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Biomedical subjects

J M Müller

Publications and source records attributed to J M Müller.

At least 19 recordsLinked to original sources

Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit.

We show that the non-DNA-binding precursor for the p50 subunit (p110), like NF-kappa B, is subject to control of nuclear uptake. In contrast to p50, p110 was excluded from nuclei and unable to associate detectably with p50 or p65 NF-kappa B subunits. The nuclear location signal in the N-terminal half of p110 was not accessible for monospecific antibodies. Removal of only 191 amino acids from the C-terminus of p110 restored antibody accessibility as well as nuclear uptake. The C-terminal half of p110, which is linked to the p50 portion via a glycine-rich hinge, could also noncovalently bind to p50. This helps to explain why p50, after cleavage of the precursor in intact cells, was still retained in an inactive form in the cytoplasm. Our study describes a novel mechanism of nuclear uptake control by masking of a nuclear location signal through a remote domain within a precursor molecule.

Amino Acid Sequence

[Resection of esophageal cancer without thoracotomy by manual dissection and eversion stripping].

At the department of surgery of the university of Cologne-Lindenthal, 184 patients (142 with squamous cell carcinoma of the esophagus, 42 with adenocarcinoma of the gastroesophageal junction) underwent blunt dissection of esophageal cancer between 1983 and 1991. Tumor expansion classified by the pathologist was stage I in 13.6%, stage II in 31.0%, stage III in 41.8%, and stage IV in 13.6% of all cases. Histological tumor differentiation was graded well in 4.3%, moderate in 71.7%, and poor in 19.6%. Principally a gastric tube was used for esophageal replacement (96.3%), while interposition of the large bowel was performed in 5 cases. All the patients were prospectively monitored for perioperative complications. 64.7% fared without any complications intraoperatively. The most frequent intraoperative complications were damage of the pleura parietalis (16.3%), rupture of the tumor during dissection (13.0%), and lesion of the spleen (11.4%). 29.9% of the patients had a postoperative course without any complications. Pleural effusion (38.6%) and insufficiency of the cervical anastomosis (22.8%) were the most frequent complications seen postoperatively. Hospital mortality amounted to 6.0%. Six months after the operation most patients deemed their quality of life satisfying or excellent, respectively. The cumulative survival rate (without hospital mortality) was 78.3% after the first year, 24.7% after the third year and 20.6% after the fifth year.

Adenocarcinoma

[Penetrating thoracic injuries].

In a period of peace in Germany and other westeuropean countries, penetrating trauma of the thorax (PTT) is much more rarer than blunt trauma. An analysis of 103 patients with PTT, treated in the Surgical Department of the University of Cologne from 1980 to 1990, showed, that these are usually isolated injuries in young patients. These occur usually following violence as stab wounds and less commonly gunshot wounds. Two thirds of the patients could be treated adequately with intensive care therapy and the use of thoracic drains. One third of the patients underwent thoracotomy, which was carried out in two thirds within one hour after hospital admission and in the remaining one third within the first 24 hours. The mortality for all PTT was 13%, being 10% for isolated thoracic injuries and 19% for patients with multiple trauma.

Adolescent

[Closure of upper median sternotomy with resorbable polyglycolic acid sutures].

Since 15 years we use absorbable polyglycolic acid sutures (Dexon) for closure of partial median sternotomies. In a consecutive series of 121 refixations, minor superficial wound infections developed in 4 patients. All infections healed completely by local treatment. No major sternal complication occurred. Of 92 patients, who were still living, 82 patients were controlled between 3 and 180 months postoperatively. 80 (98%) sternotomies were consolidated completely; 71 (87%) without any dislocation and 9 (11%) with a small dislocation of the fragments. In 2 cases (2%) an isolated pseudarthrosis of the transverse osteotomy occurred; in both cases the median osteotomy was consolidated completely. In the literature no comparable publication about closure of partial median sternotomies could be found. According to our experiences we consider, that the closure of partial upper sternotomies with polyglycolic acid sutures is as a practical and reliable method.

Adult

[Surgical treatment of esophageal cancer: Part I. European results 1980-1991].

During the past 10 years, postoperative mortality associated with resection of oesophageal carcinoma has been reduced from 30% to 11%. However, all efforts to improve longterm survival with extensive excisional procedures and adjuvant chemotherapy and radiotherapy have failed. Fifty-three of 100 patients presenting to the surgeon with an oesophageal carcinoma have resectable disease. Six of them will die from postoperative complications and 47 patients will be discharged from the hospital after an average of 3 weeks. Of these patients, 30 will survive the first, 17 th second, and 7 the fifth year. Although in may be possible to further reduce postoperative complications and mortality, the chances of improving the long-term prognosis of patients with oesophageal carcinoma seem small.

