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Biomedical subjects

U B Schaad

Publications and source records attributed to U B Schaad.

At least 91 records · Page 5Linked to original sources

Brain abscess in childhood--long-term experiences.

A retrospective evaluation was performed on 28 cases of paediatric brain abscess (male: female ratio 2.5:1; mean age 9.4 years; range 2.8-16 years) diagnosed between 1967 and 1987. In 46%, congenital cyanotic heart disease was identified as a predisposing factor, likewise sinusitis, otitis media or mastoiditis in 29% and immunodeficiency in 11%. Pathogenesis remained unclear in 14%. Initial symptoms and signs were predominantly nonspecific; loss of consciousness occurred in 32% of cases, neurological deficit and seizures each in 25%. Since the availability of CT, both diagnostic delay after hospital admission and mortality were substantially reduced: mean delay from 8.4 to 3.0 days, and mortality from 23% to 0%. Seventeen patients (61%) had follow up examinations 9.6 years (mean) after the acute illness (range 1-21 years). Neurological sequelae were diagnosed in 35% of cases, epilepsy in 29%, epileptic potentials during EEG in 12%, and CNS scars in 50%. Psychological testing revealed no statistically significant differences compared to normal populations. CNS scars, and epilepsy and/or epileptic potentials were more common after excision (7 patients) when compared to patients treated by aspiration and/or antibiotics alone (21 patients). It is concluded that excision of brain abscess should be avoided whenever possible. Therapy of choice consists of the administration of adequate antibiotics with or without CT-guided needle aspirations.

Adolescent↗

Use of quinolones in pediatrics.

Compared to nalidixic acid, the new quinolones possess an enlarged antimicrobial spectrum, greatly enhanced bactericidal activity, and substantial pharmacokinetic advantages. Because their activity against streptococci is limited the quinolones presently available will never be included in routine regimens for children. Moreover, adequate pharmacokinetic studies are still lacking in pediatrics, and potential drug toxicity warrants further long-term monitoring. Nevertheless, various studies strongly suggest that there is no quinolone-induced cartilage toxicity in humans, and the results of published clinical trials with fluoroquinolones in pediatric patients show promising efficacy and safety. From a review of the available data it is concluded that use of the quinolones in children should be limited to specific infections which are usually caused by Pseudomonas aeruginosa, Staphylococcus aureus or Staphylococcus epidermidis, and are complicated by underlying pathologic or special conditions such as cystic fibrosis or urologic abnormality. In each case, careful monitoring to determine efficacy, potential adverse effects including drug-drug interaction and toxicity, and any emergence of bacterial resistance is mandatory.

4-Quinolones↗

[HIV infection. Immunopathology and pathogenesis].

More recent knowledge on pathogenesis and immunopathology of HIV-infection permit more hope for progress in prevention and treatment. The important steps of viral replication and persistence are restated. The considerable magnitude of HIV plasma viremia during all disease stages implies relevant conclusions concerning diagnosis, therapy and virulence. Variable pathogenesis of HIV-infection is based on viral features, cofactors and immunopathological events.

Female↗

Clinical, radiologic and magnetic resonance monitoring for skeletal toxicity in pediatric patients with cystic fibrosis receiving a three-month course of ciprofloxacin.

Because of arthropathic toxicity observed in growing animals the quinolone antibiotics are not recommended for use in children. Recently, magnetic resonance imaging performed in juvenile animals was found to predict ciprofloxacin-induced cartilage damage at the knee joint. We conducted clinical, laboratory, radiologic and magnetic resonance imaging investigations in 13 prepubertal (age range, 6 to 13 years) and 5 postpubertal patients (age range, 14 to 24 years) with cystic fibrosis at the start and the end of a 3-month course of ciprofloxacin (30 mg/kg of body weight/day, administered orally in two equal doses) and at follow-up 4 to 6 months later. Our comprehensive monitoring gave no evidence for arthropathogenicity. Detailed physical skeletal function tests, height velocity values, laboratory studies of bone metabolism and conventional radiographs of both knees revealed no abnormalities. Moreover the serial magnetic resonance images of the left knee demonstrated lack of joint effusion, intact two-layer appearance of the cartilage and unaffected thickness of the articular cartilage measured at five anatomically different points. Our results together with the published data on quinolone use in pediatrics suggest that ciprofloxacin does not cause arthropathy in humans.

Adolescent↗

[Kawasaki syndrome].

