RESUMEN

More than 1900 different mutations in the CFTR gene have been reported. These are grouped into classes according to their effect on the synthesis and/or function of the CFTR protein. CFTR repair therapies that are mutation or mutation class specific are under development. To progress efficiently in the clinical phase of drug development, knowledge of the relative frequency of CFTR mutation classes in different populations is useful. Therefore, we describe the mutation class spectrum in 25,394 subjects with CF from 23 European countries. In 18/23 countries, 80% or more of the patients had at least one class II mutation, explained by F508del being by far the most frequent mutation. Overall 16.4% of European patients had at least one class I mutation but this varied from 3 countries with more than 30% to 4 countries with less than 10% of subjects. Overall only respectively 3.9, 3.3 and 3.0% of European subjects had at least one mutation of classes III, IV and V with again great variability: 14% of Irish patients had at least one class III mutation, 7% of Portuguese patients had at least one class IV mutation, and in 6 countries more than 5% of patients had at least one class V mutation.

Asunto(s)

RESUMEN

Staphylococcus aureus is the most commonly isolated pathogen in respiratory tract secretions from young patients with cystic fibrosis (CF), and several treatment strategies are used to control the infection. However, it is not known whether intensified treatment with antimicrobial agents causes eradication of S. aureus clones. We retrospectively determined the impact of intravenous (IV) antimicrobial agents on the suppression and eradication of S. aureus clones. One thousand and sixty-one S. aureus isolates cultured from 2526 samples from 130 CF patients during a 2-year study period were subjected to spa typing. Intervals between positive samples and the occurrence of clone replacements were calculated in relation to courses of IV antimicrobial agents. Of 65 patients chronically infected with S. aureus, 37 received 139 courses of IV antimicrobial agents with activity against S. aureus (mean duration, 15 days; range, 6-31 days). Administration of IV antibiotics increased the time to the next sample with growth of S. aureus: the mean interval between two positive samples was 68 days if IV treatment had been administered, in contrast to 49 days if no IV treatment had been administered (p 0.003). When S. aureus recurred in sputum after IV treatment, the isolate belonged to a different clone in 33 of 114 (29%) intervals, in comparison with 68 of 232 (29%) intervals where IV treatment had not been prescribed (OR 0.98, 95% CI 0.60-1.61). In conclusion, we show that 2 weeks of IV antimicrobial treatment can significantly suppress chronic staphylococcal infection in CF, but is not associated with the eradication of persistent bacterial clones.

Asunto(s)

RESUMEN

OBJECTIVES: In this nationwide retrospective study, we analysed species distribution, antimicrobial susceptibility and time to next occurrence of Achromobacter in Danish cystic fibrosis (CF) patients from 2000 to 2011. METHODS: Thirty-four primary isolates were identified to species level and subjected to antimicrobial susceptibility testing. Effectiveness of early antimicrobial treatment was assessed by a Kaplan-Meier estimation of time to recurrence. RESULTS: Achromobacter xylosoxidans accounted for 13 (38%) of the isolates, and an unnamed species accounted for 11 (32%) of the isolates. Meropenem, piperacillin-tazobactam and trimethoprim-sulfamethoxazole were highly active against chemotherapy-naïve Achromobacter, while ceftazidime, colistin and tobramycin were judged adequate for inhalation therapy. Fifty-five percent of 25 patients treated with inhaled ceftazidime, colistin, or tobramycin remained free of Achromobacter three years after acquisition, in contrast to 17% of 22 patients who did not receive inhaled antibiotics (P<0.01). CONCLUSIONS: Early treatment with inhaled antibiotics may prevent or postpone chronic infection with Achromobacter in CF patients.

Asunto(s)

RESUMEN

BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder, caused by heterozygous missense mutation in GJB2, encoding the gap junction protein connexin 26. The commonest mutation is the p.Asp50Asn mutation, and only a few other mutations have been described to date. AIM: To report the fatal clinical course and characterize the genetic background of a premature male neonate with the clinical and histological features of KID syndrome. METHODS: Genomic DNA was extracted from peripheral blood and used for PCR amplification of the GJB2 gene. Direct sequencing was used for mutation analysis. RESULTS: The clinical features included hearing impairment, ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar keratoderma, alopecia of the scalp and eyelashes, and a thick vernix caseosa-like covering of the scalp. On histological analysis, features characteristic of KID syndrome, such as acanthosis and papillomatosis of the epidermis with basket-weave hyperkeratosis, were seen. The skin symptoms were treated successfully with acitretin 0.5 mg/kg. The boy developed intraventricular and intracerebral haemorrhage, leading to hydrocephalus. His condition was further complicated by septicaemia and meningitis caused by infection with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Severe respiratory failure followed, and the child died at 46 weeks of gestational age (13 weeks postnatally). Sequencing of the GJB2 gene showed that the child was heterozygous for a novel nucleotide change, c.263C>T, in exon 2, leading to a substitution of alanine for valine at position 88 (p.Ala88Val). CONCLUSIONS: This study has identified a new heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) leading to KID syndrome.

