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Biomedical subjects

P Decker

Publications and source records attributed to P Decker.

At least 37 records · Page 2Linked to original sources

An improved nonisotopic test to screen a large series of new inhibitor molecules of poly(ADP-ribose) polymerase activity for therapeutic applications.

A reliable ELISA for screening large numbers of poly(ADP-ribose) polymerase (PARP) inhibitors is described. The test is based upon the drop in PARP activity estimated by the decrease in poly(ADP-ribose) synthesis in the presence of inhibitor. This ELISA is easy to perform, rapid, and specific. It is extremely sensitive because a clear inhibition of the total reaction could be visualized with molecules used in the nanomolar range. The assay uses no radioactivity, and automation is possible with robots for large-scale investigations. This test is of great interest for the screening of chemical libraries and the discovery of new inhibitors (and possibly activators) of PARP. Such molecules have important applications in all abnormal situations involving DNA damage and oxidative stress, such as cancer, autoimmunity, diabetes, myocardial dysfunctions, certain infections, aging, and radiation/chemical exposure.

Apoptosis↗

Zinc is an essential cofactor for recognition of the DNA binding domain of poly(ADP-ribose) polymerase by antibodies in autoimmune rheumatic and bowel diseases.

OBJECTIVE: To characterize autoantibody response to poly(ADP-ribose) polymerase (PARP) and to assess the significance of autoantibodies to the 2 zinc fingers of this enzyme in patients with autoimmune rheumatic and bowel diseases. METHODS: The specificity of antienzyme autoantibodies was established by dot immunoassay with recombinant human PARP and by enzyme-linked immunosorbent assay using the recombinant N-terminal fragment containing the DNA binding domain of PARP, the recombinant C-terminal catalytic domain (40-kd fragment), a peptide containing the nuclear localization signal (NLS) of PARP, 2 synthetic peptides (and mutated peptides) corresponding to zinc-finger motifs F1 and F2 that are present in the DNA binding domain, zinc fingers from other self antigens (e.g., peptides from Ro60, Ro52, and U1C proteins), and poly(ADP-ribose). Sera from patients with autoimmune rheumatic and bowel diseases were tested, as were affinity-purified antibodies. Histocompatibility typing of systemic lupus erythematosus (SLE) patients was performed by serology. RESULTS: Antibodies from the patient sera reacted only weakly with the recombinant N- and C-terminal domains and with the NLS peptide. In contrast, the 2 synthetic peptides corresponding to zinc-finger motifs F1 and F2 represented immunodominant targets for IgG antibodies from patients with SLE, mixed connective tissue disease (MCTD), Crohn's disease, and ulcerative colitis. The sera from patients with SLE and MCTD showed much weaker reactivity with mutant peptides F1 and F2, which contain mutations at the cysteine residues involved in zinc coordination. F1/F2 antibodies did not cross-react with zinc fingers from other self proteins. No correlation was found between the presence of F1/F2 autoantibodies in SLE sera and the presence of other autoantibodies typical of this disease (e.g., anti-double-stranded DNA and poly[ADP-ribose] antibodies). The presence of F2 antibodies in the serum of SLE patients was negatively associated with HLA-DR6. CONCLUSION: An autoimmune response to PARP is potentially important because this enzyme is involved in DNA repair and is rapidly cleaved during the "execution phase" of apoptosis. The high prevalence in certain autoimmune rheumatic and bowel diseases of antibodies to F1 and F2, which are directly involved in this process, is further evidence implicating involvement of the DNA repair system in chronic inflammatory diseases.

Amino Acid Sequence↗

[Diagnosis of liver tumors--what is necessary for therapy planning?].

