Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.

Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.

[Effect of nitrogen oxides and suspended dust in the air on the incidence of inpatient treatment of children with stenosing laryngotracheitis (pseudocroup). Results of an 8-year epidemiologic retrospective study based on inpatient case figures and area-related data of air measurements in the Bochum city district]. / Untersuchungen zum Einfluss von Stickoxid- und Schwebstaubgehalt der Luft auf die Häufigkeit von stationär behandelten Kindern mit stenosierender Laryngotracheitis (Pseudokrupp). Ergebnisse einer 8jährigen epidemiologischen Retrospektivstudie basierend auf stationären Fallzahlen und ortsbezogenen Luftmessdaten im Stadtgebiet Bochum.

Results of a recently published study over a test period of 18 years showed no relationship between croup incidence of hospitalized children and SO2 levels measured in the city of Bochum. In the following study 642 hospitalized children with stenosing laryngotracheitis were examined for a possible time-dependent relationship between croup incidence and NO2, NO- and dust immission levels measured in the city of Bochum (approx. 1000 000 readings). Evaluation of a 6-year period yielded a decrease of croup patients for the lower NO2 concentration range and a statistical increase of croup cases during days with higher NO2 concentrations. However no cause-effect relationship between both variables can be established because other determinants like infections, temperature, weather change influences, in door pollution etc., could not be excluded. Evaluation of NO levels over 3 years and dust levels over a test period of 1 year showed no statistical relationship with corresponding croup incidence.

[Stenosing laryngotracheitis (pseudocroup) and sulfur dioxide content of the air. Results of an 18-year retrospective long-term study of possible spatial and temporal relations]. / Stenosierende Laryngotracheitis (Pseudokrupp) und Schwefeldioxidgehalt der Luft. Ergebnisse einer 18jährigen retrospektiven Langzeitstudie über mögliche räumliche und zeitliche Zusammenhänge.

Based on the immission levels measured in the city of Bochum (approx. 20,000 readings), 1200 hospitalized children with pseudocroup were examined for a possible relationship between croup incidence and sulphur dioxide levels. Evaluation according to geographic location showed no statistically significant correlation between croup incidence and SO2 levels over a test period of 13 years. Only for 3 of 13 years did Spearman's rank correlation coefficient show a weakly significant positive correlation (P less than 0.05). In one test year, however, there was a statistically significant negative correlation (P less than 0.025). Evaluation of the 16-year study in terms of time-dependent relationships yielded no significant deviation of pseudocroup incidence from the expected mean value for the individual SO2 concentration ranges. Over the period of this study, there was therefore no cause-effect relationship between sulphur dioxide levels and pseudocroup incidence.

[Apparent central facial paralysis in Lyme borreliosis]. / Scheinbar zentrale Fazialisparese bei Lyme-Borreliose.

In childhood Lyme-Borreliosis often presents as facial palsy. This progredient infectious disease is to be treated by intravenous penicillin therapy in order to avoid future complications. In three out of four own observations facial palsy raised suspicion towards central origin. By performance of the orbicularis oculi reflex in all four cases peripheral damage of the facial nerve could be demonstrated. This simple electromyographic method seems to be a valuable tool in the differentiation of central and peripheral facial nerve palsy in childhood, preserving the affected children from painful electrodiagnostic procedure or useless search for supranuclear lesions.

[Anorexia nervosa in boys--a case report]. / Anorexia nervosa bei Knaben--ein Fallbericht.

BASIC REMARKS: In contrast to female adolescents, anorexia nervosa is rarely seen in male adolescents. In consequence, more comprehensive investigations are often carried out in the latter in a search of organic disease. CASE: A boy of thirteen-and-a-half years was referred for investigation of anorexia, loss of weight, constipation, loss of concentration and depression. Physical examination revealed bradycardia, low blood pressure, hypothermia and various endocrinological disturbances: reduced somatomedin C, tri-iodine thyronine and subnormal thyroxine levels, and delayed TSH peaking after TRH stimulation. Examination of peripheral blood revealed leukopenia with underlying hyperplastic bone marrow. A CT scan revealed widening of the ventricles of the brain, and echocardiography a mitral valve prolapse. CONCLUSIONS: Anorexia nervosa is accompanied by numerous pathological findings which, however, when weight is regained, return to normal without the need for further treatment. Before instituting invasive diagnostic measures in boys or male adolescents, consideration should be given to anorexia nervosa, and a psychiatric consultation sought.

Epidemiology of invasive Haemophilus influenzae disease in a German city.

