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Biomedical subjects

E Nagel

Publications and source records attributed to E Nagel.

At least 91 records · Page 5Linked to original sources

Antioxidative vitamins in prevention of ischemia/reperfusion injury.

Involvement of oxygen free radicals in ischemia-/reperfusion injury is based on measurement of increased products of lipid peroxidation after organ ischemia and restoration of blood flow during surgical operations and reperfusion of organ transplants. In cardiology inverse epidemiological correlations between plasma vitamin E levels and mortality due to ischemic heart disease, as well as beneficial effects of vitamin E on experimentally induced oxidative damage to the heart support the hypothesis, that vitamin E might have a protective role against myocardial ischemia-/reperfusion injury. In abdominal surgery efficiency of free radical scavengers has been intensively studied on animal models of hepatic ischemia and reperfusion. Examination of free radical scavengers and adenosine metabolites in liver tissue during hepatic ischemia revealed that vitamin E and glutathione levels as well as hepatic adenosine triphosphate levels are decreased during hepatic ischemia and reperfusion. The beneficial effects of alpha-tocopherol on hepatic viability and survival rate after ischemia and reperfusion demonstrated in these studies will be of great importance concerning further studies in organ preservation. In clinical kidney transplantation prevention of lipid peroxidation and improvement in kidney viability and function was demonstrated after infusion of a multivitamin cocktail in a prospective randomised study.

Antioxidants↗

[Possibilities and limits of evaluation research: development of evaluation methods with an example].

Given limited resources in health care, effectiveness and efficiency of medical procedures have to be evaluated logically. Rational decision making for resource allocation in health care services is based on medical, ethical and economic aspects. Systematic observation and query of medical procedures regarding their results delivers important data to this discussion. This study on kidney and liver transplantation serves as a model, transferable to other domains of health care services, and describes the most essential questions of evaluation research: When is the medical procedure necessary, reasonable and justified? How can the quality of treatment be described and guaranteed? What represents utility in quantitative and qualitative terms?

Adult↗

[Rationalization versus rationing in surgery].

In the discussion on cost savings in public health, one can differentiate between rationalisation and rationing. In this context rationalisation means increase in productivity with reduced resources, or more efficient rationing of the available means in order to obtain sufficient room for manoeuvre in the public health system. By efficient use of the existing resources and adaptation to medically appropriate and necessary options one is able to define medical standards for treatment. These treatment standards enable the preservation of medical freedom of action as well as participation in scientific-technological progress with the help of consequent evaluation of treatment patterns. This process could result in the development of a so-called priorisation, i.e. active preference of certain indications or therapies, which correspond extensively to the expectations and priorities of all concerned persons. From the medical point of view explicit rationing of health performances has to be strictly rejected.

Cost Savings↗

Assessment of systolic and diastolic LV function by MR myocardial tagging.

Heart failure has been divided into several different forms depending on etiology, clinical course and pathophysiology of left ventricular (LV) dysfunction. Systolic and diastolic dysfunction are characterized by a reduced cardiac output with normal (= diastolic dysfunction) or depressed (= systolic dysfunction) LV pump function. New diagnostic techniques such as magnetic resonance imaging (MRI) allow to determine noninvasively LV 3D motion by labelling specific myocardial regions (= myocardial "tagging") with a rectangular or radial grid. From the deformation of this grid rotational and translational motion of the heart can be derived. A "wringing" motion of the left ventricle has been described during systole which includes a clockwise rotation at the base and a counterclockwise rotation at the apex. During diastole, an "untwisting" motion has been demonstrated. In the normal heart, diastolic "untwisting" occurs primarily during isovolumic relaxation, analogous to the systolic "wringing" which takes place mainly during isovolumic contraction. A prolongation of the "untwisting" motion was found in the hypertrophied (aortic stenosis) and hibernating myocardium. Thus, heart failure is associated with profound alterations in the mechanical function of the heart which are manifested by changes in systolic "wringing" and diastolic "untwisting" motion.

Animals↗

Importance of the right ventricle in valvular heart disease.

The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.

Aortic Valve↗

Inhibition of sulfate respiration by 1,8-dihydroxyanthraquinone and other anthraquinone derivatives.

Derivatives of 9,10-anthracenedione, or anthraquinone, were shown to inhibit respiratory sulfate reduction by pure cultures of sulfate-reducing bacteria, as well as by crude enrichment cultures. Structure-activity studies showed that an increasing degree of substitution of the anthraquinone nucleus resulted in increasing 50% inhibition (I(inf50)) values for sulfate respiration. Addition of charged ring substituents also resulted in an increase in the I(inf50) concentration. Experiments carried out with 1,8-dihydroxyanthraquinone demonstrated inhibition of hydrogen-dependent sulfate respiration but not hydrogen-dependent sulfite or thiosulfate respiration. Addition of pyruvate resulted in stimulation of sulfate-dependent hydrogen oxidation in the presence of the anthraquinone. These observations, together with a direct demonstration of uncoupling in French press vesicle preparations, suggest that the underlying mechanism of inhibition is uncoupling of ATP synthesis from electron transfer reactions. The low I(inf50) values for inhibition (0.5 to 10 (mu)M) and the relatively low general toxicity of anthraquinones suggest that these compounds may be useful for inhibition of sulfide generation in situations which are incompatible with the use of broadly toxic biocides.

