[Bilateral vas deferens agenesis and inguinal hernia in a child. A rare, early presentation of cystic fibrosis]. / Agénésie déférentielle bilatérale et hernie inguinale chez un enfant. Une présentation précoce rare de la mucoviscidose.

UNLABELLED: Epididymal and ductal anomalies can be discovered incidentally during inguinal herniorraphy in children. The congenital bilateral absence of vas deferens is frequently associated with cystic fibrosis. CASE REPORT: This agenesia of vas deferens was detected in a 5-month-old boy who underwent an inguinal herniorraphy. Although the child did not present any symptoms, he actually presented cystic fibrosis: the sudoral test showed high levels of chloride (95 mmol/L) and an isolated homozygous delta F 508 deletion on the gene CFTR was evidenced on genetic investigations. CONCLUSION: The congenital bilateral absence of vas deferens is the most frequent anomaly of the male genital tract discovered in adults investigated for azoospermia. Relations with cystic fibrosis are well established but congenital bilateral absence of vas deferens discovered during infancy is an exceptional situation that requires genetic investigations to show evidence of a likely underlying cystic fibrosis.

Clinical significance of Scedosporium apiospermum in patients with cystic fibrosis.

The incidence of airway colonization by Scedosporium apiospermum and of related sensitization was investigated prospectively in 128 patients with cystic fibrosis over a 5-year period, and results were compared with clinical data. Scedosporium apio-spermum, recovered from sputum samples in 11 of 128 (8.6%) patients, was the most frequent filamentous fungus after Aspergillus fumigatus. Counterimmuno-electrophoresis, used to detect scedosporiosis serologically, was positive in 27 of 128 (21.1%) patients. The discrepancy between the mycological and serological results may be related to immune cross-reactions between Scedosporium apiospermum and Aspergillus fumigatus. However, symptoms of allergic bronchopulmonary disease were observed in two patients chronically colonized by Scedosporium apiospermum. The results clearly demonstrate that the frequency of this fungus is largely underestimated and that it may trigger an inflammatory response, thus suggesting a pathogenic role in patients with cystic fibrosis.

Imaging changes in the pancreas in cystic fibrosis: a retrospective evaluation of 55 cases seen over a period of 9 years.

BACKGROUND: Pathologic changes of the pancreas have been observed as early as the recognition of the disease termed initially "cystic fibrosis of the pancreas". Atrophy of the gland and its fatty infiltration were considered as usual features. The aim of this study was to follow-up the evolution of cystic fibrosis pancreas and to define its successive stages in correlation with the clinical, biochemical, and imaging findings. METHODS: Fifty-five patients were followed up during 9 years. The patients' genetic backgrounds were systematically performed. Blood lipase levels were analyzed systematically at each consultation of the patients and in the event of bouts of abdominal pains. Imaging using mainly echograms and tomodensitometric scans were regularly performed: echograms every 6 months, and tomodensitometric scans every 1 to 2 years. Magnetic resonance imaging was performed in four patients. RESULTS: Five groups of patients were identified on the basis of tomodensitometric scan findings: normal pancreas (n = 4), incomplete lipomatosis of the pancreas (n = 9), complete lipomatosis of the pancreas (n = 23), cystic pancreas (n = 5), macrocystic pancreas (n = 1), atrophic pancreas (n = 13). Pancreas exocrine function was not correlated with findings. Forty episodes of pancreatitis were observed in seven patients. They had bouts of abdominal pain and elevation of lipase levels. Five of these patients were composite heterozygotes (D508/other). Incomplete lipomatosis represents an intermediate stage leading toward complete lipomatosis or toward atrophy after pancreatitis. CONCLUSIONS: Studies of pancreatic function should be performed routinely in cystic fibrosis, especially in pancreatic sufficiency or in patients with normal pancreas images. Acute pancreatitis should be diagnosed and properly identified to be differentiated from other acute abdominal syndromes occurring in cystic fibrosis.

Complex allele [-102T>A+S549R(T>G)] is associated with milder forms of cystic fibrosis than allele S549R(T>G) alone.

