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Biomedical subjects

M Nagel

Publications and source records attributed to M Nagel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Human platelets as a model for the binding and degradation of thrombopoietin.

Recent studies have shown that plasma thrombopoietin (TPO) levels appear to be directly regulated by platelet mass and that removal of plasma TPO by platelets via binding to the c-Mpl receptor is involved in the clearance of TPO in rodents. To help elucidate the role of platelets in the clearance of TPO in humans, we studied the in vitro specific binding of recombinant human TPO (rhTPO) to human platelet-rich plasma (PRP), washed platelets (WP), and cloned c-Mpl. Using a four-parameter fit and/or Scatchard analysis, the approximate affinity of rhTPO for its receptor, which was calculated from multiple experiments using different PRP preparations, was between 128 and 846 pmol/L, with approximately 25 to 224 receptors per platelet. WP preparations gave an affinity of 260 to 540 pmol/L, with approximately 25 to 35 receptors per platelet, and erythropoietin failed to compete with 125I-rhTPO for binding to WP. Binding and dissociation studies conducted with a BiaCore apparatus yielded an affinity of 350 pmol/L for rhTPO binding to cloned c-Mpl receptors. The ability of PRP to bind and degrade 125I-rhTPO was both time- and temperature-dependent and was blocked by the addition of excess cold rhTPO. Analysis of platelet pellets by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that 125I-rhTPO was degraded into a major fragment of approximately 45 to 50 kD. When 125I-rhTPO was incubated with a platelet homogenate at pH = 7.4, a degradation pattern similar to intact platelets was observed. Together, these data show that human platelets specifically bind rhTPO with high affinity, internalize, and then degrade the rhTPO.

Adult↗
PubMed1997

[Surgical therapy of esophageal perforation. A determination of current status based on 4 personal cases and the literature].

We present four cases of esophageal rupture (three iatrogenic, one Boerhaave syndrome) to demonstrate the difficulty in diagnosis and therapy. The current literature is discussed and conclusions are drawn as regards the modus operandi. All our patients were operated on. The site of esophageal rupture was always closed with a primary suture and substantial irrigation and drainage were performed. In two cases the suture line was in addition covered with fibrin glue or by an omentum flap, respectively. All patients survived and recovered was unremarkable. Our own results and a subsequent analysis of literature allow the following conclusions. At an early stage of esophageal rupture surgical intervention is indicated. The method of choice is primary closure of the rupture site by suture, possibly combined with a muscle or omentum flap. In cases of delayed diagnosis with advanced mediastinitis, suture of the rupture site should also be striven for. Additional coverage is advisable in these cases. Resection procedures with or without reconstruction should be done only in exceptional cases before of the high surgical risk.

Aged↗
PubMed1997

[Peripheral aneurysm of the hepatic artery as the etiology of acute upper gastrointestinal hemorrhage].

We report the case of a 64-year-old female with an intrahepatic aneurysm of the right hepatic artery. Initially uncharacteristic upper abdominal symptoms were followed by repeated upper gastrointestinal bleeding and, eventually, hemorrhagic shock. Finding the cause of severe hematemesis was challenging due to a previous Billroth-II gastric resection. Delayed diagnosis of hemobilia necessitated coeliacography, whereby an intrahepatic aneurysm of the right hepatic artery was found and, during the same session, super-selective embolization was achieved. If the cause of upper abdominal complaints remains unknown after routine diagnostic measures and the origin of bleeding in the upper gastrointestinal tract cannot be identified, aneurysms of abdominal arteries should be considered. Hemobilia of unknown etiology should always be an indication for coeliacography. The superselective angiographic embolization of intrahepatic aneurysms is a promising form of treatment with low risk.

Angiography↗
PubMed1997

[Injuries to the pancreas].

Injuries of the pancreas seldom occur in connection with abdominal trauma (12%), but they are difficult to diagnose. There is a high complication rate (35%) after such injuries. Ultrasound, CT and other means of diagnosis are only helpful in making the diagnose only in 60-80%. A clinical examination is difficult in such patients, as they often have multiple injuries. We discuss 10 cases with different grades of pancreatic injuries (Lucas), their therapy with special attention to the diagnosis, time of laparotomy, exploration of the pancreas during operative intervention, the extent of treatment and the management of complications.

Abdominal Injuries↗
PubMed1997

Contribution to the physically anchored linkage map of the pig.