Asunto(s)

RESUMEN

BACKGROUND: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. METHODS: Transglutaminase-IgA (TGA), endomysium-IgA (EMA) and total IgA in serum were measured in 790 CF patients (48% females, 86% with pancreatic insufficiency). Six patients were diagnosed with CD prior to the study, all receiving a gluten-free diet. Patients with elevated TGA (>50 Units/mL) and a positive EMA test were offered a gastroscopy obtaining mucosal biopsies from the duodenum. RESULTS: Four new cases of CD were diagnosed. Two additional patients had positive serological tests, but normal biopsies. In total, 10 cases of CD (1.2%, 1:83) indicate a prevalence rate about three times higher than the general prevalence of CD in Norway and Sweden. No CD patients were detected in the Danish CF cohort. Patients diagnosed with untreated CD reported symptoms typical of both CF and CD (poor weight gain, loose and/or fatty stools, fatigue, irritability, abdominal pain). They improved after introduction of a gluten-free diet. CONCLUSIONS: Systematic screening for CD in a Scandinavian cohort of CF patients revealed a higher prevalence of CD than in the general population. Clinical signs of CD are difficult to differentiate from CF with malabsorption, and patients may go undiagnosed for a long time. In a population where CD is common we recommend screening for CD in patients with CF.

Asunto(s)

RESUMEN

The lectin pathway of complement activation is initiated by mannan-binding lectin (MBL) or the ficolins through the common MBL-associated serine protease-2 (MASP-2). Deficiency of MBL has been associated with poorer outcome in cystic fibrosis (CF). We investigated the MBL pathway further by analysis of the MASP-2 deficiency mutation (D105G) as well as MBL-2 genotypes. Concentrations and genotypes of MASP-2 and MBL in 109 CF patients were correlated to lung function and chronic infections. We describe the first CF patient homozygous for the mutation, a girl with extremely severe lung disease with no other precipitating factors. We suspect total MASP-2 dysfunction to be a major modifier of CF lung disease. However, heterozygosity for the D105G mutation of MASP-2 had no correlation to MBL pathway function or poor lung function. Lung function was higher in the MBL deficiency determining genotypes (XA/YO+YO/YO) than in the other genotypes.

Asunto(s)

RESUMEN

Exercise-induced increases in cardiac output (CO) and oxygen uptake (VO2) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function - such as calcitonin gene related peptide (CGRP) - may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 +/- 2 min to fatigue. Voluntary cycling performed both at VO2 similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33.8 +/- 3.1 pmol l(-1) (rest) to 39.5 +/- 4.3 (14%, P<0.05)) with a mean extraction over the working leg of 10% (P<0.05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33.2 +/- 3.8 to 46.9 +/- 3.6 pmol l-1, P<0.05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0.05). The exercise induced increase in leg blood flow was 10-12 fold in both spinal cord injured and controls at similar VO2 (P<0.05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 +/- 7 to 132 +/- 15 bpm) compared with controls and tetraplegics (P<0.05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.

Asunto(s)

Asunto(s)

RESUMEN

A case of a recurrent ovarian mucinous cystadenoma in an 11-year-old, premenarchal girl is described. The treatment of choice was cystectomy, partly because of the patient's age and partly because malignancies are uncommon in this population. The operative approach can either be by laparotomy or laparoscopy when technically feasible. But it is important to keep in mind the possibility of recurrence even of benign cysts.

Asunto(s)

RESUMEN

A case is reported of a 10-y-old boy with hypersensitivity pneumonitis probably caused by his cat. Hypersensitivity pneumonitis caused by animal hairs is reported in furriers, but hypersensitivity pneumonitis in children has only been described as caused by birds, moulds or other fungi. Steroid treatment may interfere with the possibility of finding the causative antigen.

