[Late fate of children with urinary tract infections].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W Marget.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Using the enzyme-linked immunosorbent assay (ELISA), we studied the IgG and IgM antibody titers in various groups of pediatric patients (n = 81) infected with gram-negative organisms. Unlike the control group (n = 12), IgG antibodies were detected in only five (all under four months of age) of 19 children with sepsis. We assume that either the IgG antibodies are used up during the infection, or the lack of IgG antibodies results in a disposition to sepsis; the latter is more probable. Seventeen of 18 patients with urinary tract infections and proven renal involvement were IgM-positive. This indicates a permanent antigen stimulus, possibly in the form of a fixed antigen complex. Because of the heterogeneity of the groups studied, no overall statements can be made for the 93 children studied, some of whom were studied repeatedly. These children included 17 with tracheal colonization, 17 with recurrent urinary tract infections without proven renal changes and six with wound infections.
To determine whether sera containing high titers of lipid A antibody may be applicable at effective doses in treating patients with septicemia, a pharmacokinetic study was performed in seven patients aged 24 to 73 years with gram-negative septicemia and various underlying diseases, one of whom received a placebo, and in one patient without infection. In this study, we attempted to determine the effective dosage, the number of infusions and appropriate administration interval for the prevention and treatment of endotoxin shock. Blood samples from each patient were tested for lipid A antibodies before and at regular intervals after administration using an enzyme-linked immunosorbent assay (ELISA). Selected, pooled human immunoglobulin preparations containing high titers (expressed as exponents of 10) of IgG (titer = 3-4) and IgM (titer = 2-4) lipid A antibodies were administered first at a dosage of 8 ml/kg body weight. After administration, the mean lipid A antibody titer increased from 0.4 to 2.3 for IgG and from 2 to 2.4 for IgM. The initial increase was followed by a drop in titer within 24 h, which was perhaps due to antibody consumption. Following the second administration (24 h after the first) of only 4 ml/kg body weight, the mean IgG and IgM titers increased to 2.4 and 3.3, respectively, and dropped slower. A notable increase in circulating lipid A antibody titers was achieved, and four of six treated patients recovered from the sepsis. The two patients who died entered the study in a pre-terminal state. These studies encouraged us to initiate a randomized, double-blind controlled study.
Explore the source record for details and available documents.
Lipid A is the toxic component of endotoxin in gram-negative bacteria. Antibodies to lipid A are not usually found in healthy persons (or only at a low titer) without a corresponding history of infection. Even gram-negative septicemia is found to be accompanied by only low titers. A completely different situation is seen in patients with chronic or recurrent infections due to Enterobacteriaceae and other gram-negative bacteria. Here it is notable that the antibody titer varies with the type of disorder (e.g. cystitis and pyelonephritis). A severe wound infection, e.g. due to Pseudomonas aeruginosa, also leads to measurable lipid A antibody titers. Varying antibody titers can be observed in cystic fibrosis, Crohn's disease, and severe surgical infections. One can conclude that a significantly elevated antibody titer develops during an extensive tissue involvement of long duration and indeed is caused by tissue inhibition by endotoxin. Based on clinical experience, it can be assumed that lipid A antibodies present in the body have a protective effect in septic shock.
The protective effect of high-titer anti-lipid A hyperimmune globulin with respect to the course of the disease and the mortality rate was studied in patients with septicemia verified by positive blood cultures. Six patients were treated with anti-lipid A in an open study. Dramatic improvement in fever curves and clinical condition in some of the patients encouraged us to start a randomized double blind study. So far, 17 patients have entered the study, 16 of whom were evaluable. Immediately after a positive blood culture was found, patients received either high doses of anti-lipid A or placebo (saline solution) on two subsequent days. Before and after each infusion blood samples were taken in order to assess serum bactericidal activity and anti-lipid A titers. Because of the still small numbers of patients the results of both studies were summarized. In all patients treated with anti-lipid A clear-cut increases in anti-lipid A titers were shown. Patients with repeated gram-negative infections showed higher median anti-lipid A titers than patients without such a history. The patients treated with anti-lipid A immune globulin ran a significantly milder course than the placebo group. The severe signs of septic shock were reversed in seven of 15 patients on anti-lipid A compared to two of seven patients treated with placebo. In the anti-lipid A-treated group, three of 15 patients died, and in the placebo group two of seven. This difference is not statistically significant.
Explore the source record for details and available documents.
For a better understanding of the persistence of Borrelia burgdorferi sensu lato (s.l.) after antibiotic therapy the kinetics of killing B. burgdorferi s.l. under amoxicillin, doxycycline, cefotaxime, ceftriaxone, azithromycin and penicillin G were determined. The killing effect was investigated in MKP medium and human serum during a 72 h exposure to antibiotics. Twenty clinical isolates were used, including ten strains of Borrelia afzelii and ten strains of Borrelia garinii. The results show that the kinetics of killing borreliae differ from antibiotic to antibiotic. The killing rate of a given antibiotic is less dependent on the concentration of the antibiotic than on the reaction time. Furthermore, the data show that the strains of B. afzelii and B. garinii have a different reaction to antibiotics used in the treatment of Lyme borreliosis and that different reactions to given antibiotics also exist within one species. The B. garinii strains appear to be more sensitive to antibiotics used in therapy. Furthermore, the persistence of B. burgdorferi s.l. and clinical recurrences in patients despite seemingly adequate antibiotic treatment is described. The patients had clinical disease with or without diagnostic antibody titers to B. burgdorferi.
As clinical persistence of Borrelia burgdorferi in patients with active Lyme borreliosis occurs despite obviously adequate antibiotic therapy, in vitro investigations of morphological variants and atypical forms of B. burgdorferi were undertaken. In an attempt to learn more about the variation of B. burgdorferi and the role of atypical forms in Lyme borreliosis, borreliae isolated from antibiotically treated and untreated patients with the clinical diagnosis of definite and probable Lyme borreliosis and from patient specimens contaminated with bacteria were investigated. Furthermore, the degeneration of the isolates during exposure to penicillin G in vitro was analysed. Morphological analysis by darkfield microscopy and scanning electron microscopy revealed diverse alterations. Persisters isolated from a great number of patients (60-80%) after treatment with antibiotics had an atypical form. The morphological alterations in culture with penicillin G developed gradually and increased with duration of incubation. Pleomorphism, the presence of elongated forms and spherical structures, the inability of cells to replicate, the long period of adaptation to growth in MKP-medium and the mycoplasma-like colonies after growth in solid medium (PMR agar) suggest that B. burgdorferi produce spheroplast-L-form variants. With regard to the polyphasic course of Lyme borreliosis, these forms without cell walls can be a possible reason why Borrelia survive in the organism for a long time (probably with all beta-lactam antibiotics) [corrected] and the cell-wall-dependent antibody titers disappear and emerge after reversion.