis C virus infection.

The outcome of chronic hepatitis C virus infection varies, depending on viral and host factors. Those mechanisms involved in the control of the innate and adaptive response could have an influence on the outcome of infection. The PTPN22 gene encodes an intracellular lymphoid-specific phosphatase (Lyp) with a lymphocyte activating downregulatory effect. A single-nucleotide polymorphism (SNP) C1858T located on this gene has been associated with autoimmune diseases and bacterial infections. The aim of this study was to assess whether the PTPN22 C1858T polymorphism is related to the outcome of hepatitis C viral infection. A total of 69 patients with spontaneous viral clearance (SVC), 281 patients with chronic hepatitis C (CHC), and 1036 individuals not infected with hepatitis C (NIC) were included in this study. Patients with CHC were stratified according to Scheuer score of hepatic fibrosis from F0-F2 (n = 200) and F3-F4 (n = 81), and according to their response to therapy in patients with sustained responses (SR; n = 103) and non-sustained response (NSR; n = 104). Genotyping of the C1858T polymorphism was performed using TaqMan probes. No statistically significant differences in the distribution of PTPN22 C1858T polymorphism were observed upon comparison of patient group with the NIC group. Also, when the different patient groups were compared to one another, no statistically significant differences were detected: the SVC with the CHC group (10.2% versus 12.5%; p = 0.6), the F0-F2 with the F3-F4 group (11.5% versus 14.8%; p = 0.5), and the NSR with the SR group (11.5% versus 14.6%; p = 0.4). Our results do not support a major role of this polymorphism of the PTPN22 gene in the outcome of chronic hepatitis C virus infection in the Spanish population.

CCL2-2518 A/G and CCR2 190 A/G do not influence the outcome of hepatitis C virus infection in the Spanish population.

AIM: To assess whether CCL2 or interactions between this chemokine and its receptor (CCR2) are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy. METHODS: Two hundred and eighty-four patients with chronic hepatitis C and 193 non-infected matched controls were included in this study. Patients were categorized according to their Scheuer score of hepatic fibrosis as F0-F2 (n = 202) or F3-F4 (n = 82) and according to their response to anti-Hepatitis C virus (HCV) therapy as sustained response (SR, n = 101) or non-sustained response (NSR, n = 98). Genotyping of the -2518 (A/G) CCL2 was performed using PCR-RFLP, genotyping of the 190 (A/G) CCR2 using a PCR-ARMS system, and genotyping of the rs3138042 (G/A) CCR2 using Taqman probes. RESULTS: Univariate analyses identified 4 parameters (infection duration time, viral genotype, gender and AST levels) that tended to influence fibrosis and 7 parameters (CCL2G, CCL2ACCR2A, viremia levels, fibrosis stage, viral genotype, infection duration time and AST levels) that significantly influenced or tended to influence response to treatment. Multivariate analysis identified gender and AST levels as parameters that independently influenced fibrosis stage and viral genotype and infection duration time were the two parameters that independently influenced response to treatment. CONCLUSION: Our results indicate that the mutations studied in the gene pair CCL2/CCR2 do not play a major role in the outcome and response to treatment for HCV infection in the Spanish population.

Analysis of CCR5-Delta 32 and CCR2-V64I polymorphisms in a cohort of Spanish HCV patients using real-time polymerase chain reaction and fluorescence resonance energy transfer technologies.

Nowadays it is clear that chemokine-chemokine receptor interactions are important in chronic hepatitis C virus (HCV) infection. The objective of the present study was to elucidate the involvement of the CCR5-Delta 32 and CCR2-V64I polymorphisms in the response to the HCV infection, as well as in the histological damage and the outcome of the infection. A cohort of 139 patients with hepatitis C and 100 healthy blood donors were analysed for both polymorphisms using real-time polymerase chain reaction (PCR) and LightCycler technology. We have detected the CCR5-Delta 32 allele in 15 of 278 HCV chromosomes (5.4%) and 15 of 200 control chromosomes (7.5%). The CCR2-V64I allele was present in 24 of 278 HCV chromosomes (8.6%) and 19 of 200 control chromosomes (9.5%). Analysis of the histological parameters showed no statistical significance when comparing the patients carrying the variants vs the cases with the wild-type allele. Our results seem to indicate that the CCR5-Delta 32 and CCR2-V64I polymorphisms are not related to the response to HCV infection, histological damage and outcome of infection in our cohort of Spanish HCV patients.

SLC11A1 promoter gene polymorphisms and fibrosis progression in chronic hepatitis C.

