[Variations under genetic control of onchocerca infection as a function of clinical profile in the endemic center of Cameroon]. / Variations sous contrôle génétique de l'infection onchocerquienne en fonction du profil clinique dans les foyers endémiques du Cameroun.

Onchocerciasis, also known as "river blindness", presents a plenum of clinical manifestations which vary from one individual to another, and from one area to another. This large spectrum of clinical manifestations of the disease is an indication of the complexity of the pathogenesis of onchocerciasis and suggests that many interacting factors might influence the clinical features of the disease. The present study has focused on the heterogenicity of the host immune response as a plausible explanation for differences in clinical manifestations of the infection. Host genetic factors, namely HLA genes, might play an important role in determining the nature of the immune response mounted against the parasite Onchocerca volvulus, and thus the development of different manifestations of the infection. Genetic diversity of onchocerciasis was assessed in different endemic foci in Cameroon. In order to investigate the possibility that the Major Histocompatibility Complex (MHC) genes might be associated with the different clinical types of onchocerciasis, 146 subjects living in three endemic areas of Cameroon were studied. They were classified in four groups: A (asymptomatic subjects), P (putatively immune subjects) L (patients with localised disease) and G (patients with generalised disease). The four groups differed in the distribution of HLA class II alleles as determined by Direct Heteroduplex Analysis. On the one hand, allele HLA-DQA1*0501 appeared to be associated with protection against severe onchocerciasis; on the other, allele HLA-DQB1*0201 might play an important role in the severe form of the disease.

The use of a neural network for studying the relationship between air pollution and asthma-related emergency room visits.

To establish the relationship between air pollution levels and bronchial asthma-associated emergency room (ER) visits, we adapted artificial network technology to conduct this study which focused on three different pollutants, sulphur dioxide, nitrogen oxide and ozone. The study population was comprised of adults presenting to the emergency room of a large metropolitan hospital in Israel during a 3-month period with acute exacerbation of bronchial asthma and who had a past history of intermittent airway disease compatible with bronchial asthma. The range of mean daily pollutants levels for the whole period were: O3 = 15-26 micrograms m-3, NOx = 36-108 micrograms m-3, NO = 16-70 micrograms m-3, and SO2 = 11-32 micrograms m-3. The data sets were composed of input air pollution levels and output ER visits. The first 126 data sets used for the training phase showed that maximal ER visits were mainly associated with the highest cumulative values of air pollution and mostly with nitrogen oxide. In phase two, an attempt was made to predict ER visits based on air pollution level in 49 data sets. The study findings demonstrated that ordinary network technology can be used for learning the effect of air pollution ER visits and, although limited in accuracy, to also predict future ER visits.

Racemic versus l-epinephrine aerosol in the treatment of postextubation laryngeal edema: results from a prospective, randomized, double-blind study.

OBJECTIVE: To determine whether any advantage exists using racemic epinephrine instead of the more potent and less expensive levo(1)-epinephrine in the treatment of postextubation laryngeal edema. DESIGN: Prospective, double-blind, randomized study. SETTING: Pediatric intensive care unit in a university teaching hospital. PATIENTS: Twenty-eight patients with stridor during the immediate postextubation period. INTERVENTIONS: After extubation, patients demonstrating clinically important stridor were randomized in a double-blind fashion to receive an aerosol containing either 2.25% racemic or 1% l-epinephrine. MEASUREMENTS AND MAIN RESULTS: Heart rate, respiratory rate, blood pressure, and stridor score were determined at 20, 40, and 60 mins and 4 and 8 hrs after the initial aerosol administration. Patients in both groups demonstrated significant (p < .01) reductions in stridor score after aerosol administration. No significant differences were observed between treatment groups in improvement in stridor score or the number of subsequent aerosols required. Respiratory rate decreased significantly 40 and 60 mins after l-epinephrine but not after racemic epinephrine. No significant change in heart rate or blood pressure occurred after aerosol administration in either group. CONCLUSIONS: These data suggest that aerosolized l-epinephrine is as effective as aerosolized racemic epinephrine in the treatment of postextubation laryngeal edema without additional adverse side effects. When dosed appropriately, l-epinephrine is a less expensive and more widely available alternative to racemic epinephrine for the treatment of postextubation laryngeal edema.

Sudden infant death syndrome in the Tel Aviv and Petah Tikva districts.

