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Biomedical subjects

D Wagner

Publications and source records attributed to D Wagner.

At least 73 records · Page 4Linked to original sources

Laparoscopic gastric banding for morbid obesity.

Morbid obesity is a serious disease that is responsible for several comorbid conditions. Body mass indices > 40 require surgical procedures if diet programs fail. Laparoscopic adjustable gastric banding (LAGB), a more recently introduced gastric restrictive procedure, was designed to be a minimally invasive and reversible operation. 184 patients (164 women, 20 men) with a mean body mass index of 47.8 kg/m2 (range 36-79) were operated on. All patients had been excessively overweight for > 5 years. Each patient was given general anesthesia, and an adjustable LAP-BAND was implanted laparoscopically. The pouch size was 15 ml in all cases; and 3-4 sutures were placed to prevent dislocation. The conversion rate was 0%. The median operating time was 65 min (range 45-190). The mortality was 0%. The mean hospital stay was 5 days (range 4-6). The mean excess weight loss was 16% in 4 weeks, 23% in 3 months, 31% in 6 months, 58% in 1 year, and 87% in 2 years. The patient satisfaction index was 97.6%. Once a surgeon has acquired the necessary laparoscopic surgical experience, LAGB is a feasible, safe, and simple procedure with excellent postoperative results. LAGB does not permanently modify the anatomy of the stomach and maintains the natural continuity of the alimentary tract, while at the same time ensuring a steady weight reduction in morbidly obese patients. The fact that the gastric band can be applied laparoscopically is a significant advantage in this group of high-risk patients, who have less pain, faster postoperative recovery, more rapid return to normal activities, fewer wound infections, fewer hernia problems, and better cosmetic results. The rate of postoperative complications is approximately 9%. In 1.1% of patients, erosion occurred, and in 2.2%, slippage of the band. The rate of port-related complications was 3.2%. Reoperations were necessary in 6.4% of the patients.

Adult↗

Selective eosinophil transendothelial migration triggered by eotaxin via modulation of Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions.

We have recently cloned eotaxin, a highly efficacious eosinophilic chemokine involved in the development of lung eosinophilia during allergic inflammatory reactions. To understand more precisely how eotaxin facilitates the specific migration of eosinophils, we have studied which adhesion receptors are essential for eotaxin action both in vivo and in vitro. Experiments using mice genetically deficient in adhesion receptors demonstrated that molecules previously reported to be involved in both leukocyte tethering/rolling (P-selectin and E-selectin) and in sticking/ transmigration (ICAM-1 and VCAM-1) are required for eotaxin action in vivo. To further elucidate the mechanism(s) involved in this process, we have used an in vitro transendothelial chemotaxis model. mAb neutralization studies performed in this system suggest that the integrins Mac-1 (CD11b/18), VLA-4 (alpha4beta1) and LFA-1 (CD11a/18) are involved in the transendothelial chemotaxis of eosinophils to eotaxin. Accordingly, the expression of these integrins on eosinophils is elevated by direct action of this chemokine in a concentration-dependent manner. Taken together, our results suggest that eotaxin-induced eosinophil transendothelial migration in vivo and in vitro relies on Mac-1/ICAM-1 and VLA-4NCAM-1 interactions, the latter ones becoming more relevant at later time points of the eotaxin-induced recruitment process.

Animals↗

Linked insurance-tumor registry database for health services research.

OBJECTIVE: Breast cancer screening and treatment data are often limited to restricted populations, including women older than 65 years old. The goal of this project was to develop procedures to link tumor registry and insurance claims databases on women younger than 65 years old with breast cancer and to assess the accuracy and validity of the linked dataset. METHODS: Iowa Cancer Registry (ICR) and Wellmark Blue Cross/Blue Shield of Iowa (BC/BS) membership files of women with incident in situ or invasive breast cancer from 1989 to 1996 were linked. An automated deterministic match was followed with visual inspection from three independent reviewers applying a matching protocol. Matched and overall registry data were compared to assess population representativeness. Claims from BC/BS for incident cases during 1994 were examined for coding of a recent breast cancer diagnosis or treatment. RESULTS: The final dataset included 4,397 matched cases of patients aged 21 years and older from 1989 to 1996. The sociodemographic and tumor characteristics of the ICR population younger than 65 years old (n = 7,469) with breast cancer or carcinoma in situ were nearly identical with those of the matched patients younger than 65 years old (n = 3,449). Nearly all (96%) of the 445 matched incident cases in 1994 had claims data (CPT, DRG, or ICD-9 code) indicative of breast cancer. Treatment patterns varied by data source, with agreement ranging from 76% to 82%. CONCLUSIONS: The validity and generalizability of these data demonstrate their potential for further health services research among younger insured women with breast cancer. Additionally, the process outlined may be useful for developing other datasets to study other cancers in the population younger than 65 years old.

Adult↗

Agroterrorism. Agricultural infrastructure vulnerability.

