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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 271 records · Page 15Linked to original sources
PubMed1999

Lower lipoteichoic and teichoic acid CSF concentrations during treatment of pneumococcal meningitis with non-bacteriolytic antibiotics than with ceftriaxone.

In the rabbit model of Streptococcus pneumoniae meningitis, treatment with rifabutin, quinupristin-dalfopristin, moxifloxacin and trovafloxacin led to smaller increases of the CSF concentrations of the pro-inflammatory cell wall components lipoteichoic and teichoic acids (LTA and TA) than did treatment with ceftriaxone. Low doses of moxifloxacin were associated with higher LTA and TA concentrations in CSF than were high doses.

Animals↗
PubMed1999

Dialectical behavior therapy for patients with borderline personality disorder and drug-dependence.

A randomized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy (DBT), an effective cognitive-behavioral treatment for suicidal individuals with borderline personality disorder (BPD), would also be effective for drug-dependent women with BPD when compared with treatment-as-usual (TAU) in the community. Subjects were randomly assigned to either DBT or TAU for a year of treatment. Subjects were assessed at 4, 8, and 12 months, and at a 16-month follow-up. Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow-up than did subjects assigned to TAU. DBT also maintained subjects in treatment better than did TAU, and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow-up than did those assigned to TAU. DBT has been shown to be more effective than treatment-as-usual in treating drug abuse in this study, providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems.

Adolescent↗
PubMed1999

A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.

Autosomal dominant hypercholesterolemia (ADH), one of the most frequent hereditary disorders, is characterized by an isolated elevation of LDL particles that leads to premature mortality from cardiovascular complications. It is generally assumed that mutations in the LDLR and APOB genes account for ADH. We identified one large French pedigree (HC2) and 12 additional white families with ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we named "FH3." A LOD score of 3.13 at a recombination fraction of 0 was obtained at markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at 1p34.1-p32. We tested four regional markers in another set of 12 ADH families. Positive LOD scores were obtained in three pedigrees, whereas linkage was excluded in the others. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32, outside the critical region, showing no identity with FH3. Our results show that ADH is genetically more heterogeneous than conventionally accepted.

Adult↗
PubMed1999

Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: phenotypic and genetic profiling of virulence traits and evidence for clonality.

The virulence profiles of most non-O157 Shiga toxin (Stx)-producing Escherichia coli (STEC) are unknown. STEC belonging to serogroups O26, O103, and O111 were characterized to determine clonality and to profile virulence traits. Isolates within STEC serogroups O26, O111, and O103 were >80% identical in their randomly amplified polymorphic DNA pattern, suggesting clonality in these serogroups. The serogroups were distantly related to each other and to E. coli O157:H7. stx restriction fragment length polymorphism differentiated some STEC with the same randomly amplified polymorphic DNA pattern. The hemolytic phenotype of STEC O103:H2 isolates resembled that of alpha- and not enterohemorrhagic E. coli hemolysin. Virulence gene (eae, E-hly, espP, etp, katP, stx) probing demonstrated serogroup-specific profiles. Pathogenic STEC O26, O103, and O111 belong to their own lineages and have unique profiles of virulence traits that are different from the virulence profile of E. coli O157:H7.

Bacterial Toxins↗
PubMed1999

Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis.

Compared with beta-lactam antibiotics, rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitro. Mice infected intracerebrally with S. pneumoniae were treated subcutaneously with 2-mg doses of rifampin or ceftriaxone (n=43 each) every 12 h for 3 days and then observed for another 3 days. Rifampin reduced overall mortality from 49% to 26% (P=.04). Kaplan-Meyer analysis revealed a substantial reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: P=.007). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampin-treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: <0.5 vs. 27.0 ng/mL, P=.02; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 206.0 ng/mL). Thus, the use of rifampin appears promising for reducing the release of proinflammatory bacterial components and decreasing early mortality in bacterial meningitis.

Animals↗
PubMed1999

spp42, identified as a classical suppressor of prp4-73, which encodes a kinase involved in pre-mRNA splicing in fission yeast, is a homologue of the splicing factor Prp8p.

