PubMed Health⌕ Search

Biomedical subjects

G Steinbach

Publications and source records attributed to G Steinbach.

At least 19 recordsLinked to original sources

Efficacy of neodymium:YAG laser therapy for gastric antral vascular ectasia (GAVE) following hematopoietic cell transplant.

We determined the incidence of severe bleeding from gastric antral vascular ectasia (GAVE) after myeloablative hematopoietic cell transplant and the outcomes after treatment with endoscopic neodymium:YAG laser photocoagulation. From 1992 to 2005, the incidence of severe bleeding from GAVE was 6/4491 (0.13%). All patients had received oral busulfan and four had sinusoidal obstruction syndrome. Gastrointestinal bleeding began a median of 53 days after transplant (range 15-2952). After GAVE was diagnosed by endoscopic and histologic findings, a median of three (range 2-7) sessions of laser therapy were required to control the bleeding with a median of 2737 J (range 1117-6160 J) per session. A median of 16 units (range 4-44) had been transfused prior to laser therapy and a median of four additional units (range 0-113) were transfused until bleeding was controlled. All patients were followed for at least 70 days after the last laser therapy session, with no further episodes of bleeding. Complications were mild and included abdominal pain and asymptomatic ulceration; however, one patient required gastrectomy due to gastric necrosis following transarterial embolizations. In summary, severe bleeding from GAVE is rare following hematopoietic cell transplant. Treatment with endoscopic therapy using the Nd:YAG laser is safe and effective.

Adolescent↗

Whole blood interleukin 8 and plasma interleukin 8 levels in newborn infants with suspected bacterial infection.

AIM: To evaluate a new micro-method technique for measurement of interleukin 8 in detergent-lysed whole blood (whole blood IL-8) applicable to capillary blood sampling as a test for bacterial infections in neonates. METHODS: Whole blood IL-8 was measured at the first suspicion of infection along with IL-8 determined in plasma (plasma IL-8), C-reactive protein and blood cultures in 154 consecutive newborn infants with clinical signs of bacterial infection. Only 20 microl of whole blood were required for the new assay. RESULTS: Blood culture-proven infections were diagnosed in six infants and clinical infection (defined as a combination of clinical and laboratory signs) in 20 infants. 1000 pg/ml was determined as the suitable threshold for whole blood IL-8 by ROC-curve analysis. At that threshold, whole blood IL-8 detected blood culture-proven infections with a sensitivity of 83% and a specificity of 67%. The areas under the ROC curves were similar for whole blood IL-8 and plasma IL-8. CONCLUSIONS: Compared with plasma IL-8, whole blood IL-8 offers the advantages that measurements of whole blood IL-8 require a smaller blood sample volume and are not altered by haemolysis. The diagnostic accuracy of whole blood IL-8 remains to be studied in more detail in the future.

Bacterial Infections↗

IL-6 and PGE2 release by human osteoblasts on implant materials.

Regarding orthopaedic implant loosening it has been hypothesized that particle-activated macrophages release interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). This in turn stimulates osteoblasts to release interleukin-6 (IL-6) and prostaglandin E(2) (PGE(2)). These mediators recruit and activate osteoclasts and may therefore lead to bone resorption and loss of implant fixation. In this study we compared the ability of different materials to induce the release of IL-6 and PGE(2) from primary isolated, human osteoblasts without preceding activation by macrophages. We tested stainless steel, cobalt-chromium alloy (CoCrMo), commercially pure titanium (cpTi), Ti-6Al-7Nb and Ti-6Al-4V processed in the same manner as corresponding clinical implants. After 12 and 24h the cells had actively secreted IL-6 and PGE(2). There were no clear differences among the implant materials or with the plastic control. The amount of factors the cells released in our study compare well with the findings of other authors who investigated osteoblasts on plastic. In comparison with the literature these amounts are lower than secretion levels of osteoblasts stimulated with implant particles, IL-1 or TNF-alpha. Moreover, other authors found that osteoclasts require higher concentrations of PGE(2) to become activated than the concentrations measured in our experiments. Therefore, the amount of PGE(2) released from the osteoblasts in our study is probably not sufficient to induce osteolytic activity. Because of contradictory statements in the literature it is unclear if the measured IL-6 concentrations promote osteolytic activity. Differences in material composition does not significantly influence the release of these factors if the materials have similar surface roughnesses.