Kawasaki syndrome was first described in 1967 in Japan. It is due to a generalized vasculitis of probably infectious etiology. Diagnosis is based exclusively on clinical criteria. Both morbidity and mortality are mainly determined by coronary artery involvement. The principal purpose of the present analysis of the 32 patients treated for Kawasaki syndrome at the University Children's Hospital in Berne (22 males = 69%, 11 females = 31%; mean age +/- SD = 2.7 +/- 2 years) was to describe the clinical and laboratory presentation and to evaluate high-risk factors and therapeutic efficacy with regard to course of the disease and cardiac involvement. Treatment has included aspirin and, since 1986, intravenous immunoglobulins (IVIG) as well. Routine electrocardiographic and echocardiographic checks detected 10 patients (31%) with cardiovascular complications, all of whom remained clinically asymptomatic: 9 with carditis (28%) and 3 with coronary artery aneurysms (CAA) (9%). The 3 patients with CAA were boys aged 18-25 months who presented an extremely long duration of fever (12-30 days) and markedly elevated ESR (100-128 mm/h). Since the therapeutic use of high-dose IVIG (9 patients), no CAA has been observed, and carditis in only 2 patients (22%). All patients are clinically cured. The carditis findings and 2 of the 3 CAA completely resolved; one patient has persistent CAA and myopathic cardiomegaly after more than 3 1/2 years. This study, together with the review of the literature, should enable the physician to diagnose and correctly manage the childhood disease Kawasaki syndrome.

Aspirin↗

A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children.

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Adolescent↗

Serotype-specific serum IgG antibodies to lipopolysaccharides of Pseudomonas aeruginosa in cystic fibrosis: correlation to disease, subclass distribution, and experimental protective capacity.

Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to LPS of nine PA-serotypes and to toxin A were performed with serum of 78 CF patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA-serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n = 46), these antibody titers were significantly (p less than 0.005) higher than in patients with intermittent PA colonization (n = 22). Mean serum antibody titers to LPS of PA IT-1, IT-2, Habs-3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA1. The IgG antibodies to LPS of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific PA serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with CF show adequate functional immune response to LPS of PA, and it is possible that vaccination against PA before colonization could induce protective immunity.

Adolescent↗

Incidence and diagnosis of rotavirus infection in neonates: results of two studies.

The present study investigates the incidence of human rotavirus excretion in neonates of two hospitals. From April 1, 1983 to March 31, 1984, rotaviruses were detected with Rotazyme in the feces of 57 (15%) of 383 neonates at the Department of Pediatrics, University of Berne, in a total in 71 (5.2%) of the 1369 stool samples tested. Of the 57 neonates with Rotazyme-positive stool samples, 53 (93%) were asymptomatic. The problems of the specificity of Rotazyme in neonatal feces and the possibility of rapid testing on neonatology wards are discussed. In a prospective study carried out in April 1986 at the "Schweizerische Pflegerinnenschule in Zurich", rotaviruses were detected with genome gel electrophoresis in the feces of 15 (63%) of 24 risk neonates in the premature baby ward and in 36 (46%) of 79 neonates from the infant nursery, in a total in 63 (34%) of the 188 stool samples tested. In this rotavirus outbreak all rotaviruses detected showed the same band pattern, and therefore had an identical electrophorotype. Symptoms and hospital hygiene aspects of this outbreak will be dealt with in subsequent papers.

Diarrhea↗

Antipseudomonal therapy in cystic fibrosis: aztreonam and amikacin versus ceftazidime and amikacin administered intravenously followed by oral ciprofloxacin.

In order to determine the optimal antipseudomonal therapy in patients with cystic fibrosis aztreonam plus amikacin was compared to ceftazidime plus amikacin, and these two-week hospital regimens were followed by oral ciprofloxacin given for four weeks. Fifty-six cases of acute pulmonary exacerbation of the disease in 42 patients associated with isolation of Pseudomonas aeruginosa from the sputum were randomly treated with either aztreonam or ceftazidime (300mg/kg/day i.v.; maximum daily dose 12g) in combination with amikacin (36mg/kg/day i.v.; maximum daily dose 1,500mg). Other aspects of the two-week treatment were constant. The two therapy groups were comparable in all respects. Both regimens were well tolerated and resulted in similar improvements in clinical, bacteriologic, radiologic and laboratory findings, and pulmonary function. Fifty patients could be reevaluated after subsequent outpatient therapy consisting of oral ciprofloxacin (30mg/kg/day; maximum daily dose 1,500mg) given for four weeks. During this period, the clinical and laboratory improvements persisted, and the rate of eradication of Pseudomonas aeruginosa from sputum decreased from 62% to 34%. Ciprofloxacin was well tolerated and there was no drug toxicity or serious adverse effect. In the 25 prepubertal patients there was neither subjective nor objective evidence of skeletal drug toxicity. In patients with cystic fibrosis, aztreonam or ceftazidime in combination with amikacin represents an effective and safe systemic anti-pseudomonal therapy. Subsequent oral ciprofloxacin therapy for four weeks prolongs the beneficial effects and is well tolerated.

