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Biomedical subjects

A Jaffé

Publications and source records attributed to A Jaffé.

At least 19 recordsLinked to original sources
PubMed2005

Assessment of hypoxia in children with cystic fibrosis.

Hypoxia during sleep and exercise may occur in an important number of patients with cystic fibrosis (CF). Despite its recognition, no clear definition for hypoxia in CF exists, and nor do guidelines for commencing oxygen therapy. CF patients with hypoxia may have increased pulmonary artery pressure, reduced exercise ability, and skeletal muscle strength, and most importantly of all worse sleep quality, and a worse quality of life. Laboratory and rodent evidence exists to suggest that hypoxia may contribute to the decline in lung function in CF by upregulating lung inflammation, and encouraging growth of Pseudomonas aeruginosa, the most important pathogen associated with CF lung disease. The effects of hypoxia in childhood CF need to be fully studied, and a potential expanded role for oxygen as therapy in CF may be worthy of exploration.

Adolescent↗
PubMed2005

Transbronchial biopsies provide longitudinal evidence for epithelial chimerism in children following sex mismatched lung transplantation.

BACKGROUND: Recent reports have shown evidence of host derived parenchymal engraftment in several human allografts including the lung, leading to speculation that stem cell therapy may be useful for lung repair in diseases such as cystic fibrosis (CF). To date, previous studies have looked at single surgical or autopsy specimens and no longitudinal studies have been reported. The aim of this study was to assess whether transbronchial biopsies could be used to study the time course of chimerism following lung transplantation. METHODS: Specimens of archived transbronchial lung biopsies from five time points taken for clinical purposes from two boys who had received a sex mismatched heart-lung transplant for end stage CF were examined. Sections were dual stained for cytokeratin (epithelium) and a mixture of leucocyte common antigen and CD68 for inflammatory cells. Co-localisation of cells containing a Y chromosome was confirmed by fluorescent in situ hybridisation. RESULTS: Evidence of chimerism was found in up to 6.6% of epithelial cells in bronchial (median 1.4% (range 0-6.6)) and alveolar (median 3.6% (range 2.3-5.5) tissue without apparent evidence of fusion. This engraftment was seen as early as 3 weeks and remained relatively constant up to 37 months. CONCLUSIONS: This study has demonstrated proof of principle for long term chimerism in lung epithelium. Transbronchial biopsies may provide a new method for studying the kinetics of stem cell engraftment in the lung.

Biopsy↗
PubMed2002

Are annual blood tests in preschool cystic fibrosis patients worthwhile?

AIM: To investigate whether routine annual assessment blood tests in cystic fibrosis (CF) patients under 5 years influence management. METHODS: Retrospective review of the results of the first annual assessment blood tests of patients with CF less than 5 years of age during a four year period (1995-99). Management changes were identified from a follow up letter to the general practitioner or local paediatrician. RESULTS: A total of 169 patients (100 female), median age 2.2 years (range 0.3-4.9) were identified. Venepuncture was successful in 93% of patients. Of the 32 individual blood parameters measured, the overall success rate in obtaining a result was 81%. Eleven per cent of patients underwent subsequent management changes, including liver ultrasound, fasting glucose, and a short course of iron. Of particular importance, vitamin A and E concentrations were low in 9% of patients, which prompted an increase in prescribed dose. CONCLUSIONS: These results support the recommendations for routine blood tests at annual review in preschool CF children. The results may help to rationalise which tests are performed and thus reduce laboratory costs.

Child, Preschool↗
PubMed2001

Anti-inflammatory effects of macrolides in lung disease.