Biocompatible Materials↗

Effects of various applications of lipopolysaccharides on blood parameters of pigs.

In five experiments, lipopolysaccharides (LPS) of Escherichia coli O26:B6 and O111:B4 were applied intravenously, intramuscularly, subcutaneously or intrabronchially in doses of 5000-15,000 U/kg body mass to a total of 47 weaner pigs and compared with the application of sodium chloride. Different parameters of blood cells were investigated, including cell numbers, in vivo interleukin secretion, radical formation, phagocytosis capacity and IL-6 as well as TNFalpha formation ex vivo. Non-specific effects and dependencies on the type of application and LPS dose are discussed.

Animals↗

Estimating the prevalence of Salmonella spp. in swine herds--influence of sensitivity and specificity of Salmonella detection.

Information about the proportion of truly Salmonella-free herds is required for an evaluation of the epidemiological situation, the development of control strategies and their implementation. Findings regarding the presence of salmonellas in faeces and intestinal lymph nodes as well as the presence of Salmonella antibodies in meat juice from slaughtered pigs were obtained in the context of a study conducted by a number of institutes. These data were used for an analysis of the validity of data on the prevalence of infected animals within herds and on the prevalence of infected herds. The proportion of batches or herds with exclusively negative individual findings was found to depend not only on the true proportion of truly Salmonella-free animals within herds but quite essentially also on the distribution of the proportion of infected animals within herds, the sensitivity of the methods of examination and sample sizes. When taking into account the existing dependencies, it was found that among the swine, the real numbers of Salmonella carriers were much higher than shown by bacteriological and serological examination. Regarding salmonellosis in swine, also a number of contaminated herds must be expected which is far higher than that shown by the number of herds with positive findings in at least one animal. Even a low contamination of all or almost all herds would result in the numbers of 'negative' batches observed, i.e. batches with exclusively negative individual findings. A rating of the salmonella exposure of herds as high, low, or very low is possible and may, and should be, used for measures of consumer protection, irrespective of the proportion of truly Salmonella-free herds.

Animal Husbandry↗

A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial adenomatous polyposis (FAP). Their role in the duodenum of these patients is less certain. The disease modifying activity of specific COX-2 inhibitors has not been explored in humans. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally twice daily for six months to patients with FAP. Efficacy was assessed qualitatively by blinded review of shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months and quantitatively by measurement of the percentage change in duodenal area covered by discrete and plaque-like adenomas from photographs of high and low density polyposis. RESULTS: Shuffled and blinded video review showed a statistically significant effect of 400 mg twice daily celecoxib compared with placebo treatment (p=0.033) with all five independent observers scoring a beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a 14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436). However, patients with clinically significant disease at baseline (greater than 5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400 mg twice daily compared with 8% on placebo (p=0.049). CONCLUSIONS: A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help this otherwise untreatable condition.

Adenomatous Polyposis Coli↗

Circulating procalcitonin and cleavage products in septicaemia compared with medullary thyroid carcinoma.

OBJECTIVE: Raised plasma levels of procalcitonin (proCT) represent an early marker for septicaemia. They are related to disease severity and inversely to outcome and response to treatment. ProCT is presumably synthesised in tIssues other than the thyroid C-cells which are the source of calcitonin (CT) in normal physiology. This study compares proCT and its cleavage products in the serum of patients with septicaemia with those in medullary thyroid carcinoma (MTC). METHODS: Immunoreactive proCT and its cleavage products were extracted from the serum of patients with septicaemia or MTC using octadecylsilyl silica columns and characterised by reversed phase HPLC and Western blot analysis. ProCT, CT(1-32) and the flanking peptides PAS-57 and PDN-21 were recognised with antibodies specific for the individual peptides. RESULTS: ProCT and a 10 kDa polypeptide were recognised with antibodies to PAS-57, CT(1-32) and PDN-21. An 8 kDa proCT fragment was detected with antibodies to CT and PDN-21. However, intact CT(1-32), PAS-57 and PDN-21, found in the serum of MTC patients, were undetectable. The results indicate partial cleavage of proCT in septicaemia different from that in MTC patients. CONCLUSIONS: ProCT and 10 and 8 kDa proCT fragments were recognised in the circulation of septic patients. They were different from the known proCT-processing products PAS-57, CT(1-32) and PDN-21 identified in the serum of normal subjects and of MTC patients. Distinct cleavage of proCT may contribute to the symptoms of septicaemia.

