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Biomedical subjects

D Wagner

Publications and source records attributed to D Wagner.

At least 19 recordsLinked to original sources

Long-term outcome of chronic hepatitis B in heart transplant recipients.

BACKGROUND: Hepatitis B is common in organ transplant recipients. It adversely affects the prognosis after liver and kidney transplantation. The long-term outcome of hepatitis B virus (HBV) infection in heart transplant recipients has not been studied before. METHODS: Between July 1984 and June 1993, 436 patients underwent heart transplantation at the Hannover Medical School. A total of 345 patients survived for more than 1 year and were included in this study. Of these, 74 were found to be hepatitis B surface antigen (HBsAg)-positive during follow-up; 69 acquired HBV infection at known time points 25+/-17 months after transplantation, and 5 had already been infected before heart transplantation. Mean follow-up was 105 (range, 25-157) months. RESULTS: Patients developed significant alanine aminotransferase (ALT) elevations after HBV infection, which peaked and then remained above normal. Preinfection levels of ALT were 15.4+/-6.4 U/L, peak values were 71.2+/-47.2 U/L, and mean values after HBV infection were 28.9+/-14.6 U/L. All patients remained HBsAg-positive. Thirteen patients (18%) became HBeAg-negative during follow-up, 10 with negative quantitative HBV-DNA assays. Mean HBV-DNA levels in the remaining patients were 292+/-267 (range, 0-978) pg/ml. Thirty-four patients died during follow-up (45.9%) compared to 78/271 (28.8%) in the control group (P=0.008). Six of the HBsAg-positive patients (17.1%) died of liver failure 6.2-10.6 years (mean, 8.6) after transplantation. Histology of 25 HBsAg-positive patients more than 5 years after infection revealed severe fibrosis or cirrhosis in 14 (56%), mild fibrosis in 9 (36%), and chronic hepatitis without fibroproliferation in 2 (8%). CONCLUSIONS: Hepatitis B infection after heart transplantation leads to chronic liver disease in the majority of the affected patients, causing cirrhosis in more than 55% within the first decade after transplantation. Liver failure is a common cause of death in the infected group of patients. Active HBV vaccination is mandatory for all organ transplant candidates, in particular before heart transplantation.

Adult

Rational design, synthesis, and X-ray structure of selective noncovalent thrombin inhibitors.

We have designed, synthesized, and tested in vitro a novel class of noncovalent thrombin inhibitors. The main feature of these inhibitors is a 6,5-fused bicyclic core structure that fills the S2 pocket of the active site of thrombin. The bicycle introduces conformational constraint into the ligand and locks the Xaa-Pro amide bond into the desired trans configuration. Among the known ring systems, we selected by molecular modeling the 7-thiaindolizidinones (BTD) as our basic template. The influence of several structural features was analyzed: the length of the argininal side chain, the stereochemistry at C6, and the importance of making optimal use of the S3 pocket. Finally, an X-ray crystal structure of inhibitor 15 bound to thrombin was obtained at a resolution of 2.3 A. These designed thrombin inhibitors, which were prepared by an efficient synthesis, showed high selectivity over trypsin and other serine proteases. Further derivation based on the information obtained by X-ray crystallography should certainly allow to improve the potency.

Animals

[Management and therapy of postoperative complications after "gastric banding" for morbid obesity].

Laparoscopic gastric banding has become a common procedure in bariatric surgery. Early as well as late complications are, in comparison to conventional techniques, rare. Complications arising from the operative technique are: perforation, early pouch dilatation, gastric slippage, infections of the port and the band, erosion and defects of the band tube. Insufficient weight loss and late pouch dilatation arise from unsatisfactory compliance on the part of the patient. In 7.5% of 146 cases, reoperations were necessary. Obstruction of the pouch stoma and a slippage resulted in total food intolerance. After radiologic diagnosis the band system should be deflated first and a naso-gastric tube applied. If this does not result in the pouch collapsing, a revision operation is needed.

