Search PubMed⌕ Search

Biomedical subjects

G Steinbach

Publications and source records attributed to G Steinbach.

At least 37 records · Page 2Linked to original sources

The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.

Adenomatous Polyposis Coli↗

Is interleukin 6 an early marker of injury severity following major trauma in humans?

HYPOTHESIS: Interleukin 6 (IL-6), a multifunctional cytokine, is expressed by various cells after many stimuli and underlies complex regulatory control mechanisms. Following major trauma, IL-6 release correlates with injury severity, complications, and mortality. The IL-6 response to injury is supposed to be uniquely consistent and related to injury severity. Therefore, we designed a prospective study starting as early as at the scene of the unintentional injury, to determine the trauma-related release of plasma IL-6 in multiple injured patients. PATIENTS AND METHODS: On approval of the local ethics committee, 94 patients were enrolled with different injuries following trauma (Injury Severity Score [ISS] median, 19; range, 3-75). The patients were rescued by a medical helicopter. Subsets were performed according to the severity of trauma--4 groups (ISS, <9, 9-17, 18-30, and >32)-and survival vs nonsurvival. The first blood sample was collected at the scene of the unintentional injury before cardiopulmonary resuscitation, when appropriate. Then, blood samples were collected in hourly to daily intervals. Interleukin 6 plasma levels were determined using a commercial enzyme-linked immunosorbent assay test. The short-term phase protein, C-reactive protein, was measured to characterize the extent of trauma and to relate these results to IL-6 release. RESULTS: As early as immediately after trauma, elevated IL-6 plasma levels occurred. This phenomenon was pronounced in patients with major trauma (ISS, >32). Patients with minor injury had elevated concentrations as well but to a far lesser extent. In surviving patients, IL-6 release correlated with the ISS values best during the first 6 hours after hospital admission. All patients revealed increased C-reactive protein levels within 12 hours following trauma, reflecting the individual injury severity. This was most pronounced in patients with the most severe (ISS, >32) trauma. CONCLUSIONS: To our knowledge, this is the first study that elucidates the changes in the IL-6 concentrations following major trauma in humans as early as at the scene of the unintentional injury. The results reveal an early increase of IL-6 immediately after trauma. Moreover, patients with the most severe injuries had the highest IL-6 plasma levels. There is strong evidence that systemic IL-6 plasma concentrations correlate with ISS values at hospital admission. Therefore, IL-6 release can be used to evaluate the impact of injury early regardless of the injury pattern.

Adolescent↗

Genomic rearrangements of the APC tumor-suppressor gene in familial adenomatous polyposis.

Germline mutations of the adenomatous polyposis coli (APC) tumor-suppressor gene result in the hereditary colorectal cancer syndrome familial adenomatous polyposis (FAP). Almost all APC mutations that have been identified are single-nucleotide alterations, small insertions, or small deletions that would truncate the protein product of the gene. No well-characterized intragenic rearrangement of APC has been described, and the prevalence of this type of mutation in FAP patients is not clear. We screened 49 potential FAP families and identified 26 different germline APC mutations in 30 families. Four of these mutations were genomic rearrangements resulting from homologous and nonhomologous recombinations mediated by Alu elements. Two of these four rearrangements were complex, involving deletion and insertion of nucleotides. Of these four rearrangements, one resulted in the deletion of exons 11 and 12 and two others resulted in either complete or partial deletion of exon 14. The fourth rearrangement grossly altered the sequence within intron 14. Although this rearrangement did not affect any coding sequence of APC at the genomic DNA level, it caused inappropriate splicing of exon 14. These rearrangements were initially revealed by analyzing cDNAs and could not have been identified by using mutation detection methods that screened each exon individually. The identification of a rearrangement that did not alter any coding exons yet affected the splicing further underscores the importance of using cDNA for mutation analysis. The identification of four genomic rearrangements among 30 mutations suggests that genomic rearrangements are frequent germline APC mutations.

Adenomatous Polyposis Coli↗

Studies of the phenomenon of host adaptation in Salmonella.