Aged↗

Prediction of gram-negative bacteremia in patients with cancer and febrile neutropenia by means of interleukin-8 levels in serum: targeting empirical monotherapy versus combination therapy.

In a prospective observational study of 133 neutropenic episodes, interleukin (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53% and a specificity of 97% as a predictor of gram-negative bacteremia (GNB; positive predictive value, 73%; negative predictive value, 94%). The rates of early death differed significantly between patients with high and those with low IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever define a low-risk subgroup of patients who can safely be treated with monotherapy.

Adolescent↗

Endovascular stent-graft placement versus conventional open surgery in infrarenal aortic aneurysm: a prospective study on acute phase response and clinical outcome.

BACKGROUND: For the treatment of aortic aneurysm, stent-graft implantation is an alternative method to open surgery. There is no study comparing both methods with regard to endotoxaemia, the acute phase cascade, and clinical outcome. METHODS: In this prospective study, we enrolled 40 patients (34 males, 6 females; mean age 72.1+/-7.5 [58-92] years) with infrarenal abdominal aortic aneurysm who underwent aortic surgery. Comparable groups of patients were treated with open (n=20) or endovascular (n=20) stent-graft implantation. To characterize the inflammatory response, plasma levels of endotoxin, endotoxin-neutralizing capacity (ENC), interleukin-6 (IL-6), C-reactive protein (CRP), and white blood cell count were determined. In all patients, measurements were performed on admission, skin suture, 4 h and from the first to fifth postoperative day. As parameters for the clinical outcome, we assessed daily temperature, lung function, pain, duration of postoperative hospital stay, and morbidity. Wilcoxon rank test was used for statistical analysis. RESULTS: In both groups, a significant increase of endotoxin plasma levels and a decrease of ENC was found already after skin incision. IL-6 levels peaked 4 h postoperatively in both groups, whereas CRP rose at the first postoperative day, reaching a maximum at day 2. Conventionally operated patients had significantly higher plasma levels of endotoxin, IL-6, and CRP and lower ENC during and after surgery than patients with stent-graft implantation. Moreover, patients with endovascular stent grafting had significant less postoperative pain, less restriction of total vital capacity, a shorter hospital stay, and a lower morbidity. CONCLUSIONS: Endovascular stent grafting of infrarenal aortic aneurysm seems to be superior not only in terms of the inflammatory response but also in overall clinical outcome.

Acute-Phase Reaction↗

Hypertension as a risk factor for cerebral injury during cardiopulmonary bypass. Protein S100B and transcranial Doppler findings.

We studied 22 patients aged 53-78 years scheduled for cardiac surgery under cardiopulmonary bypass. Blood pressure, cardiac output, transcranial Doppler blood flow velocity, arterial blood gases, body temperature and protein S100B, as a marker for cerebral integrity, were evaluated in normotensive and hypertensive patients. Pre-operative mean (SD) arterial blood pressure was 93 (11) mmHg in the normotensive group compared with 116 (15) mmHg in the hypertensive group. We found an increase in protein S100B levels in both groups. Serum protein S100B concentrations in the hypertensive group were significantly higher than in the normotensive group (p < 0.001). The highest mean (SD) values were 2.04 (0.65) micromol x l(-1) in the normotensive group and 7.02 (4.55) micromol x l(-1) in the hypertensive group. These results suggest that cardiopulmonary bypass is associated with a significantly higher rate of cerebral injury in hypertensive patients than in normotensive patients. This may be due to altered autoregulation and insufficient cerebral perfusion. Modifications of cardiopulmonary bypass management for hypertensive patients might be made to decrease the risk of cerebral injury.