We studied the epidemiology and incidence of the sudden infant death syndrome (SIDS) in the Tel Aviv and Petah Tikva districts during the period April 1980 to March 1983. Sixty-nine infants were diagnosed as SIDS and 38 of them had autopsies. Four cases were excluded because their autopsy revealed other diagnoses. When calculating for 24,183 live births per year during the study period, the rate of SIDS was found to be 0.47-0.90:1,000 live births. Other epidemiologic characteristics were: female:male [corrected] ratio 1:1.3; peak incidence at 2-4 months age, with 80% before age 6 months; increased incidence during the autumn and winter months (85% of SIDS cases); and highest incidence between midnight and 8:00 AM (84% of SIDS cases). None of the infants had a history of a previous apparent life-threatening event. Birthweight of infants who died of SIDS was not significantly different from that in the general population. No statistical relation to DTP (diphtheria, tetanus, pertussis) vaccination was found. Half the cases had mild respiratory illness during the week that preceded the sudden death. The incidence of parental cigarette smoking was higher than in the general population (56.5% vs. 36-53%; P less than 0.005) as well as the incidence of maternal smoking during pregnancy. We conclude that the incidence of SIDS in Israel is relatively low. The epidemiologic characteristics of SIDS in Israel are very similar to the presentation of the syndrome in other countries.

Low frequency oscillatory ventilation through the suction channel of a pediatric bronchoscope.

To determine whether low frequency oscillatory ventilation (LFOV) may be safely applied through the suction channel of a pediatric fiberoptic bronchoscope, we devised a system using a combination of jet ventilation and constant air suction, both delivered with a single interface valve. The system was tested on an in vitro lung model and on rabbits. With tidal volumes of 12 mL, inadvertent increase in functional residual capacity (FRC) measured in the lung model was minimal. All rabbits experienced marked hypoventilation (PaCO2 62 +/- 2 torr) on introduction of the bronchoscope, which promptly improved with administration of LFOV (PaCO2 41 +/- 4 torr). That baseline FRC remained stable indicated that air trapping did not occur. We conclude that LFOV improves ventilation in rabbits during bronchoscopy without causing air trapping. A similar system might be applied during bronchoscopy in full-term and premature infants, thus facilitating safer and more complete visualization of their airways and preserving the possibility of obtaining samples by suction.

Suppression of lymphocyte proliferation by Pseudomonas aeruginosa phenazine pigments.

Pseudomonas aeruginosa culture supernatants have been shown to inhibit lymphocytes proliferation as measured by [3H]TdR uptake. The phenazine pigment pyocyanine has been identified as one of the inhibitors present in those supernatants. To determine the mechanism of the inhibitory action of P. aeruginosa supernatants and pyocyanine, we studied their effect on the early stages of T-cell activation. Both P. aeruginosa supernatant and pyocyanine inhibited lymphocyte stimulation induced by the lectin concanavalin A. Analysis of Interleukin-2 receptor expression on the T-cell membrane showed that it was inhibited by both. This inhibition is dose dependent and not due to cellular toxicity. There was a parallel inhibition of growth in cell volume as well as [3H]TdR uptake. The results reported here suggest that P. aeruginosa culture supernatant and purified pyocyanine may interfere with cellular immune responses that may be necessary for eradication of chronic infection with P. aeruginosa in patients with cystic fibrosis.

Studies on the mechanism of T cell inhibition by the Pseudomonas aeruginosa phenazine pigment pyocyanine.

Pseudomonas aeruginosa and its products have been shown to inhibit mitogen-induced human lymphocyte blastogenesis as measured by [3H]TdR uptake. The phenazine pigment pyocyanine has been identified as one of the inhibitors present in cellfree culture supernatants. To determine the mechanism of the inhibitory action of pyocyanine, we studied its effect on the early stages of T cell activation. Pyocyanine inhibited lymphocyte stimulation induced by specific antigens, the lectin concanavalin A and the calcium ionophore, ionomycin, suggesting that its inhibitory effect is not dependent on interference with the T cell antigen receptor complex itself. Using quin-2, we showed that pyocyanine did not interfere with the mitogen-induced increase in cytosolic-free Ca2+. We also showed that pyocyanine did not interfere with the function of calmodulin stimulated Ca2+-Mg2+ ATPase activity, indicating that the mechanism of action of pyocyanine differs from that of the structurally related phenothiazine compounds. Analysis of IL 2 production and IL 2 receptor expression clearly showed that pyocyanine inhibits the production of this essential lymphokine as well as the expression of IL 2 receptors on the T cell membrane. This inhibition is dose dependent and not due to cellular toxicity. There was parallel inhibition of growth in cell volume as well as [3H]TdR uptake. Thus, our results demonstrate that pyocyanine inhibits T cell proliferation by decreasing the production of the critical lymphokine IL 2 and by decreasing the expression of the IL 2 receptor. Local suppression of lymphocyte stimulation by phenazine pigments such as pyocyanine may interfere with cellular immune responses that may be necessary for eradication of chronic infection with P. aeruginosa.

Acute hepatic failure after open-heart surgery in children.