Thirty-three microsatellites have been mapped on the PiGMaP porcine genetic map. By comparison with the previously published PiGMaP maps, the maps of chromosome 2 (140 cM/70 cM) and chromosome 3 (180 cM/110 cM) were extended and new markers were mapped on the p-arm extremity of chromosome 7 and on the centromeric extremity of chromosome 15. New orders are proposed for markers on chromosomes 3 and 17. Six microsatellites isolated from cosmids were also localized on the cytogenetic map by fluorescent in situ hybridization. We tested the subcloning ligation mixture-polymerase chain reaction (SLiM-PCR) method for isolating microsatellites from cosmids. Subcloning is more effective when the cosmid harbours several microsatellites whereas SLiM-PCR is more straightforward when the cosmid contains a single microsatellite. Fifteen anonymous microsatellites were regionally assigned by using a hybrid cell panel. For map integration, the determination of a regional assignment of anonymous microsatellites by using a hybrid cell panel offers an alternative to microsatellite isolation from cosmids and their localizations by in situ hybridization.

Animals↗
PubMed1997

[Guidelines in surgical intensive care medicine--central venous catheter].

Central venous catheterisation (CVC) is an invasive procedure, which needs a severe indication. It allows the measurement of central venous pressure, the infusion of hypertonic or irritant solutions, the application of vasoactive drugs and an access for special purposes (like pulmonary artery catheter or continuous haemodiafiltration). There exist some specific compliations associated with insertion and also associated with the CVC being in place. Therefore it is necessary to document the indication, the control of placement, the duration of catheterisation and the complications.

Catheterization, Central Venous↗
PubMed1997

[Intraoperative determination of parathyroid hormone--an alternative to preoperative localization diagnosis].

The results of localization procedures in hyperparathyroidism are not satisfying and amount to 65% for ultrasonography, 63% for CT-scan, 75% for MRI, and 74% for Tc-Mibi scintigraphy. Since 1994, we have performed intraoperative measurement of PTH with a modified immunochemiluminiscence assay in 44 patients. Ten minutes after exstirpation of pathological parathyroid glands, the PTH concentration decreases to less than 40% of the starting PTH level. We think that intraoperative PTH measurement is a rapid and safe method for controlling the success of surgery in HPT and makes preoperative localization procedures unnecessary.

Adenoma↗
PubMed1996

[Clinical significance of cytokines Il-6, Il-8 and C-reactive protein in serum of patients with acute pancreatitis].

The detection of cytokines may elucidate the pathophysiological mechanisms that produce early systemic complications in acute interstitial (i) or necrotizing (n) pancreatitis (AP). The increase in the level of cytokines in the blood of patients with AP may correlate with the severity of the disease. In a prospective clinical trial from October 1992 to August 1993, 23 patients with AP were recruited and blood samples taken for cytokine detection by commercially available Elisa kits and C-reactive protein (CRP) by laser nephelometry. Six of 11 patients with nAP died either early (n = 1) or of late septic complications. None died of iAP. The peak of cytokine and CRP level in the first 3 days of hospitalization was used for calculation. The IL-6 concentration in the blood reached up to 2600 pg/ml in the 1st few days, depending on the severity of AP, and dropped to almost zero in the next days, independently of the clinical course. The differentiation of i- versus nAP, using a cut-off line of 600 pg/ml, was correct in 20 patients [87%, sensitivity (SE): 82%, specificity (SP): 91%, P < 0.001]. The blood levels of IL-8 reached a maximum of 1381 pg/ml in the 1st few days, depending on the severity of AP, and showed a correlation with the clinical course in the following days. The peak of IL-8 blood levels indicated correctly the severity of AP in 18 out of 23 patients using a cutoff level of 200 pg/ml (accuracy: 78%, SE: 82%, SP: 75%, P < 0.01). The CRP levels increased up to a maximum of 535 mg/l and indicated the course of AP correctly in 18 out of 22 patients (SE and SP 82%, P < 0.01). There was no correlation between cytokine blood levels and mortality. In the blood samples of five patients with i- or nAP, no TNF-alpha was detectable. The blood levels of IL-6, and to a lesser extent of IL-8 and CRP, can predict the severity and early systemic complications of AP. The excessive rise in cytokines can be explained by the stimulation of immunological cells (macrophages, lymphocytes and endothelial cells) in the course of AP, inducing early systemic complications.

Acute Disease↗
PubMed1996

Mesoderm migration in the Xenopus gastrula.