Aged↗

Interleukin-8: a valuable tool to restrict antibiotic therapy in newborn infants.

UNLABELLED: This study was conducted to evaluate the accuracy and kinetics of interleukin 8 (IL-8) as a test for early-onset bacterial infections (EOBI) in neonates and to examine whether IL-8 would allow "unnecessary" antibiotic therapy to be reduced. First, IL-8 was measured 378 times on admission, along with C-reactive protein (CRP), immature to total neutrophil ratio (IT ratio) and blood cultures, in full-term and preterm neonates with suspected EOBI. Combined culture-proven and clinical EOBI were detected on admission by the combination of IL-8 > or = 70 pg ml(-1) and/or CRP > 10 mg l(-1) with 92% sensitivity and 74% specificity. An increased IL-8 was found in 62% of the infected infants, while CRP was still normal. In a second study period, IL-8 was determined prospectively in 331 infants who presented clinical signs of EOBI or had a birth history of amniotic infection. Antibiotic therapy was restricted to those infants with suspected infection who also had an increased IL-8 and/or CRP (n = 158). Another 39 infants received antibiotics on the basis of clinical signs despite negative IL-8 and CRP. Of 150 non-infected infants in whom IT ratio, IL-8 and CRP were available, treatment would have been indicated for 93 infants based on IT ratio and/or CRP (n = 77) or clinical signs (n = 16), but was only initiated in 55 infants based on IL-8 and/or CRP (n = 28) or clinical signs (n = 27), an apparent reduction in "unnecessary" antibiotic therapy of 40%. CONCLUSION: The combination of IL-8 and CRP is a reliable test for the diagnosis of EOBI and may be helpful in enabling antibiotic therapy to be reduced in newborn infants.

Anti-Bacterial Agents↗

A comparison of the endotracheal tube and the laryngeal mask airway as a route for endobronchial lidocaine administration.

Drug administration via the endotracheal tube is recommended as a second-line approach in emergency settings such as cardiac arrest. It is unknown what amount of drugs are absorbed when they are given through the laryngeal mask airway as compared with the endotracheal tube. We administered lidocaine at a dose of 2 mg/kg diluted in 10 mL normal saline to 20 anesthetized patients undergoing routine surgical procedures. Ten patients received lidocaine into the endotracheal tube and 10 patients received lidocaine into the laryngeal mask airway. Blood samples were taken for measurement of lidocaine plasma concentrations, and the pharmacokinetics were calculated. Therapeutic plasma concentrations (>1.4 microg/mL) could be achieved in 10 of 10 patients after endotracheal tube instillation but in only 4 of 10 patients after laryngeal mask instillation (P < 0.05). Peak lidocaine concentrations (2.47 and 1.09 microg/mL) (P < 0.05) and the area under the time versus plasma concentration curve (117.7 and 91.2 microg x min x mL(-1)) (P < 0.05) were higher after lidocaine administration into the endotracheal tube than into the laryngeal mask airway. In conclusion, the laryngeal mask airway is not a reliable route for the recommended dose of endobronchial lidocaine administration compared with the endotracheal tube.

Adult↗

Electrocardiographic exercise stress testing for cardiac risk assessment in patients undergoing noncardiac surgery.