During the past five decades there has been increasing interest in the potential anti-inflammatory effects of macrolide antibiotics. Low-dose macrolide therapy has dramatically increased survival in patients with diffuse panbronchiolitis, a disease with many similarities to cystic fibrosis (CF). This has led to further investigation into the potential use of macrolides in chronic lung diseases with an inflammatory component. This review summarizes the proposed anti-inflammatory mechanisms for this group of antibiotics, and examines the effect of macrolides on modulation of the inflammatory pathways, neutrophil function, bronchoconstriction, Pseudomonas biofilm, mucus rheology, bacterial adherence, and multidrug-resistant protein. It discusses the current status of clinical studies in children with CF, bronchiectasis, and asthma. While there are much in vitro data for different proposed anti-inflammatory effects, randomized controlled clinical trials in children with CF, bronchiectasis, and asthma are still just beginning. The benefits and potential side effects need to be determined before routine use can be advised.

Anti-Bacterial Agents↗
PubMed2001

Routine ventilation scans in children with cystic fibrosis: diagnostic usefulness and prognostic value.

Krypton ventilation scans (VS) provide an index of peripheral lung function, and may be particularly useful in children unable to perform pulmonary function testing. This communication reports on three linked studies which investigated whether a routine VS in young children with cystic fibrosis (CF) is diagnostically or prognostically useful. Study 1: In a preliminary study in 1991, VS were compared with clinical examination and chest radiography (CXR) in 50 CF children (29 females, 21 males) aged 0.4-5.2 years (median 2.2 years). The chest was divided into six zones, and abnormalities scored from 0 (normal) to 2 (very abnormal). Clinical examination was unhelpful in predicting abnormalities on imaging. In five children (10%) with a normal CXR, VS was abnormal, and in a further eight children (16%), CXR markedly underestimated VS changes. Study 2: In order to determine the long-term prognostic significance of VS abnormalities, we followed up 27 (19 females, 8 males) of the children from study 1, who had had their first VS at presentation at median age 1.6 years (range 0.4-5.2), scoring the same six zones from 0 to 2. Follow-up was for a mean of 11.6 years (range 7.8-14.8). Spirometry at age 7 years showed a mean forced expiratory volume in 1 s (FEV1) of 96% (range 46%-145%) and a mean forced vital capacity (FVC) of 96% (range 46%-145%). A poor VS score at presentation was correlated with percent predicted FEV1 at age 7 (r=0.4, P=0.042, 16% of variance explained). Those with a normal VS at presentation had a mean FEV1 at presentation of 99% (range 80%-129%). Whereas four patients had an abnormal VS, a normal CXR and a low FEV1 at age 7 years, no patient had a normal VS, an abnormal CXR and a low FEV1 at age 7 years. Study 3: Fifty children (29 females, 21 males) aged 0.5-6.0 years (median 3.8) were prospectively studied in 1998, to determine whether the findings in study 1 were stable over time, and to assess whether VS altered clinical management. Symptoms and clinical examination did not predict abnormalities on imaging. Thirty (60%) children had a normal VS while only five (10%) had a normal CXR. There was a significant correlation between the total scores of CXR and VS (P=0.007, 14% of variance explained). Further, VS detected additional abnormalities in seven patients (14%). Sixty-five percent of patients with an abnormal VS had modifications of treatment, including bronchoscopy, compared with 23% of those with a normal VS. We conclude that VS is a simple, safe and non-invasive technique giving additional information to that provided by clinical examination and chest radiography in a number of children with CF and can be used to modify clinical management. VS at presentation gives prognostic information, which may be of use in early intervention studies. Whether using VS to guide treatment improves long-term prognosis requires a larger prospective trial.

Child↗
PubMed2001

Genetic contributions to rare childhood lung diseases.

Epidemiological studies have suggested that many rare diseases with respiratory involvement have a genetic component. Molecular advances have increased the understanding of the pathophysiology of these diseases which has led to better diagnostic and prognostic methods. There may be many genes responsible for diseases such as primary ciliary dyskinesia and systemic lupus erythematosus in addition to the effect of modifier genes. The genotype:phenotype correlation in these diseases remains to be elucidated. In some diseases, such as familial dysautonomia and sickle cell, the gene has been identified which allows for accurate pre-natal testing. Further, in diseases where the genetic abnormality is known, such as chronic granulomatous disease, gene therapy remains a realistic prospect and phase I studies are about to commence or currently underway. This article reviews those rare diseases in which there is or is likely to be a significant genetic contribution.