During Xenopus gastrulation, the mesoderm involutes at the blastopore lip and moves on the inner surface of the BCR toward the animal pole of the embryo. Active cell migration is involved in this mesoderm translocation. In vitro, mesoderm cells migrate non-persistently and intermittently by extending and retracting multiple lamellipodia, which pull the cell body in their direction. Lamellipodia formation is induced by FN. FN fibrils are present on the BCR as part of the in vivo substrate of mesoderm migration. Mesoderm cells can attach to the BCR independently of FN, but interaction with FN is required for lamellipodia extension and cell migration on the BCR. In contrast to preinvolution mesoderm, involuted migrating mesoderm always stays on the surface of the BCR cell layer: migrating mesoderm cells do not mix with BCR cells, and a stable interface between tissues is maintained. A corresponding change in cell sorting behavior occurs during mesoderm involution. In Xenopus, the mesoderm moves as a multilayered coherent cell mass held together by cadherin-mediated cell adhesion. Aggregate formation changes mesoderm cell behavior, rendering it more continuous, persistent and directional, i.e. more efficient. The mesoderm possesses an intrinsic tissue polarity which biases the direction of its movement. In addition, the fibrillar FN matrix of the BCR contains guidance cues which also direct the mesoderm toward the animal pole. Haptotaxis is most likely not involved in this substrate-dependent guidance of the mesoderm, but intact FN fibrils seem to be required. A polarity of the BCR cell layer which underlies this anisotropy of the BCR matrix develops under the influence of the marginal zone in the late blastula. Although in other amphibian species, gastrulation depends critically on mesoderm cell migration, in Xenopus, convergent extension of the axial mesoderm seems to provide the main driving force for gastrulation.

Animals↗
PubMed1996

Newcastle disease virus-infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma.

An active specific immunization (ASI) procedure with two types of autologous tumor cell vaccines (ATVs) is tested for adjuvant immunotherapy of resected colorectal carcinoma to provide preliminary information on local immunological skin responses, side effects, and 2-year survival rates. For vaccine preparation, the tumor-derived freshly isolated and cryopreserved cells were thawed, purified by Percoll density centrifugation, and depleted of tumor-infiltrating lymphocytes by immunomagnetic beads. After inactivation by 200 Gy, the cells of this ATV were either infected by Newcastle disease virus (NDV) or they were admixed with Bacillus Calmette Guérin (BCG) organisms. Vaccination was performed in the arm beginning 6-8 weeks after operation, three times at 2-week intervals. Of 57 patients that received ASI, 48 were treated by virus-infected ATV (ATV-NDV) and 9 were treated with the BCG-admixed vaccine (ATV/BCG). The mean value of delayed hypersensitivity skin reactions from ATV-NDV-treated patients was 18 mm for the first vaccination and 26 and 29 mm for the succeeding ones. Although the application of ATV-NDV was associated with only mild side effects, the ATV/BCG vaccine led to long-lasting ulcers and to more serious side effects. The 2-year survival rate obtained with ATV-NDV was 97.9%, whereas the survival rate with ATV/BCG was 66.7%. The mean survival of 661 patients from a historical control was 73.8%. These data suggest that the type and quality of the tumor vaccine for ASI treatment is important. The findings with ATV-NDV necessitate corroboration in a prospective, randomized controlled study.

Aged↗
PubMed1994

[Results of surgical therapy of soft tissue sarcoma of the retroperitoneum].

Between 1.1.1973 and 30.6. 1993 57 patients underwent operation for soft-tissue sarcoma of the retroperitoneum. The histological classification showed in 21 cases a liposarcoma and in 14 cases a leiomyosarcoma. Other histological types like fibrosarcoma, malignant fibrous histiocytoma or malignant schwannoma were only rarely seen. Complete resection (R-0-resection) was possible in 39 cases (73.5%). 6 patients underwent partial resection (R-2-resection) and 8 patients had only an explorative laparotomy because of an unresectable tumor. To realize a complete resection in 23 cases a multivisceral resection was necessary. The postoperative staging according to AJCC showed for 47.7% of the patients a stage III- or stage IV- disease. The clinical follow-up was observed between 3 months and 14.3 years. The cumulative 5-year-survival-rate for all patients was 38.2%. The most important factor for prognosis was the complete resection, while other factors like sex and age of patients, size of the tumor and histological type did not predict outcome. After complete resection the cumulative 5-year-survival-rate was 46.7%, while after partial resection or explorative laparotomy no patient survived 5 years.

