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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 91 records · Page 5Linked to original sources
PubMed1999

[A method for continuous monitoring of total peripheral and pulmonary vascular resistance in high risk cardiac patients].

In this study we present a computer-assisted monitoring system ("Opserver") which allows a continuous registration of directly measured values: hear rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP, MAP): systolic, diastolic and mean pulmonary arterial pressure (PAPs, PAPd, PAPm), central venous pressure (CVP), mixed venous oxygen saturation (SvO2), pulse-oxymetrically measured oxygen saturation (SaO2), cardiac output (CO) and calculated haemodynamic parameters: cardiac index (CI), total peripheral vascular resistance (TPVR) and pulmonary vascular resistance (PVR). The basic principle of this on-line monitoring system is the registration of calculated parameters combining data of various devices by specially-developed software. The procedure is shown in several clinical examples. The advantages of this system are:--monitoring of critical haemodynamic responses in cardiac high-risk patients relating to induction and finishing of anaesthesia including in- and extubation, recovery from anaesthesia, operation and transport and--exact documentation of the data for the purpose of clinical studies. Based on continuous measurement, this monitoring system allows an optimum evaluation of cardiorespiratory acute incidents, thereby permitting a problem-oriented therapy in high-risk patients with vasoactive medication in the perioperative period and in the intensive care unit.

Anesthesia, General↗
PubMed1998

Micronucleus formation in human amnion cells after exposure to 50 Hz MF applied horizontally and vertically.

Micronucleus (MN) induction as a genotoxic effect of extremely-low-frequency electromagnetic fields (ELF-EMF, 50 Hz, 1 mT) was studied in human amniotic fluid cells (AFC) after continuous exposure to magnetic fields (MF), oriented horizontally and vertically with respect to the surface of the culture medium, at different time points. To compare the effectiveness of different exposure systems, a Helmholtz-coil system and a so-called Merritt-coil system was used. A statistically significant increase in MN frequency could be detected in exposed cells compared to controls after 72 h continuous exposure to MF applied vertically in the Merritt-coil system, while no effect was found after exposure in the Helmholtz-coil system. Furthermore, a significant increase in MN induction occurred after 24, 48 and 72 h exposure to MF applied horizontally in the Helmholtz-coil system in comparison to controls, whereas horizontally MF generated in the Merritt-coil system induced no genotoxic effects. To exclude suppression of indirect EMF-induced DNA-lesions, we studied MN formation in the presence of N-Acetyl-p-aminophenol (APAP, Paracetamol(R)), which is an inhibitor of DNA-repair mechanisms. We found a dose-dependent increase of MN formation in APAP-treated AFC cells, but no significant further increase in MN frequency after additional MF exposure. Therefore we conclude, that EMF-induced MN formation is not caused by directly or indirectly induced clastogenic mechanisms. The obtained results show that the orientation of MF with respect to the cell culture dish and the physical condition of the exposure system is of major importance for the induction of micronuclei in certain cell types. Therefore, the reason for inconsistent results published in the literature may be caused by the variability of exposure systems, the exposure conditions and the cell types used.

Acetaminophen↗
PubMed1998

Screening for hemochromatosis and iron deficiency in employees and primary care patients in Western Germany.

BACKGROUND: Many physicians still believe that iron overload (hemochromatosis) is an uncommon disorder. OBJECTIVE: To estimate the frequency of iron overload and iron deficiency in a group of employees and a group of outpatients. DESIGN: Prospective screening study. SETTING: Western Germany. PARTICIPANTS: 3012 asymptomatic employees and 3027 outpatients of nine practitioners. MEASUREMENTS: Serum ferritin levels and transferrin saturation were measured. Participants with repeatedly abnormal results had thorough clinical evaluations to identify the cause of iron deficiency or overload. RESULTS: Gross iron overload (elevated transferrin saturation and ferritin levels) was proven by liver biopsy and phlebotomy treatment in 28 participants (0.4% of female outpatients, 0.7% of male outpatients, 0.2% of female employees, and 0.4% of male employees) and in six siblings of these participants. Of the 34 participants with iron overload, 30 were precirrhotic. Because 60% of an unselected group of employees with elevated transferrin saturation but normal ferritin levels were assumed to have early hemochromatosis, the prevalence of hemochromatosis was estimated to be 1.8% among patients (1.9% in women and 1.6% in men) and 1.0% among employees (1.1% in women and 1.0% in men). Iron deficiency was found in 6.8% of female patients, 2.4% of male patients, 6.0% of female employees, and 0.5% of male employees. CONCLUSIONS: Iron deficiency was more common in women, and iron overload was more common in men. Among male employees, iron overload was almost as common as iron deficiency.

Adult↗
PubMed1998

Prognosis of chronic hepatitis C: results of a large, prospective cohort study.