Adolescent↗

Relation between tumor necrosis factor-alpha and granulocyte elastase-alpha 1-proteinase inhibitor complexes in the plasma of patients with cystic fibrosis.

Patients with cystic fibrosis suffer from a chronic, progressively destructive bronchitis characterized by colonization of the airways by Pseudomonas aeruginosa. Cell wall lipopolysaccharides from P. aeruginosa may stimulate secretion of cytokines such as tumor necrosis factor alpha (TNF alpha) by monocytes/macrophages. We found elevated levels of TNF alpha (150 +/- 60 pg/ml), interleukin-1 alpha (144 +/- 205 pg/ml), and interleukin-1 beta (62 +/- 100 pg/ml) in plasma from 25 patients with cystic fibrosis. In patients with less advanced disease, elevated plasma levels of TNF alpha correlated with high levels of complexes between neutrophil elastase and alpha 1-proteinase inhibitor, suggesting that TNF alpha may be a mediator of neutrophil degranulation. TNF alpha, by its chemotactic effect on neutrophils, may also contribute to the massive influx of neutrophils into and around the bronchial tree. Our findings raise the questions whether in patients with cystic fibrosis TNF alpha acts as cachectin and whether it mediates the anorexia that often results in weight loss.

Adolescent↗

Reversible ceftriaxone-associated biliary pseudolithiasis in children.

Serial abdominal ultrasonography was performed in 37 children being treated with ceftriaxone for serious infections. Biliary concrements developed in 16 patients, causing symptoms in 3, one of whom also had urolithiasis with renal colic and obstructive ureteropyelectasia. After cessation of ceftriaxone treatment, ultrasound abnormalities and symptoms gradually disappeared, with complete sonographic resolution after 2 to 63 days.

Adolescent↗

Solubilization of immune precipitates by complement in the absence of properdin or factor D.

Various experiments have demonstrated that immune precipitates (IPs) are not solubilized by complement in the absence of alternative pathway function. To determine whether the characteristics of the IPs were responsible for these observations, we studied the solubilization (Sol) of IPs formed by bovine serum albumin (BSA)-rabbit antiBSA and tetanus toxoid (TT)-human antiTT. Sera deficient in properdin solubilized a fraction of BSA-antiBSA precipitates, although only when the IPs were formed in antibody excess. The same sera solubilized TT-antiTT precipitates with some delay but almost as efficiently as normal serum. Factor D-depleted serum solubilized a fraction of TT-antiTT precipitates too, indicating that Sol may proceed through activation of the classical pathway only. Thus, the requirements for complement-mediated Sol depend on the characteristics of the IPs and do not necessarily include alternative pathway function.

Antibodies↗

Intravenous immune globulin in symptomatic paediatric human immunodeficiency virus infection.

Seven paediatric patients with symptomatic human immunodeficiency virus (HIV) infection were prospectively studied for 6-24 months after the start of intravenous immune globulin (IVIG) therapy. There was substantial clinical benefit during IVIG treatment with marked reduction of febrile and infectious episodes, normalization of physical and psychomotor development, and absence of mortality. The immunologic monitoring revealed some discrete objective improvements. The results of this study favourably compare to previous reports. It is concluded that IVIG should be standard therapy for symptomatic childhood HIV infection.

AIDS-Related Complex↗

Fibronectin-cleaving activity in bronchial secretions of patients with cystic fibrosis.

In cystic fibrosis, colonization of the airways with Pseudomonas aeruginosa follows colonization with Staphylococcus aureus and is related to accelerated deterioration of pulmonary function. Because P. aeruginosa adheres better to cell surfaces devoid of fibronectin, we searched for fibronectin-cleaving activity in bronchial secretions and saliva from 24 patients with cystic fibrosis who were followed up for 4.5 y and from two control groups. Proteolytic activity against 125I-labeled fibronectin was continuously present in cystic fibrosis bronchial secretions; significantly higher fibronectin-cleaving activity was found in older vs. younger patients, in patients with advanced disease stages determined by a five-stage scoring system, and in those colonized with P. aeruginosa. The fibronectin-cleaving activity was due to neutrophil elastase and cathepsin G. Cystic fibrosis bronchial secretions had proteolytic activity against surface fibronectin of airway mucosal cells. Thus fibronectin-cleaving activity of bronchial secretions rather than of saliva may favor P. aeruginosa colonization of the upper respiratory tract in individuals with cystic fibrosis.

Adolescent↗

Effects of antimicrobial agents used for therapy of CNS infections on dissociated brain cell cultures.

The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity (p less than 0.001 or less than 0.01) and to a lesser extent (p less than 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections.

Amikacin↗