Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 379 records · Page 21Linked to original sources

PubMed1997

Homologous recombination in the fission yeast Schizosaccharomyces pombe: different requirements for the rhp51+, rhp54+ and rad22+ genes.

The Schizosaccharomyces pombe rhp51+, rad22+ and rhp54+ genes are homologous to RAD51, RAD52 and RAD54 respectively, which are indispensable in the recombinational repair of double-strand breaks (DSBs) in Saccharomyces cerevisiae. The rhp51Delta and rhp54Delta strains are extremely sensitive to ionizing radiation; the rad22Delta mutant turned out to be much less sensitive. Homologous recombination in these mutants was studied by targeted integration at the leu1-32 locus. These experiments revealed that rhp51Delta and rhp54Delta are equally impaired in the integration of plasmid molecules (15-fold reduction), while integration in the rad22Delta mutant is only reduced by a factor of two. Blot-analysis demonstrated that the majority of the leu+ transformants of the wild-type and rad22Delta strains have integrated one or more copies of the vector. Gene conversion events were observed in less than 10% of the transformants. Interestingly, the relative contribution of gene conversion events is much higher in a rhp51Delta and a rhp54Delta background. Meiotic recombination is hardly affected in the rad22Delta mutant. The rhp51Delta and rhp54Delta strains also show minor deficiencies in this type of recombination. The viability of spores is 46% in the rad22Delta strain and 27% in the rhp54Delta strain, as compared with wild-type cells. However, in the rhp51Delta mutant the spore viability is only 1.7%, suggesting an essential role for Rhp51 in meiosis. The function of Rhp51 and Rhp54 in damage repair and recombination resembles the role of Rad51 and Rad54 in S. cerevisiae. Compared with Rad52 from S. cerevisiae, Rad22 has a much less prominent role in the recombinational repair pathway in S. pombe.

DNA Helicases↗

PubMed1997

Molecular characterization of a novel fission yeast gene spUAP2 that interacts with the splicing factor spU2AF59.

A protein essential for pre-mRNA splicing, the U2 auxiliary factor (U2AF), is composed of a large and small subunit. Previously we cloned and characterized both subunits, spU2AF59 and spU2AF23, from fission yeast. We now report a novel U2AF-associated-protein, spUAP2, which interacts with both subunits. SpUAP2 contains a classical and a degenerate RNA recognition motif (RRM), both of which are required for interaction with spU2AF59. Interaction also requires the arginine/serine-rich region and the first RRM of spU2AF59. A null allele of the gene for spUAP2 is lethal.

Amino Acid Sequence↗

PubMed1997

[Adherence of staphylococci of different hydrophobicity. Study of various intraocular lenses].

BACKGROUND: A major goal in research on intraocular lenses (IOL) is the development of new polymers and modifications to reduce foreign-body reactions after implantation. This effect may be achieved by a reduction in the surface hydrophobicity of the polymers. To illustrate the influence of surface modifications on bacterial adhesiveness, the most often isolated organism in "low-grade" postoperative endophthalmitis, Staphylococcus epidermidis, was used. MATERIALS AND METHODS: For this reason three strains of this species, the type strain ATCC 14990 and two clinical isolates (8687, 6579 I) with different hydrophobic surface properties were studied. IOL, used in the experiments were either made of PMMA or silicone with modified surfaces (unpolished, polished, heparinized). The adhesiveness of H3-thymidin-labeled bacteria was calculated/mm2 of lens surface. Each experiment was performed in triplicate and repeated three times. RESULTS: The hydrophobic-type strain showed stronger adherence to unpolished PMMA surface (8000 bacteria per mm2) compared to the polished (5200 bacteria/mm2). In contrast, the hydrophilic strain adhered with 2000 bacteria/mm2 to the unpolished and with 4200 bacteria/mm2 to the polished surface. Polishing PMMA lenses diminished the differences between the three strains. However, surface passivation of silicone lenses increased the adhesion rate of the hydrophilic strain up to 9600 bacteria/mm2. Treatment of PMMA lenses with heparin increased the adhesiveness of the hydrophilic strain and reduced the adhesion rate of the hydrophobic type strain to 250 bacteria/mm2. CONCLUSIONS: It was demonstrated that bacterial adherence to IOL also involves hydrophobic interactions. Obviously, however, that adherence reflects a complex of interactions between the two surfaces.

Bacterial Adhesion↗

PubMed1997

Increased glutamine synthetase immunoreactivity in experimental pneumococcal meningitis.