Journal Article↗

[Economic aspects of oncologic surgery: what do we know, are they relevant; must--may--we regard them?].

Economic aspects of medical care play an increasingly more important part in evaluation of diagnostics and therapeutics. Therefore it seems necessary to examine the present studies and their results carefully. In meta-analysis of cancer care, different techniques of economic analysis are used. Stage-specific analyses of direct costs in patients with colorectal neoplasms show a major influence of the stage at diagnosis on total costs of initial care. In contrast to this, increased age and increased comorbidity of patients did not function as a cost increasing factor in each stage of the disease. Net costs, that is attributable costs, are the difference between costs of the care of each subject and the average costs of controls. Net costs of continuing care decreased with age in patients with colorectal neoplasms. Cost-effectiveness analyses in patients with colon and breast cancers demonstrated lower medicare payments per year of survival for tumors diagnosed at earlier stages. From the date presented, no relevance of health economic aspects on individual planning of therapy can be deduced. Health economic aspects are appropriate in order to develop guidelines and are a basis of discussion at the level of macro-allocation. They can be used in the scope of a multi-dimensional evaluation of a new treatment and serve medical and therapeutic definitions of goals.

Colorectal Neoplasms↗

[What is the role of nutrition in ulcerative colitis? A contribution to the current status of diet therapy in treatment of inflammatory bowel diseases].

Nutritional therapy for ulcerative colitis (UC) is controversial. Studies are usually designed to investigate total parenteral (TPN) or total enteral nutrition (TEN), and before these can be compared it is necessary to differentiate between the different therapeutic aims. The aims of artificial nutritional support in patients with UC are the readjustment of the nutritional status, possible remission of disease activity, and decrease in the incidence of surgical intervention or postoperative complication. Owing to the heterogeneity of the results published so far, it is still difficult to compare studies. Nevertheless, they indicate that the extent and severity of the colitis and the patient selection are of paramount importance in the implementation of nutritional therapy. Positive effects of TPN reported from non-controlled studies were not confirmed by controlled trials. Moreover, TPN was no more effective than an oral diet. Regarding remission rates or operative interventions needed, TPN had more side effects than and no defined advantages over TEN. TEN seems to be useful for certain patients. In some patients with UC, it seems to be accompanied by fewer postoperative complications. However, a definitive conclusion on the effects of TEN or TPN is not yet possible. In this context, certain fatty acids may have an important role in the treatment of UC. In prospective, randomized and controlled studies omega-3 fatty acids were found to be therapeutically useful. A reduction of the steroid doses needed is particularly important. Another therapeutic approach in distal UC is seen in the rectal administration of short chain fatty acids.

Colitis, Ulcerative↗

Influence of heated and nonheated partially hydrogenated dietary fats on ileal chyme fat and fatty acid composition of ileal mucosa in pigs.

In this study the effects of partially hydrogenated chemically processed fats (CPF) and non-CPF on the ileal chyme fat and the fatty acid (FA) profile of the ileal mucosa and the subcutaneous tissue were analyzed. Samples were collected via an ileocutaneous fistula. For three months pigs were fed a control meal or diets containing either non-CPF high on 16:0, non-CPF high on 18:2 n6, CPF with 50% trans-18:1 or 20% trans-18:1. The latter fat was used after heat treatment. With both CPF diets, the fat content in the ileal chyme was three times higher than with non-CPF. In contrast to subcutaneous tissue reflecting dietary composition, changes in FA profile of ileal mucosa were restricted. Each non-CPF resulted in an increase of the characteristic major dietary FA. Both CPF increased the mucosal trans-FA percentage from 0 to 12% on average, although dietary composition was different. This study suggests: (1) less effects of trans-FA on the regulation of intraluminal fat load compared to saturated and cis-polyunsaturated FA, and (2) higher mucosal incorporation of trans-FA with heated CPF. This may play a role in the development of epithelial lesions in the ileum, which are known following ingestion of these fats.

Animals↗

Scanning electron-microscopic lesions in Crohn's disease: relevance for the interpretation of postoperative recurrence.