This study was done to analyze the epidemiology of invasive Haemophilus influenzae disease in Bochum city area. Forty-eight children with invasive Haemophilus influenzae infections were treated at the University Children's Hospital in Bochum during the study period from January 1971 to June 1992. Clinical manifestations included meningitis (n = 34), epiglottitis (n = 8), pneumonia (n = 2), bacteremia (n = 2), cellulitis (n = 1) and osteomyelitis (n = 1). The overall yearly incidence rate for all invasive Haemophilus influenzae infections was 13 per 100,000 children younger than five years of age, with a marked increase in the last six years. Haemophilus influenzae meningitis showed no significant change during the study period with an overall yearly incidence of 9 per 100,000 children younger than five years. Twenty-eight cases (58%) of all invasive Haemophilus influenzae infections occurred in patients under two years of age and five cases (10%) were younger than six months. Invasive Haemophilus influenzae disease showed no seasonal prevalence. All isolates were susceptible to ampicillin. No deaths occurred, but severe bilateral deafness resulted in one patient with meningitis. Prospective epidemiologic studies are needed to estimate clinical efficacy of the Haemophilus influenzae type b immunization program in Germany.

Frequency of infections associated with implanted systems vs cuffed, tunneled Silastic venous catheters in patients with acute leukemia.

A total of 75 central venous catheters were used for prolonged chemotherapy in 39 children with acute lymphocytic leukemia and 21 patients with acute myelocytic leukemia. Infection rates were 2.2 per 100 catheter days with the use of cuffed, tunneled, single-lumen Silastic catheters, 2.0 per 1000 catheter days with cuffed, tunneled, double-lumen Silastic catheters, and 0.5 per 1000 catheter days with the use of implanted venous access systems. Eighty-one percent of catheter sepsis episodes were successfully treated without removal of the catheter. All tunnel infections required withdrawal of the catheter for cure. The microorganisms were gram-positive bacteria in 15%, gram-negative bacteria in 7%, and fungi in 4%. Coagulase-negative staphylococci and Pseudomonas aeruginosa were the most commonly isolated organisms. Three of six fatal sepsis episodes were caused by disseminated fungal infections. We conclude that the use of intracorporeal venous catheter systems in patients with acute lymphocytic leukemia is associated with a lower infection rate than that with cuffed, tunneled Silastic single- or double-lumen catheters and that most septicemias can be cured with antimicrobial therapy without removal of the catheter.

Ring chromosome 22: a case report.

A three year old girl with ring chromosome 22 is described. The clinical findings include epicanthus, flat nasal bridge, hypertelorism, long eye-lashes, lymphoedema, hypoplastic toe nails, hydrocephalus and muscular hypotonia. Speech and language development is delayed. At three years the child begins to walk.

[Pigeon breeder's disease in childhood]. / Die Taubenzüchterlunge im Kindesalter.

Pigeon breeder's disease is a common form of hypersensitivity pneumonitis, which is rarely diagnosed in children. We report a seven year old boy, who developed cough, easy fatigue, anorexia and weight loss over a period of two months after having contact with pigeons. The findings on physical examination were tachypnoea and reduced thoracic movements. Chest radiograph showed widespread fine nodular shadowing in both lung fields. Pulmonary function tests demonstrated a restrictive defect and an impaired diffusion. Lymphocytes were highly increased in bronchoalveolar lavage (BAL) fluid. Precipitating antibodies against pigeon excreta was found in the serum. Environmental control of pigeon protein and a course of systemic corticosteroids over 4 months resulted in clinical and lung function improvement. However clinical recovery stopped over several months after discontinuation of steroid therapy. Therefore steroid therapy was reinstalled and continued until complete clinical recovery and pulmonary function occurred, that was 20 months after onset of the disease. Essential for the patient was to avoid further contact with birds. However a prolonged steroid therapy was necessary to achieve complete resolution. Lung function tests were useful for follow up and decisions on further treatment.

[Effect of various weather parameters on the incidence of inpatient treated children with stenosing laryngotracheitis (pseudocroup)]. / Einfluss verschiedener Wetterparameter auf die Häufigkeit von stationär behandelten Kindern mit stenosierender Laryngotracheitis (Pseudokrupp).

A total of 1470 hospitalized children with croup in the cities of Bochum and Herne were examined over a period of 19 years, with the aim of checking whether there was any relationship between croup incidence and changes in different weather parameters such as temperature, air pressure, absolute and relative air humidity, and wind speed. The incidence of croup was seasonal, being higher in the months of January, February, and March and from September to December. Statistical evaluation by discriminant analysis, t-test and chi 2-test showed a significant correlation (alpha greater than or equal to 0.95) between croup incidence and individual weather parameters in some months. The results seem to indicate a higher frequency of croup after decreases in temperature and influx of dry air masses (decreases in absolute humidity). In some months an increased incidence of hospitalized children with croup was observed after decreases in air pressure and during weather with extremely high (w greater than 4.5) or low (w less than 1.5) wind speed. In summary, no clear and consistent relationship between incidence of croup and particular weather parameters could be found.

Urinary excretion of leukotriene E4 and eosinophil protein X in children with atopic asthma.