We have identified two classical extragenic suppressors, spp41 and spp42, of the temperature sensitive (ts) allele prp4-73. The prp4(+) gene of Schizosaccharomyces pombe encodes a protein kinase. Mutations in both suppressor genes suppress the growth and the pre-mRNA splicing defect of prp4-73(ts) at the restrictive temperature (36 degrees ). spp41 and spp42 are synthetically lethal with each other in the presence of prp4-73(ts), indicating a functional relationship between spp41 and spp42. The suppressor genes were mapped on the left arm of chromosome I proximal to the his6 gene. Based on our mapping data we isolated spp42 by screening PCR fragments for functional complementation of the prp4-73(ts) mutant at the restrictive temperature. spp42 encodes a large protein (p275), which is the homologue of Prp8p. This protein has been shown in budding yeast and mammalian cells to be a bona fide pre-mRNA splicing factor. Taken together with other recent genetic and biochemical data, our results suggest that Prp4 kinase plays an important role in the formation of catalytic spliceosomes.

Fungal Proteins↗
PubMed1999

Quinupristin/dalfopristin attenuates the inflammatory response and reduces the concentration of neuron-specific enolase in the cerebrospinal fluid of rabbits with experimental Streptococcus pneumoniae meningitis.

The inflammatory response following initiation of antibiotic therapy and parameters of neuronal damage were compared during intravenous treatment with quinupristin/dalfopristin (100 mg/kg as either a short or a continuous infusion) and ceftriaxone (10 mg/kg/h) in a rabbit model of Streptococcus pneumoniae meningitis. With both modes of administration, quinupristin/dalfopristin was less bactericidal than ceftriaxone. However, the concentration of proinflammatory cell wall components (lipoteichoic acid (LTA) and teichoic acid (TA)) and the activity of tumour necrosis factor (TNF) in cerebrospinal fluid (CSF) were significantly lower in the two quinupristin/dalfopristin groups than in ceftriaxone-treated rabbits. The median LTA/TA concentrations (25th/75th percentiles) were as follows: (i) 14 h after infection: 133 (72/155) ng/mL for continuous infusion of quinupristin/dalfopristin and 193 (91/308) ng/mL for short duration infusion, compared with 455 (274/2042) ng/mL for ceftriaxone (P = 0.002 and 0.02 respectively); (ii) 17 h after infection: 116 (60/368) ng/mL for continuous infusion of quinupristin/dalfopristin and 117 (41/247) ng/mL for short duration infusion, compared with 694 (156/2173) ng/mL for ceftriaxone (P = 0.04 and 0.03 respectively). Fourteen hours after infection the median TNF activity (25th/75th percentiles) was 0.2 (0.1/1.9) U/mL for continuous infusion of quinupristin/dalfopristin and 0.1 (0.01/3.5) U/mL for short duration infusion, compared with 30 (4.6/180) U/mL for ceftriaxone (P = 0.02 for each comparison); 17 h after infection the TNF activity was 2.8 (0.2/11) U/mL (continuous infusion of quinupristin/dalfopristin) and 0.1 (0.04/6.1) U/mL (short duration infusion), compared with 48.6 (18/169) U/mL for ceftriaxone (P = 0.002 and 0.001). The concentration of neuron-specific enolase (NSE) 24 h after infection was significantly lower in animals treated with quinupristin/dalfopristin: 4.6 (3.3/5.7) microg/L (continuous infusion) and 3.6 (2.9/4.7) microg/L (short duration infusion) than in those treated with ceftriaxone (17.7 (8.8/78.2) microg/L) (P = 0.03 and 0.009 respectively). In conclusion, antibiotic treatment with quinupristin/dalfopristin attenuated the inflammatory response within the subarachnoid space after initiation of antibiotic therapy. The concentration of NSE in the CSF, taken as a measure of neuronal damage, was lower in quinupristin/dalfopristin-treated rabbits than in ceftriaxone-treated rabbits.

Animals↗
PubMed1999

Efficacy of silver-coating central venous catheters in reducing bacterial colonization.