For the surgical treatment of liver tumors, two initial steps are necessary: functional operability must be proven and oncological and local inoperability must be ruled out. The diagnostic process consists of a series of steps, beginning with non-invasive procedures such as laboratory findings and sonography, continuing with CT, CTAP, laparoscopy in the case of hepatic cirrhosis, up to explorative laparotomy. The potential operability is re-checked after each step. Punction, MRI and scintigraphy are implemented in special cases. The early implementation of MRI is of particular value for the diagnosis of certain benign processes.

Diagnostic Imaging↗

[Aortic rupture and retroperitoneal bleeding im Behcet disease].

Although retroperitoneal hemorrhage is a rather seldom complication of Behçet's syndrome it is in no way unusual. Younger patients in particular those from the eastern Mediterranean or east Asian regions in whom a retroperitoneal hemorrhage or an aneurysm in the aorto-iliaco-femoral flow region has be diagnosed must be considered for the differential diagnosis of Behçet's syndrome. The consequences for the surgeon are resection deep into healthy tissue and in general an appropriately close follow-up with strict avoidance of arterial angiography.

Aorta, Abdominal↗

[Palliative therapy of esophageal carcinoma].

For palliative endoscopic treatment of malignant dysphagia many different techniques are practiced. The differentiated usage of all techniques depending on the characteristics of the tumor leads to a good result with favorable costs. The following differentiated palliative regimen is presented: in the cervical part of the esophagus laser therapy or stent implantation are used, depending on the type of tumor growth. In the center section and the distal part of the esophagus usually palliative endoscopic pertubation is performed. If the stenosis is very soft and short a stent is implanted as alternative. In the gastroesophageal part flexible stents achieve the best results. Alternative laser therapy can be used.

Aged↗

[The employment schedule act from the viewpoint of the ordinary surgeon].

In Germany, the law of labor time was instituted in hospitals on January 1st, 1996 to regulate working hours, times of rest, breaks, and Sunday and holiday work. Problems in the realization of this law arise in daily practice, especially with regard to maximum working hours and post on-call times of rest. The compliance with the law would necessitate an enormous increase in new jobs for physicians, which is associated with an unfinanceable rise in costs. Solutions are either a reduction in performance or the omission to document the productivity. Therefore, surgeons in salaried employment in German hospitals constantly face the conflict of legality and legitimacy.

Attitude of Health Personnel↗

[Women in surgery--equal surgeons].

In the specialty "surgery" women are underrepresented, especially in leading positions. The reason for that is not less motivation, less ability or less capacity of women, but the working conditions. For women in surgery working conditions are so unfavourable that only few women make their career in surgery.

Career Choice↗

Development of a fast optimization preview in radiation treatment planning.

PURPOSE: Having the capability of fast previewing an expected optimization result for a defined combination of optimization parameters is essential to reach a better optimization result. In order to achieve this goal, the well-tried Cimmino optimization algorithm requires modification. MATERIALS AND METHODS: Usually, the speed of convergence of some iterative algorithms is restricted to a bounded relaxation parameter. Exploiting the special altering behavior of the weighting factors at each step, many iteration steps are avoided by overrelaxing this relaxation parameter. Therefore, the relaxation parameter is increased as long as the optimization result is improved. This can be performed without loss of accuracy. RESULTS: Our optimization technique is demonstrated by the case of a right lung carcinoma. The solution space for this case is 36 isocentric X-ray beams evenly spaced at 10 degree. Each beam is restricted to 23 MV X-ray fields with a planning target volume matched by irregular field shapes, similar to that produced by a multileaf collimator. Four organs at risk plus the planning target volume are considered in the optimization process. The convergence behavior of the optimization algorithm is shown by overrelaxing the relaxation parameter in comparison to conventional relaxation parameter control. CONCLUSION: The new approach offers the ability to get a fast preview of the expected final result. If the clinician is in agreement with the preview, the algorithm is continued and achieves the result proven by the Cimmino optimization algorithm. In the other case, if the clinician doesn't agree with the preview, he will be able to change the optimization parameters (e.g., field entry points) and to restart the algorithm.