To study the phenomenon of host adaptation in Salmonella, a mathematical model has been developed which permits a definition and experimental investigation of the specific interaction between the adapted serovar and the adequate host. After experimental infection using a mixture of equal parts of two Salmonella strains, A and B, the bacterial concentrations CA and CB were determined in the organs of the animals infected. If an animal of species a and an animal of species b are infected with the same mixture of strain A adapted to a and strain B adapted to b, an expression: log10Qab = log10CaA + log10CbB - log10CaB - log10CbA may be calculated which describes the influence of the specific serovar-host interaction on the dynamics of the bacterial count. The variable Qab was determined using four Salmonella dublin, four Salmonella choleraesuis and five Salmonella gallinarum/pullorum strains in a total of 63 pairs of different hosts (calf and pig, calf and chicken, or pig and chicken). On this basis, the following statements can be made. The epidemiologically defined host adaptation of Salmonellas is accompanied by a specific agent-host interaction between the adapted serovar and adequate host. It promotes adherence and spreading of the agent in the adequate host. The effect was particularly expressed on day 3 post-infection and could be detected both in the lumen of the anterior sections of the intestine and in the intestinal lymph nodes and the liver. In part, the host-independent strain characteristics had a greater influence than the specific serovar-host interaction on the dynamics of the bacterial count. Strains of non-adapted serovars may thus result in a more intense colonization and invasion of the host than simultaneously administered bacteria of a serovar which is adapted to the respective host. The effects of a specific serovar-host interaction on colonization of and spreading in the host should be considered only as a component which contributes to the phenomenon of host adaptation.

Adaptation, Physiological↗

Serum amyloid A versus C-reactive protein in acute pancreatitis: clinical value of an alternative acute-phase reactant.

OBJECTIVES: The acute-phase reactant C-reactive protein (CRP) is currently the serum variable of choice for an early, accurate, and cost-effective severity assessment of acute pancreatitis in the daily clinical routine. Serum amyloid A (SAA) proteins comprise a family of apolipoproteins that constitute another major acute-phase reactant and thus could be a potential alternative to CRP assessment. In the present study we investigated the clinical usefulness of SAA determinations in acute pancreatitis using an automated immunoassay technique. DESIGN: Cohort study, comparing patients with complicated and mild acute pancreatitis; control groups included individuals with further abdominal disorders and healthy volunteers. SETTING: A collaborative study between the department of general surgery and the routine laboratory of the department of clinical chemistry/pathobiochemistry. PATIENTS: We enrolled 66 patients with acute pancreatitis in the present study. Control groups consisted of healthy subjects (n = 30), patients with chronic pancreatitis (n = 20), patients with pancreatic carcinoma (n = 20), and patients with acute appendicitis (n = 20). INTERVENTIONS: Blood samples were collected during 14 consecutive days in patients with acute pancreatitis. A single blood specimen was taken in all control groups after the diagnosis was established. MEASUREMENTS AND MAIN RESULTS: SAA concentrations were 3 mg/L (median; range, 3-93) in healthy subjects. Although SAA and CRP both reached their maximum within 4 days after onset of symptoms in patients with acute pancreatitis, SAA concentrations rose faster above normal ranges and reached 676 mg/L (median; range, 12-1880), higher than CRP, which reached 313 mg/L (median; range, 29-613). As observed for CRP, SAA was significantly higher in patients who developed complications such as necrosis, infection of necrosis, or multiple organ dysfunction syndrome or in patients who died. SAA achieved best results in discriminating between necrotizing pancreatitis and interstitial edematous pancreatitis. However, CRP provided an earlier differentiation between both entities and a significantly better overall accuracy, as shown by receiver operating characteristics analysis. SAA concentrations in patients with chronic pancreatitis were 6 mg/L (median; range, 3-756). In patients with pancreatic carcinoma, SAA concentrations were 7 mg/L (median; range, 3-492), and in patients with acute appendicitis, they were 50 mg/L (median; range, 3-2140). CONCLUSION: SAA is a nonspecific and rapidly produced variable in inflammatory abdominal disorders with a wider dynamic range than CRP. The current assay technique renders SAA an applicable and readily available variable under clinical routine conditions. In cases of acute pancreatitis, however, CRP is still superior to SAA for early and accurate stratification of patients with a complicated course.

