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Biomedical subjects

M Imhof

Publications and source records attributed to M Imhof.

At least 73 records · Page 4Linked to original sources

Molecular aspects of membrane stabilization by ursodeoxycholate [see comment].

BACKGROUND: Ursodeoxycholate, used for therapy in biliary liver diseases, prevents bile salt damage in animal experiments. Using isolated red blood cell and both canalicular and basolateral hepatocyte membranes, the present study examined this protective effect. METHODS: Membranes were incubated with chenodeoxycholate, with chenodeoxycholate and ursodeoxycholate simultaneously, and first with ursodeoxycholate followed by chenodeoxycholate. Changes in membrane structure were investigated by electron paramagnetic resonance spectroscopy, using different spin labels. Data were confirmed by analysis of membrane lipids and studies with 14C-labeled bile acids. RESULTS: The increase of polarity in the apolar domain of the membrane caused by chenodeoxycholate corresponded to the amount of solubilized lipids. After preincubation with ursodeoxycholate or its conjugates, membrane damage by subsequent chenodeoxycholate incubation was prevented. This effect was caused by binding of ursodeoxycholate in the apolar domain, of its conjugates in the interface of the membrane. CONCLUSIONS: Chenodeoxycholate solubilizes membrane lipids and permits water to permeate into plasma membranes. The steroid nucleus of ursodeoxycholate is bound to the apolar domain and that of the conjugates to the interface of the membrane, thus stabilizing membrane structure.

Animals↗

Effects of interleukin-1, -2, -4, -6, interferon-gamma and granulocyte/macrophage colony stimulating factor on human vascular endothelial cells.

Human vascular endothelial cells (HUVEC) exhibit various immunological functions, i.e. expression of HLA class-II antigens after incubation with IFN-gamma or antigen presenting function. It has also been reported that HUVEC are able to produce IL-1, IL-6, GM-CSF and immunologically active cleavage products of arachidonic acid. In our study we investigated whether various cytokines, namely IL-1, IL-2, IL-6, GM-CSF and IFN-gamma, do alter the proliferative capacity of HUVEC, the production of van Willebrandt factor (vWF) and the expression of MHC class-II antigens. HUVEC were prepared by the collagenase digestion of human umbilical veins. Monolayers of cells were incubated with cytokines in different concentrations for 24 and 48 h. IFN-gamma inhibits the HUVEC [3H]thymidine uptake in a dose-dependent manner. Suppression of proliferation (40.1%) could be observed after 24 h incubation with 100 U IFN-gamma/ml. IL-1 was a more effective inhibitor of HUVEC proliferation (54% at 10 U/ml and 24 h incubation and 48.4% after 48 h) than IFN-gamma. IL-6 and GM-CSF showed an increasing effect on proliferation with 226% and 151% of the control group, respectively. IFN-gamma after an incubation period of 12 h and IL-1 after 24 h reduced the vWF content by about 30%. Bright MHC class-II expression was induced only by IFN-gamma. In conclusion, some of the immunoregulative cytokines might play an important role in the control of HUVEC proliferation.

Cell Division↗

Serum-soluble CD4 as clinical and immunological marker in patients with dilated cardiomyopathy.

Serological markers of cell-mediated immunity, i.e., soluble CD4, soluble interleukin-2 (Il-2) receptor and beta 2-microglobulin, were determined in 60 patients with dilated cardiomyopathy. Compared with normal healthy donors (n = 30) and controls who had coronary artery disease with preserved left ventricular function (n = 20), significantly increased levels associated with the New York Heart Association functional classes have been found in the cardiomyopathy patients, irrespectively of the etiology. Out of the immunological variables tested, serum-soluble CD4 most closely reflected the clinical and hemodynamic stage, predicted the presence of lymphocytic aggregates in the myocardium and correlated with the CD4/CD8 ratios of endomyocardial lymphocytes (r = 0.6, P < 0.05). Conversely, focal mononuclear infiltration of the myocardium was associated with significantly elevated CD4/CD8 ratios (2.1 +/- 0.6 vs. 1.3 +/- 0.2, P < 0.05), higher total numbers and percentages of endomyocardial lymphocytes expressing the pan T-markers CD2 and CD3, more CD45RO/UCHL1-positive cells and more CD4-positive T-helper cells, compared with non-reactive cases the lymphocytes of which were scattered throughout the myocardium. In conclusion, in a subset of cardiomyopathy patients lymphocytic clusters in the myocardium indicated an enhanced cellular immune response predominantly mediated by CD4-positive T-helper lymphocytes with active memory function. This immunopathological condition in the heart can be monitored by serum-soluble CD4.