Esophageal Neoplasms

[Resection of liver metastases of colorectal carcinoma: claims and reality].

Results of resection of potentially operable liver metastases from colorectal carcinomas were evaluated by analysis of 50 publications between 1985 and 1990, as well as own datas (88 patients). Average 1, 3 and 5-year survival rates without treatment were 71 +/- 14%, 18 +/- 10% and 3 +/- 4%, respectively. The extent of metastasization at the time of diagnosis was the decisive prognostic factor. After resection of metastases 80 +/- 21% of patients survived for 1 year, 43 +/- 12% for 3 years and 28 +/- 11% for 5 years. But only a small group of patients, those with single and small metastasis, limited to one liver lobe and without extrahepatic tumour deposits, clearly profited from resection, as long as this could be accomplished with a wide enough margin of safety. Studies on growth characteristics of metastases suggest that in a large proportion of the remaining patients the natural history of the disease is not significantly changed by the operation.

Colorectal Neoplasms

[Palliative surgical treatment of cancer of the esophagus].

Palliative surgery, including cleaning resection, colon or stomach bypass, intubation or fistula is all one can offer to the majority of patients suffering from oesophageal carcinoma due to an usually advanced tumor stage at the time of diagnosis. The primary goal is to prevent or resolve dysphagia. A prolongation of survival time can - with the exception of cleaning resection - not be expected by these procedures. The average survival time was 9.4 months after cleaning resection and 4.7 months after other palliative procedures in our series. If a cleaning resection is not possible, the endoscopic implantation of an endotube is the treatment of choice because of its low mortality and morbidity.

Adenocarcinoma

[Thoracotomies in thoracic injuries--indications and results].

Most thoracic injuries can be treated adequately with intensive care, pleural drainage and judicious physiotherapy. From the total of 571 patients with severe thoracic injuries treated in the Surgical Department of the University of Cologne over the last 10 years, 14% of those with blunt trauma (BT) and 33% with penetrating trauma (PT) underwent thoracotomy. Thoracotomy for PT was usually performed earlier and gave better results than thoracotomy for BT. With one exception, all PT underwent thoracotomy in the first 24 h after admission. For thoracotomy carried out for BT however, 38% took place after 24 h and 21% after 5 days. Postoperative mortality for BT was 3 times higher than for PT (56% vs. 18%). Reasons for this are to be found in the severe thoracic and general injuries associated with BT. The surgical procedure will depend on the type and extent of the thoracic and general injuries and on the general condition of the patient.

Adolescent

[The effectiveness of hypercaloric and hypocaloric postoperative parenteral nutrition in large abdominal surgery. A prospective randomized study].

By means of a prospective randomised trial protein turnover and general energy expenditure were measured after stomach or bowel resections in patients receiving either hypercaloric or hypocaloric parenteral nutrition. The results were correlated with the availability of various blood proteins and amino acids as well as the concentration of different substrates of the intermediary metabolism. The results show that there is no need for a hypercaloric parenteral nutrition even after major abdominal surgery. Apart of a slightly better nitrogenbalance, which is, however, connected with an increased nitrogen impact on the organism there was no advantage over hypocaloric intravenous nutrition at least until the fifth day after the operation.

Blood Glucose

[Treatment of advanced non-small cell bronchial cancer--a review of the literature of the last 5 years].

In the course of a metaanalysis concerning adjuvant therapy and the therapy of inoperable non-small-cell carcinoma of the lung, undertaken from 1.1. 1985 to 1.5. 1990, 376 publications were evaluated on a point system based on a decision tree. Out of a maximum of 71 obtainable points only 5.4% of the publications on adjuvant therapy and only 7.3% of publications on palliative therapy obtained more than 45 points. Regarding inoperable cases X-ray therapy with a median survival of 11 months and satisfactory life quality demonstrated the best results. Significant increases in survival are also possible with chemotherapy (7.4 months) in standard-dose pair combinations which, however, are associated with negative side effects on the treated patients. Immune and radio-chemotherapy cannot be recommended on account of treatment toxicity without a gain in life quality. Adjuvant therapy shows no life-prolonging effect. Consequently surgical treatment remains the first choice of therapy.

Carcinoma, Non-Small-Cell Lung

[Surgical therapy of bronchial cancer. Healing or palliation?].

In spite of the revolutionary innovations concerning diagnostic and intensive care techniques as well as better understanding of tumour biology during the last decade, rates of resection and long-term survival in bronchogenic carcinoma could not be improved. Nevertheless there is no reason for therapeutic nihilism. On the contrary all efforts are to be done in investigation on practicable, suitable, and supportable screening programmes to improve the patients outcome.