OBJECTIVE: To compare silver-coated and uncoated central venous catheters regarding bacterial colonization. To assess the relative contribution of catheter hub and skin colonization to catheter tip colonization. DESIGN: Prospective, randomized clinical trial. SETTING: Intensive care unit in a university hospital. PATIENTS: Patients after cardiac surgery who required a central venous double-lumen catheter (DLC). INTERVENTIONS: Sixty-seven adult patients were prospectively randomized to receive either a silver-coated (S group, n = 34) or an uncoated control (C group, n = 33) DLC. Blood cultures were drawn at catheter removal, and removed catheters were analyzed with quantitative cultures. Typing of microorganisms included DNA fingerprinting. MEASUREMENTS AND MAIN RESULTS: Catheters were removed if no longer necessary and aseptically divided into three segments: segment A, the catheter tip; segment B, an intermediate section; and segment C, the subcutaneous portion. Bacterial catheter colonization was quantitatively measured using sonication to detach adherent bacteria from the catheter segments in the broth and subsequent culture of an aliquot. Selected isolates of coagulase-negative staphylococci and other bacteria from catheter segments were examined by means of pulsed-field gel electrophoresis (PFGE) after macrorestriction digestion of bacterial DNA to study colonization pathogenesis. Quantitatively lower bacterial colonization could be demonstrated on the silver-coated catheters (200 +/- 550 colony forming units [CFUs]/cm catheter segment; mean +/- SD). The difference in the control catheters (1120 +/- 5350 CFUs/cm catheter segment; mean +/- SD) was not, however, significant (p = .25). The frequency of colonization of at least one catheter segment was 52.9% for the silver-coated catheters and 57.6% for the control catheters (p= .44), without any significant differences in the colonization of corresponding catheter segments. The rate of significant catheter colonization (i.e., > or = 10(3) CFUs/cm catheter by quantitative catheter culture or > or = 10(3) CFUs/mL by luminal flush) was nine in the silver group and seven in the control group, a difference that failed to reach significance (p = .41). Two patients in both groups developed catheter-related bacteremia. Pattern analysis after PFGE demonstrated that about 70% of the isolates found on the catheter tip were identical with those on the skin at the insertion site, whereas about 75% were identical with those recovered from the hub. In 29% of colonized catheters, identical bacteria were found on the hub and the skin at the insertion site. CONCLUSIONS: Silver-coating of DLCs did not significantly reduce bacterial catheter colonization compared with the control catheters. PFGE analysis of coagulase-negative staphylococci and other bacteria demonstrated various pathogenic routes of catheter-related colonization, whereby the microorganisms of the skin flora around the insertion site must be regarded as the main source of catheter-related infections.

Adult↗
PubMed1999

Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A- and immunoglobulin M-enriched preparation in anergic patients undergoing cardiac surgery.

OBJECTIVE: To evaluate the efficacy of a commercial immunoglobulin (Ig) A- and IgM-enriched immunoglobulin preparation containing high antibody titers against various human pathogens in the prevention of postoperative infections in anergic patients undergoing cardiac surgery. DESIGN: A single-center, prospective, double-blind, randomized study comparing the effect of a polyvalent intravenous human immunoglobulin (IVIG) preparation vs. placebo. LOCATION OF THE STUDY: Institute of Anesthesiology and Department of Thoracic and Cardiovascular Surgery, University Hospital, Wurzburg, Germany. PATIENTS: A total of 515 patients awaiting elective open-heart surgery with the aid of cardiopulmonary bypass were tested for their in vivo immune response to intradermally administered recall antigens. Forty patients who were preoperatively shown to be anergic in this skin test, and therefore at high risk of developing serious postoperative infections, were selected from this group. Twenty patients with normal immune responses, and thus having a normal risk of infection, were randomly selected from the same patient group to serve as an immunoreactive control group. INTERVENTIONS: After obtaining approval from the local institutional review board and informed consent from patients, the 40 anergic patients were randomized and assigned either to the IVIG group (n = 19), to receive a commercially available human IgA- and IgM-enriched immunoglobulin preparation (dose, 20 g), or to the placebo group (n = 21), to receive physiologic saline. These treatments were started 4 hrs after surgery as a 400-mL continuous infusion over a period of 53 hrs. Patients were observed for the development of postoperative infection for the next 2 wks. Group comparisons were made using repeated-measures analysis of variance and Fisher's exact test. A p value < .05 was considered statistically significant MEASUREMENTS AND MAIN RESULTS: Postoperative infections were detected in nine of 21 patients (43%) in the placebo group but in only one of 19 patients (5%) in the IVIG-treated group (p = .007; Fisher's exact test). Three of the 20 patients (15%) with normal immune response who received standard postoperative treatment developed postoperative infections. CONCLUSIONS: A commercially available IgA- and IgM-enriched intravenous immunoglobulin preparation administered immediately after cardiac surgery significantly reduced the incidence of postoperative infections in preoperatively anergic patients.

Adult↗
PubMed1999

Circulating intercellular adhesion molecule-1 as an early predictor of hepatic failure in patients with septic shock.