CD4 Antigens↗

Peptic ulcer bleeding: medical and surgical point of view. Results of a prospective interdisciplinary multicenter observational study. DUSUK Study Group.

Various treatment policies and clinical disciplines compete for the treatment of bleeding peptic ulcer. In a prospective multicenter and interdisciplinary study performed during a 1-year period at ten hospitals in Düsseldorf, all patients admitted for peptic ulcer bleeding were recorded. The characteristics of patients admitted to surgical and to medical departments, the distribution of endoscopic treatment, indications for surgery, type of surgical procedures, and outcome were investigated. In the study period 387 bleeding peptic ulcers were recorded. Of these patients 82% were primarily admitted to medical and 18% to surgical departments. No differences in terms of severity of ulcer disease or bleeding activity were noted between the groups of medical and surgical patients. However, accompanying or underlying diseases were detected more often in patients admitted to medical departments. Endoscopy treatment was performed in the majority of patients with arterial spurting bleeding (88%) or a visible vessel (80%). Injection therapy with epinephrine or polidocanol was mainly used (78%). In 16% of cases the patients underwent operation; 44% of the patients primarily admitted to a surgical department were operated (medical departments, 10%). About half of the operated patients underwent emergency surgery; in the majority of cases resections were performed (gastric ulcer, 76%; duodenal ulcer, 56%). Overall mortality was 11%, with no difference between surgical and medical patients. A high mortality was observed in the subgroup of patients with late recurrent bleeding (27%). It is concluded that for optimal treatment of peptic ulcer bleeding intensive cooperation between physicians and surgeons is necessary, and that agreed and evaluated treatment policies are needed.

Aged↗

[Sonomorphology of stress cholecystitis].

Acute acalculous cholecystitis is a well-known complication in postoperative and particularly in severely traumatized unit patients. All that is known so far of "stress"-cholecystitis is based on episodic case reports and retrospective analyses. An incidence between 0.5 and 4.2%, a complicated clinical course and a lethality up to 75% have been reported. In intensive-care unit patients a clinical diagnosis of suspected acute cholecystitis is rarely reliable; greater reliance is placed on the ultrasound findings as seen in our prospective study. According to the literature, the established ultrasound criteria of cholecystitis include: hydrops, thickening of the gallbladder wall, sludge, subserosal oedema, pericholecystic fluid collection and fragmentation of the gallbladder wall. Other factors, however, may also lead to morphological changes of the gallbladder, and hence there is no agreement about the definitive sonomorphology of this entity. The variability of sonomorphological criteria is reviewed and compared to the results of a series of our own.

Acute Disease↗

Acute cholecystitis: a complication in severely injured intensive care patients.

Acute cholecystitis is an often unrecognized and potentially life-threatening complication seen among ICU patients with multiple injury. To investigate the epidemiology of this entity and to evaluate significant etiologic precursors, a prospective clinical and sonographic study was performed in 45 consecutive patients (mean age, 29 years) treated for multiple trauma (mean ISS, 27) in the ICU. Eight of 45 patients developed a cholecystitis during intensive care treatment (18%). Six patients recovered with conservative therapy; in two instances a cholecystectomy was necessary. There was no mortality as a result of cholecystitis. A significant relationship between the severity of the initial trauma (p less than 0.05), the number of blood transfusions (p less than 0.01), and the incidence of acute cholecystitis was found. Other factors such as prolonged shock, respiratory failure, or parenteral alimentation were less prevalent and were not temporally related to the onset of the disease. All patients had large amounts of narcotics administered over a prolonged period, so that narcotic-induced biliary stasis appeared to be another eminent factor involved in the genesis of posttraumatic cholecystitis. Our results lead to the conclusion that acute cholecystitis occurs with an unexpectedly high incidence and that a high remission rate can be expected following conservative treatment provided that appropriate serial ultrasound examinations are performed.