Adult

The Apache III prognostic system: customized mortality predictions for Spanish ICU patients.

OBJECTIVE: To customize the Acute Physiology and Chronic Health Evaluation (APACHE) III mortality equation for Spanish admissions to the intensive care unit (ICU) and evaluate its discrimination and calibration. DESIGN: Prospective multicenter inception cohort study. SETTING: 86 ICUs located in all regions of Spain. PATIENTS: 10,929 adult patients selected by a systematic sampling method. All types of critical care patients were included, including coronary bypass patients, but excluding those with burn injury, those admitted for pacemaker implants, patients under 16 years of age, and patients with length of ICU stay < 6 h. MEASUREMENTS AND RESULTS: Data collection in the first 24 h after patient admission included: APACHE III score, treatment location prior to ICU admission, and main ICU admission diagnosis. Using these variables, a model for predicting hospital mortality was constructed, adapted to Spain, and its discriminating ability was assessed by the area below the ROC curve, which was 0.83. The model was validated using the jacknife method and the area below the receiver operating characteristic (ROC) curve for the cross-validated predictions was 0.82. The percentage of patients correctly classified at 0.50 risk of death was 82.3%. Model calibration was evaluated by analysis of the agreement between the observed and cross-validated predicted mortality using the Hosmer-Lemeshow test, which gave a value of (H) 12.27, with no statistical significance, i.e., good calibration. CONCLUSIONS: We have customized the APACHE III mortality prediction system for the Spanish population. This adapted model has demonstrated the requisite validation, calibration, and discrimination for its use among Spanish critical care patients.

APACHE

[The fluoroscopy-guided implantation of subcutaneous venous ports: the complications and long-term results].

PURPOSE: Evaluation of technical success rate, long-term outcome and initial complication rate in patients with fluoroscopically guided port implantation. MATERIAL AND METHODS: Between January 1994 and April 1997 124 ports were implanted under fluoroscopic guidance in 120 patients. Indications for port implantation were anti-cancer chemotherapy, antibiotic and supportive therapy in patients with tumours or cachexia. RESULTS: Implantation was technically successful in 98.4% of the patients. We had a 3.2% minor complication rate that did not necessitate further treatment. One pneumothorax required a chest tube (0.8%). During a total of 17,534 days, complications occurred in 10.8% of all ports, 6.9% of the ports had to be explanted because of these complications. CONCLUSIONS: Insertion of ports under fluoroscopic guidance has a low complication rate and good long-term results. The rate of 93.1% of functioning ports is superior to that reported in other studies. It is less costly and has a lower complication rate than surgical implantation. Therefore it seems to be the method of choice for patients requiring long-term subcutaneous venous access for chemotherapy or supportive therapy in malignant tumours or other emaciating diseases.

Adult

[The assessment of the morphological changes after ventral diskectomy by thin-section computed tomography].

PURPOSE: We examined the changes of the intervertebral body space, the morphology of bone cement interponates and vertebrae after cervical discectomy and ventral fusion with high resolution CT. MATERIALS AND METHODS: CT scans were performed on 25 patients preoperatively, one week and six months after cervical discectomy and ventral fusion. RESULTS: There was no change in the size of the interponates. During follow-up new ossifications were found in 18 of the patients, two of them with neurological deficits. While directly after surgery the sagittal spinal canal diameter was enlarged, six months later particularly the lateral width was found to be reduced. After surgery soft tissue already narrowed the spinal canal in similar shape as the former prolapse. CONCLUSION: We conclude that postoperative neurologic deficits can only be partially explained by the described structural changes, because similar findings were made in uncomplicated postoperative courses as well as in patients with deficits.

Adult

Determination of endogenous growth factors in human wound fluid: temporal presence and profiles of secretion.