Acute hepatic failure (AHF) combined with acute renal failure (ARF) is a well-known complication of open-heart surgery in adults. The occurrence of this complication in two children after open-heart surgery for correction of congenital heart disease is reported. Hypotension occurred during the operation and was treated by catecholamine vasopressors. AHF set in during the postoperative course; it was manifested by impaired consciousness, hypoglycemia, hyperbilirubinemia, hyperammonemia, elevated liver enzymes and prolongation of the prothrombin time with failure of hemostasis. ARF also developed in both children. One of the patients survived the acute episode of hepatic failure. The importance of early diagnosis, routine close monitoring, and appropriate selection of vasopressors is emphasized.

Adenovirus type 3 infection with systemic manifestation in apparently normal children.

Between July 1983 and February 1984, eight children with adenovirus Type 3 infection, proven by virus isolation from sputum, stool or nasopharyngeal swabs and a fourfold increase in complement fixation antibody titers against the virus, were treated in our department. All eight patients had fever lasting at least 7 days, hepatomegaly, diffuse pulmonary infiltrates and abnormal liver function tests. Seven of the patients exhibited dyspnea and pulmonary wheezing. Six of the patients developed changes in state of consciousness, and three had repeated convulsions. EEG patterns in three of the patients were compatible with encephalopathy. Other clinical manifestations included: follicular tonsillitis in two patients, diarrhea in two, pneumothorax in one, and shock with disseminated intravascular coagulation in one. The spectrum of adenovirus Type 3 infection reported here has been described previously only in the viral hemorrhagic fevers. This adenovirus Type 3 infection shares the potential for disseminated disease that has been described previously for Type 7, simulating Reye's syndrome.

Possible Waardenburg syndrome with gastrointestinal anomalies.

We describe a patient with possible Waardenburg syndrome associated with anal atresia and oesophageal atresia with tracheooesophageal fistula. Three other published cases with atretic gastrointestinal anomalies associated with the Waardenburg syndrome are reviewed. We conclude that the association between atretic lesions of the gastrointestinal tract and the Waardenburg syndrome may be a significant one.

Hereditary heat-labile hexosaminidase B: a variant whose homozygotes synthesize a functional HEX A.

Homozygosity for a mutant allele at the beta-chain locus of hexosaminidase (HEX), resulting in a variant of heat-labile HEX B, is reported for the first time in two healthy children. HEX activity in their sera, leukocytes, and cultured skin fibroblasts is severely deficient when measured on the synthetic substrate 4-MU-GLcNAc. However, their cultured skin fibroblasts synthesize and process both alpha and beta chains of HEX, and their lymphoid cells hydrolyze normally the natural ganglioside GM2. This mutation is, therefore, different from at least one of the beta-chain mutations found in previously published families with heat-labile HEX B.

Direct hyperbilirubinemia complicating ABO hemolytic disease of the newborn.

A retrospective study of the diagnostic implications of conjugated hyperbilirubinemia complicating ABO hemolytic disease of the newborn (HDN) was done by studying the records of 264 infants with ABO-HDN. Direct hyperbilirubinemia was found to complicate ABO-HDN in 3 per cent of the infants, all being full term. Eighty-seven per cent were female and familial occurrence was noted in half of the cases. Most of the infants presented with anemia on the first day of life. Our data suggest that this is a benign complication of ABO-HDN which clears within a month.

Syndrome of inappropriate antidiuretic hormone secretion in newborn infants with respiratory problems.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has not often been described in newborn infants. Of 61 infants with respiratory problems who were admitted to our neonatal intensive care unit over a six-month period from July 1978, three had SIADH, diagnosed on the basis of hyponatremia, weight gain and the excretion of highly concentrated urine. In one infant the onset of marked hyponatremia was very rapid and resulted in deep coma. The occurrence of this syndrome in 5% of infants under intensive care for neonatal respiratory problems makes it essential to monitor these infants closely for deviations in fluid and electrolyte balance.

Hereditary heat-labile hexosaminidase B: its implication for recognizing Tay-Sachs genotypes.

Two pairs of alleles, at the two loci of hexosaminidase (HEX), were found to segregate in an Arab inbred family: the normal and the mutant Tay-Sachs (TSD) alleles of HEX A, and the normal and a mutant allele of HEX B. Since the mutant HEX B is heat labile, no reliable identification of TSD genotypes can be obtained in its presence, as long as the proportions of HEX A and B are estimated by the routinely used heat-inactivation method. The genotypes may be correctly identified in such cases by separation of the two isoenzymes on ion-exchange chromatography, estimating their individual activities, and calculating the ratio between them. Of the nine genotype combinations possible with these two pairs of alleles, five have been identified in the reported family by this procedure.