A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Bacterial pericarditis in infancy and childhood.

The authors report on a cooperative study of 43 cases of bacterial pericarditis observed in children. This disorder was suspected in patients with septicemia who developed symptoms and signs of pericarditis (precordial pain, muffled heart sounds, pericardial friction rub, cardiomegaly). Early diagnosis of this condition is now facilitated by echocardiography. A combination of medical and surgical treatments (appropriate antibiotic therapy after culture and sensitivity tests and early pericardial drainage) led to complete recovery in almost all of the cases (42 of 43). After long-term follow-up, no cases of constrictive pericarditis were observed.

The MxA protein levels in whole blood lysates of patients with various viral infections.

Interferon alpha (IFNalpha), a type I interferon, can be considered as a viral infection marker because this cytokine is induced during many viral infections. However, it is quite difficult to detect IFNalpha in sera. Investigations are interested in various intra-cellular IFNalpha-induced proteins as viral infection markers. However the activity of these enzymes increased not only in response to type I IFNs but also to type II IFN. MxA protein can be detected in the cytoplasm of IFNalpha/beta-treated cells, whereas other cytokines, including IFNgamma, are poor inducers. Using an immunochemiluminescent assay, we studied MxA protein in whole blood of 34 patients with various viral infections. The whole blood was drawn into sterile vacuum tubes containing heparin or EDTA. MxA values were relatively similar in heparin-treated samples and EDTA-treated samples, with differences not exceeding 1 ng/ml. The levels of MxA protein were compared in whole blood obtained by using two different lysis procedures. A correlation was found between the MxA levels obtained by using procedure I and procedure II, but higher amounts of MxA protein were found with procedure II. The second procedure is rapid and more convenient than the other and it is carried out in one step which reduce technical problems. High levels of MxA protein were found in peripheral blood cells of patients with acute viral infections (Rotavirus, Adenovirus, RSV, CMV), but MxA protein was not elevated in bacterial infections. The MxA levels were also studied in peripheral blood of 32 HCV positive patients. MxA protein was not found in most of IFNalpha-untreated patients, even those with high viral load. In contrast, high levels of MxA protein were found in IFNalpha-treated patients. MxA quantitation can be considered as a specific marker of acute viral infections, and could be useful in the management of treatment with IFNalpha.

[Anomalous origin of the left coronary artery. The form in infants]. / L'anomalie de naissance de la coronaire gauche. Forme du nourrisson.

Twenty-four cases of anomalous origin of the left coronary artery from the pulmonary artery are reported. These cases were collected over 27 years divided into three 9-year periods according to the years of the initial studies. The clinical aspects and diagnostic investigations (notably echocardiography, myocardial radioisotope imaging and various angiographic procedures) are reviewed; aortography seems to be, even now, the best exploratory method. Treatment is analyzed according to the periods of observations. From the earliest cases it may be concluded that ligation proved ineffective in infants and medical treatment often failed. Progressively, medical treatment with digitalis (now better controlled), potassium-sparing diuretics and vasodilators has become more effective. On the other hand, direct reimplantation of the left coronary artery onto the aorta has become the preferred surgical procedure. Among the 8 most recent cases (seen between 1977 and 1986), 4 were cured by medical treatment under the age of 3 and subsequent reimplantation. In the other 4 patients asystolia responded to medical treatment, and these children are now awaiting reimplantation.

[Chronic diarrhea caused by VIP-secreting ganglioneuroblastoma in children. Apropos of a case with a review of the literature]. / Diarrhée chronique par ganglioneuroblastome (GNB) sécrétant du VIP chez l'enfant. A propos d'un cas avec revue de la littérature.

A literature review was conducted in relation to a case of chronic diarrhea associated with a VIP (vasoactive intestinal polypeptide) producing ganglioneuroblastoma (GNB), in an 18-month old female baby. This is a rare entity characterized by premonitory, persisting diarrhea, causing fluid and electrolyte changes typical of the WDHA syndrome, associating watery diarrhea, hypokalemia, and achlorhydia. Elevated VIP plasma levels are an indication for an echographic and/or CT-scan search for the causal secreting tumor. Although the prognosis of this condition seems favorable, the recommended treatment is surgery. The VIP substance represents an excellent biological monitoring marker. Ganglioneuroblastomas are tumors of the sympathetic nervous system, which, according to Pearse's cell and embryologic theory (1966), have to be linked to the APUD system tumors (paraneuromas). VIP-producing forms are rare in children, and only 29 case studies have been compiled in the literature since 1970, when the VIP substance was discovered. The case reported in this study illustrates the diagnostic problems raised by such lesions, and allows us to confirm VIP's imputability for the occurrence of the chronic diarrhea condition in this child.

[Hydrocholecystitis in children and newborn infants. Apropos of 3 cases]. / L'hydrocholécyste chez l'enfant et le nouveau-né. A propos de trois observations.

We report two cases of hydrocholecystitis in children and one in a neonate. One child had hepatitis A and the other had typhoid fever. A beta-hemolytic group B streptococcal infection was found in the neonate. In all three cases, the first manifestation was an abdominal mass and treatment of the causative disease ensured recovery. These three observations provided us with the opportunity for reviewing the literature. Isolated hydrocholecystitis is distinguished from hydrocholecystitis as a symptom. The clinical evaluation and diagnostic investigations are described in detail; special attention is given to abdominal ultrasonography. Etiology and pathophysiology, as well as management are discussed. Our three cases and the review of the literature confirm the benign prognosis of this condition.

MxA protein in capillary blood of children with viral infections.

Capillary blood of febrile children was lysed by using a lysis buffer containing ascorbic acid. MxA quantitation was performed by an immunochemiluminescent assay. The MxA values were significantly higher in capillary blood of infants with viral infections due to adenovirus (n = 5), rotavirus (n = 15), or respiratory syncytial virus (n = 28), than in capillary whole blood from infants with bacterial infections (n = 6) and healthy control patients (n = 20). A strong correlation was found between the MxA values in capillary whole blood and peripheral whole blood (r' = 0.86, P < 0.0001, n = 48). The MxA values found at these two sites were compared with the levels of IFN-alpha obtained by a dissociation enhanced lanthanide fluoroimmunoassay. A correlation between these two values was found. The results show that the combination of collection of blood by finger prick and specific immunochemiluminescent assay for MxA protein measurement may be of value for the diagnosis of viral infections in children.