Growth factors are important substances in the central control of wound healing during the exudative phase. Although these peptides have been applied frequently to chronic wounds in clinical studies, little is known about the naturally occurring levels at the wound site in correlation to healing in superficial wounds. We have therefore investigated the presence of these cytokines in partial thickness wounds. In 16 patients undergoing reconstructive surgery, split-thickness skin wounds were enclosed in cutaneous vinyl chambers filled with 2.5 ml of saline. Chambers placed over unwounded skin served as controls. After 24 hours, the accumulated wound fluid was harvested and replaced by 2.5 ml of saline until the wounds were healed. Wound fluid was centrifuged, aliquoted, and frozen at -70 degrees C. Samples were analyzed for protein and growth factors (insulin-like growth factor-1, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor-AB, interleukin-1alpha, and transforming growth factor-beta1 and -beta2) and insulin-like growth factor-binding proteins 1 and 3 using a monoclonal Sandwich enzyme-linked immunosorbent assay and radioimmunoassay. All wounds healed in the liquid environment within 7 days (macroscopically) and 11 days (barrier function), respectively. In wound fluid, protein concentrations dropped from 5 mg/ml on day 1 to a baseline of 0.1 mg (unwounded skin), indicating a return of the barrier function. All growth factors could be measured already after 24 hours postwounding. However, the concentrations measured varied from 10 to more than 10,000 pg/ml between the different factors. The highest range was found for insulin-like growth factor-1 (21,000 to 41,000 pg/ml), the lowest for epidermal growth factor (3 to 63 and 3 to 88 pg/ml, respectively). Two different patterns of kinetics were distinguished: (1) a high initial peak decreasing to baseline values or below serum levels by the time of healing (insulin-like growth factor-1, insulin-like growth factor binding protein-1, -3, basic fibroblast growth factor, epidermal growth factor, platelet-derived growth factor-AB, transforming growth factor-beta1) and (2) a low initial concentration followed by an increase to a maximum at the time of epithelialization (interleukin-1alpha, transforming growth factor-beta2). Comparing the growth factor levels measured to serum baseline values, it was found that four of the growth factors appeared in wound fluid at above serum concentrations (interleukin-1alpha, transforming growth factor-beta2, basic fibroblast growth factor, epidermal growth factor); the other factors never reached serum values in wound fluid (insulin-like growth factor, transforming growth factor-beta1, platelet-derived growth factor-AB). It is concluded that the different profiles of secretion might reflect different functions of polypeptide growth factors such as stimulation of epithelialization (epidermal growth factor, insulin-like growth factor-1), matrix synthesis (transforming growth factor-beta), and inflammatory stimulation (interleukin-1alpha). The concentrations determined could serve as guidelines for adapted administration of growth factors once correlations to healing disorders such as overhealing and ulceration are established.

Adult

Prevalence of symptoms of posttraumatic stress disorder in German professional firefighters.

OBJECTIVE: This study investigated the prevalence of posttraumatic stress disorder (PTSD) and comorbid symptoms among professional firefighters in Germany and examined not only primary but also secondary traumatic stress disorder experienced by these firefighters who were exposed to the sufferings of others. METHOD: To estimate the prevalence of trauma-related disorders, a representative group of 402 professional firefighters from the State of Rheinland-Pfalz in Germany was surveyed through use of the General Health Questionnaire, a PTSD Symptom Scale, a stress coping questionnaire, and a self-rating scale to assess bodily complaints. RESULTS: The current prevalence rate of PTSD symptoms among professional firefighters was 18.2%. About 27% of the recruited subjects had a mental disorder according to the General Health Questionnaire. Predictors for the extent of traumatic stress were longer job experience and the number of distressing missions during the last month. Traumatic stress also predicted psychiatric impairment beyond PTSD, such as depressive mood, psychosomatic complaints, social dysfunction, and substance abuse. CONCLUSIONS: The high prevalence of PTSD and other psychiatric impairments in firefighters indicates that they often fail to cope with primary and particularly secondary stress in their daily work. This problem, together with the individual psychological consequences and expenses related to work absenteeism and early retirement, seems to be very specific for the profession of firefighters. The present findings provide a better understanding of the relationship between secondary traumatic stress and PTSD in professional helpers and high-risk populations such as firefighters, emergency workers, and the police.