Acute Disease↗

[Possibilities for standardization of ELISA for detection of Salmonella antibodies in sera and meat juices of pigs].

Programmes for controlling salmonella infections in German piggeries are based on the meat-juice-ELISA conducted in various investigation centres by using different test-kits. A usual procedure for harmonization (standardisation) of results is the calculation of the percentage of antibody-concentration from field samples in relation to the extinctions of a set of control-sera with known antibody concentrations. Whether this system is still acceptable in case of using different test-kits seems to be questionable. In principle, difficulties arise by calculating field results from the regression curve of control-sera because the calculated percentages of antibodies do not represent the antibody concentration but, instead, the percentages of the extinctions measured, and secondly, because control-sera presently in use are directed against different salmonella serovars. In regard to the number of laboratories involved and because of a variety of test-kits used it seems to be more adequate to include only one anti-Salmonella Typhimurium standard-serum at a given antibody concentration which is to be tested repeatedly on every test-plate. Simultaneously, further controls should include another anti-Salmonella Typhimurium and one anti-Salmonella Choleraesuis serum which should provide results similar to the Danish system which is regarded as a standard. As well, a negative serum must be included in the test and a minimum difference in extinctions between this negative serum and the standard positive control-serum should be reached to prove the validity of results from the test plate.

Animals↗

Combination of vaccination and competitive exclusion to prevent Salmonella colonization in chickens: experimental studies.

Vaccination and competitive exclusion (CE) represent accepted prophylactic measures to control Salmonella infections in chickens. To use the advantages of both the CE technique and vaccination with live Salmonella vaccines the combination of these methods was studied. In three experiments, SPF chickens were pre-treated using combined or unique administration of CE and vaccination with a live Salmonella typhimurium strain on days 1 and 2 of life and challenged with the antibiotic resistant, but otherwise isogenic mutant of this Salmonella typhimurium strain on days 3, 15 or 40 of life. The caecal colonization of both the vaccine and the challenge strain and the antibody response after infection were examined to evaluate the protective effects of the different combinations. The exclusion effect of CE cultures against Salmonella infection could be seen in very young chicks and was still considerable on day 40 of life of the birds. The Salmonella wild-type strain used as vaccine alone also resulted in a substantial protective effect against homologous challenge. The combined administration of competitive exclusion and immunization using the Salmonella wild-type strain as vaccine resulted in a considerable additional protective effect above the level of the respective exclusive application of these prophylactic measures. Administration of the Salmonella vaccine strain prior to or simultaneously with the CE culture produced the best protective effect, because such combinations ensure an adequate persistence of the vaccine strain as prerequisite for the expression of colonization inhibition effects and a strong immune response. The full exploitation of this potential using attenuated live Salmonella vaccines will require the presence of high inhibitory and immunogenic properties in the vaccine strain after attenuation of a selected parent strain. The combination of competitive exclusion and vaccination as a new measure in integrated control programmes against Salmonella infection in poultry could result in a considerable increase of protection in both very young and older chickens.

Animals↗

Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial.

BACKGROUND: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth. OBJECTIVE: To determine the response of gastric MALT lymphoma to antibiotic treatment. DESIGN: Prospective, uncontrolled treatment trial. SETTING: University hospital referral center and three collaborating university and community hospitals. PATIENTS: 34 patients with stage I or stage II N1 gastric MALT lymphoma. INTERVENTION: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate. MEASUREMENTS: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors. RESULTS: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach. CONCLUSIONS: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.

Anti-Bacterial Agents↗

Regulation of cyclooxygenase-2 pathway by HER2 receptor.