The intentional contamination of animal feed to reduce the availability of animal-derived human food or to infect human populations is seldom mentioned, but animal feed could be an easy target for bioterrorists. The period of delay between the contamination of the animal feed and adulteration of the human food product provides an additional degree of uncertainty about the source of the contamination and minimizes the possibility of apprehending the terrorist. The less obvious and more natural the source of biological contamination, the greater the likelihood that the animal feed contamination will be mistaken as a natural phenomenon. However, the problems related to managing natural food contamination and intentional food contamination remain the same. Rapid testing and separation of contaminated feed are important steps, followed by the more specific identification of the contaminant to determine the source of adulteration and/or the possibility of decontamination. At this time identification of the bioagents is dependent on the availability of antibody-specific test systems. The rapid development of specific antibodies for the development of sensitive and specific test kits is the key to identifying contamination and dealing effectively with the disposal or decontamination of the animal feed and, ultimately, preventing the contamination of animal-derived human food products.

Agriculture↗

Dual role of the basic helix-loop-helix transcription factor scleraxis in mesoderm formation and chondrogenesis during mouse embryogenesis.

Scleraxis is a basic helix-loop-helix (bHLH) transcription factor shown previously to be expressed in developing chondrogenic cell lineages during embryogenesis. To investigate its function in embryonic development, we produced scleraxis-null mice by gene targeting. Homozygous mutant embryos developed normally until the early egg cylinder stage (embryonic day 6.0), when they became growth-arrested and failed to gastrulate. Consistent with this early embryonic phenotype, scleraxis was found to be expressed throughout the embryo at the time of gastrulation before becoming restricted to chondrogenic precursor cells at embryonic day 9.5. At the time of developmental arrest, scleraxis-null embryos consisted of ectodermal and primitive endodermal cell layers, but lacked a primitive streak or recognizable mesoderm. Analysis of molecular markers of the three embryonic germ layers confirmed that scleraxis mutant embryos were unable to form mesoderm. By generating chimeric embryos, using lacZ-marked scleraxis-null and wild-type embryonic stem cells, we examined the ability of mutant cells to contribute to regions of the embryo beyond the time of lethality of homozygous mutants. Scleraxis-null cells were specifically excluded from the sclerotomal compartment of somites, which gives rise to the axial skeleton, and from developing ribs, but were able to contribute to most other regions of the embryo, including mesoderm-derived tissues. These results reveal an essential early role for scleraxis in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages, and suggest that scleraxis target genes mediate these processes.

Animals↗

Quality-of-life outcome after laparoscopic adjustable gastric banding for morbid obesity.

BACKGROUND: The definition of success and failure of a bariatric procedure should include weight loss as well as improvement of comorbidity and quality-of-life (QoL) assessment. QoL measures changes in physical, functional, mental, and social health in order to evaluate benefits of new programs and interventions. MATERIAL AND METHODS: From April 1995 until March 1999, 287 patients underwent laparoscopic adjustable silicone gastric banding (LASGB) at Northwest Hospital Frankfurt a.M. (Germany). In this study, 100 of 287 patients (preoperative mean BMI 48.3 kg/m2; mean age 35.2 years) with a follow-up >18 month were evaluated. All patients underwent anonymous questionnaire (26 questions with a maximum score of 60) about different aspects of QoL outcome after LSAGB. RESULTS: In this study, 4 of 100 patients refused to give an answer to the QoL questions. Therefore 96 patients were evaluated. The QoL auto-evaluation of the patients shows that QoL generally improved after surgery in 92%. Using the scoring system, 44% of patients have excellent, 52% good, and only 4% bad results. The 4 patients who refused had to be classified as failure. General acceptance of LSAGB is wide, but gastrointestinal side effects are recognizable in more than 78% of operated patients. Successful weight loss is followed by an improvement of comorbidities. CONCLUSIONS: Safe, effective bariatric procedures increase the quality of life in morbidly obese patients markedly. Bariatric surgeons are committed to support and help their patients until they reach a new quality of life after obesity surgery.

Activities of Daily Living↗

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↗

[Significantly increased concentrations of the angiogenic growth factor bFGF in malignant soft tissue tumors].

Soft tissue sarcomas of the extremities contribute to only 0.9% of all neoplasms. Even in experienced hand radical surgical resection is followed by a recurrency rate of 7 to 35%. The reasons for this high percentage are not yet clear. Since a angiogenesis is a key factor in tumor growth we have investigated concentrations of the angiogenic peptides bFGF, TGF-beta 1, TGF-beta 2 and VEGF in systemic and tumor venous blood of 50 soft tissue sarcoma patients undergoing radical surgical tumor-resection. Systemic blood was obtained preoperatively, during surgery, 1 hour, 1 day and 1 week after surgery. 10cc of venous blood was collected from tumor veins during surgery. Levels of cytokines were measured by Sandwich-ELISA. Preoperative and intraoperative levels were significantly elevated compared to values postoperative. Concentrations of bFGF determined in tumor blood were significantly higher than serum levels but lower than controls obtained from large soft tissue wounds. VEGF and TGF were not elevated.

Endothelial Growth Factors↗