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Biomedical subjects

A Augarten

Publications and source records attributed to A Augarten.

At least 37 records · Page 2Linked to original sources
PubMed1997

The critical first six months in cystic fibrosis: a syndrome of severe bronchiolitis.

The syndrome of infantile bronchiolitis in cystic fibrosis (CF) carries a high mortality. Fifteen cases of CF encountered over the past 19 years with severe bronchiolitis with onset during the first 6 months of life are described. Treatment include steroids in high doses. All patients recovered. Further progress resembled the usual natural course of CF and showed no evidence of persisting lung damage. The mechanism of this syndrome is not clear and is probably dependent on many factors involved in early lung disease in CF. The frequency of severe bronchiolitis in cystic fibrosis may not be high, but it continues to be seen in clinical practice today.

Bronchiolitis↗
PubMed1997

Nephrotic syndrome and fibrillary glomerulonephritis.

A 28-year-old female with cystic fibrosis presented with nephrotic syndrome and progressive renal failure. In addition, she complained of blurred vision and there was a purpuric skin eruption localized to her legs. A renal biopsy revealed fibrillary glomerulonephritis. Skin biopsy demonstrated swelling of capillary endothelium, thickening of arteriolar walls and deposition of IgA, C3 and fibrinogen by immunofluorescence. Opthalmoscopy and fluorescein angiography disclosed cotton wool spots with intraretinal haemorrhages and ischaemia of the macula. Albumin infusions resulted in worsening of eye symptoms and signs. The presence of these three clinicopathologic entities in a patient with CF may indicate the possibility of systemic involvement related to continued exposure to chronic bacterial lower lung infection.

Adult↗
PubMed1997

A cystic fibrosis transmembrane conductance regulator splice variant with partial penetrance associated with variable cystic fibrosis presentations.

Some patients express various features of cystic fibrosis (CF) even though essential characteristics of the disease might be absent. Such patients may suffer from respiratory disease without pancreatic insufficiency and normal sweat chloride levels. Others may present as male infertility because of congenital bilateral aplasia of the vas deferens (CBAVD) with no other signs of CF. The 5T allele, a DNA variant in a noncoding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that reduces the level of the normal CFTR transcripts, was found in increased frequency among male patients with CBAVD. The purpose of this study was to investigate the possibility that the 5T allele is associated with dysfunction of organs other than the male reproductive system, leading to CF or atypical CF. Analysis of the 5T allele was performed on 148 subjects (29 with CF, 61 with atypical CF, and 58 with CBAVD) carrying 232 chromosomes with unidentified CFTR mutations, and on 142 non-CF chromosomes from healthy subjects of Ashkenazi origin. The frequency of the 5T allele among chromosomes from patients of Jewish Ashkenazi origin with CF and atypical CF (six of 33; 18%) was significantly higher than the frequency in the normal Ashkenazi population (eight of 142; 6%; p = 0.03). Analysis of the clinical presentation of the five patients with CF and the 12 patients with atypical CF carrying the 5T allele indicated that most patients suffered from respiratory disease presenting as asthma like symptoms, nasal polyposis, chronic sinusitis, chronic bronchitis, or bronchiectasis. Six patients had pancreatic insufficiency, two with meconium ileus. Sweat Cl- levels ranged from normal to elevated. Of the six male patients with respiratory disease who were old enough to be evaluated for fertility status, five were fertile and one had pancreatic insufficiency. Among male patients with CBAVD, 41% suffered from respiratory symptoms. Thus, the 5T allele is a variant with partial penetrance causing disease with an extreme variability of clinical presentation: from normal healthy fertile subjects or male patients with CBAVD to those with atypical or typical clinical phenotype of CF.

Adolescent↗
PubMed1997

A missense cystic fibrosis transmembrane conductance regulator mutation with variable phenotype.

OBJECTIVE: Cystic fibrosis (CF) has variable clinical presentation. Disease severity is partially associated with the type of mutation. The aim of this study was to report genotype-phenotype analysis of the G85E mutation. PATIENTS: The phenotype of 12 patients (8 were from the same extended family, and 5 of them were siblings from 2 families) carrying at least one copy of the G85E mutation was evaluated and compared with the phenotype of 40 patients carrying the two severe mutations, W1282X and/or DeltaF508 (group 1), and with 20 patients carrying the splicing mutation, 3849+10kb C->T, which was found to be associated with milder disease (group 2). RESULTS: A high phenotypic variability was found among the patients carrying the G85E mutation. This high variability was found among patients carrying the same genotype and among siblings. All the studied chromosomes carrying the G85E mutation had the 7T variant in the polythymidine tract at the branch/acceptor site in intron 8. Of the G85E patients, 25% had pancreatic sufficiency and none had meconium ileus, compared with 0% and 32%, respectively, of patients from group 1, and 80% and 0%, respectively, from group 2. Two patients carrying the G85E mutation had sweat chloride levels <60 mmol/L whereas all the others had typically elevated levels >80 mmol/L. Compared with group 2, patients carrying the G85E mutation were diagnosed at an earlier age and had higher sweat chloride levels, with mean values similar to group 1 but significantly more variable. Forced expiratory volume in 1 second (FEV1) was similar in the three groups, with no differences in the slope or in age-adjusted mean values of FEV1. The levels of transcripts lacking exon 9 transcribed from the G85E allele measured in 3 patients were 55%, 49%, and 35% and their FEV1 values were 82%, 83%, and 50% predicated, respectively. CONCLUSIONS: The G85E mutation shows variable clinical presentation in all clinical parameters. This variability could be seen among patients carrying on the other chromosome the same CFTR mutation, and also among siblings. This variability is not associated with the level of exon 9 skipping. Thus, the G85E mutation cannot be classified either as a severe or as a mild mutation.