Glutamine synthetase (GS), glial fibrillary acidic protein (GFAP) immunohistochemistry and neuronal apoptotic cell death were evaluated in a rabbit model of pneumococcal meningitis. Meningitis caused an increase of GS immunoreactivity in the cerebral cortex, but not in the hippocampal formation. GFAP immunoreactivity remained unchanged. This may represent a protective mechanism for cortical neurons. The inability of hippocampal GS to counteract the detrimental effects of glutamate may be the cause of neural apoptosis observed in the dentate gyrus during meningitis.

Animals↗

PubMed1997

Congenital microgastria, growth hormone deficiency and diabetes insipidus.

UNLABELLED: Microgastria is a rare malformation of the stomach always associated with variable patterns of malformations of the lung, heart, aortic arch, skeleton, and central nervous system. Many cases present with asplenia and hepatic symmetry as well as intestinal malrotation. We report a first case of a 4.5-year-old girl with congenital microgastria in association with growth hormone deficiency, diabetes insipidus, brachyoesophagus, hernia of the diaphragm, gastro-oesophageal reflux, intestinal malrotation, enlarged symmetrical liver, asplenia, as well as mental and statomotor retardation. CONCLUSION: Congenital microgastria is always associated with malformations of other organs. Patients at any age presenting one of the symptoms: failure to thrive, vomiting, asplenia, midline defects and parts of the VACTERL association should be carefully examined to exclude microgastria.

Abnormalities, Multiple↗

PubMed1997

Body growth in primary de Toni-Debré-Fanconi syndrome.

Body growth in nine children with primary de Toni-Debré-Fanconi syndrome was followed from birth to adolescence or adult life. At the time of diagnosis, corresponding to the start of treatment, the median age was 2.3 (range 0.4-13.9) years and height standard deviation score (SDS) was always decreased (median -3.5, range -6.8 to -2.1). Despite continuous electrolyte and bicarbonate supplementation only four patients showed a slight improvement in growth. At the time of the last observation at the age of 17.2 (4.5-20.1) years median height was -4.7 (-5.9 to -1.8) SDS. The median difference between height at last observation and target height was -4.5 SDS. Final height (n = 5) ranged between -1.8 and -5.5 (median -4.3) SDS. The pubertal growth spurt was absent in two children. Metabolic acidosis was identified as a significant growth-retarding factor. Mean serial blood bicarbonate levels and height SDS at the last observation were correlated (r = -0.87, P < 0.01). No correlation was observed between last height SDS and the degree of hypokalemia, hypophosphatemia, or hypercalciuria. In conclusion, patients with primary de Toni-Debré-Fanconi-syndrome present severe growth failure at the time of diagnosis which persists into adult life. Supportive therapy is frequently unable to prevent further loss of relative height.

Adolescent↗

PubMed1997

Cardiac enzymes and autotransfusion of shed mediastinal blood after myocardial revascularization.

BACKGROUND: Autotransfusion of shed mediastinal blood reduces blood requirement after coronary artery bypass grafting. Recently, two nonrandomized trials indicated that autotransfusion elevates the levels of cardiac enzymes after cardiac operations. METHODS: Prospective, randomized controlled studies involving 120 patients (study A) and 15 patients (study B) having elective uncomplicated coronary artery bypass grafting were performed. Autotransfusion of shed mediastinal blood was performed for 18 hours in the patients allocated to autotransfusion. Serum levels of cardiac enzymes were measured. In study B cardiac enzyme levels in shed mediastinal blood and circulating blood were measured 1 hour postoperatively. RESULTS: Cardiac enzyme levels were significantly elevated in the patients receiving autotransfusion. In patients with a perioperative myocardial infarction. The level of creatine kinase-MB was much higher than in the autotransfused patients without myocardial infarction. The level of cardiac enzymes was higher in shed mediastinal blood compared with circulating blood. CONCLUSIONS: Postoperative autotransfusion of shed mediastinal blood causes elevation of cardiac enzyme levels after coronary artery bypass grafting.

Aspartate Aminotransferases↗

PubMed1997

Effect of the 21-aminosteroid tirilazad mesylate on leukocyte adhesion and macromolecular leakage during endotoxemia.