Algorithms↗

[Delayed appendico-cutaneous fistula--a rare complication of simple abdominal drainage].

Appendicocutaneous fistula represents a rare form of enterocutaneous fistulas, that can occur following acute appendicitis, drainage of a perityphlitic abscess or an appendectomy. This case report describes the unique occurrence of an appendicocutaneous fistula as complication of abdominal drainage in absence of one of the above mentioned diseases.

Aged↗

[Surgery in the elderly--extent and status in surgery].

The results of selected elective and emergency operations of patients treated in the surgical department of Bonn University in 1994 and 1995 are presented and compared to the ASA-score. It was possible to show that old age itself is not a contraindication for major surgical interventions but that lethality mainly depends on concurrent diseases, i.e. the biological age. The numeric age is not an important factor. Physiological ageing only leads to diminished functional capacity, which can be partly compensated by more intensive care combined with early medical treatment. An age-specific factor which cannot be measured is the psychosocial age, the mental health. Mental health has an important influence on surgery in the aged patient.

Aged↗

[Significance of therapy timing for the effects of systemic and local therapy with the ACE inhibitor captopril on intestinal microcirculation in manifest mesenteric ischemia. An animal experiment study in the swine].

We present the results of a study based on an animal model concurring whether captopril can improve microcirculation in the small intestine in nonocclusive mesenteric ischemia dependent on when therapy is begun. Cardiogenic shock was produced by pericardial tamponade with starch solution. The flow in the carotid artery could be reduced to 43% of the preshock value. In four therapy groups and a control group the intestinal microcirculation was examined by laser Doppler flowmetry in the serosa and mucosa. The measurements were taken at regular intervals during the 4 h of the experiments. Captopril was either given systemically or locoregionally through the upper mesenteric artery. Therapy was given at the beginning of the shock or 1 h after induction of shock at a dosage of 0.25 mg/kg body weight as a bolus and continuous application of 10 micrograms/kg body wt. Concerning the hemodynamic changes during shock the group receiving captopril systemically at the beginning of shock showed a significant (P = 0.05) improvement in microcirculation compared to the controls and other therapy groups. Flow reduction was seen in the controls (156-32 relative flow units = RFU) in group Ia (systemic therapy 1 h after shock), as well as the controls (129 to 12 RFU) and, in group Ib (systemic therapy beginning with shock) a flow rise could be seen (307 to 481 RFU). In group IIa (local therapy 1 h after shock) (a steady flow was seen (168-170 RFU) and in group IIb (local therapy beginning with shock) and group Ib an increase in flow was also measured (226-303 RFU). This positive effect of captopril on the intestinal perfusion was observed when applied 1 h after the induction of shock.

Angiotensin-Converting Enzyme Inhibitors↗

[Radiological diagnosis before and after laparoscopic cholecystectomies].

PURPOSE: To study the diagnostic value of radiological imaging modalities in patients undergoing endoscopic cholecystectomy. PATIENTS AND METHODS: In 286 patients with endoscopic cholecystectomy ultrasound and intravenous cholecystography was performed for preoperative work-up. Postoperatively all patients were examined with ultrasound. RESULTS: ERCP showed a stone in the common bile duct in 12 patients with suspected stones on ultrasound, cholecystography or laboratory values. All 12 patients were treated with papillotomy. Postoperative ultrasound detected increasing fluid in the peritoneal cavity in three patients. Laparotomy of one patient showed bleeding from the cystic artery, in the second patient, injury of the right bile duct. One patient showed an accessory hepatic duct, another patient demonstrated pancreatitis. CONCLUSION: Ultrasound and intravenous cholecystography are suitable for preoperative imaging. Postoperative ultrasound is useful in detecting complications.

Adult↗

[Bile duct injuries after laparoscopic cholecystectomy].