BACKGROUND AND AIMS: The solute carrier family 11 member 1 (SLC11A1) gene (formerly Nramp1) encodes for the protein solute carrier family 11, member 1. It affects susceptibility and clinical outcome of autoimmune and infectious diseases. We investigated the possible role of the functional polymorphism located in the promoter region of SLC11A1 and tumour necrosis factor (TNF) genes in the progression of fibrosis in chronic hepatitis C. METHODS: A total of 242 Caucasian Spanish patients with biopsy proven chronic hepatitis C and 194 healthy control subjects were genotyped for SLC11A1 and TNF promoter polymorphisms. RESULTS: No significant differences in the distribution of frequencies among patient and control groups were observed. The SCL11A1 homozygous 2/2 genotype was rarely detected among patients showing advanced fibrosis (2/82; 2.4%) but was highly represented in those with mild fibrosis (29/160; 18.1%; odds ratio (OR) 8.85 (95% confidence interval (CI) 1.9-55.2, p(c) = 0.002). In patients carrying allele 3 of SLC11A1, the presence of -238 TNF A/G was associated with advanced fibrosis (14/26 (53.8%) v 68/216 (31.4%); OR 2.53 (95% CI 1.03-6.23); p = 0.02). CONCLUSIONS: SLC11A1 gene promoter polymorphism could influence fibrosis progression in chronic hepatitis C in that the homozygous genotype 2/2 exerts a protective effect against cirrhosis development. Also, the combination of TNF -238 A/G and the presence of allele 3 is conducive to progression to pre-cirrhotic or cirrhotic stages of the disease.

[Non-immunoallergic hepatotoxicity due to mesalazine]. / Hepatotoxicidad no inmunoalérgica por mesalazina.

Mesalazine is an aminosalicillic derivative considered as a safe alternative to the relative frequency (5-55%) of adverse effects observed with sulfasalazine. The well known hepatoxicity associated with sulfasalazine and attributed to its sulfamidic fraction is limited to few cases described in the treatment with mesalazine. We herein present a new case of hepatoxicity by mesalazine in a patient with lymphocytic colitis. The possible pathogenic mechanism is also commented upon.

[Exhaled and nasal nitric oxide in normal and asthmatic children]. / Oxido nítrico exhalado y nasal en niños normales y asmáticos.

OBJECTIVE: Our aim was to study the concentration of nitric oxide in the exhaled (ENO) and nasal (NNO) air of normal children and asthmatic children who are clinically and functionally stable. PATIENTS AND METHODS: Using a nitric oxide chemiluminescence analyze and a register for CO2, pressure and flow, we studied 73 schoolchildren (6-17 years of age). This included 37 controls and 36 asthmatic children, 21 with mild asthma without antiinflammatory treatment and 15 treated with inhaled corticosteroids. We used the technique of slow exhalation against resistance for (ENO) determination and aspiration with stable flow in nasal cavity while holding the breath for (NNO) determination. RESULTS: The mean ENO was 3.1 ppb (1-6) in the control group, 8.3 ppb (1.7-29.3) in the mild asthma group and 7.7 ppb (2-18.3) in the asthmatics treated with corticosteroids. There were significant differences (p = 0.0001) between the controls and both asthmatic groups. The mean NNO in the controls was 898 ppb and differences between this group and the asthmatic children were found. The ENO and NNO did not change in relation to age or sex. We did not find any relationship between ENO and lung function. There is a significant correlation between ENO and NNO in both asthmatic groups, but not in the control group. CONCLUSIONS: The ENO was higher in asthmatics than in control children. The slow exhalation against resistance technique prevents the contamination of exhaled air with nasal air and this technique can be applied to children over 6 years of age. The NNO was similar in the asthmatic groups and the control group.

[Assessment of 2 portable peak expiratory flow meters and reference values for students 6 to 16 years of age]. / Evaluación de dos medidores portátiles de flujo espiratorio máximo y valores de referencia para escolares de 6 a 16 años.

OBJECTIVE: This study examines the technical characteristics of two different peak expiratory flow meters, of high range, and the reference values of peak expiratory flow (PEF) for schoolchildren. PATIENTS AND METHODS: The gauge accuracy and precision were previously determined in 20 units of each model (PF-Control and Mini-Wright), with a syringe servocontrolled by simulating 4 predetermined PEF fluxes (125, 262, 424 and 587 L/min). Relatives were asked about passive smoking and the childhood background concerning asthma, recurrent bronchitis or recent respiratory infection. The PEF of 1,142 schoolchildren, 669 boys and 473 girls between 6 and 16 years of age and coming from 6 different locations of different demographic and social characteristic of Catalonia, Spain, were measured. RESULTS: Readings of both gauges differed in accuracy, although they presented a good intradevice precision. The PF-control is within the reliance intervals for fluxes of 425 and 587 L/min, with a suprareading of 15.3% for the 262 L/min and infrareading of 19.2% for the 125 L/min controls. Flux with the Mini-Wright shows systematic over-reading of between 17.9% and 30.2%, with an accurate reading only in the 587 L/min control flux. No significant correlation was found between the PEF and family passive smoking (56.3%), pupils with asthma background (7.1%), recurrent bronchitis (11%) or recent respiratory infection (7.7%). CONCLUSIONS: The accuracy difference forces the use of diverse percentile tables for each of the PEF gauge patterns; hence, we present the reference tables for each gauge, in means of 10, 50 and 90 percentiles, which can be used as reference values for our school population according to their age, size and sex.