Emerging lines of evidence suggest that in addition to growth factors, the process of colorectal tumorigenesis may also be driven by the upregulation of the inducible form of cyclooxygenase-2 (COX-2), an enzyme responsible for the conversion of arachidonic acid to PGEs. The present study was undertaken to investigate the expression and activation of the HER family members, and to explore the regulation of COX-2 expression by the HER2 pathway in human colorectal cancer cells. Here, we report that human colorectal cancer cell lines express abundant levels of HER2 and HER3 receptors, and are growth-stimulated by recombinant neu-differentiation factor-beta 1 (NDF). NDF-treatment of colorectal cancer cells was accompanied by increased tyrosine phosphorylation and heterodimerization of HER3 with HER2. In addition, we demonstrated that HER2 and HER3 receptors in colorectal cancer cells are constitutively phosphorylated on tyrosine residues and form heterodimeric complexes in the absence of exogenous NDF. Inhibition of HER2/HER3 signaling by an anti-HER3 mAb against the ligand binding site resulted in a decrease in the levels of constitutively activated HER2/ HER3 heterodimers, and the unexpected reduction of COX-2 expression. Activation of the HER2/HER3 pathway by NDF induced the activation of COX-2 promoter, expression of COX-2 mRNA, COX-2 protein and accumulation of prostaglandin E2 in the culture medium. Finally, we demonstrated that NDF promotes the ability of colorectal cancer cells to survive in an extracellular matrix milieu, such as Matrigel, and also to invade through a 8 microm porous membrane. These biological activities of NDF and its stimulation of cell proliferation are blocked by a specific inhibitor of COX-2. Taken together, our findings provide the first biochemical evidence of a possible role of the COX-2 pathway in the mitogenic action of NDF in colorectal cancer cells where it may be constitutively upregulated due to the autocrine/paracrine activation of HER2/ HER3 heterodimers.

3T3 Cells↗

Diagnostic value of procalcitonin serum levels in neutropenic patients with fever: comparison with interleukin-8.

We assessed the predictive value of procalcitonin (PCT) serum levels in neutropenic patients with fever and various types of infection, using a prospective 3 times weekly blood sampling protocol during 103 patient episodes. Compared with pre-fever levels, median PCT levels increased after fever onset from 0.16 ng/ml (day -1) to 0.34 ng/ml (day +1). In samples obtained within 32 h after fever onset, PCT levels differed significantly between (clinically or microbiologically) documented infection and unexplained fever (median 0.51 vs. 0.26 ng/ml), between bacteraemia and non-bacteraemic infection (median 0.8 vs. 0.27 ng/ml) and between Gram-negative bacteraemia and all other episodes (median 1.28 vs. 0.31 ng/ml). Receiver-operating-characteristic (ROC) curves indicated that the discriminatory power of PCT was best for predicting bacteraemia vs. non-bacteraemic infection (sensitivity 73%; specificity 86%; area under the ROC curve 0.795; cut-off value 0.5 ng/ml). Compared with interleukin-8 (IL-8) serum levels, test characteristics were similar in the prediction of bacteraemia vs. non-bacteraemic infection and in the prediction of documented infection vs. unexplained fever, while IL-8 was better than PCT in the prediction of Gram-negative bacteraemia (area under the ROC curve 0.965 vs. 0.758).

Adolescent↗

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.

Animals↗

Early biochemical characterization of soft-tissue trauma and fracture trauma.

