Carrier detection and prenatal diagnosis of X-linked agammaglobulinemia.

We investigated the pregnant mother of a boy with X-linked agammaglobulinemia (XLA) but with no family history of immune disease. The X-inactivation pattern was found, using a methylation-sensitive probe, to be skewed in the maternal B cells but random in the polymorphonuclear cells, indicating carrier status and a 50% risk of inheritance for her male fetus. Using probes assigned to regions on either side of the XLA locus and defining RFL polymorphism, we excluded for the first time a diagnosis of XLA on a chorionic villus sample, with a risk of error less than 0.003. Immunological studies performed at the 19th week of gestation and 3 days after birth confirmed normality. Carrier detection based on the X-chromosome inactivation pattern, together with prenatal studies using probes close to the disease locus, thus permits prenatal diagnosis in families with isolated cases of XLA.

Idiopathic pulmonary fibrosis in infants.

Idiopathic pulmonary fibrosis is a poorly characterized disease in infants. In the present report, we reviewed our experience with 10 infants during a 10-year period. In 9 patients, onset of symptoms occurred before the age of 2 months and included tachypnea, cough, and inadequate weight gain. However, despite the presence of these symptoms, diagnosis was delayed for 3 months at which time the infants were referred to the pediatric pulmonary department, when the diagnosis was confirmed by open lung biopsy. At the time of admission, bronchoscopy with alveolar lavage was performed in 9 children and showed severe alveolitis with an increase in the neutrophil count. Nine infants were treated with prednisone alone or in combination with chloroquine, colchicine, or cyclophosphamide; all these patients died despite treatment. One infant was treated with pulses of methylprednisolone because of a failure in response to oral prednisone. This girl who displayed similar clinical, radiological, and histological abnormalities as the other children at the time of diagnosis is the only child still alive after 3 years of follow-up. She is now free of respiratory symptoms and has a normal growth curve. The present report raised two important points: (1) a thorough evaluation of characteristic symptoms should lead to an early diagnosis of pulmonary fibrosis in infants; and (2) administration of pulse therapy using corticosteroids has been helpful and needs to be evaluated further.

[Problems of congenital toxoplasmosis. Evolution over four decades]. / Le problème de la toxoplasmose congénitale. L'évolution sur quatre décennies.

EFFECT OF PREVENTIVE MEASURES: The development of reliable routine serology tests and the demonstration of the high prevalence of toxoplasmosis in France led to mandatory prospective screening of pregnant women in 1978, followed by prenatal screening in 1985. In addition, in utero diagnosis, first on fetal blood and now with the reliable and safe method using polymerase chain reaction on amniotic fluid, formally identifies the parasite. THE SITUATION TODAY: A comparison of the experience of a specialized center in Paris during three different periods over the last 40 years showed that currently 71% of all cases of congenital toxoplasmosis are infraclinical at birth and only 5% are severe. Mean incidence of seroconversion during pregnancy is 1.48%, with a 40% risk of fetal contamination if no treatment is given. The risk of overt fetopathy predominantly concerns maternal infections occurring prior to 26 weeks gestation. IN UTERO TREATMENT: Positive PCR diagnosis on amniotic fluid imposes serial ultrasound examinations to identify any fetopathy and an in utero treatment by giving the mother the pyrimethamine-sulfadiazine combination. Biological results are favorable. POST-NATAL TREATMENT: Post-natal treatment is indicated even in latent forms and should be continued for the first year of life. The pyrimethamine-sulfadiazine combination is the only pharmaceutical regimen with well-proven efficacy. New compounds should allow better prophylaxis against maternofetal contamination or improved post-natal treatment. RECURRENCE: In 70% of the cases, serology tests become positive again, but are not associated with significantly increased risk of ocular recurrence.

[Acquired toxoplasmosis of ocular or neurologic site: 49 cases]. / Toxoplasmose acquise à localisation oculaire ou neurologique: 49 cas.

OBJECTIVES: Over a period of 13 years (1982-1995), 49 cases of acquired toxoplasmosis complicated with ocular and/or neurologic or meningeal involvement were observed in our toxoplasmosis laboratory. This series includes 43 cases of isolated ocular lesions, 3 cases of meningoencephalitis (associated with retinochoroiditis in 1 case), 1 case of meningitis with uveitis, 1 case of polyradiculoneuritis and 1 case of facial nerve palsy. METHODS: The patients were aged 1 to 62 years. None had either spontaneous or iatrogenic immunodeficiency. There were two steps in the diagnosis. First congenital infection was eliminated on one or several of the following criteria: any possibility of maternal infection during pregnancy ruled out in 26 cases, evidence of recent acquired infection (i.e. clinical and/or serological evidence of recent acquired toxoplasmosis in 17 cases, retinochoroiditis in non-twin siblings in 3 cases). The second step was to confirm the diagnosis of toxoplasma infection. Apart from serological evidence of recent infection, confirmation included specific local antibody synthesis in the aqueous humor of the eye and/or in cerebro-spinal fluid or ocular lesions characteristic of toxoplasmosis and absence of other etiology. RESULTS: Ocular lesions were unilateral in 43 cases among 45. A mean follow-up of 37.9 months revealed relapses in 14 among 36 patients (39%). As routine serological examination for toxoplasmosis is compulsory in France since 1978, it was possible to document retrospectively the immune status of the mothers of many of the patients of the present series during pregnancy and to rule out congenital toxoplasmosis in a number of cases. This might explain the discrepancy between the relatively large number of cases in the present series and the fact that complicated acquired toxoplasmosis has been considered hitherto as relatively rare in immunocompetent patients. CONCLUSION: Based on the epidemiology of ocular toxoplasmosis and the data obtained here, it is suggested that the acquired pattern of ocular toxoplasmosis might be more frequent than estimated up to now.