BACKGROUND: Interstitial accumulation of leukocytes has been related to the development of multiple organ failure after sepsis. Oxygen radicals are involved in the process of leukocyte adherence to the microvascular wall. This study investigates the effects of the oxygen radical scavenger tirilazad mesylate on leukocyte-endothelial interactions, macromolecular leakage, and microhemodynamics in mesenteric venules during endotoxemia. METHODS: Male Wistar rats were randomly allocated to receive tirilazad mesylate (group A, n = 10), its vehicle (group B, n = 10), or saline 0.9% (group C, n = 10) before a 120-minute infusion of endotoxin (2 mg/kg/hr). Furthermore, a control group without receiving endotoxin (group D, n = 10) was investigated. Leukocyte adherence, emigration of leukocytes, and macromolecular leakage were determined in postcapillary venules of the mesentery by using intravital videomicroscopy. RESULTS: During the administration of endotoxin the number of adherent leukocytes per square millimeter of vessel surface progressively increased in group B (baseline, 431 +/- 35 cells/mm2; 120 minutes, 1121 +/- 71 cells/mm2) and group C (baseline, 398 +/- 44 cells/mm2; 120 minutes, 1290 +/- 116 cells/mm2). In group A no increase in leukocyte adherence was observed after 120 minutes (baseline, 415 +/- 81 cells/mm2; 120 minutes, 638 +/- 87 cells/mm2). In control animals the leukocyte adherence remained unchanged (baseline, 347 +/- 41 cells/mm2; 120 minutes, 507 +/- 75 cells/mm2). After 120 minutes, tirilazad mesylate prevented the increase in leukocyte emigration observed in group B and C. Increased macromolecular leakage during endotoxemia (groups B and C) was not influenced by pretreatment with tirilazad. Tirilazad did not affect the decrease in red cell velocity, volumetric blood flow, and venular shear rate observed during endotoxemia. CONCLUSIONS: This study demonstrates inhibitory effects of tirilazad on endotoxin-induced leukocyte adherence and emigration, suggesting a potential therapeutic role for this substance in the prevention of sepsis-induced multiple organ failure.

Animals↗

PubMed1997

Changes in intrathoracic fluid volumes during weaning from mechanical ventilation in patients after coronary artery bypass grafting.

PURPOSE: Although it is known that weaning from mechanical ventilation is associated with alterations in intrathoracic pressure, lung volume, and venous return, changes in intrathoracic fluid volumes during weaning are not reported. Especially in patients with impaired cardiac function, the development of pulmonary edema during weaning has been described. Thus, we investigated changes in intrathoracic fluid volumes in patients after coronary artery bypass grafting after changing the ventilatory pattern from mechanical to spontaneous ventilation. MATERIALS AND METHODS: Intrathoracic blood volume index (ITBVI), pulmonary blood volume index (PBVI), and extravascular lung water (EVLW) were calculated during mechanical ventilation (T1), T-piece breathing (T2), and spontaneous breathing after extubation of the trachea (T3) in 72 consecutive patients after coronary artery bypass grafting using a combined dye-thermal dilution method. RESULTS: Changing from mechanical ventilation to T-piece breathing resulted in an increase in ITBVI from 880 +/- 22 mL/m2 to 970 +/- 22 mL/m2 (P < .01), and in PBVI from 162 +/- 6 mL/m2 to 173 +/- 6 mL/m2 (P < .01). After extubation of the trachea, both parameters decreased again (ITBVI, 879 +/- 20 mL/m2; PBVI, 160 +/- 7 mL/m2). EVLW remained unchanged after transition to T-piece breathing (T1, 5.8 +/- 0.3 mL/kg; T2, 6.0 +/- 0.3 mL/kg), but increased to 6.6 +/- 0.5 mL/kg (P < .01) after extubation of the trachea. However, pathological values of EVLW were not observed. CONCLUSIONS: In patients after coronary artery bypass grafting, changes in intrathoracic intravascular fluid volumes during weaning are restricted to the period of T-piece breathing and reflect an increased venous return. The maintenance of EVLW in the normal range during weaning indicates that cardiac function was matched to this elevated preload.

Blood Volume↗

PubMed1997

Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat.

PURPOSE: The gut plays a pivotal role in sepsis. Intestinal hypoperfusion with subsequent ischemia leads to translocation of endotoxin. Dobutamine has been demonstrated to increase mesenteric blood flow during endotoxic shock; however, its effects on mucosal blood flow especially in intestinal villi is not known. Therefore, we investigated its influence on the blood flow and the arteriolar diameters in intestinal villi in a model of normotensive endotoxemia. MATERIALS AND METHODS: Twenty-one male Wistar rats were divided into three groups: (1) control, saline; (2) endotoxin, endotoxin 1.5 mg/kg during 60 minutes; and (3) dobutamine, endotoxin 1.5 mg/kg (60 minutes) and dobutamine 2.5 micrograms/kg/min during 120 minutes. Villus blood flow and arteriolar diameters were determined at 0 minutes, 60 minutes, and 120 minutes in each group using intravital microscopy. RESULTS: Villus blood flow was constant in the control group, significantly reduced at 120 minutes in the endotoxin group (120 minutes, 55.1 +/- 7.4%), and remained at baseline values in the dobutamine group. The arteriolar diameters remained constant in the control and the dobutamine groups, but they were significantly reduced in the endotoxin group at 120 minutes (7.8 +/- 0.2 to 6.5 +/- 0.7 micron). CONCLUSION: Our results indicate that in rats with normotensive endotoxemia, arteriolar diameters and blood flow in intestinal villi were reduced. Dobutamine prevented arteriolar constriction and maintained villus blood flow at preendotoxemic values.