Adult↗
PubMed1994

[Management of abdominal stab injuries].

This is a retrospective study of 56 abdominal stab wounds analysed with reference to aetiology, pattern of injury, diagnostic and therapeutic procedures and indications for surgery. Indications for mandatory laparotomy were a manifest haemorrhagic shock (n = 20), evisceration (n = 13) and persisting presence of a weapon in the abdomen (n = 2). All patients who did not undergo immediate surgery were observed closely in repeated physical examination, in some cases complemented by ultrasound examination or peritoneal lavage. The indications for surgery were then based on the development of clinical signs. As a result of this selective approach, 31 patients underwent surgery immediately, 21 patients within 4 h and 4 patients more than 4 h after the initial assessment. The unnecessary laparotomy rate was 10.8%. The mortality rate was 3.5%, but in no case did death result from the selective approach.

Abdominal Injuries↗
PubMed1994

[Results of treatment of esophageal cancer].

From 1.10.1972 until 1.1.1993 176 patients underwent esophageal resection for cancer of the esophagus. There were 72.7% squamous cell carcinomas and 24.4% adenocarcinomas. pTNM staging was as follows: Stage I: 7.3%; stage IIa: 33.5%; stage IIb: 11.9% and stage III 47.1%. The resection was performed in 92.6% by an abdominothoracic approach. Reconstruction was usually performed by transposition of the stomach. Only in 8 patients colon was used for esophageal replacement. The complication rate was 34.6%, mainly pulmonary complications were seen. The rate of anastomotic insufficiency was 6.2%. Hospital mortality was 15.3%, but decreased from 29.1% in the years 1972-1982 to 10.1% in the last decade. There was a significant correlation between the 5-year-survival-rate and the tumor staging respectively the lymph node involvement. The long-term results showed a relatively high percentage of reflux complaints and persistent dysphagia. But the general condition and quality of life were considered subjectively by 53.5% as good and by 42.8% as moderate. From these results it can be concluded, that surgery today offers the best chances for potential cure and a high quality of life.

Adenocarcinoma↗
PubMed1992

[The quality of life after total gastrectomy for stomach carcinoma. Esophagojejunal plication with pouch versus esophagojejunostomy without pouch].

A group of 178 patients with total gastrectomy for gastric carcinoma were divided into two groups matched for sex, age, tumour stage and follow-up interval (29 pairs, 46 men and 12 women; mean age 63.4 [39-74] years) according to the type of reconstruction performed, oesophagojejunal plication with pouch or simple oesophagojejunostomy without pouch. Those with left-extended gastrectomy, follow-up period of 9 months or less, and local recurrence or metastasis were excluded. Quality of life was evaluated by means of three standardized questionnaires sent to all the patients: (1) general physical complaints; (2) satisfaction with life; and (3) psychosocial burden. Patients with pouch reconstruction declared more favourable results in 90 of the 94 questions contained in the questionnaire (96%) than the patients without pouch. Patients in the former group also had significantly fewer general physical complaints (P less than or equal to 0.05) and were significantly more satisfied with life (P less than or equal to 0.05) than those without pouch. Correlation analysis for the entire group (n = 58) indicated significant relationships especially between quality of life and postoperative nutrition and body weight. Technical surgical problems of total gastrectomy having largely been solved, the question of quality of life must increasingly determine the choice of treatment.

Anastomosis, Surgical↗
PubMed1992

Cell interaction and its role in mesoderm cell migration during Xenopus gastrulation.

In the Xenopus gastrula, the mesoderm moves as a coherent cell aggregate across the blastocoel roof toward the animal pole. We show that the cohesion of the mesoderm is not only mechanically necessary, but that aggregate formation has profound effects on the migratory behavior of mesoderm cells. Whereas isolated mesoderm cells are bi- or multipolar, move stepwise and change their direction of movement frequently, aggregated mesoderm cells migrating on their in vivo substrate appear unipolar and move continuously and persistently. Moreover, only mesoderm cell aggregates, but not single cells, can follow guidance cues present in the extracellular matrix of the blastocoel roof substrate. Thus, the cohesion of the mesodermal cell mass is an essential feature of mesoderm migration during Xenopus gastrulation. We show that the Ca(2+)-dependent cell adhesion molecule U-cadherin is involved in mediating this cohesion.

Animals↗