[Skin sensitisation profiles of outpatients with symptoms of respiratory allergies]. / Profils de sensibilisation cutanée aux pneumallergènes des patients consultant pour allergie respiratoire.

AIM: The main objective of the survey was to determine the frequency of the mono and polysensitizations in patients consulting for respiratory allergy, rhinitis or/and asthma. The secondary objectives were to evaluate the severity, the number and the type of the sensitizations, the frequency of the asthma or rhinitis as a function of the sensitizations, the evolution of the sensitizations with age, and identify the principal responsible pneumallergens. PATIENTS AND METHODS: The multicentric survey included a patient questionnaire allowing the collection and anonymous treatment of data on socio-demographic characteristics, clinical symptoms, cutaneous tests and sensitizations. RESULTS: A sample of 505 patients, mean age 24 years, consulting for rhinitis or asthma, monosensitized (36%) or polysensitized (64%), was evaluated. The percentage of polysensitized patients was similar in asthmatics, patients with rhinitis, and patients with both asthma and rhinitis (60%, 65%, and 63%, respectively). The mean number of the sensitizations was 2.4 for patients with asthma, 2.6 for those with rhinitis, and 2.6 for patients with both asthma and rhinitis. The greater the severity of the rhinitis or asthma, the higher the number of the sensitizations. Sensitizations to acarids, gramineae and cat were the most frequent. When practioners were asked about their intention to undertake desensitization in polysensitized patients, 52% of them replied positively. CONCLUSION: Data collected during this survey showed that a large proportion of the patients who consulted for rhinitis or asthma were monosensitized (36%). Sensitization to acarids was the most frequent. Even in polysensitized patients, more than half the practioners said they would use desensitization.

[Augmentation therapy with alpha-1 antitrypsin: 20 year- follow-up of a deficient patient]. / Traitement substitutif par alpha-1 antitrypsine: suivi sur 20 ans d'un patient déficitaire.

INTRODUCTION: Alpha one antitrypsin deficiency is a rare genetic disorder occurring principally in patients with the PiZZ phenotype. This deficiency can lead to pulmonary emphysema which impairs quality of life and which may progress to respiratory failure. The diagnosis is based on the presence of emphysema typically with a basal preponderance and airflow obstruction and is confirmed by measuring A1AT levels. A1AT replacement is the only specific therapy for this condition. OBSERVATION: We describe the 1st patient with A1AT deficiency treated in this way in France. The patient was 52 years old at the start of treatment with A1AT replacement, initially in hospital and then at their place of residence. Treatment was initiated in the context of progressive breathlessness, the presence of emphysema and confirmation of the biochemical deficit. The patient received 4 g of AIAT per week in combination with inhaled corticosteroids and ongoing physical rehabilitation. Follow up over 20 years has revealed a slowing in the decline in spirometric measurements. No problems with tolerating the treatment have been reported. CONCLUSION: In this clinical case replacement therapy appeared to show clinical benefits and was well tolerated.

High levels of cytokeratin 19 fragments but no evidence of cytokeratins 1, 2, 10/11, 14 or filaggrin in the serum of squamous cell lung carcinoma patients.

The CYFRA 21-1 assay detects circulating fragments of cytokeratin 19, which is a sensitive marker for the diagnosis of lung cancers, particularly squamous cell carcinomas and adenocarcinomas. Epidermis-type proteins, such as cytokeratins 1, 2, 10/11 and 14 or filaggrin, are also expressed in squamous cell carcinomas. These could also be pertinent tumor markers, ideally as sensitive as CYFRA 21-1 and more specific for squamous cell lung cancer. To verify this hypothesis, using monoclonal antibodies produced in our laboratory, we developed immunoassays specific for these proteins. After optimization, the immunoassays were evaluated in sera from 91 controls and 138 patients with squamous cell lung cancer and compared to conventional tumor markers (CEA, SCC Ag and CYFRA 21-1). Less than 14% of the sera were above the lower limit of detection of the cytokeratin- and filaggrin-specific immunoassays. Moreover, part of these positive sera were induced by the presence of interfering heterophilic antibodies in sera. Thus, in patients with squamous cell lung cancer, we confirmed the high diagnostic sensitivity of CYFRA 21-1 (55.6%) but were unable to detect significant levels of epidermis-type cytokeratins or filaggrin.

Frequency of prenatal diagnosis of birth defects in Houston, Galveston and the Lower Rio Grande Valley, Texas 1995.