Injuries to the extrahepatic bile duct present a severe complication in laparoscopic cholecystectomy occurring in 0-2.6%. From June 1991 to September 1994 four patients were treated to the Department of Surgery at Bonn University with bile duct injuries after laparoscopic cholecystectomy. All had complete sections of the common bile duct. They were treated twice with a biliodigestive anastomosis and once by direct suturing of the d choledochus. One of our own patients suffered an injury of the right hepatic duct, most probably due to a thermic lesion. In all cases anatomy was irregular or unclear. To avoid these complications an intraoperative cholangiography should be performed in these situations. The reconstruction after inadvertent injuries of the bile duct depends on the localisation and the age of the lesion.

Adolescent↗

[Self-expanding nitinol stent--use in esophageal carcinoma].

In recent years the implantation of self-expanding metal-stents has been recommended as a palliative kind of therapy for dysphagia caused by esophageal carcinoma. The metal-stent has a high flexibility, so that it can fit according to the preformed angel of the esophagocardial transition and does not cause a feeling of pressure when placed in the cervical position. From July 1992 to February 1995 in the surgical department of the University of Bonn 21 patients have got a self-expanding Nitinol stent. No dislocation, bleeding or perforation occurred. The dysphagia improved in all patients. The lethality rate was 9.5%, the mean survival rate 4,6 month. The growth of the tumor through the mesh of the stent was a problem which occurred from the tenth week onwards after implantation. Even when the self-expanding metal-stent does not solve all problems, it enlarges the spectrum of palliative kinds of therapy.

Adult↗

[The nitinol stent as a palliative measure in inoperable carcinoma of the esophagus and cardia. Possibilities and limitations of the procedure].

Nitinol stents were used in ten patients as palliative treatment for carcinoma of the esophagus and the cardia. Following insertion of the stent the severity of dysphagia decreased on average from 3.2 to 1.5 (on a scale from 0-4). Difficulties with stent opening and passage through the gut were found particularly in the region of metal sutures at esophago-jejunal anastomoses. One stent, which had been obstructed by mucosal folds, had to be removed and replaced. One stent which had been incorrectly placed was extended by introducing a second stent by a coaxial technique. During the period of observation, six patients died after an average of 4.6 months. The palliative effect of the stent lasted on average for eleven weeks. In two patients the tumour grew beyond the stent and in three there was tumour growth into the stent.

Adenocarcinoma↗

[Traumatic foreign body embolism from the basilic vein].

Foreign body embolisms can be traumatic and iatrogenic. Traumatic foreign body emulsion are almost always induced by gunshot wounds. Central vessels with a large lumen are the most frequent site of entry. Foreign bodies are transported to peripheral body areas or produce pulmonary embolism. Clinical manifestations are dependent on the size and place of the foreign body. In this report a case of traumatic foreign body embolism is presented, in which the basilic vein was the site of entrance and the foreign body was transported to the right lower lobe of the lung. Foreign body embolism should always be considered in the differential diagnosis in the case of patients with no visible foreign body in the injury. Treatment is dependent on the clinical signs and on size and shape of the foreign body. Symptomatic foreign body embolism and large irregularly shaped foreign bodies should be extracted. When only a small foreign body with no clinical symptoms is present conservative management is most appropriate.

Adult↗

Identification of a new polymorphism in the human proteolipid protein gene.

A polymorphism in the gene for proteolipid protein has been identified, using amplification by the polymerase chain reaction, restriction enzyme digestion, and fragment separation by polyacrylamide gel electrophoresis. The polymorphism is located in the transcribed 3'-untranslated region, a region with potential regulatory signals. The mutation consists of a single base pair insertion into a Hae III restriction site, producing a larger rare fragment of 409 bp as compared with the more frequent 325 bp fragment. The gene for proteolipid protein is on the X chromosome; thus the males are hemizygous for the rare allele and the females are heterozygous carriers. The polymorphism occurs with a frequency of 0.046 in a population of European origin and also has a rare frequency in multiple sclerosis patients.

Animals↗