OBJECTIVE: The long-term outcome of trauma patients basically depends on the relation between the clearance capacity of the organism, e.g., the lungs, and the antigenic (inflammatory) load in relation to the amount of damaged and perfused tissue. It is necessary to determine quality and quantity of fracture and soft-tissue damage by clinical means as early as possible. It is unknown whether biochemical markers and the impact of soft-tissue trauma correlate and whether there is a predictive value on clinical outcome. METHODS: A total of 107 trauma patients were prospectively enrolled in the study. Blood samples were collected immediately at the site of accident, at hospital admission, and every 2 hours for an interval of 24 hours, then daily. In addition to the biochemical analysis of 20 different substances, the following data were collected and correlated to the laboratory results: Injury Severity Score, polytrauma score of Hannover, modified fracture index, and soft-tissue index. These primary clinical findings as well as the laboratory data were correlated to criteria of clinical outcome such as length of stay in the intensive care unit, length of hospital stay, infections, systemic inflammatory response syndrome, sepsis, multiple organ failure score according to Goris, and finally to primary (< 72 hours), secondary (> 72 hours), and overall lethality. The determination of individual extent and severity of soft-tissue trauma is based on standard partial body volumes derived from healthy volunteers. In addition, clinical estimation of the degree of soft-tissue damage according to the usual classifications was performed. RESULTS: Significant (p > 0.05) correlations were found between fracture as well as soft-tissue trauma and intensive care unit stay, hospital stay, infections, systemic inflammatory response syndrome, multiple organ failure score, serum concentrations/activities of serum interleukin-6 and -8 and creatine kinase during the first 24 hours after trauma. Severe soft-tissue trauma was related to secondary lethality, however, without statistical significance. CONCLUSION: The amount of fracture and soft-tissue damage can be estimated early by analysis of serum interleukin-6 and creatine kinase and is of great importance with regard to long-term outcome after trauma.

Adolescent↗

Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants.

OBJECTIVE: To evaluate procalcitonin (PCT) as a test for early diagnosis of bacterial infections (BI) in newborn infants and to compare the results of PCT with those of interleukin 8 (IL-8), C-reactive protein (CRP) and differential white blood cell count. STUDY DESIGN: PCT was prospectively measured along with IL-8, CRP and differential white blood cell counts and blood cultures in 197 newborn infants at the first suspicion of bacterial infection. PCT, IL-8, CRP and differential white blood cell counts were analyzed for sensitivity, specificity and positive and negative predictive values after receiver operating characteristic curve analysis for best thresholds. The kinetics of PCT was determined in infants with and without BI. RESULTS: Forty-six infants were diagnosed clinically as having BI, of whom 9 had BI with positive blood cultures. At a cutoff value of 0.50 microg/l, PCT detected combined culture-proved and clinical BI with a sensitivity of 57% (95% confidence interval, 41%, 71%) and a specificity of 66% (95% confidence interval, 57%, 74%). The combination of IL-8 > or =70 ng/l and/or CRP >10 mg/l achieved a sensitivity of 91% (95% confidence interval, 79%, 98%) and a specificity of 73% (95% confidence interval, 64%, 81%). PCT values of infected and not infected infants tended to rise for 24 h after initial evaluation and then decreased. CONCLUSION: The combination of IL-8 and CRP is more reliable than PCT as a test for early diagnosis of BI in newborn infants.

Bacterial Infections↗

Endotoxin release due to ciprofloxacin measured by three different methods.

Antibiotics are known to induce the release of bioactive endotoxin (LPS) from gram-negative bacterial cells. Because varying data have been published on the influence of quinolone antibiotics on LPS liberation, we studied the effect of ciprofloxacin on a culture of Escherichia coli by determining bacterial killing and free LPS concentrations in comparison with imipenem and ceftazidime. LPS levels were measured by three different methods, namely (1) the Limulus amebocyte lysate test, (2) an ELISA method based on capture of LPS by monoclonal antibodies, and (3) indirect determination by measuring the ability of antibiotic-induced LPS to trigger TNFalpha release from a monocytic cell line. With both the Limulus and ELISA tests, a low endotoxin-releasing activity of ciprofloxacin was confirmed. In contrast to previous studies, this LPS also had low bioactivity in terms of TNFalpha induction. Limulus LPS determinations correlated more precisely with LPS bioactivity than did ELISA values, an observation which underlines the crucial role of LPS determination methods in studies of antibiotic-induced LPS release.

Anti-Infective Agents↗

Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections.