[Respiratory virus infections in children]. / Viroses respiratoires chez l'enfant.

Eighty to ninety percent of pathogens responsible for acute respiratory infections in children are viruses, but despite advances in virology these organisms are isolated in only 20 to 45 percent of the cases. Studies conducted outside hospitals have provided epidemiological data. The virus most frequently encountered is the respiratory syncytial virus. The main clinical feature of these respiratory viral infections is obstruction of the bronchioles, and their immediate or delayed danger is the risk of chronic obstructive bronchitis. Treatment is symptomatic, but specific antiviral agents, notably ribavirin, are useful in severe infections.

[Congenital toxoplasmosis. 5 cases of mother-to-child transmission of pre-pregnancy infection]. / Toxoplasmose congénitale. Cinq cas de transmission à l'enfant d'une infection maternelle antérieure à la grossesse.

Five cases of congenital toxoplasmosis consecutive to a maternal toxoplasma infection that had preceded pregnancy were observed. One woman with normal immune system had developed a well-documented lymph node toxoplasmosis 2 months before conceiving. Four women had chronic toxoplasmosis diagnosed in the course of an immunosuppressive disease: Hodgkin's disease in 1 case, systemic lupus erythematosus in 2 cases and pancytopenia in 1 case. Toxoplasmosis had been recognized 3, 5 and 10 years respectively before conception in 3 women, and at an uncertain date in 1 woman. Three women had received corticosteroids during pregnancy, and 2 had undergone splenectomy. Among the 6 children (2 were twins), 1 presented with severe foetal disease at birth, 1 developed lethal systemic toxoplasmosis after birth, 1 showed hydrocephalus with therapeutically well-controlled chorioretinitis, 1 had isolated eye lesion and 2 had asymptomatic infection. The parasite seems to have been transmitted after the 20th week of pregnancy in all cases. The physiopathology of mother-to child toxoplasma transmission, the role played by maternal immunodeficiency and the practical implications of these exceptional cases are discussed.

[Heart or heart-lung transplantation and toxoplasmosis]. / Transplantation cardiaque ou cardio-pulmonaire et toxoplasmose.

Among all organ transplantations, those of heart or heart-lung carry the greatest risk of toxoplasmosis. The disease is observed mainly when the donor is seropositive and the recipient seronegative. In these mismatched couples the risk may be as high as 57 percent. Cardiac tissue transplants are responsible for most contaminations. A subclinical serological reactivation can be observed in seropositive recipients. Patent forms are associated with seroconversion in seronegative subjects. Toxoplasmosis is often severe with multivisceral foci; interstitial pneumonia is possible. The serological diagnosis is easy in cases with significant antibody movements, but it may be difficult if the titre is low or stable. The parasitological diagnosis rests on the isolation of toxoplasma in blood, cerebrospinal fluid, bronchoalveolar lavage fluid and cardiac or cerebral biopsy. Immune defence against toxoplasmosis is primarily cellular, with lymphocytosis and inversion of the CD4/CD8 ratio. Macrophages play a crucial role. Interferon-gamma is the major mediator of cellular resistance. In spite of its immunosuppressive action, cyclosporin clearly has an antiparasitic action in vitro and in vivo. A cytomegalovirus infection might facilitate toxoplasma reactivation. Prevention of toxoplasmosis in transplant recipients includes systematic serology of the recipient and, if possible, the donor, detection of mismatched couples and systematic treatment with pyrimethamine of recipients at risk (in seronegative recipients, this drug has reduced the risk from 57 to 14 percent). Cyclosporin should be used as immunosuppressant in preference to other drugs of this kind. Corticosteroids administered in rejections increase the risk of toxoplasmosis.

[Prenatal diagnosis and genetic diseases of the lung]. / Diagnostic anténatal et maladies génétiques pneumologiques.

Currently two genetic pulmonary disorders can be diagnosed before birth: alpha-1-antitrypsin deficiency and mucoviscidosis. For the latter there are two possible diagnostic techniques: first a study of the intestinal enzymes of the amniotic fluid, a reliable method only at the 18th week, and also a study of DNA markers (ADN) of the trophoblastic cells using molecular biological techniques: this can be performed from the 10th to 11th week of pregnancy but presupposes a family study in which there is already a subject suffering from the disorder. Foetal echocardiography enables various pulmonary abnormalities to be detected: pleural effusion, cyst, pulmonary hypoplasia and other disorders. This technique however has some limits, at least at present. Most often these severe malformations are revealed at birth such as respiratory distress or stillbirth. Adenomatous cystic malformations or congenital lobar emphysema, a posterior diaphragmatic hernia, and oesophageal atresia with oesophagotracheal fistula are the most frequent and are curable surgically.