OBJECTIVE: To investigate whether endotoxin, interleukin-6, and circulating adhesion molecules, measured sequentially in blood, can predict mortality and organ dysfunction in sepsis. DESIGN: Inception cohort study with follow-up for 28 days. SETTING: Surgical intensive care unit at a university hospital. PATIENTS: A total of 14 consecutive patients were enrolled in the study within the first 24 hrs after onset of septic shock. Seven healthy subjects were studied as controls. INTERVENTIONS: Patients were analyzed for mortality and development of organ dysfunction. MEASUREMENTS AND MAIN RESULTS: At the end of the 28-day follow-up period, seven of the patients were still alive (survivors) but the other seven (nonsurvivors) had died. At the time of enrollment in the study (day 0), the Acute Physiology and Chronic Health Evaluation II score was 28.4 in survivors (n = 7) and 28.7 in nonsurvivors (n = 7). In contrast, circulating intercellular adhesion molecule-1 (ICAM-1) was significantly higher in nonsurvivors than in survivors. Circulating ICAM-1 predicted mortality in patients with septic shock with a sensitivity and a specificity of 71.4% each. Endotoxin, interleukin-6, circulating L-selectin, P-selectin, E-selectin, and platelet endothelial cell adhesion molecule-1, however, did not distinguish between survivors and nonsurvivors. In addition, circulating ICAM-1 at day 0 showed a significant correlation with the highest serum bilirubin observed during the entire study period (r2 = 0.963). CONCLUSIONS: Because only circulating ICAM-1 was higher in nonsurvivors than in survivors at day 0, circulating ICAM-1 may serve as an early prognostic marker for outcome in septic shock. In addition, measurement of circulating ICAM-1 facilitates identification of those patients with the highest risk of developing liver dysfunction.

APACHE↗
PubMed1999

Molecular characterisation of verocytotoxin-producing Escherichia coli of serogroup O111 from different countries.

A collection of epidemiologically unrelated verocytotoxin (VT)-producing Escherichia coli (VTEC) strains of serogroup O111 isolated from human patients and cattle with diarrhoeal disease in five different countries were characterised by determination of their VT genotypes, the presence of other virulence factors such as the intimin-coding eae gene and the enterohaemorrhagic E. coli (EHEC) plasmid, and their antibiotic susceptibility patterns. The genetic relatedness among isolates was evaluated by genomic DNA fingerprinting techniques such as restriction fragment length polymorphism analysis of ribosomal RNA genes (ribotyping) and pulsed-field gel electrophoresis. The results indicated that the VTEC O111 examined belong to two distinct clonal lineages. The first group was constituted mainly of non-motile, eae-positive, EHEC plasmid-positive isolates from both man and cattle. The second lineage was represented by an O111:H2 epidemic strain, isolated during an outbreak of haemolytic uraemic syndrome in France and exhibiting an unusual combination of virulence factors: VT production and aggregative adhesion to HEp-2 cells associated with an enteroaggregative E. coli (EAEC) plasmid.

Adhesins, Bacterial↗
PubMed1999

Network of characterizing functions for stationary populations.

A variety of open systems in nature and society exist under dynamic equilibrium, maintained by statistical counterbalance between the entering and leaving of individuals and the stationarity of the exchange processes. A network of functions characterizing the dynamics of such a stationary population is established and discussed, which allows the mutual transference of system properties without the need of any explicit information about the microdynamic processes. In order to illustrate the potential benefit of these interdependence relations, examples taken from diverse branches of research (adsorption and reaction kinetics, demographic analysis, and coronary blood flow diagnosis) are given.

Journal Article↗
PubMed1999

Transduction of enteric Escherichia coli isolates with a derivative of Shiga toxin 2-encoding bacteriophage phi3538 isolated from Escherichia coli O157:H7.

We investigated the ability of a detoxified derivative of a Shiga toxin 2 (Stx2)-encoding bacteriophage to infect and lysogenize enteric Escherichia coli strains and to develop infectious progeny from such lysogenized strains. The stx(2) gene of the patient E. coli O157:H7 isolate 3538/95 was replaced by the chloramphenicol acetyltransferase (cat) gene from plasmid pACYC184. Phage phi3538(Deltastx(2)::cat) was isolated after induction of E. coli O157:H7 strain 3538/95 with mitomycin. A variety of strains of enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), Stx-producing E. coli (STEC), enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), and E. coli from the physiological stool microflora were infected with phi3538(Deltastx(2)::cat), and plaque formation and lysogenic conversion of wild-type E. coli strains were investigated. With the exception of one EIEC strain, none of the E. coli strains supported the formation of plaques when used as indicators for phi3538(Deltastx(2)::cat). However, 2 of 11 EPEC, 11 of 25 STEC, 2 of 7 EAEC, 1 of 3 EIEC, and 1 of 6 E. coli isolates from the stool microflora of healthy individuals integrated the phage in their chromosomes and expressed resistance to chloramphenicol. Following induction with mitomycin, these lysogenic strains released infectious particles of phi3538(Deltastx(2)::cat) that formed plaques on a lawn of E. coli laboratory strain C600. The results of our study demonstrate that phi3538(Deltastx(2)::cat) was able to infect and lysogenize particular enteric strains of pathogenic and nonpathogenic E. coli and that the lysogens produced infectious phage progeny. Stx-encoding bacteriophages are able to spread stx genes among enteric E. coli strains.