Acute Disease↗

Incidence and pattern of peptic ulcer bleeding in a defined geographical area. DUSUK Study Group.

Despite the introduction of effective medical treatment for peptic ulcer disease, no decrease in the incidence of bleeding has been observed. Unfortunately, most incidence studies rely on a questionable case ascertainment and poor data. We therefore conducted a prospective study, to achieve an unbiased estimate of incidence and pattern of peptic ulcer bleeding in Düsseldorf (Germany). In a 1-year period all patients with endoscopically verified peptic ulcer bleeding who were admitted to the departments of internal medicine or surgery in nine hospitals or seen by nine general practitioners offering endoscopic service were included in the study. Incidence rates were calculated in accordance with sociodemographic variables and expressed per 100,000 person-years of observation. The overall incidence of peptic ulcer bleeding was 51.4, with almost even rates for gastric (26.5) and duodenal (24.9) ulcer. Age was associated with an increased likelihood of bleeding in gastric ulcer patients of 19 per decade from about 40 years onwards (duodenal ulcer, 15). The incidence was about twice as high in men as in women (relative risk = 1.9). The pattern of peptic ulcer bleeding was similar in gastric and duodenal ulcers with regard to ulcer size, multiple lesions, and bleeding activity at endoscopy. However, patients with gastric ulcer bleeding had significantly more often accompanying or underlying diseases. No significant differences were observed between gastric and duodenal ulcer bleeding with regard to nonsteroidal antiinflammatory drug intake and ulcer history. The incidence rates in our study are in the upper range of the literature and comparable to rates from the USA and UK both before and after the introduction of H2 blockers. We hypothesize that the persistently high incidence rate is a superposition of two trends: higher incidences due to a more elderly and diseased population and more NSAID intake, and lower incidences due to effective medical treatment.

Adult↗

[The coronary sinus as a source of activated T-lymphocytes in patients after orthotopic heart transplantation].

Mononuclear cells are the component of blood responsible for allograft recognition, rejection and acceptance. Shifts in the patterns of various mononuclear cell subpopulations were often used as a diagnostic tool in detection of heart rejection. The specificity of mononuclear cell monitoring has remained a controversial point until today, because infections led to similar changes as organ rejection. In this study we investigated whether mononuclear cells taken from coronary sinus blood give more information about the immunological status of the transplanted heart than those taken from central verous blood. After endomyocardial biopsy, coronary sinus blood was sampled by catheterization under X-ray control. Blood from the right atrium was taken for control measurement. Mononuclear cells obtained by density gradient cytocentrifugation were stained with monoclonal fluorescein conjugated antibodies detecting CD4- (T helper)-, CD8- (T suppressor)-, CD25- (Interleukin-2 receptor), and the CD71- (Transferrin receptor) antigens. Endomyocardial biopsies were graded according to the Billingham scheme. In the absence of rejection, the phenotypes of mononuclear cells from the coronary sinus did not differ from those of right atrial cells. Mild rejection led to a statistically insignificant increase of CD4- CD25- and CD7-antigen bearing cells in the coronary sinus blood, whereas the CD8 positive cells remained stable as compared to mononuclear cells from the right atrium. However, patients with moderate rejection showed a significant elevation of CD4 positive cells and activated T-cells (CD15-, CD71-positive cells) in the coronary sinus as compared with cells from the right atrium. The T helper/suppressor ratio (Th/s-ratio) shifted towards the T-helper population.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-CD8 Ratio↗