[Isolation of mycobacteria in patients with cystic fibrosis: a prospective study]. / Aislamiento de micobacterias en pacientes con fibrosis quística: estudio prospectivo.

OBJECTIVE: A prospective study to assess the incidence of mycobacterial infection in patients with cystic fibrosis in our geographical area was performed. PATIENTS AND METHODS: A monitored follow-up was carried out in 91 patients over a period of 20 months, during which time 522 respiratory samples were obtained. These were processed by standard techniques of decontamination with sodiumlaurylsulphate, cultured on Löwenstein-Jensen medium and identified by biochemical and cultural characteristics and hybridization by specific probes. At the same time, the clinical reports of the patients with positive culture were reviewed. RESULTS: Positive cultures of mycobacteria were obtained from 4 patients. Environmental mycobacteria were isolated in three of them (M. xenopi, M. fortuitum and M. avium) and M. chelonei and later M. tuberculosis in the forth. None of the isolations of environmental mycobacteria were associated with deterioration of pulmonary function, while the isolation of M. tuberculosis in one of the patients coincided with an episode of decompensation in respiratory function. None of the patients presented sensitivity of the tuberculin skin test. CONCLUSIONS: It is advisable to investigate the mycobacteria in the presence of exacerbation of the respiratory process, above all taking into account the high incidence of tuberculosis in our geographical area. The isolation of environmental mycobacteria was not associated with pulmonary deterioration, but they represent a potential danger as opportunist pathogens, affecting patients of which many are candidates for lung transplants.

Action of beta-phenylethylamine and related amines on nigrostriatal dopamine neurotransmission.

The present paper describes the effect of beta-phenylethylamine and its metabolites phenylethanolamine, tyramine, acetyl-phenylethylamine and phenylacetaldehyde on the dopaminergic nigrostriatal system. The rotational behavioural response to the i.v. injection of these drugs was quantified in animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system. Only beta-phenylethylamine and acetyl-phenylethylamine induced rotations ipsilateral to the side of the brain lesion. None of the compounds under study stimulated contralateral rotations. Acetyl-phenylethylamine was 90% less active than beta-phenylethylamine. After beta-phenylethylamine injection all animals (16/16) showed ipsilateral rotations. The dose-response curve showed that at doses as low as 1.75 mg/kg ipsilateral turns increase, with a dose-related rotational response between 1.75 mg/kg and 11.66 mg/kg, no differences being found at doses between 11.66 and 29.16 mg/kg. Rotations began a few seconds after beta-phenylethylamine injection. The highest response was found 30-60 s after the injection. The duration of the response was dose-related (4 min for the 3.5 mg/kg doses). The inhibition of dopamine-beta-hydroxylase activity with [1-3,5-difluorobenzyl)imidazole-2-thiol (SKF102698) did not modify the rotational response to beta-phenylethylamine. The inhibition of type B monoamine oxidase activity with l-deprenyl induced a slight increase in the ipsilateral rotational response to beta-phenylethylamine. The inhibition of tyrosine hydroxylase activity with alpha-methyl-p-tyrosine decreased the rotational response to beta-phenylethylamine. The dopamine receptor antagonist, haloperidol, completely blocked the ipsilateral rotational response to beta-phenylethylamine. The blocking of dopamine uptake into storage vesicles with reserpine increased the rotational action of beta-phenylethylamine. Taken together, the data suggest that, at low doses, beta-phenylethylamine stimulates the release of dopamine from the cytoplasmic pool and behaves as a dopamine receptor agonist with a very rapid and brief action.

beta-Phenylethylamine regulation of dopaminergic nigrostriatal cell activity.