BACKGROUND: The value of exercise electrocardiography in the prediction of perioperative cardiac risk has yet to be defined. This study was performed to determine the predictive value of exercise electrocardiography as compared with clinical parameters and resting electrocardiography. METHODS: A total of 204 patients at intermediate risk for cardiac complications prospectively underwent exercise electrocardiography before noncardiac surgery. Of these, 185 were included in the final evaluation. All patients underwent follow-up evaluation postoperatively by Holter monitoring for 2 days, daily 12-lead electrocardiogram, and creatine kinase, creatine kinase MB, and troponin-T measurements for 5 days. Cardiac events were defined as cardiac death, myocardial infarction, minor myocardial cell injury, unstable angina pectoris, congestive heart failure, and ventricular tachyarrhythmia. Potential risk factors for an adverse event were identified by univariate and multivariate logistic regression analysis. RESULTS: Perioperative cardiac events were observed in 16 patients. There were 6 cases of myocardial infarction and 10 cases of myocardial cell injury. The multivariate correlates of adverse cardiac events were definite coronary artery disease (odds ratio, 8.8; 95% confidence interval [CI], 1.1--73.1; P = 0.04), major surgery (odds ratio, 4.7; 95% CI, 1.3--16.3; P = 0.02), reduced left ventricular performance (odds ratio, 2.0; 95% CI, 1.1--3.8; P = 0.03), and ST-segment depression of 0.1 mV or more in the exercise electrocardiogram (odds ratio, 5.2; 95% CI, 1.5--18.5; P = 0.01). A combination of clinical variables and exercise electrocardiography improved preoperative risk stratification. CONCLUSIONS: This prospective study shows that a ST-segment depression of 0.1 mV or more in the exercise electrocardiogram is an independent predictor of perioperative cardiac complications.

Adult↗

Trauma severity-dependent changes in AT III activity.

Trauma may cause a relevant reduction in antithrombin (AT) III activity, which is associated with adverse events. The very early changes in AT III activity after accident trauma are still unclear and possible relations with Interleukin (IL)-6, which is known to interact with AT III, have not been investigated so far. Upon approval of the IRB/IEC, 30 patients were enrolled with multiple injuries (ISS 9-75). Groups were performed according to injury severity, IL-6 concentration, and survivors versus non-survivors. Blood samples were collected at the scene of accident then at 2, 4, 6, 12, and 24 h and at day 3, 5, 10 and 15. No patient received AT III concentrates. In all groups a reduction in AT III activity occurred, which was most pronounced in very severe injuries. The activity re-increased spontaneously and steadily in all groups regardless of the IL-6 concentration. There was no clear impact of the AT III activity on survival.

Adolescent↗

Inflammatory response during abdominal and thyroid surgery: a prospective clinical trial on mediator release.

Several studies have been demonstrated that endotoxin is a potent stimulus of the acute inflammatory response following traumatic injury. Although numerous studies have indicated that the extent of surgical intervention correlates well with the inflammatory response, the potential role of endotoxin as a trigger under those conditions still remains unknown. Therefore, the aim of this study was to elucidate whether or not the up-regulated inflammatory mediators are paralleled by increased endotoxin plasma levels during and following surgery, and whether the extent of surgical intervention represents a crucial factor under those conditions. To study this, plasma was collected at various time points during and after surgery from 52 patients subjected to abdominal surgery (i.e., major surgery) and 25 patients subjected to thyroid surgery (i.e., minor surgery). Plasma was assessed for endotoxin, endotoxin neutralizing capacity (ENC), and inflammatory mediators (leucotriene-C4 [LTC4]-, 6-keto-prostaglandin-F-1-alpha [PGF]-, thromboxane-B2 [TxB2], interleukin-6 [IL-6], and C-reactive protein [CRP]). Furthermore, splanchnic blood circulation was measured by determination of the intraluminal pH of the stomach and sigma (pHi) by intraluminal tonometry. Mesenteric lymph nodes were also collected at the time point of organ mobilization in the major surgery group and were assessed for bacterial translocation. Among all parameters investigated, endotoxin showed the most rapid changes. A significant increase in plasma levels of endotoxin and a decrease of ENC were found in the major surgery groups following induction of anesthesia and in the minor surgery groups after skin incision. Moreover, the incidence of elevated endotoxin levels was significantly higher (89% with elevated endotoxin levels) than the incidence of bacterial translocation (35% with gram-negative bacteria) in mesenterial lymph nodes of the major surgery group. pHi decreased significantly in both groups after skin incision, but no difference was observed between the major and minor surgery groups. Plasma mediators of the arachidonic acid cascade (LTC4, PGF, and TxB2) were only elevated in individual patients during and following surgery in both groups. Conversely, the post-operative increase in the acute phase mediators was significantly different in the major and minor surgery groups. IL-6 plasma levels peaked higher and earlier after major surgery than after minor surgery and the delayed increase of CRP was significantly greater in the major surgery group. In conclusion, the results indicate that plasma levels of endotoxin significantly correlate with the severity of the surgical intervention and may play an important role in inducing mediators of the acute phase reaction under such conditions.