Asunto(s)

RESUMEN

This document is the first recommendation on the presentation of properties in reproduction and fertility and their values in clinical laboratory sciences from The International Society of Andrology, IFCC and IUPAC. It forms part of the ongoing effort to standardise requests and reporting of laboratory data for transmission across cultural and linguistic domains, without attempting to standardise the language used by clinicians and laboratory practitioners. The document is accessible on Internet from C-NPU home page address: http://inet.uni-c.dk/ home/ifcc_iupac_cnpu.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

During exercise the transcranial Doppler determined mean blood velocity (Vmean) increases in the middle cerebral artery (MCA) and reflects cerebral flood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate Vmean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether Vmean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 +/- 20 to 92 +/- 21 beats min-1 and mean arterial pressure (MAP) from 87 +/- 7 to 105 +/- 9 mmHg (mean +/- SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 +/- 9 mmHg). During handgrip contralateral MCA Vmean increased from 65 +/- 10 to 75 +/- 13 cm s-1 and this was more than on the ipsilateral side (from 63 +/- 10 to 68 +/- 10 cm s-1; P < 0.05). On both sides of the brain Vmean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 +/- 24 to 116 +/- 39 units) but the elevation became statistically significant during PEMI (135 +/- 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, Vmean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: To study if factors at birth are associated with later development of atopic dermatitis. DESIGN: Historical follow up by record linkage from Danish medical birth register. Children were followed up for 5.5 to 8.5 years. Second historical follow up study comprising questionnaire to mothers of singleborn children 6.5 to 9.5 years after birth. SETTING: Private dermatology clinics and dermatology and paediatric departments in the municipality of Aarhus, Denmark. SUBJECTS: 7862 singletons born in hospital between 1 January 1984 and 31 December 1986 to mothers living in the municipality of Aarhus. Questionnaires sent to 985 mothers. MAIN OUTCOME MEASURES: Gestational age, birth weight, parity, and age of mother at the time of birth. Atopy in children diagnosed by specialists in dermatology and physicians. Family size; diagnosis of atopic dermatitis, allergic rhinitis, and asthma; family predisposition; and mothers' smoking habits during pregnancy determined from questionnaires. RESULTS: Of 7862 children, 403 were diagnosed as having atopic dermatitis by a specialist; the cumulative incidence at age 7 was 5.6%. High gestational age and low parity were associated with an increased risk of atopic dermatitis. Among 985 children atopic dermatitis had been diagnosed by any physician in 184; the cumulative incidence at age 7 was 18.7%. High birth weight, high gestational age, and family history of atopy were associated with increased risk of atopic dermatitis. CONCLUSION: In both studies the incidence of atopic dermatitis was associated with high gestational age and in one with high birth weight also. The causes for these associations are at present unknown but may indicate that even during gestation factors associated with atopic dermatitis influence maturation.

Asunto(s)

Asunto(s)

RESUMEN

To evaluate a possible role for beta-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-alpha and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or beta-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma beta-endorphin was too small to influence the modulation of the cellular immune system.

Asunto(s)

RESUMEN

The term designating a substance being an active ingredient of a drug may be a generic name, a nonproprietary name, a registered trade name, a fantasy name or other. This causes difficulties in the transmission of request and report on such substances to and from the clinical laboratories, and in the collating of this information from different sources. The document comprises a list of properties of drugs of abuse in biological fluids as defined by the International Olympic Committee Medical Code for use in electronic transmission systems. Standard systematic names are presented with a code value for each. The coding schemes thus prepared are accessible on Internet from C-NPU Home page address: http://inet.uni-c.dk/ qukb7642.

Asunto(s)

RESUMEN

The hardware and software facilities for electronic storage, transfer and handling of data is such that multipurpose databases can be made accessible without geographic restriction at low cost. The versatile and flexible underlying structures allow for ease of access and retrieval of data and gives presentation formats fully comparable to printed counterparts. Because of the apparent ease of use and because of the wider distribution of the information, misinterpretation is more likely to occur than in oral or written presentation for more restricted and more culturally homogeneous audiences. This necessitates some degree of harmonisation/standardisation of data on transfer, while allowing local expression forms at sender and receiver ends (Fig. 1). This document is part of an ongoing international effort to agree on some sort of "standardisation" of the transmission and presentation of "laboratory results". It centers on the domain of drugs of abuse as defined by the International Olympic Committee.

Asunto(s)