Bacterial Toxins↗
PubMed1999

A genomic island, termed high-pathogenicity island, is present in certain non-O157 Shiga toxin-producing Escherichia coli clonal lineages.

Shiga toxin-producing Escherichia coli (STEC) strains cause a wide spectrum of diseases in humans. In this study, we tested 206 STEC strains isolated from patients for potential virulence genes including stx, eae, and enterohemorrhagic E. coli hly. In addition, all strains were examined for the presence of another genetic element, the high-pathogenicity island (HPI). The HPI was first described in pathogenic Yersinia species and encodes the pesticin receptor FyuA and the siderophore yersiniabactin. The HPI was found in the genome of distinct clonal lineages of STEC, including all 31 eae-positive O26:H11/H(-) strains and 7 of 12 eae-negative O128:H2/H(-) strains. In total, the HPI was found in 56 (27.2%) of 206 STEC strains. However, it was absent from the genome of all 37 O157:H7/H(-), 14 O111:H(-), 13 O103:H2, and 13 O145:H(-) STEC isolates, all of which were positive for eae. Polypeptides encoded by the fyuA gene located on the HPI could be detected by using immunoblot analysis in most of the HPI-positive STEC strains, suggesting the presence of a functional yersiniabactin system. The HPI in STEC was located next to the tRNA gene asnT. In contrast to the HPI of other pathogenic enterobacteria, the HPI of O26 STEC strains shows a deletion at its left junction, leading to a truncated integrase gene int. We conclude from this study that the Yersinia HPI is disseminated among certain clonal subgroups of STEC strains. The hypothesis that the HPI in STEC contributes to the fitness of the strains in certain ecological niches rather than to their pathogenic potential is discussed.

Amino Acid Sequence↗
PubMed1999

Escherichia coli O157:H7 and O157:H(-) strains that do not produce Shiga toxin: phenotypic and genetic characterization of isolates associated with diarrhea and hemolytic-uremic syndrome.

We have isolated one sorbitol-nonfermenting (SNF) Escherichia coli O157:H7 isolate and five sorbitol-fermenting (SF) E. coli O157:H(-) isolates that do not contain Shiga toxin (Stx) genes (stx). Isolates originated from patients with diarrhea (n = 4) and hemolytic-uremic syndrome (HUS) (n = 2). All isolates harbored a chromosomal eae gene encoding gamma-intimin as well as the plasmid genes E-hly and etp. The E. coli O157:H7 isolate was katP and espP positive. Respective sera obtained from the patient with HUS contained antibodies to the O157 lipopolysaccharide antigen. The stx-negative E. coli O157:H7 isolate is genetically related to stx-positive SNF E. coli O157:H7. All stx-negative SF E. coli O157:H(-) isolates belong to the same genetic cluster and are closely related to stx-positive SF E. coli O157:H(-) isolates. Our data indicate that stx-negative E. coli O157:H7/H(-) variants may occur at a low frequency and cannot be recognized by diagnostic methods that target Stx.

Antibodies, Bacterial↗
PubMed1999

Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2.

Glucagon-like peptide-1-(7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis. Recent experimental evidence in animals and healthy subjects suggests that GLP-1 has a role in controlling appetite and energy intake in humans. We have therefore examined in a double-blind, placebo-controlled, crossover study in 12 patients with diabetes type 2 the effect of intravenously infused GLP-1 on appetite sensations and energy intake. On 2 days, either saline or GLP-1 (1.5 pmol. kg-1. min-1) was given throughout the experiment. Visual analog scales were used to assess appetite sensations; furthermore, food and fluid intake of a test meal were recorded, and blood was sampled for analysis of plasma glucose and hormone levels. GLP-1 infusion enhanced satiety and fullness compared with placebo (P = 0.028 for fullness and P = 0.026 for hunger feelings). Energy intake was reduced by 27% by GLP-1 (P = 0.034) compared with saline. The results demonstrate a marked effect of GLP-1 on appetite by showing enhanced satiety and reduced energy intake in patients with diabetes type 2.

Appetite↗