BACKGROUND: Estimates of the proportion of birth defects diagnosed before birth exist for only a few types of birth defects and for a few geographic regions in the United States. This population-based study examines rates of prenatal diagnosis for previously unstudied birth defects in a new geographic region. METHODS: Active surveillance of 23 categories of birth defects among 111,902 infants born in 77 birthing hospitals in Texas in 1995 identified 852 infants or fetuses with major birth defects. Surveillance was conducted by the Texas Birth Defects Monitoring Program of the Texas Department of Health. Two regions were covered, the Houston/Galveston metropolitan area as well as the Lower Rio Grande Valley of Texas. Rates of prenatal diagnosis were evaluated for 23 different types of birth defects, using proportions and 95% confidence intervals. RESULTS: One third of the 852 infants or fetuses with birth defects were prenatally diagnosed. Diagnosis rates varied greatly depending on the type of birth defects and were lower among infants born to Black and Hispanic women. More than 60% of anencephaly, encephalocele, gastroschisis and trisomies 13 and 18 were diagnosed antenatally. Many of the fetuses that were electively terminated had birth defects or combinations of birth defects that were potentially lethal. Prevalence rates for birth defects generally do not include fetuses that die or are electively terminated before 20 weeks of gestation. Thus, 36% of anencephaly, 21% of omphalocele, 15% of encephalocele and between 7 and 10% of spina bifida, hydrocephaly, renal agenesis, and trisomies 13, 18, and 21 were not included in our published rates. CONCLUSIONS: Published rates for specific types of birth defects are spuriously low. This should be considered when investigating alleged clusters and comparing rates of birth defects across geographic areas. Since many elective abortions are for lethal or potentially lethal birth defects, a major effect of prenatal diagnosis is the resultant decrease in infant mortality attributable to birth defects.

Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions.

Carcinoembryonic antigen (CEA), carbohydrate antigens 15-3, 19-9 and 72-4 (CA 15-3, CA 19-9 and CA 72-4), cytokeratin 19 fragments (CYFRA 21-1), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) were evaluated in pleural fluid for the diagnosis of malignant effusions. With a specificity of 99%, determined in a series of 121 benign effusions, the best individual diagnostic sensitivities in the whole series of 215 malignant effusions or in the subgroup of adenocarcinomas were observed with CEA, CA 15-3 and CA 72-4. As expected, a high sensitivity was obtained with SCC in squamous cell carcinomas and with NSE in small-cell lung carcinomas. CYFRA and/or CA 15-3 were frequently increased in mesotheliomas. Discriminant analysis showed that the optimal combination for diagnosis of non-lymphomatous malignant effusions was CEA + CA 15-3 + CYFRA + NSE: sensitivity of 94.4% with an overall specificity of 95%. In malignant effusions with a negative cytology, 83.9% were diagnosed using this association. The association CYFRA + NSE + SCC was able to discriminate adenocarcinomas from small-cell lung cancers. Regarding their sensitivity and their complementarity, CEA, CA 15-3, CYFRA 21-1, NSE and SCC appear to be very useful to improve the diagnosis of malignant pleural effusions.

[Recurrent pneumopathy of the middle lobe...]. / Une pneumopathie récidivante du lobe moyen....

We report a case of a persistent middle-lobar pneumonia, which did not respond to antibiotics. Only a second bronchial endoscopy, with a third thoracic densitometry and histopathological results give the final diagnostic of tracheobronchial foreign body. The choking history happened more than 10 months before. The bronchoscopic extraction restablished the patient.

[Respiratory complications of the vinorelbine-mitomycin combination]. / Complications respiratoires de l'association vinorelbine-mitomycine.

The respiratory toxicity of vinca alkaloids only appears when they are associated with mitomycin. Few reports have been noted with vinorelbine, the last molecule of this class. We report 4 cases of acute dyspnea induced by the association mitomycin-vinorelbin, The 4 patients were treated for lung cancer. At the end of the injection of vinorelbin appeared an acute bronchospasm. In 3 cases, the symptoms disappeared with broncho-dilatators and corticoids. The fourth patient needed an additional respiratory support. After the acute syndrome, a chronic respiratory insufficiency developed in three patients. Two patients required continuous oxygenotherapy. The pulmonary toxicity of the mitomyin-vinca alkaloids association is characterized by an acute dyspnea. The dyspnea appears within 2 hours after the end of the administration of vinorelbine. The frequent existence of airflow obstruction in patients with lung cancer exposes to high risk of severes incidents. These treatments must be stopped at onset of the first pulmonary symptom. The association of mitomycin with vinorelbine (as for all vinca alkaloids) in chemotherapy protocols for treatment of non-small-cell lung cancer should not be indicated because there is an increase of the toxicity without increase of efficiency.

[Respiratory variant of constrictive pericarditis. Report of 4 cases]. / Forme respiratoire des péricardites constrictives. A propos de 4 cas.

Constrictive pericarditis was diagnosed in four patients who presented respiratory impairment and pleural effusion, associated with right ventricular failure in two. The cause was probable tuberculosis in two cases, post-irradiation lesions in one and unknown in one. The diagnosis was suspected due to the normal heart volume and pathological electrocardiogram as well as the computed tomographic findings demonstrating pericardial morphology. Right catheterism confirmed the diagnosis: increased right ventricular telediastolic pressure with a dip plateau and equivalent pressures in the right atrium and ventricle. Early diagnosis allowed pericardectomy in two cases. In one case, the subacute epicardopericarditis regressed with corticosteroids and antituberculosis therapy.

Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions.