Age of Onset↗
PubMed1997

The molecular basis of partial penetrance of splicing mutations in cystic fibrosis.

The splicing variant, 5T allele, in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was shown to be associated with partial penetrance of the clinical expression. This splicing variant leads to two possible transcripts: one normal and the other aberrantly spliced that lacks exon 9. The aim of this study was to analyze the molecular basis of the partial penetrance in individuals carrying the 5T allele. We analyzed the level of the correctly spliced RNA transcribed from the 5T allele in nasal and epididymal epithelium and correlated it with disease expression. Semiquantitative nondifferential reverse-transcriptase-PCR showed a considerable variability (6%-37%) in the total level of correctly spliced RNA transcribed from the 5T allele in nasal epithelium from 11 patients. A significant nonlinear correlation (r = .82, P = .002) between the level of the normal CFTR transcripts and the severity of lung disease was shown. No individuals with normal lung function and minimal or no lung disease (FEV1 >80% predicted) had <25% of normal transcripts, and individuals with <15% of normal transcripts did not have FEV1 >80%. The level of normal transcripts in epididymal epithelial cells from four infertile males with congenital bilateral absence of the vas deferens was low (6%-24%). In infertile males with normal lung function the level of correctly spliced transcripts in the nasal epithelium was higher than the level in the epididymal epithelium. These results indicate that there is variability in the efficiency of the splicing mechanism, among different individuals and between different organs of the same individual. This variability provides the molecular basis of the partial penetrance of cystic fibrosis disease in patients carrying the 5T allele.

Adolescent↗
PubMed1996

Micromanipulation improves in-vitro fertilization results after epididymal or testicular sperm aspiration in patients with congenital absence of the vas deferens.

In all, 58 couples suffering from infertility because of congenital bilateral absence of the vas deferens underwent a total of 67 combined microsurgical epididymal aspiration or testicular sperm extraction (TESE) and in-vitro fertilization (IVF) treatments. The oocytes recovered were inseminated by either the microdroplet IVF technique (N = 20), subzonal insemination (SUZI; n = 10) or intracytoplasmic sperm injection (ICSI; n = 37). Of the ICSI cycles, 12 were performed using spermatozoa obtained by TESE. Fertilization rates for epididymal spermatozoa were significantly higher for SUZI (17.9%, 17/95) and ICSI (34.4%), 137/398) than for microdroplet IVF (5.2%, 18/343) cycles. The proportion of cycles in which fertilization was achieved was higher in the SUZI (80%) and ICSI (95%) cycles than in the IVF cycles (45%). Delivery or an ongoing pregnancy was achieved in one (5%) IVF cycle, two (20%) SUZI cycles and seven (18.95) ICSI cycles. SUZI or ICSI using epididymal or testicular spermatozoa significantly improved the oocyte fertility rate. The ICSI procedure was especially advantageous in patients for whom spermatozoa were obtained from a testicular biopsy.

Cytoplasm↗
PubMed1995

The significance of sweat Cl/Na ratio in patients with borderline sweat test.

Recently a few cystic fibrosis (CF) patients with borderline or normal sweat tests have been reported. These patients present a diagnostic challenge. We aimed to study the sweat Cl/Na ratio in cystic fibrosis patients and to assess whether this ratio could be used as a diagnostic criteria. The mean sweat Cl/Na ratio of 3 groups was compared: Group A: 71 CF patients carrying 2 mutations known to be associated with severe disease presentation (delta F508, W1282X, G542X, N1303K, 1717-1G --> A). Group B: 10 compound heterozygous patients who carry one mutation associated with mild clinical disease (3849 + 10 kb --> T). Group C: 142 normal subjects. Sweat chloride levels higher than those of sodium were found in 96% of patients in Group A as compared to 3% of patients in Group C. In Group B 40% of the patients had sweat chloride levels higher than or equal to sodium levels. The mean Cl/Na ratio of Group A (1.2 +/- 0.1) differed significantly from that of Group B (0.94 +/- 0.1) and both groups had significant higher mean Cl/Na ratio compared to Group C (0.7 +/- 0.4) (P < 0.001). Thus in individuals with a borderline sweat test and a Cl/Na ratio > or = 1 the diagnosis of CF should be considered. However, a Cl/Na ratio < 1 does not exclude CF, since patients carrying mild mutations may have sweat sodium levels higher than those of chloride. Our findings suggest that the sweat Cl/Na ratio in CF is genetically determined and it may be of help in establishing the diagnosis of CF in patients with a borderline sweat test.