Carcinoma, Bronchogenic

[Does parenteral linoleic acid modify tumor growth? Studies with the Yoshida sarcoma model].

In an experimental study with sprague-dawley-rats we tested the effect of parenteral substituted LCT-fats on tumor growth of the Yoshida sarcoma in its ascites form. Therefore we tested 4 groups with 10 tumor-bearing and 10 non-tumor-bearing rats. We added group 1-3 LCT-fats in different doses. Group 4 was fed enterally. We found that tumor-bearing rats had a higher nitrogen retention than non-tumor-bearing rats. Non-tumor-bearing rats showed a higher nitrogen concentration in the muscles. The portion of nitrogen increased with increasing portion of fat. The content of nitrogen in the ascites, the quantity and the number of tumor cells was reversed in proportion to the portion of fat. For the host we showed that he cannot make use of the energy directly. The tumor does not grow in proportion to the available energy but has to support itself from the catabolism of the host.

Animals

[Postoperative nitrogen loss].

Total nitrogen excretion was studied prospectively in 54 surgical patients during the first and second postoperative day by the Chemiluminescence method. The results were compared to three different methods for approximation of the total nitrogen excretion. Daily total nitrogen excretion was 13.13 +/- 5.7 g after peripheral vascular procedures, 15.97 +/- 8.1 g after major surgical procedures and 20.42 +/- 5.2 g in septic patients. The assessment of total nitrogen excretion by the three other methods underestimated real nitrogen losses by 20-52%. The nitrogen concentration in various secretions was relatively constant. We conclude that measuring the urine nitrogen losses only and adjusting them for the calculation of the total nitrogen excretion by several factors in incorrect. Direct measurement of total nitrogen excretion is too costly for the use in daily clinical practice.

Adult

[Does varied parenteral zinc administration modify interaction between tumor and host? Studies based on an animal model].

Zinc speeds up a lot of metabolic processes because it is essential for a lot of enzymatic reactions. A modification of the zinc pool may influence the tumor growth. We used an animal model where we applied the Yoshida sarkoma intraperitoneally in its ascites form to parenterally fed Sprague-Dawley rats. Four groups with ten tumor bearing (TBR) and ten non-tumor-bearing rats (NTBR) each received different parenteral nutrition. The normocaloric Group 1 and the hypocaloric (reduced to 1/3 energy) Group 2 were fed without zinc. In Groups 3 (normocaloric) and (hypocaloric) high doses of zinc (0.519 mg/500 g Kg/d) were substituted. In Group 3 we found the quantitatively and qualitatively highest proof of tumor mass. The nitrogen content of the ascites wasn't significantly changed within the groups. We found a weight loss of the NTBR with zinc substitution. Zinc improves the synthesis of the tumor and leads to a weight loss of the host in our animal model.

Animals

[Effect of accidental splenectomy on long-term outcome in colorectal tumor surgery].

In the period from 1967 till 1988 an accidental splenectomy was carried out at 1318 colon resections because of a malignant tumor in 34 cases (2.5%). The preoperative risk of this patient group was increased clearly in opposite to the whole patient clientele. So every fifth suffering from ileus or subileus was operated as in emergency. The complication rate, time of rest and clinic lethality were increased. The five-years survival rate did not change significantly in stage T1 and T2 in comparison with the whole patient clientele. In the stage T3, however, a significant prolonged survival rate was found out in the target group. Therefore the oncological aspect does not supply any reason to preserve the spleen in colorectal tumor surgery.

Adenocarcinoma

Surgical therapy of oesophageal carcinoma.

During the past 10 years, postoperative mortality associated with surgical treatment of oesophageal carcinoma has been reduced by one-half. However, it appears that all efforts to improve long-term survival with extensive excisional procedures and adjuvant chemotherapy and radiotherapy have failed. Fifty-six of 100 patients presenting to the surgeon with an oesophageal carcinoma have resectable disease. Recent studies suggest that seven of them will die from postoperative complications and 49 patients will be discharged from the hospital after an average of 3 weeks. Of these patients, 27 will survive the first, 12 the second, and ten the fifth year. Although it may be possible to further reduce postoperative complications and mortality, the chances of improving the long-term prognosis of patients with oesophageal carcinoma seem small.

Combined Modality Therapy

[Monitoring and management of the central nervous system in treatment of tumor cachexia].

After palliative surgery artificial nutrition is indicated primarily in patients receiving postoperative chemotherapy or radiotherapy. The techniques of ambulatory enteral or parenteral nutrition have been standardized during the past decade. They can be used with minimal risk even in patients with advanced cancer. An improvement of the nutritional status can be expected in most of the patients. Further clinical trials are needed to determine whether the patients' quality of life improves.

Cachexia