6-Ketoprostaglandin F1 alpha↗

Changes of gut barrier function during anesthesia and cardiac surgery.

The aim of this clinical study was to investigate the time sequence between intraoperative and postoperative endotoxemia, changes in intramucosal pH(I), mediator release, and acute phase proteins and their relationship to postoperative infections. In 60 patients (median age 61 [33-72] years, male/female: 50/10) plasma levels of endotoxin, endotoxin neutralizing capacity (ENC), leukotriene-C4 (LTC4), 6-ketoprostaglandin-F-1alpha (PGF), thromboxane-B2 (TxB2), interleukin-6 (IL-6), and C-reactive protein (CRP) were measured before, during, and after cardiac surgery. The intraluminal pH(I) of the stomach was assessed as a marker of splanchnic blood circulation. Patients were divided in one group with postoperative infections (group A, n = 8) and another groups without infections (group B, n = 52). Among all measured parameters, endotoxin plasma levels showed the most rapid changes. A significant increase of endotoxin plasma levels and a decrease in ENC appeared after the induction of anesthesia, culminating in a peak after reperfusion. Endotoxin showed a significantly higher increase in group A (14fold) compared to group B (sixfold, p<0.001), whereas ENC decreased by eightfold in both groups. The parameters of the arachidonic cascade increased and pH(I) decreased, however, there were no significant differences between both groups. The latest increase was observed for the acute phase proteins IL-6 and CRP. IL-6 levels peaked 6 hours postoperatively with a 20fold (group B) and 30fold (group A) increase (p < 0.001 vs baseline; no differences between groups), whereas CRP rose at the first postoperative day with a 21 fold (group B) and 25fold (group A) increase at day 2 (p<0.001 vs baseline, no difference between groups). Differences between both groups appeared at the second postoperative day for IL-6 (median values group A/B: 421/219 pg/mL; p <0.05) and at the fifth postoperative day for CRP (median values group A/B: 321/81 mg/L; p < 0.05). In conclusion, endotoxin seems to be the earliest trigger of the mediator cascade in acute phase response and may indicate infections in the postoperative course.

Acute-Phase Proteins↗

Inactivation of germline mutant APC alleles by attenuated somatic mutations: a molecular genetic mechanism for attenuated familial adenomatous polyposis.

Germline mutations of the adenomatous polyposis coli (APC) tumor-suppressor gene result in familial adenomatous polyposis (FAP). Patients with FAP typically develop hundreds to thousands of benign colorectal tumors and early-onset colorectal cancer. A subset of germline APC mutations results in an attenuated FAP (AFAP) phenotype, in which patients develop fewer tumors and develop them at an older age. Although a genotype-phenotype correlation between the locations of APC germline mutations and the development of AFAP has been well documented, the mechanism for AFAP has not been well defined. We investigated the mechanism for AFAP in patients carrying a mutant APC allele (APC(AS9)) that has a mutation in the alternatively spliced region of exon 9. APC(AS9) was found to down-regulate beta-catenin-regulated transcription, the major tumor-suppressor function of APC, as did the wild-type APC. Mutation analysis showed that both APC(AS9) and the wild-type APC alleles were somatically mutated in most colorectal tumors from these patients. Functional analysis showed that 4666insA, a common somatic mutation in APC(AS9) in these tumors, did not inactivate the wild-type APC. Our results indicate that carriers of APC(AS9) develop fewer colorectal tumors than do typical patients with FAP because somatic inactivation of both APC alleles is necessary for colorectal tumorigenesis. However, these patients develop colorectal tumors more frequently than does the general population because APC(AS9) is inactivated by mutations that do not inactivate the wild-type APC.

Adenomatous Polyposis Coli↗