Adaptation, Psychological

Optimal timing of phase II rehabilitation after cardiac surgery. The cardiologist's view.

Structured programmes of rehabilitation have been shown to be effective in restoring functional capacity, increasing return to work and improving the psychosocial status of patients following open heart surgery. However, uncertainty still exists about the optimal timing of rehabilitation after cardiac surgery. Data in the literature suggest that phase II rehabilitation can begin as early as one week after open heart surgery without having a negative influence on infections, mortality or readmissions. Early rehabilitation can even improve graft patency after CABG. However, age, operative complications and co-morbidities must be considered individually for each patient when determining the beginning of phase II rehabilitation.

Cardiology

[Laparoscopic gastric banding for treatment of morbid obesity].

The laparoscopic implantation of the LAP-BAND is a minimal invasive technique in obese patients. The effectiveness is comparable to that of gastroplasty. In all 186 patients were treated laparoscopically. The conversion rate was 0%. There were no death. In 0.5% there were intraoperative complications; 3% complications were caused by the port system; and 4% of the late postoperative complications were related to the LAP-BAND (pouch dilatation, slippage).

Adult

[Genetic methods in experimental xenogenic nerve transplantation].

The ready availability of xenografts and the promising results of genetic engineering both may offer new methods in peripheral xenotransplantation. FK506 and RS61443 are able to prolong survival of nerve xenografts. The incorporation of adenoviral sequences in xenogeneic tissues is possibly a new option for decreasing the toxicity of immunosuppressive drugs and immunogenicity of grafts.

Animals

[Selenium substitution in acute myocardial infarct].

BACKGROUND: Previous examinations have demonstrated decreased selenium levels in serum and full blood in patients with myocardial infarction. PATIENTS AND METHOD: 28 patients received a selenium treatment additional to the usual treatment of myocardial infarction. 19 patients with myocardial infarction with no supplementary selenium treatment served as a control group. Selenium levels in serum, full blood and urine were measured and the complications of the myocardial infarction documanted. RESULTS: There was a significant increase of serum and full blood selenium and glutathione peroxidase levels under i.v. selenium therapy in the acute phase of myocardial infarction (first to third day). Left heart failure more rarely occurred in the selenium group (20%) than in control patients (57%). Acute tachycardial cardiac rhythm disturbances such as ventricular extrasystoles and couplets diminished in both groups; ventricular extrasystoles decreased in the selenium group. CONCLUSIONS: Selen should be substituted in patients with acute myocardial infarction and decreased selen levels. It would be useful to carry out a prospective double-blind study.

Administration, Oral

L-[1-(13)C] Phenylalanine oxidation as a measure of hepatocyte functional capacity in end-stage liver disease.

BACKGROUND: Liver disease is associated with impaired metabolism of these amino acids phenylalanine and tyrosine. Decreased metabolism of these amino acids leads to abnormal plasma elevations and impaired clearance rates. We have developed a noninvasive breath test that measures hepatic cytosolic enzyme activity. METHODS: The rate of hepatic phenylalanine metabolism was quantitatively calculated from the appearance of 13CO2 in the breath using the nonradioactive tracer L-[1-(13)C]phenylalanine. RESULTS: Normal controls (n = 47) oxidized phenylalanine more than twice that of end-stage liver disease patients (n = 117). Significant differences in the percent of phenylalanine oxidized per hour (mean +/- SEM) were found between controls (7.08% +/- 0.33%, 95% CI: 6.42%-7.74%) and Child Pugh classification patients, class A (4.96% +/- 0.69%, 95% CI: 3.50%-6.42%), class B (2.88% +/- 0.13, 95% CI: 2.39%-3.38%) and class C (1.75% +/- 0.13, 95% CI: 1.50%-2.01%). The phenylalanine breath test score significantly correlated with albumin levels, prothrombin time and total bilirubin. CONCLUSION: We have demonstrated that phenylalanine oxidation is significantly decreased with end-stage liver disease and is correlated with the best clinical measures of liver disease.