Anemia, Sickle Cell↗
PubMed2001

Cystic fibrosis: review of the decade.

The median estimated life expectancy of children with cystic fibrosis (CF) born in 1990 is 40 years which represents a doubling in the last 20 years, and nearly half of all patients are now adults. Since the identification of the gene, more than 1000 gene mutations have been discovered. This gene encodes for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that is thought to have a role in ion transport, mucus rheology, inflammation and bacterial adherence. Various therapeutic mechanisms are currently being investigated in an attempt to overcome these abnormalities. Recombinant human DNase is beneficial in many patients and the use of anti-inflammatory agents such as steroids, ibuprofen and macrolides have potential. Despite these advances in treatment it is essential that these patients are diagnosed early. Whilst the case for neonatal screening is not absolutely conclusive the evidence is highly suggestive that it would be beneficial. It may be that, in the future, new treatments such as gene therapy will be more effective in those patients who have not yet developed lung disease. Whilst gene therapy and other new treatments such as bilateral living lobar lung donation give our patients optimism for the future it is important to remember that the increase in survival is a result of good physiotherapy, nutrition, aggressive antibiotic use and an increase in our understanding of the disease. It is important that patients continue to be referred early to tertiary CF centres.

Adolescent↗
PubMed2000

Cationic lipid-mediated gene transfer to the growing murine and human airway.

Gene therapy in patients with cystic fibrosis may need to be commenced before the onset of lung disease which may be evident as early as 4 weeks after birth. We assessed the efficacy of cationic lipid-mediated transfer of a reporter gene, chloramphenicol acetyltransferase, in the growing murine and human respiratory tract. Gene expression was greater in adult mice (greater than 8 weeks old) compared with 9- and 16-day-old animals, despite a relatively greater proportion of complex delivered to the younger mice. Subsequent experiments compared 16-day-old and adult mice. Whilst higher gene expression occurred in the parenchyma compared with conducting airways in both groups, significantly greater expression was seen in the conducting airway of adult mice compared with 16-day-old animals. This expression persisted beyond 18 days in the adults but was undetectable in the younger group at this time-point. In an ex vivo model there was no difference in gene expression between the two groups. Further, no differences were observed in gene expression between growing (age 5 weeks to 14 years 8 months) and adult human lung tissue in either parenchyma or conducting airway. These data suggest age-dependent differences in gene transfer in vivo, which are not seen in an ex vivo setting. Proof-of-principle has been demonstrated for cationic-lipid mediated gene transfer to the growing human lung. Gene Therapy (2000) 7, 273-278.

Adolescent↗
PubMed1999

If you can't stand the rash, get out of the kitchen: an unusual adverse reaction to ciprofloxacin.

Ciprofloxacin, a quinolone antibiotic, is used to treat a wide variety of infections including Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Photosensitivity is a well-known complication of treatment with this group of antibiotics, and it is more common in patients with CF. We report on a case of photosensitivity induced by indoor fluorescent strip-lighting (spectral range, 295-760 nm) in a 12-year-old girl with CF treated with ciprofloxacin. This type of lighting emits UVA rays (320-400 nm) which cause skin damage in the presence of sensitizing agents. Patients taking ciprofloxacin are usually advised to protect their skin from direct sunlight. We suggest that more attention should be paid to indoor sources of UV light.

Anti-Infective Agents↗
PubMed1998

Distal 10q trisomy syndrome with unusual cardiac and pulmonary abnormalities.

Since its description in 1965, distal 10q trisomy has become recognised as a well defined, although rare syndrome, almost always the result of an unbalanced translocation. Typical features consist of psychomotor delay, a distinctive dysmorphic appearance, growth retardation, and, in some cases, cardiac, renal, and ocular abnormalities.

Abnormalities, Multiple↗