In the present paper, the action of beta-phenylethylamine on electrophysiological activity of dopaminergic nigrostriatal neurons is described. 10 s after its i.v. injection and during 2-4 min, beta-phenylethylamine decreased the firing rate, the number of spikes within and out of burst and the number of bursts per second of these neurons. This was a dose-related action with statistical differences starting from 1.4 mg/kg for total and out of burst firing rate and from 2.4 mg/kg for within burst firing rate and for the number of bursts per second. The standard deviation and the variation coefficient of inter-spike intervals increased in a dose-related way. The marked effect found after low-dose administration suggests that under physiological conditions endogenous beta-phenylethylamine levels regulate the nigrostriatal dopaminergic cell activity. After peripheral low dose administration, beta-phenylethylamine behaves as a dopaminergic agonist with a very fast and brief action.

[Cystic fibrosis: a microbiological study over an 8-year period]. / Fibrosis quística: estudio microbiológico durante un período de 8 años.

OBJECTIVE: To study the microbiology of cystic fibrosis in our hospital for the period from 1985 to 1992. MATERIAL AND METHODS: The number of samples analyzed totalled 1,034, most of which were sputum and nasopharyngeal aspirates belonging to 113 patients (49 women and 64 men). The average age was 10 years (range: 15 days-33 years). RESULTS AND DISCUSSION: Only 1.7% of the samples were negative. Normal flora were found in 10.8% and one or more potentially pathogenic microorganisms were found in the remaining 87.4%. Colonies were over 10(6) UFC/ml in size in 77.8% of the quantified cultures. The most frequently identified microorganisms in the population overall were P. aeruginosa (53.9%), S. aureus (30.3%) and H. influenzae (22.0%). In patients less than 12 months old, however, the most common isolations were of S. pneumoniae and B. catarrhalis; cultures from patients older than 16 years old most often yielded filiform fungi, mainly Aspergillus spp. We found no strains of Legionella spp. and P. cepacia was found in only 3 cases, in which the clinical outcome was good. In addition to the 3 most common organisms, we recorded several consecutive isolations of Proteus mirabilis, Xanthomonas maltophilia and Serratia marcescens in patients older than 11 years old; this finding suggests that given the improved survival of cystic fibrosis patients over the coming years and the antibiotic pressure placed on them, there may be slight changes in the bacterial ecology typical of this disease. No strain of S. aureus proved resistant to methicillin, but P. aeruginosa was shown to be resistant to gentamycin (58.2%) among the aminoglycosides and also to some of the beta-lactams considered to be effective, as follows: 25.2% to piperacillin, 22.6% to ceftazidime and even 19.8% to aztreonam. There was slight resistance of ciprofloxacin (6.3%).

[Adenomatous cystic pulmonary malformations: presentation of 26 cases]. / Malformación adenomatoidea quística pulmonar. Presentación de 26 casos.

We present our experience of 26 cases of cystic adenomatoid malformations of the lung (CAM), treated in the Department of Pediatric Surgery in our hospital between 1967-1991. There were two clinical pictures: one neonatal severe respiratory distress and successive repeated pulmonary infection appearing after the patient's first year of life and requiring both urgent diagnosis and treatment. Embryological development determines the pathologic classification of this entity in 3 types. Basic examinations by image are analyzed, bearing in mind their diagnostic value and the patterns they show. After analysing all the conditioning factors, no explanation has been found to the different course that this affectation (< 1 month and > 1 year of age respectively). Normally, neonatal mortality is closely related to other malformations, particularly to cardiovascular ones. Differential diagnosis is very important in the neonatal period, especially with regard to diaphragmatic hernia, lobar emphysema and pulmonary cysts. All these cases have been verified and classified by means of a pathologic study, which has shown the need for surgical operation. In the follow up of the patients no alteration has been noticed in the pulmonary function.

[Congenital lobar emphysema: report of 38 cases]. / Enfisema lobar congénito. Presentación de 38 casos.

We present our experience of 38 patients suffering from congenital lobar emphysema (CLE) treated in the Department of Pediatric Surgery in our hospital between 1966-1991. 22 of these patients had to undergo surgical correction due to the severity of their respiratory symptoms. The other 16 presented mild respiratory symptoms: 8 of them received conservative treatment and the remainin 8 had to be operated on due to broncial compression caused by the vascular malformation. In most cases the main symptoms were dyspnea and cyanosis, which indicate the severity of the process. 20 cases presented during the patient's first month of life, 10 within the first 6 months and the remaining 8 between the first 6 months and 5 years. The different aetiologics forms in our study are analysed and compared with those described in the literature. The main diagnostic tested and revied, specially radiology tested led to a correct differential diagnosis and subsequently to an adequate therapeutic treatment. It is possible to carry out other tests since they do not actually help diagnosis, we have considered them unnecessary. All the surgical operations used are analysed as well as the complications observed. The clinical course of the patients has proved to be particularly good, since there was no mortality and the morbility rate was low.