Child↗
PubMed1995

HLA-B5 in the diagnosis of Behcet's disease.

Behçet's disease, a multisystem disease is, by its nature, difficult to diagnose. The first manifestation of the disease may precede the appearance of other symptoms and signs essential for diagnosis by many years. In patients of Mediterranean origin, the early manifestations of the disease, may be confused with those of familial Mediterranean fever (FMF). Determination of HLA-B5 may, however, contribute to the diagnosis in children with partial manifestations of Beh,cet syndrome.

Adolescent↗
PubMed1994

Congenital bilateral absence of vas deferens in the absence of cystic fibrosis.

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.

Cystic Fibrosis↗
PubMed1994

[Endobronchial mass caused by tuberculosis].

A 2-year-old girl who presented with cough, had been started on prednisone and bronchodilators 10 days prior to admission because of presumed hyperactive, small airway obstruction. Fluoroscopy revealed hyperinflation of the right lung and mediastinal shift to the left on expiration. Bronchoscopy disclosed an endobronchial mass. At that time the tuberculin test was negative. Since such lesions are rare in young children, thoracotomy was performed. An enlarged mediastinal lymph node was removed and the histopathological findings were suggestive of tuberculosis. The tuberculin test 1 month following prednisone therapy was positive, suggesting that previously the skin reaction to tuberculin had been altered by the prednisone. Tuberculosis should be considered in the differential diagnosis of an endobronchial mass even in an otherwise apparently healthy child.

Airway Obstruction↗
PubMed1994

Similar levels of mRNA from the W1282X and the delta F508 cystic fibrosis alleles, in nasal epithelial cells.

The effect of nonsense mutations on mRNA levels is variable. The levels of some mRNAs are not affected and truncated proteins are produced, while the levels of others are severely decreased and null phenotypes are observed. The effect on mRNA levels is important for the understanding of phenotype-genotype association. Cystic fibrosis (CF) is a lethal autosomal recessive disease with variable clinical presentation. Recently, two CF patients with mild pulmonary disease carrying nonsense mutations (R553X, W1316X) were found to have severe deficiency of mRNA. In the Jewish Ashkenazi CF patient population, 60% of the chromosomes carry a nonsense mutation, W1282X. Patients homozygous for this mutation have severe disease presentation with variable pulmonary disease. The presence of CF transcripts in a group of patients homozygous and heterozygous for this mutation was studied by reverse transcriptase PCR of various regions of the gene. Subsequent hybridization to specific CF PCR probes and densitometry analysis indicated that the CF mRNA levels in patients homozygous for the W1282X mutation are not significantly decreased by the mutation. mRNA levels were compared for patients heterozygous for the W1282X mutation. The relative levels of mRNA with the W1282X, and the delta F508 or the normal alleles, were similar in each patient. These results indicate that the severe clinical phenotype of patients carrying the W1282X mutation is not due to a severe deficiency of mRNA. In addition, the severity, progression, and variability of the pulmonary disease are affected by other, as yet unknown factors.

Alleles↗
PubMed1993

Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849 + 10 kb C-->T mutation.

Different mutations in the cystic fibrosis (CF) gene appear to contribute to heterogeneity of the CF phenotype. We investigated 15 patients with CF who have the 3849 + 10 kb C-->T mutation. All were Ashkenazi Jews. Their clinical features were compared with those of CF patients with the delta F508/delta F508, W1282X/W1282X, W1282X/delta F508 mutations, which are known to be associated with a severe disease. Patients with the 3849 + 10 kb mutation were older, had been diagnosed as having CF at a more advanced age, and were in a better nutritional state. Sweat chloride values were normal (below 60 mmol/L) in 5 3849 + 10 kb patients (33%). 4 of these patients and 6 others (total 66%) had normal pancreatic function. However, age-adjusted pulmonary function did not differ between the two groups. None of the patients with 3849 + 10 kb C-->T had had meconium ileus or had liver disease or diabetes mellitus. We conclude that this mutation is associated with a mild type of CF.

Age Factors↗
PubMed1993

Ethnic differences in lung function in Israeli children.

BACKGROUND: The population of Israel consists of immigrants from many different countries. It is not known whether a single nomogram can be used for spirometric values of children of different ethnic descent. METHODS: Spirometry was performed in 753 second or third generation Israeli children (7-14 years) of different ethnic groups. Both parents of 503 of the children were of the same ethnic background. Subjects were allocated to six ethnic groups (European, Iraqi, North African, Indian, Yemenite, and Georgian). RESULTS: Standing height contributed most to the prediction of spirometric values (forced expiratory volume in one second, forced vital capacity), whereas sitting height did not contribute further. Statistical analysis showed significant ethnic differences. The Georgians had higher spirometric values for FEV1 than all the other ethnic groups, and higher FVC values than those of the Yemenite, North African, and Indian groups. FVC was lower among the Indian than all other groups. CONCLUSION: Differences in normal spirometric values were found among second or third generation Israeli children of different ethnic origins. European, North African, Iraqi, and Yemenite children could be characterised by single equation, whereas children of Georgian and Indian descent needed different predicting equations.

Adolescent↗