We recently reported a novel complex allele in the cystic fibrosis transmembrane regulator (CFTR) gene, combining a sequence change in the minimal CFTR promoter (-102T>A) and a missense mutation in exon 11 [S549R(T>G)]. Here we compare the main clinical features of six patients with cystic fibrosis (CF) carrying the complex allele [-102T>A+S549R(T>G)] with those of 16 CF patients homozygous for mutation S549R(T>G) alone. Age at diagnosis was higher, and current age was significantly higher (P=0.0032) in the group with the complex allele, compared with the S549R/S549R group. Although the proportion of patients with lung colonization was similar in both groups, the age at onset was significantly higher in the group with the complex allele (P=0.0022). Patients with the complex allele also had significantly lower sweat test chloride values (P=0.0028) and better overall clinical scores (P=0.004). None of the 22 patients reported in this study had meconium ileus. All 16 patients homozygous for S549R(T>G), however, were pancreatic insufficient, as compared with 50% of patients carrying the complex allele (P=0.013). Moreover, the unique patient homozygous for [-102T>A+S549R(T>G)] presented with a mild disease at 34 years of age. These observations strongly suggest that the sequence change (-102T>A) in the CFTR minimal promoter could attenuate the severe clinical phenotype associated with mutation S549R(T>G).

Chronic airway colonization by Penicillium emersonii in a patient with cystic fibrosis.

Penicillium emersonii Stolk, the conidial state of Talaromyces emersoniii Stolk, is a heat-resistant fungus usually isolated from soil. In this paper the authors report, to our knowledge, the first human case in which P. emersonii chronically colonized the respiratory tract and induced an immune response in a patient with cystic fibrosis.

Improvement of cystic fibrosis airway mucus transportability by recombinant human DNase is related to changes in phospholipid profile.

The aim of this study was to test whether changes in mucus surface properties by rhDNase treatment could be related to an increased recovery of phospholipids. Purulent sputa from 18 patients with cystic fibrosis (CF) were incubated with either rhDNase (4 microg/ml) or control excipient. The incubation of mucus samples with rhDNase induced a significant increase (p < 0.002) in the sol phase proportion (33.7 +/- 24.0%) compared with that obtained with excipient (12.6 +/- 12.4%). Phospholipids were recovered in significantly (p < 0.05) greater amounts from both mucus gel and sol phases after incubation with rhDNase. The phosphatidylglycerol content of mucus sol phase was significantly increased by rhDNase (p < 0.03), as well as the mucus gel phase surface properties and transport by ciliary activity and by cough (p < 0.05). The improvement of mucus gel surface properties and transport capacity by ciliary activity were significantly related to the increased recovery of phosphatidylglycerol (r = -0.74, p < 0.03 and r = 0.94, p < 0.05, respectively). These results suggest that rhDNase is able to increase the free water content and alter the phospholipid profile of mucus, with a related improvement in CF mucus transportability.

Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa.

Secretion of Pseudomonas aeruginosa elastase, exotoxin A, and alkaline protease in sputum during bronchopulmonary exacerbations was examined in 18 cystic fibrosis patients chronically infected with this microorganism. The patients were studied during one or several exacerbation periods necessitating hospitalizations of 12 to 20 days. In all cases, P. aeruginosa was present in bronchial secretions at admission and was not eradicated after treatment. The P. aeruginosa density decreased significantly after antibiotic therapy but remained greater than 10(6) CFU/g of sputum in most cases. Significant amounts of P. aeruginosa exoproteins were measured in total homogenized bronchial secretions by immunoenzymatic assays. The detection of higher levels of exoproteins at admission, the significant decrease after treatment, and the absence of exoproteins during intercrisis phases constituted arguments for a renewal of virulence of P. aeruginosa during exacerbations. Nevertheless, the concomitant changes in bacteria load and the triggering of the inflammatory process and immune complex formation could also contribute to pulmonary exacerbations.

Mutation analysis in 600 French cystic fibrosis patients.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 600 unrelated cystic fibrosis (CF) patients living in France (excluding Brittany) was screened for 105 different mutations. This analysis resulted in the identification of 86% of the CF alleles and complete genotyping of 76% of the patients. The most frequent mutations in this population after delta F508 (69% of the CF chromosomes) are G542X (3.3%), N1303K (1.8%), W1282X (1.5%), 1717-1G-->A (1.3%), 2184delA + 2183 A-->G (0.9%), and R553X (0.8%).

[Production of elastase, exotoxin A and alkaline protease during bronchopulmonary exacerbations in patients with mucoviscidosis chronically infected by Pseudomonas aeruginosa]. / Production d'élastase, exotoxine A et protéase alcaline au cours des exacerbations bronchopulmonaires chez les patients mucoviscidosiques porteurs chroniques de Pseudomonas aeruginosa.