[Pneumological aspects of bronchial foreign bodies in children. Experience with 100 cases]. / Les aspects pneumologiques du corps étranger bronchique chez l'enfant. Expérience de 100 cas.

100 cases of bronchial foreign body seen over a period of 4 years represent 1.2% of the admissions of a paediatric pneumology unit; 73% of the children were aged between 6 months and 3 years. The foreign body was vegetable in 61% of cases (a peanut in 44% of cases). The time between the inhalation and the endoscopic diagnosis was greater than 7 days in 70% of cases and greater than 30 days in 37% of cases. Removal of the foreign body was possible in all but one case. In particular, the authors studied the pneumological implications of a foreign body: the value of a quantitative bacteriological study of the bronchial secretions, which was significant in 43% of cases, and detection of the sequelae by prospective clinical and functional surveillance with a follow-up of 3 to 24 months. After 6 months, persistent radiological abnormalities were found in 40% of cases, perfusion disorders were found in 35% and ventilation disorders were found in 64%. A surgical operation was performed in 7 cases: one case of bronchotomy for extraction of the foreign body and 6 cases of parenchymal excision, including 2 total pneumonectomy for a destroyed lung. These were no death. The pathophysiology of the complications of functional disorders and of dilatation of the bronchi is discussed in the context of the experience gained from this series.

[Treatment understanding and compliance in asthma of children. Results of a prospective survey]. / Connaissance et adhésion au traitement de l'asthme de l'enfant: résultats d'une enquête prospective.

Compliance with treatment is a crucial factor in the management of asthmatic children which depends on the understanding of the disease and its treatment. The understanding of, and compliance with treatment were evaluated by means of a questionnaire in 50 parents of asthmatic children. 50% of these parents used anti-histamines as maintenance treatment and 30% also used these drugs during attacks. Half the parents knew about the bronchodilator effects of theophylline and B2-agonists. 42% and 30% respectively of the parents thought that the side-effects of theophylline or corticosteroids were few or inexistent; 86% claimed regular attendance to out-patient clinics, but 30% confessed that they had forgotten such drugs as theophylline and antihistamines. 50% took the appropriate therapeutic measures when confronted with a moderate or severe attack of asthma. Each child received 2.3 drugs on average for his or her asthma. This study shows that parents have an insufficient knowledge of asthma treatments, and this may partially explain the poor compliance with therapy as well as the morbidity and mortality associated with childhood asthma.

[Congenital deglutition disorder revealing cerebral stem disorders. 12 cases with neurophysiological study]. / Trouble congénital de la déglutition révélateur d'une atteinte du tronc cérébral. 12 observations avec étude neurophysiologique.

BACKGROUND: Respiratory problems in neonates and infants may be the result of a variety of neuromuscular dysfunctions. Neurologic evaluation of functions, such as sucking and swallowing, may be difficult in these very young infants and can be helped by neurophysiological studies. METHODS: 12 infants admitted because of repeated episodes of respiratory obstruction due to difficulties of sucking and/or swallowing took part in the study. The neurophysiological studies included electromyography of the facial, lingual and pharyngeal muscles, brain stem auditory evoked potentials and measurement of the blink reflexes. The results were correlated with events during the perinatal period and those that occurred during the follow-up. RESULTS: Dysphagia was evident from the neonatal period; it was complicated by nasal reflux and aspiration bronchopneumopathy. Facial diplegia was observed in 8 patients. 9 patients failed to thrive. The electromyographic patterns showed partial denervation of the facial, lingual and pharyngeal muscles in all cases; the blink reflex was altered in 11 cases, and the brain stem evoked potentials were abnormal in 3 of the 8 cases tested. 7 of the infants had histories of pregnancy and obstetrical abnormalities, and/or fetal distress. The swallowing function partially improved within several months. CONCLUSIONS: Neurophysiological studies indicate neurofunctional alterations in the VII, IX, X and XII cranial nerve nuclei, V and VII pathways and the auditory tract. These lesions and the time course of improvement suggest that they are due to pre- or perinatal anoxo-ischemic brain stem injury.

[The Wurzburg titanium miniplate system: evaluation of 3-year utilization]. / Het Wurzburg titanium miniplatensysteem: een evaluatie van 3 jaar gebruik.

In this article the use of Titanium miniplates in the maxillo-facial surgery is being examined. After a literature-study concerning the qualities of Titanium and the advantages, disadvantages aswell as indications of the miniplates, the stability of osteotomies using this system is being traced, aswell as its eventual developments. From this research it becomes clear that the miniplates indeed contribute to greater stability of the skeletal fixation in maxillo-facial surgery.