BACKGROUND/AIMS: Endoscopic postoperative recurrence often occurs a few months after surgical therapy for Crohn's disease, even if the resection margins were macroscopically free of disease. Why the disease primarily recurs at the anastomotic site is not known. This study investigated resection margins in Crohn's disease in an attempt to clarify whether early lesions are relevant to the interpretation of postoperative recurrence. METHODS: Specimens of surgically resected bowel from 29 patients with Crohn's disease and tissue from 11 controls were studied with a scanning electron microscope. RESULTS: In Crohn's disease, a triad of early lesions occurring in both histopathologically unaffected and affected mucosa was revealed; the triad consisted of mucosal architectural alterations, epithelial bridge formation, and goblet-cell hyperplasia or hypertrophy or both. Seventy-three percent of patients showed early alterations within histopathologically unaffected margins in the small bowel, and 71% had such alterations in the large bowel. CONCLUSIONS: The findings provide further evidence for the concept of diffuse involvement of the whole gastrointestinal tract by the disease process. The endoscopic recurrence rate in the first year after the operative procedure is almost identical to the number of early lesions present during surgery. The term "postoperatively recurrent disease" should be used only if relevant clinical parameters change.

Crohn Disease↗

Ileal and colonic fatty acid profiles in patients with active Crohn's disease.

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.

Acute Disease↗

[Directional coronary atherectomy: effect of vessel size on primary results and long-term results].

Of 325 consecutive patients undergoing DCA, 263 patients with 277 stenoses were successfully treated with DCA alone and had angiographic follow-up 3-6 months later. Depending upon the initial reference diameter (RD) patients were divided into two subgroups: group I (n = 159) with a RD > 3 mm and group II (n = 104) showing a RD < or = 3 mm. In contrast to other series DCA was predominantly performed with 7F atherectomy devices using balloon inflation pressures of approximately 5 atm. Angiographic data including the minimal luminal diameter (MLD), percentage of stenosis (%D) and reference diameter (RD) were assessed by quantitative computer-assisted analysis before (pre), after (post) DCA and at a 3-6 months angiographic follow-up (FU). The percentage of diameter stenosis pre/post/FU in group I was 59.9 +/- 12.6%/18.4 +/- 12.8%/29.8 +/- 17.6%, and in group II 55.6 +/- 10.8%/17.8 +/- 12.3%/33.7 +/- 16.1% with a net gain at FU of 1.0 +/- 0.89 mm for group I and 0.86 +/- 0.66 mm for group II. Based on an angiographic restenosis criterion of at least 50% diameter obstruction at FU and or recurrence of symptoms warranting interventional re-treatment of the target lesion, the incidence of restenosis in group I was 20.6% and in group II 28.0% (p: n.s.). There was no significant difference between the two groups concerning complications. Our data show that DCA leads to a satisfying long-term result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Early morphological changes in Crohn's disease. Transmission electron-microscopic findings and their interpretation: an overview.

Recent ultrastructural investigations revealed early epithelial lesions in Crohn's disease, while a specific morphological pattern was not identifiable. An increase in plasma cells, lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic granulocytes, as well as focal edema and inflammation of tissue structures was seen in the lamina propria, submucosa and deeper layers. The results are consistent with the frequent discussion about a pathogenetically significant defect of the mucosal 'barrier function', which consists of mechanical, cellular, humoral, immunological and nonimmunological mechanisms, including different histotopographically defined lines of defense of the epithelium and lamina propria. An intact epithelial layer plays an important role as the first line of defense. It is evident that components of the epithelial barrier (absorptive cells, goblet cells, Paneth cells, M cells) show ultrastructural signs of alteration or injury, while the primary agent or event remains unknown. Another pathomechanism would be a preexisting defect in intestinal 'barrier function'. Such a defect would result in an increased uptake of, or an inadequate immune reaction to, ubiquitously occurring antigens/agents (with genetic predisposition). However, no primary defect of epithelial or inflammatory cells has been definitely identified so far. Direct toxic damage of tissue secondarily introducing the inflammatory changes is also possible. Although the morphological alterations in Crohn's disease are not yet clearly understood and exactly interpreted, transmission electron microscopy has been helpful in defining early lesions and has led to further knowledge about the pathogenesis of this disease.

Crohn Disease↗

[Animal experiment studies of ultrastructural changes in the lamina propria of the ileum caused by dietary fats and comparison with cytopathology in Crohn disease].

Experimental investigations have shown alterations of the ileal mucosal surface after specific fat diets resembling early changes in Crohn's disease. An animal experiment in pigs has been conducted. After creation of an anisoperistaltic segment these were fed either a specific fat diet containing chemically processed, partially hydrogenated fats or a low fat control diet over a period of 3 months. Defined areas of the ileal lamina propria were examined by transmission electron microscopy with the underlying question to what extent ultrastructural alterations could be compared to Crohn's disease. In comparison to the control group these areas were characterized by a dense infiltration of "inflammatory" cells like lymphocytes, histiocytes, macrophages and plasma cells indicating a hyperplasia and activation of lympho-plasmocytotic cells. Additionally, a focal prominent infiltration of mast cells with degranulation was observed as well as a dilatation of axons with depletion of axonal organelles in half of the animals after fat-feeding. Compared to patients with Crohn's disease the results show obvious similarities. It is concluded, that chemically processed fats could cause direct stimulation of immunologically-specific and non-specific cells in the lamina propria mucosae or directly injure the intestinal mucosa with secondary infiltration of inflammatory cells into the lamina propria.

Animals↗