Adult

Influence of n-6 and n-3 polyunsaturated fatty acids on the resistance to experimental tuberculosis.

It has previously been shown that the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (20:5(n-3)) and docosahexaenoic acid (22:6(n-3)) possess antiinflammatory properties and can interfere with immune functions. To evaluate whether this would affect resistance to infection, we studied the influence of different types of fatty acids (FAs) on experimental tuberculosis in an animal model. Three groups of 26 weanling guinea pigs were fed isocaloric diets with 26 cal% fat that differed in FA composition with respect to saturated FAs, linoleic acid (18:2(n-6)), eicosapentaenoic acid (20:5(n-3)), and docosanexaenoic acid (22:6(n-3)) as follows: (1) reference (REF) group: 14.8 cal% saturated FAs and 2.8 cal% linoleic acid; (2) n-6 group: 4.6 cal% saturated FAs and 15.4 cal% linoleic acid; (3) n-3 group: 6.3 cal% saturated FAs, 10 cal% linoleic acid, 1.4 cal% eicosapentaenoic acid, and 0.9 cal% docosahexaenoic acid. After 13 weeks, 18 animals from each group were intramuscularly injected with 180 colony-forming units (CFU) Mycobacterium tuberculosis strain H37Rv. Eight noninfected animals per group served as controls. Seven weeks later, the mean number of mycobacteria recovered from the spleens of the n-3 group (log 4.34 CFU, standard error of the mean [SEM], 0.12) was significantly higher than from the REF group (log 3.90 CFU; SEM, 0.15) and the n-8 group (log 3.93 CFU; SEM, 0.13; P < .05). In addition, the Root Index of Virulence (RIV) showed the most pronounced progression of the disease in the n-3 group. The mean size of the tuberculin reaction was larger in the n-3 group than in the other groups (P < .05). There was no significant difference between the n-6 group and the REF group. We conclude that supplementing the diet with n-3 FAs eicosapentaenoic acid and docosahexaenoic acid can affect resistance to M tuberculosis, whereas supplementing with n-6 FAs does not.

Animals

[The plain-film radiological changes in the cervical spine following a ventral fusion operation with bone cement].

PURPOSE: The usual treatment in cervical nerve root compression syndrome is the ventral fusion with bone cement. We examined the influence of this interponate on the postoperative changes of the cervical spine. MATERIALS AND METHODS: 33 patients were followed-up postoperatively over 6 months, who were treated with 39 ventral fusions because of cervical myelopathy. The lateral view of the cervical spine was used to measure the size of the bone cement interponate, the height of the intervertebral body space and the angle of both vertebral bodies. RESULTS: There was no change on the size of the interponate. Postoperatively there was a slight enlargement of the intervertebral body space. During further follow-up examinations there was a decrease to the preoperative size because of the destruction of the endplates. Similar to this observation, there was a change of the angle in the operated segment. First there was a decrease of the angle, later an increase. 6 months postoperatively the preoperatively status was re-attained. Clinical examination of the patients revealed new neurologic deficits in 10% of the cases. CONCLUSION: We conclude that the postoperative deficits can be only partially explained because the structural changes occur with both the uncomplicated postoperative courses and in patients with postoperative deficits.

Adult

[Status epilepticus late in pregnancy--eclampsia or subarachnoid hemorrhage?].

After a largely inconspicuous pregnancy, a 31-year old primipara suffered from a status epilepticus in the third trimenon. The convulsions could not be terminated by emergency medical services, resulting in aspiration of gastric contents. Assuming eclampsia, an emergency caesarean section was performed immediately in a central hospital. Postoperatively, a pathological pattern of tendon reflexes was noticed. A CT scan revealed subarachnoid haemorrhage. The causal aneurysm of the right A. pericallosa was clipped subsequently. Eclampsia is the leading cause of epileptic seizures during pregnancy. However, a different aetiology should always be considered, especially if medical history does not reveal symptoms of pre-eclampsia.

Adult