The authors have studied the production of exoproteins by Pseudomonas aeruginosa in the sputa of 18 patients suffering from cystic fibrosis, during 29 bronchopulmonary exacerbations and also after the recovery of a stable state. Significant levels of exoproteins were detected but with a large heterogenity of intra and inter individual variations. A significant decrease in the production of the three exoproteins was found after twelve days of antibiotherapy, without any correlation between exoprotein levels and colony forming units in the sputa. During the intercrisis phase, exoproteins levels were practically undetectable. These facts and the good correlation between clinical symptoms support the hypothesis of a renewal of virulence of Pseudomonas aeruginosa during these periods of bronchopulmonary exacerbation in cystic fibrosis.

Cystic fibrosis and portal hypertension interest of partial splenectomy.

Extra pulmonary complications can be major in patients suffering of cystic fibrosis who survive long enough without pulmonary problems. Hepatic cirrhosis is often present and is responsible for portal hypertension with splenomegaly, hypersplenism and esophageal varices. In six patients we have performed a partial splenectomy with conservation of the upper pole of the spleen vascularized by gastrosplenic omentum and its vessels. The post-operative complications (3 scar ruptures but no pulmonary decompensation) are not very important considering the benefits: Normal spleen according to clinical, ultrasonic examination and scintigraphy Correction of hypersplenism Diminution of esophageal varices Stability of hepatic functions. With a post-operative follow-up between 2.5 and 7 years, none of the patients had an increased risk of infection. This technique allows a good survival for those patients waiting for pulmonary transplantation.

Effects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis.

Ursodeoxycholic acid, 10 to 20 mg/kg per day, was administered for 1 year to 22 patients with cystic fibrosis and chronic cholestasis, resulting in significantly improved liver enzyme values. However, evidence of cholestasis continued, as shown by the pattern of alkaline phosphatase isoenzymes.

[Lung transplantation and cystic fibrosis]. / Transplantation pulmonaire et mucoviscidose.

It is only in 1983-84 that lung transplantation has been contemplated in cystic fibrosis patients. The French programme, reported here, began in 1987. The criteria of inclusion are detailed, including antibiotic dependence, oxygen dependence, poor spirometric profile, destabilized nutritional status and very low Shwachman's score. The hepatic, cardiac, pulmonary, gastrointestinal, endocrine and psychological situations leading to temporary or definitive exclusion are defined. Once this evaluation has been made, the patients to be put on the waiting list are chosen collegially. The principles of medical and surgical treatment are exposed: immunodepressants and anti-infectious agents are prescribed to get over the immediate postoperative period (rejection and infectious complications) and to prevent the constitution of the much feared bronchiolitis obliterans; the indications of surgical techniques (HLT and BPT) should be more accurate. Among the 100-150 cases of lung transplantation recorded in the world, 30 were performed in France. We can safely say that 70 p. 100 of these patients are still alive and 40 p. 100 are in a remarkably good condition. This overall view is both exciting and disappointing, considering the results obtained and the ever-increasing waiting lists (more than 100 cases in France); hence the need for improving the present programme side by side with genetic and therapeutic studies which will eventually make surgery unnecessary.

Behaviour of serum immunoreactive trypsin after serum activation by enterokinase in normal and cystic fibrosis patients. Evidence of a trypsin-alpha 1-proteinase inhibitor complex in some cystic fibrosis patients.

Serum immunoreactive trypsin (IRT) concentrations are elevated in newborn children with cystic fibrosis (CF) and subsequently fall, in most cases, to values below normal. To evaluate the molecular form(s) of IRT present in serum, we have performed serum activation by enterokinase and have measured serum IRT before and after activation. This approach is based on the postulate that enterokinase converts trypsinogen into trypsin, and this trypsin would then be mainly trapped by alpha 2-macroglobulin, thus escaping the assay. This assumption was confirmed in the 28 controls studied, where the mean percentage (+/- S.D.) of IRT recovery after serum activation was 13.7 +/- 2.9. Previous inhibition of alpha 2-macroglobulin by methylamine raised the recovery over 85%, confirming that most of the serum IRT present in controls was in the form of trypsinogen. Identical results were obtained in the serum of 10 obligate heterozygotes and in 57 out of 80 CF patients. In 23 CF patients the mean percentage of IRT recovery after serum activation was 41.6 +/- 17.6. Gel-filtration studies were performed on the sera of the CF patients showing an abnormal increase in the IRT recovery after serum activation. We could demonstrate that IRT was distributed in two fractions: one eluted with the Mr 25,000 protein as usually found in controls and other CF sera, and the other eluted with the Mr 75,000 protein corresponding to a complex of trypsin with alpha 1-proteinase inhibitor. These results show that, in these sera, active trypsin has been directly released in blood. These findings suggest that in some patients with CF, subclinical attacks of acute pancreatitis may occur.