OBJECTIVE: To examine whether the determination of interleukin 8 (IL-8) and C-reactive protein (CRP) in neonates with suspected nosocomial bacterial infection (NBI) is feasible and cost-effective in reducing antibiotic therapy. METHODS: Between April 1996 and May 1997, IL-8 was measured 260 times along with blood cultures, CRP, and immature-to-total-neutrophil (IT) ratio for suspected NBI in term and preterm neonates. All infants were retrospectively analyzed for NBI. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for IL-8, CRP, and IT ratio. Receiver-operating characteristic curves were analyzed to determine optimal thresholds. Between June 1997 and June 1998, IL-8 was measured 215 times in newborn infants with suspected NBI and the decision to start antibiotic therapy was based on increased IL-8 and/or CRP values. A cost-effectiveness analysis was performed and sensitivity, specificity, and receiver-operating characteristic curves were reevaluated. RESULTS: At the first suspicion of NBI, the combination of IL-8 >/= 53 pg/mL and/or CRP >10 mg/L detected culture-proven NBI with 96% sensitivity. The combined culture-proven and clinical NBI were detected with 93% sensitivity and 80% specificity. The use of IL-8 reduced unnecessary antibiotic therapy for suspected NBI by 73% and was cost-effective when compared with initiating antibiotic therapy based on clinical signs alone or based on clinical signs and an increased IT ratio and/or CRP. CONCLUSIONS: The combination of IL-8 and/or CRP is a reliable and early test for the diagnosis of NBI in newborn infants. Using the combination of IL-8 and/or CRP to restrict antibiotic therapy to truly infected infants reduces unnecessary antibiotic therapy and is cost-effective.

Anti-Bacterial Agents↗

[Necessity of double testing of meat juice samples from pigs using ELISA for the determination of Salmonella status in pig farms].

According to the test protocol of the "meat juice ELISA" for detection of salmonella antibodies in pigs, all meat juice samples and serum controls are to be tested in duplicate. Results from routine investigations of repeatedly double tested meat juice and serum samples have been used to analyze the effect of double testing versus single testing with regard to the reliability of the final result. In case of an individual animal, testing of samples in duplicate increases the reliability of the results significantly, especially, if samples are retested at different occasions. In contrast, such a difference between mono and double testing of samples is not of importance when a group of animals is tested in order to determine the mean antibody rate in a herd. Here, results from double testing practically do not contribute to a higher reliability of the final result. This observation provides the possibility to reduce the costs for investigation programmes drastically.

Animal Husbandry↗

[Salmonella infections in swine herds--epidemiology and importance for human diseases].

Based on pertinent literature and research work performed by the authors, a report is presented on the presence of salmonellas in swine herds and the importance of these organisms as agents of disease in swine and source of infection for human salmonellosis. The share among human cases of salmonellosis which are caused by salmonellas originating from swine is estimated at ca. 20%. It has to be assumed that a very large proportion of swine herds is contaminated by Salmonella. Salmonellas may be introduced through infected pigs (parent animals, pigs from other herds added to the herd) or carriers among other animal species (e.g. rodent pests, birds) as well as by feeding stuffs with primary or secondary contamination. So far, the individual importance of the various routes cannot be reliably assessed. It appears that the level of Salmonella prevalence within a herd essentially depends on the hygienic conditions, the mode of keeping and the management of the animals. Serological examinations of meat juice permit conclusions as to the level of Salmonella contamination in slaughtered pigs. The results can thus be used for programmes to reduce the introduction of salmonellas into the food chain.

Abattoirs↗

[Attempt to estimate the share of human Salmonella infections, which are attributable to Salmonella originating from swine].

On the basis of the data obtained in 1996 and 1997 in Germany on the frequency of detection of Salmonella and also of single Salmonella serovars in foods and infected humans, attempts were made to assess the relevance of Salmonella from swine as a source of human infection. Four assumptions considered as reasonable were made concerning the development of human salmonellosis. On the basis of these assumptions, a model for the estimation of the share of human Salmonella infections attributable to the swine population is proposed. According to this, ca. 20% of human cases of salmonellosis have been caused by Salmonella originating from swine.

Animals↗