Treatment of chronic active hepatitis and primary biliary cirrhosis with ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) improves liver function tests in patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). UDCA will reduce biochemical parameters of both cholestasis and hepatocellular damage. The effects may be less beneficial in patients with advanced stages of chronic liver disease: in PBC we found the improvement of laboratory parameters in stage I and II very impressive, in stage III and IV it was less marked. Data of two controlled trials in PBC showed an improvement in liver histology, in one study the improvement was statistically significant. UDCA can be administered for at least 10 years without any adverse effects, the treatment is safe and improves life quality. The mode of action of UDCA seems to be in its displacement of toxic hydrophobic bile salts from the bile acid pool and the hepatocellular membrane. In in-vitro investigations a direct protective effect of UDCA on isolated sinusoidal hepatocyte membranes against toxic bile salts has been shown. This protective effect of a more general nature may explain the efficacy of UDCA in different chronic, especially cholestatic liver diseases.

Adult↗

[Peritoneal lavage in the diagnosis of blunt injuries of hollow intra-abdominal organs].

In some cases of blunt abdominal trauma lesions of gastrointestinal tract are occasionally found. The difficulty with these injuries lies in establishing the diagnosis. Clinical examination alone does not reliable evidence, particularly if the patient is unconscious and therefore unable to respond subjectively. Although abdominal sonography ist becoming increasingly important in the diagnosis of blunt abdominal trauma lesions of the gastrointestinal tract frequently remain undetected or are diagnosed to late where this method of examination is used exclusively. In the retrospective analysis of our patients we have encountered serious complications such as peritonitis and even cases resulting in death. On the other hand when peritoneal lavage was employed, no false negative results occurred. Consequently the value of this method in the diagnosis of blunt abdominal trauma and possible lesions of the gastrointestinal tract is indisputable.

Abdominal Injuries↗

[Errors in lavage therapy in diffuse peritonitis].

The suppurative peritonitis is still one of the major clinical concerns for surgeons in these days. The presence of bacteria and endotoxins within the peritoneal cavity activate a chain of reactions, which mostly are still unknown, but frequently determinate the course of the disease. Because of the multifactorial system of the biochemical processes, we are coming to the paint to ask for a final chemical reaction of all these processes. The final reaction in this high toxic systems is taken place in an acidic pH range. Our experiments show, that the intraperitoneal alcalisation by lifting up the pH in the physiological range or even higher produces a stop in the septical reactions. Consequently because of these results we changed our treatment for severe peritonitis as followed: 1. Focus sanitation: Consequent treatment for the underlying cause of infection. 2. Continuous abdominal lavage over 4 catheters in each of the quadrants of the abdominal cavity with 101 of saline solution together with 8.4% Na-bicarbonate up to a pH-range of 7.6. 3. First revision of abdomen after 12 h after removing the catheters the normal intraoperative lavage with 10-15 1 saline solution with 8,5% Na-bicarbonate is performed. 4. The abdomen remains open and daily revisions and lavage with Na-bicarbonate are performed. 5. Early clinical data support the experimental findings.

Animals↗

[Problems and incidence of abdominoperineal impalement injuries].

In our population of trauma patients abdomino-perineal impalement injuries are very rare. With reference to our own patients we demonstrate the problems that arise with impalement injuries: infection, hemorrhage, intraabdominal organ lesions and difficulty in recognizing these. The necessity for elicitation of a precise history and meticulous diagnostic examination is undisputed. In our own patients we have always tried to achieve definitive therapy as a primary procedure. There have been no lethal complications.

Abdominal Injuries↗

[A new concept in surgical treatment of anal incontinence].

A new treatment of anal incontinence has been presented. This method combines the postanal repair of Parks with a sphincteroplasty by autologous large saphenous vein. The vein has no trophic requirements and has a high containing economy. Manometrically, a highly active high pressure zone has been proven. Histologic examinations have shown flubless healing in the intestinal wall of the free vein transplant when prestretched accordingly.

Anal Canal↗