Adrenergic beta-Agonists↗

PubMed1997

Gastric intramucosal pH: a predictor of survival in cardiac surgery patients with low cardiac output?

OBJECTIVE: To assess the value of gastric intramucosal pH measurement in patients with low output after cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Fifteen patients with low output after cardiac surgery were included. Those who survived the first postoperative day (n = 14) remained in the study. INTERVENTIONS: Gastric intramucosal pH and arterial lactate concentrations were measured 6, 12, and 24 hours after admission to the intensive care unit. Intravenous infusion of buffer solutions was strictly avoided during the equilibration period and in the half hour before injection of saline into the gastric balloon of the tonometer. MEASUREMENTS AND MAIN RESULTS: Eight patients survived during the 28-day observation period, and six patients died. On admission to the intensive care unit, no difference in cardiac index (1.56 v 1.54 L/min/m2) or pulmonary capillary wedge pressure (17.3 v 17.7 mmHg) was found between survivors and nonsurvivors. During the first 24 hours after surgery, arterial lactate was significantly higher in the nonsurvivor group (61 v 23 mg/dL), but there was no difference between the gastric intramucosal pH of survivors and nonsurvivors (7.41 v 7.42 on admission). CONCLUSIONS: Calculated gastric mucosal pH is not an early predictor of survival in cardiac surgery patients with postoperative low cardiac output syndrome. Further studies are required to assess whether the gradient between arterial and intramucosal partial pressure of carbon dioxide (PCO2) might be a more useful predictive value.

Adult↗

PubMed1997

Low-density lipoprotein receptor mRNA in human breast cancer cells: influence by PKC modulators.

It was reported previously that low-density lipoproteins (LDL) differentially stimulate cell growth of hormone-responsive (ER+) and hormone-unresponsive (ER-) mammary tumor cell lines. Here we examined the mRNA levels of the LDL-receptor (LDL-R) gene with RNAse protection analysis in ER- (MDA-MB-231 and HBL-100) and ER+ (MCF-7 and ZR75-1) cells, and compared them with the estrogen receptor (ER) status. Measurable amounts of ER mRNA were only found in ER+ cells as expected. LDL-R mRNA abundance was 3-5 fold higher in ER- cells as compared to ER+ cells. Incubation with phorbol-12-myristate-13-acetate led to a significant increase (p < 0.005) of LDL-R mRNA in ER+ cells, whereas in ER- cells LDL-R mRNA levels remained merely unchanged. Incubation of cells with dioctanoylglycerol, a synthetic homolog of diacylglycerol, increased LDL-R mRNA in ER+ but not in ER-. Inhibition of protein kinase C (PKC) by H7 resulted in a highly significant reduction of LDL-R mRNA both in ER+ and ER- cells. PKC seems to be an important regulator of LDL-R mRNA abundance in mammary tumor cells. It is hypothesized that in human-breast cancer the process of conversion from hormone-responsive to hormone-unresponsive status is accompanied by a change in PKC activity and PKC might exert cell specific differences on the regulation of LDL-R mRNA levels, which in turn influences the delivery of exogenous cholesterol to cancer cells.

Breast Neoplasms↗

PubMed1997

Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies.

Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 microg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441-5435 pg/ml), TNF-alpha 37.3 pg/ml (3.75-524 pg/ml) and ECP 33 ng/ml (1.5-250 ng/ml) versus age-matched healthy controls: IL-8 median 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) and ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-4556 pg/ml; TNF-alpha 13.9 pg/ml, 4.1-291.6 pg/ml; ECP 32.3 ng/ml, 3.7-58.4 ng/ml). Our results demonstrate that conventional management of sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.

Acetylcysteine↗

PubMed1997

In-use contamination of propofol. A clinical study.

Reports about post-operative infections associated with the use of propofol prompted us to investigate the in-use contamination of lipid-formulated intravenous (i.v.) anaesthetics used for general anaesthesia or for sedation of intensive care patients in this department. The level and incidence of extrinsic contamination of propofol ('Diprivan') and of another intravenous anaesthetic, etomidate, formulated in lipid solution ('Etomidat-lipuro') was found to be low during two study periods. However, the need to observe strict aseptic precautions in handling these intravenous drugs must be emphasized.