CYFRA 21-1 assay, measuring cytokeratin 19 fragments, was compared with carcinoembryonic antigen (CEA) assay, as an addition to cytological analysis for the diagnosis of malignant effusions. Both markers were determined with commercial enzyme immunoassays in pleural fluid from 196 patients. Cytological analysis and/or pleural biopsy confirmed the malignant origin of the effusion in 99 patients (76 carcinomas, nine pleural mesotheliomas and 14 non-epithelial malignancies). Effusions were confirmed as benign in 97 patients (33 cardiac failures, 39 infectious diseases--including 12 tuberculosis-- and 25 miscellaneous effusions). Both markers were significantly higher in malignant than in benign effusions. All the patients with non-epithelial malignancies presented CYFRA and CEA values lower than the 95% diagnostic specificity thresholds (100 and 6 ng ml(-1) respectively). The diagnostic sensitivity in the group of carcinomas and mesotheliomas was similar for CYFRA (58.8%) and CEA (64.7%). However, CEA had a significantly higher sensitivity in carcinomas (72.4% vs 55.3%), while CYFRA had a clearly higher sensitivity in mesotheliomas (89.9% vs 0%). Interestingly, 12 out of the 16 malignant effusions with a negative cytology were CEA and/or CYFRA positive. Regarding their high diagnostic sensitivity and their complementarity, CEA and CYFRA appear to be very useful for the diagnosis of malignant pleural effusions when cytology is negative.

Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours.

Plasma DNA that circulates mainly as mononucleosomes is a cell death marker. Its significance and prognostic value in cancer as compared to other tumour markers was investigated in 68 patients hospitalised for lung cancers. Prognostic values of the various studied parameters were evaluated using the Cox's model. The cellular origin of plasma DNA was further investigated in nude mice transplanted with human lung adenocarcinoma. Plasma DNA concentrations were increased in cancer patients as compared to normal subjects (P < 0.01). They were higher in patients with extended (Stage 4) disease than in patients with limited stage disease (P < 0.05). Plasma DNA concentrations, serum lactate dehydrogenase activities and neuron-specific enolase concentrations were correlated all together in small cell lung carcinoma (SCLC) and in non-SCLC. Similar relationships were found between survival and each of these three cell death/tumour markers (P < 0.02-0.005). Plasma DNA from mice bearing human tumour hybridised with both mouse and human plasma DNA, while plasma DNA from endotoxin-injected mice hybridised only with mouse plasma DNA. In conclusion, in patients suffering from lung cancer, plasma DNA as well as LDH and NSE represent cell death markers that are correlated with survival. At a time when apoptosis pathways appear to be potential targets for cancer therapy, plasma DNA is a cell death/tumour marker that should be taken into account in studying the cancerous process in human diseases.

[Alveolar opacities and busulfan pneumonia]. / Opacités alvéolaires et pneumopathie au busulfan.

A case of toxic pneumonia due to busulfan is reported in a man aged 65 treated for three years with busulfan for chronic myeloid leukaemia. He was admitted to hospital for dyspnoea, cough, fever and presented with crepitations, dense alveolar opacities, and a restrictive ventilatory defect. Trans-bronchial biopsy showed a filling of the alveoli by fibroblastic tissue, as well as voluminous dystrophic pneumocytes. Four months later in spite of steroid therapy the clinical state and respiratory function were worse. The alveolar opacities have regressed but some diffuse interstitial opacities had appeared. This new case is a reminder that the appearance of alveolar opacities in a patient treated with busulfan should raise the possibility of a toxic pneumonitis to busulfan in the differential diagnosis. This observation also underlines the role of the initial endo-alveolar fibrosis in the ultimate development of interstitial fibrosis.

Clinical pharmacokinetics of alpha 1-antitrypsin in homozygous PiZ deficient patients.

A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to the extravascular compartment where some retention occurred. No significant difference in AAT metabolism was observed between the 3 groups. The half-life of the injected protein is slightly longer than 2.5 days. The AAT protein was not stored. These results confirm the observations collected during the clinical trials. That is, a weekly infusion is necessary to obtain stable serum AAT concentrations. Monthly infusions are unable to maintain a 'plateau' phase. The periodicity may be limited to every 2 weeks.

[Evaluation after 2 years of substitutive treatment of PiZZ emphysema with alpha-1 antitrypsin. 9 cases]. / Bilan à deux ans du traitement substitutif de l'emphysème PiZZ par l'alpha 1-antitrypsine. Neuf cas.

Homozygous PiZZ individuals with a serum deficiency due to a defect in the secretion of the alpha 1-antitrypsin protein are at risk of developing severe panlobular emphysema. Tobacco smokers are particularly exposed to the disease which begins at an earlier age. Treatment by substitutive therapy with alpha 1-antitrypsin concentrates seems to be the only possibility. A two years' clinical trial was performed in 9 PiZZ patients, with more than 1,500 infusions being administered weekly. Serum AAT levels were used as guidelines to follow biochemical changes in the protease-antiprotease balance. From 0.16 g/l initially, the AAT level rose to 0.57 g/l after 7 months. No adverse reaction was observed during the trial; the concentrated protein was well accepted, ant the antielastase activity of the protein recovered after injection was equivalent to the activity injected. An attempt to administer the infusions monthly was stopped when we observed a dramatic decrease of the serum AAT level. Clinically, stabilization of the symptoms was noted. No degradation was observed in the patients who took part in the trial, even if no real improvement was detected.