Measurement of leukotriene E4 (LTE4) in urine is a noninvasive method for assessing changes in the rate of total body cysteinyl leukotriene production. Eosinophil protein X (EPX) has been used to assess eosinophil activity and monitor inflammation in bronchial asthma. The aim of the study was to look for differences in urinary LTE4 and EPX concentrations between children with stable atopic asthma and healthy controls and to compare asthmatic children with different disease severity. In addition the relationship was evaluated between urinary LTE4 and EPX levels and lung function. LTE4 was also measured (enzyme immunoassay) together with EPX (radioimmunoassay) in urine and lung function tests were carried out in children with mild asthma (steroid-naive) (n=49), moderate to severe asthma (using inhaled steroids) (n=31) and healthy control subjects (n=28). Urinary leukotriene E4 (LTE4) was significantly higher in children with asthma than in controls (median [25-75 percentile] 238.5 (126.5-375.7) SD 191.8 versus 189 (51-253.2) SD 131.7 pg.mg(-1) creatinine; p=0.021). Urinary EPX was also significantly increased in asthmatic children compared with controls (85.5 [64-131.5] SD 76.2 versus 48.5 [43.2-90] 112.1 microg x mmol(-1) creatinine; p=0.006). There were no differences in urinary LTE4 and EPX between the group of mild and the group of moderate to severe asthmatic children. There were significant associations between the urinary LTE4 and intrathoracic gas volume (ITGV), residual volume (RV), forced expiratory volume in one second (FEV1), forced expiratory capacity (FVC) and maximum expiratory flow rate at 25% of vital capacity (MEF25). Urinary EPX was only correlated with maximum expiratory flow rate at 75% of vital capacity (MEF75). Thus measurement of urinary LTE4 may predict the degree of airflow obstruction in asthmatic children. Urinary LTE4 and EPX are useful markers of airway inflammation and can be helpful in guiding asthma management. There was no correlation between LTE4 and EPX levels.

Dexamethasone attenuation of cytokine-mediated articular cartilage degradation in experimental lapine Haemophilus arthritis.

The role of cytokines in the regulation of articular inflammation and cartilage degradation was evaluated in the rabbit model of Haemophilus influenzae type b arthritis. At 6 and 12 h after intraarticular infection, treatment with IB4 monoclonal antibody to the CD18 leukocyte receptor alone or in combination with dexamethasone resulted in significant reduction of synovial fluid (SF) neutrophil concentration. Treatment with dexamethasone alone was associated with lower SF concentrations of interleukin-1 (IL-1), tumor necrosis factor-alpha, and stromelysin than in other groups. At 24 h after infection, increased cartilage degradation was detected in untreated controls and in animals treated with IB4 alone or in combination with dexamethasone compared with those treated with dexamethasone alone. Multiple regression analyses indicated SF concentration of IL-1 and stromelysin as the significant predictors of cartilage degradation. These data suggest that IL-1 mediates cartilage degradation by regulation of metalloproteinases, such as stromelysin, during acute experimental bacterial arthritis.

Effects of antifungal therapy on inflammation, sterilization, and histology in experimental Candida albicans meningitis.

To assess the effects of antifungal therapy on the course of Candida albicans central nervous system infection and inflammation, we inoculated intracisternally 10(5) CFU of C. albicans into rabbits. Fluconazole (10 mg/kg of body weight) or amphotericin B (1 mg/kg) was infused intravenously daily for 14 days. Treatment was initiated 24 h or 5 days after infection. Cerebrospinal fluid (CSF) was repeatedly obtained to culture the organisms, assess the level of inflammation, and measure drug concentrations. Brain tissue was obtained at the end of therapy for culture, drug concentration determinations, and histopathology. The median number of days of treatment required to sterilize CSF cultures was 4 days for fluconazole therapy and 1 day for amphotericin B therapy (P = 0.037). There was a significant reduction in tumor necrosis factor alpha and leukocyte concentrations in the CSF of animals treated early versus those in untreated control animals (P < 0.05 and P < 0.001, respectively; analysis of variance). Compared with treated animals, a higher proportion of cultured CSF samples from untreated animals were positive for Candida (P < 0.001). A cultured brain sample from 1 of the 12 animals treated early with amphotericin B was positive for C. albicans (P < 0.01 versus controls); cultures of brain samples from 3 of 12 animals treated early with fluconazole were positive, whereas cultures of brain samples from 10 of 12 controls were positive (P < 0.05). The mean density of C. albicans was lower in the single culture-positive amphotericin B recipient (1 x 10(1) CFU/g of brain tissue) than in those treated with fluconazole (1 x 10(3) CFU/g) and in controls (8 x 10(4) CFU/g). In animals treated late, the density of C. albicans in the brain in relation to the number of days of therapy was significantly lower in amphotericin B recipients than in those treated with fluconazole (P < 0.01) and untreated controls (P < 0.01; analysis of covariance). By histopathology, a larger proportion of untreated animals compared with those treated early demonstrated features of severe infection such as perivasculitis, ventriculitis, and evidence of fungal organisms. Compared with amphotericin B-treated rabbits, those given fluconazole had a trend toward more severe pathologic lesions. Reduced susceptibility to both fluconazole and amphotericin B was observed in the C. albicans organisms isolated from the brain of one fluconazole-treated animal. These data suggest that amphotericin B is the preferred treatment for C. albicans infections of the central nervous system.