Anesthetics, Intravenous↗

PubMed1997

EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V.

In this study, we identified and characterized a novel secreted protein, the extracellular serine protease EspP, which is encoded by the large plasmid of enterohaemorrhagic Escherichia coli (EHEC) O157:H7. The corresponding espP gene consists of a 3900 bp open reading frame that is able to encode a 1300-amino-acid protein. EspP is synthesized as a large precursor which is then processed at the N- and C-termini during secretion. It can be grouped into the autotransporter protein family. The deduced amino acid sequence of EspP showed homology to several secreted or surface-exposed proteins of pathogenic bacteria, in particular EspC of enteropathogenic E. coli and IgA1 proteases from Neisseria spp. and Haemophilus influenzae. Hybridization experiments and immunoblot analysis of clinical EHEC isolates showed that EspP is widespread among EHEC of the serogroup O157 and that it also exists in serogroup 026. A specific immune response against EspP was detected in sera from patients suffering from EHEC infections. Functional analysis showed that EspP is a protease capable of cleaving pepsin A and human coagulation factor V. Degradation of factor V could contribute to the mucosal haemorrhage observed in patients with haemorrhagic colitis.

Antibodies, Bacterial↗

PubMed1997

Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas.

BACKGROUND & AIMS: The molecular mechanisms responsible for initiation and progression of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas are largely unknown. The aim of this study was to analyze the p16 tumor suppressor gene in MALT lymphomas of the stomach and colon. METHODS: Tumor samples were obtained from 28 patients with low-grade (n = 12) and high-grade (n = 14) gastric MALT lymphomas and from 2 patients with colonic MALT lymphomas. DNA was extracted from microdissected areas with at least 80% tumor cells. To detect homozygous p16 deletions, a semiquantitative polymerase chain reaction assay was used, whereby either p16 exon 1 or exon 2 was coamplified with an unrelated sequence as internal control. RESULTS: Homozygous p16 deletions were found in 2 of 14 (14%) cases with high-grade gastric MALT lymphomas. Both patients had Helicobacter pylori-associated gastritis; however, DNA extracted from areas of gastritis showed a normal p16 complement. No deletion was found in any of the low-grade gastric or the colonic MALT lymphoma specimens. CONCLUSIONS: In a subset of gastric MALT lymphomas, homozygous p16 deletions are acquired and may contribute to the transformation from a low-grade to a high-grade malignancy.

Carrier Proteins↗

PubMed1997

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations.

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.

Child↗

PubMed1997

Trovafloxacin delays the antibiotic-induced inflammatory response in experimental pneumococcal meningitis.

This study evaluates the ability of the new fluoroquinolone trovafloxacin to attenuate the inflammatory burst known to occur after initiation of antibiotic treatment in pneumococcal meningitis. After exposure to trovafloxacin or ceftriaxone for 3 h in vitro, Streptococcus pneumoniae was injected intracisternally (i.c.) into rabbits every 3 h over 9 h (n = 6 for each antibiotic). Ceftriaxone-treated S. pneumoniae induced consistently higher CSF leucocyte counts (median 2568/microL versus 543/microL at 6 h; P = 0.03; 4560/microL versus 2207/microL at 18 h; P = 0.03) than trovafloxacin-treated bacteria. Meningitis induced in rabbits by i.c. injection of live S. pneumoniae was treated with equal doses of trovafloxacin or ceftriaxone i.v. (ten per group). The bactericidal rates of both antibacterial agents in CSF were almost identical. In comparison with ceftriaxone, trovafloxacin resulted in lower tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta) CSF levels 2 h after the initiation of treatment (TNF levels, median 26 U/mL versus 141 U/mL; P = 0.02; IL-1beta levels 455 pg/mL versus 1399 pg/mL; P = 0.02). Twelve hours after initiation of therapy, however, TNF and IL-1beta were higher in trovafloxacin-treated animals (TNF, 61 U/mL versus 7 U/mL; P = 0.001; IL-1beta, 4320 pg/mL versus 427 pg/mL; P = 0.006). The increase in CSF lactate was less during trovafloxacin therapy than with ceftriaxone (median: 2.0 mmol/L versus 4.0 mmol/L; P = 0.03). In conclusion, S. pneumoniae treated in vitro with trovafloxacin induced less CSF leucocytosis than ceftriaxone-treated S. pneumoniae. After i.c. inoculation of live S. pneumoniae, trovafloxacin therapy delayed, but did not inhibit, the release of the proinflammatory cytokines TNF and IL-1beta, probably by slowing the liberation of bacterial cell wall components into the subarachnoid space.

Adult↗