The prognosis of chronic hepatitis C virus (HCV) infection is still ill-defined. The present study prospectively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti-HCV and HCV-RNA-positive patients who were followed for 50.2 +/- 26.9 months (mean +/- SD; range, 6-122 months) in a prospective protocol. During follow-up, 62 patients died (31 from liver disease and 31 from other causes), and 12 patients needed liver transplantation. When compared with a matched general population, hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry. During follow-up, a further 30 patients developed nonlethal complications of cirrhosis. By multivariate regression, survival was decreased by cirrhosis, long disease duration, history of intravenous drug abuse, and excessive alcohol consumption, whereas interferon therapy improved survival. Alanine transaminase (ALT), bilirubin, sex, and genotype had no effect on survival. The risk of hepatocellular carcinoma (HCC) (n = 17) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin, whereas interferon therapy, genotype, and other factors had no effect. Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis. Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis. The age at diagnosis therefore should play a major role in therapeutic considerations. The present data also suggest that interferon therapy has a long-term clinical benefit, although it did not reduce the risk of liver cancer.

Adult↗
PubMed1998

Practical experience with the design and analysis of a three-armed equivalence study.

OBJECTIVE: While there is a lot of experience with the design, conduct and interpretation of bioequivalence studies, the methodology of trials concerning therapeutic equivalence is still at an early stage of development. Two-armed equivalence studies involve special problems of interpretation, which can be partly solved by the introduction of a third (placebo) arm. We describe a trial in which the therapeutic equivalence of horse chestnut seed extract (HCSE) and compression treatment was to be demonstrated in patients with chronic venous insufficiency (CVI). Compression is regarded as the standard therapy in this field. However, the efficacy of compression in terms of the variable of primary interest, namely oedema reduction, has never been demonstrated according to current methodological rules. Thus, the 'standard' had to be established in the trial itself. This can be achieved by demonstration of relevant superiority in comparison with placebo. METHODS: Two hypotheses had to be tested: (1) the relevant superiority of compression compared with placebo as a precondition for (2) the at most irrelevant inferiority of HCSE in comparison with compression ('equivalence'). For both corresponding statistical tests, the irrelevance criterion -- formulated as standardized difference -- was set to 0.5. RESULTS: Therapeutic equivalence could not be demonstrated following this design, because compression failed to be relevantly superior compared with placebo, even though HCSE was shown to be at most irrelevantly inferior compared with compression. Explorative analyses show that it is not possible to reject simultaneously both null hypotheses with the obtained data when using equal irrelevance limits for both tests. CONCLUSION: Although the primary objective of the trial could not be achieved, the results were encouraging. Thus, a new study was planned and started based on the observed data. The concept of a shifted null hypothesis may be applied to 'routine' clinical trials too; using 'no difference' as the null hypothesis in a trial does not seem to be meaningful when in fact an at least relevant difference is required.

Clinical Trials as Topic↗
PubMed1998

Recombinant or plasma-derived antisecretory factor inhibits cholera toxin-induced increase in Evans blue permeation of rat intestinal capillaries.

The effect of cholera toxin on small intestinal capillary function, utilizing the Evans blue dye method, was analyzed. The modulatory influence of plasma-derived or recombinant human antisecretory factor on this variable was also investigated. Male Sprague-Dawley rats were briefly anesthetized with ether, and a jejunal loop was constructed that was challenged for 90 min with phosphate-buffered saline or cholera toxin. Five minutes prior to death, the rats received an intravenous injection of Evans blue. The tissue content of dye in the loop was quantitated spectrophotometrically or demonstrated histochemically. Cholera toxin increased the recovery of Evans blue; extravasation of the dye was prominent in the top of the villi, while the crypts were spared. It is suggested that the toxin caused increased transcapillary permeation of albumin in a heterogenous fashion in the gut wall. This effect of the toxin was prevented by pretreatment with the antisecretory factor.

Animals↗
PubMed1998

Endovascular therapy of brain AVMs prior to radiosurgery.

The purposes of this study were to determine the safety and efficacy of embolization of brain AVMs prior to radiosurgery and to evaluate the total obliteration rate achieved. The brain AVMs of 64 patients were subselectively embolized mainly with NBCA, platinum microcoils and/or PVA. The aim of embolization was the reduction of the target volume and/or the elimination of vascular structures bearing an increased risk of hemorrhage. Presenting symptoms were intracranial hemorrhage in 33 patients, a seizure disorder in 21 patients, and headache in 6 patients. Four AVMs had been detected as an incidental finding. The initial AVM volume was in the range of 0.5 to 84 cc (mean 17 cc). Grading of the AVMs according to the Spetzler-Martin scale showed the following distribution: grade I, 3x; II, 13x; III, 11x; IV, 17x; V, 4x; VI, 16x. A total of 300 endovascular procedures including 47 subselective catheterizations without and 253 with embolization were performed. A size reduction of the AVMs between 10% and 95% (mean 63%, median 70%) was achieved. Neurological symptoms due to treatment complications were transient in 12 patients, of minor clinical significance but permanent in 4 patients. Following radiosurgery, one patient died due to recurrent intracerebral hemorrhage. Three patients are doing well but refused final follow-up angiography. A total of 30 patients is currently within the latency interval after radiosurgery. Radiosurgery failed to obliterate the embolized AVMs in 16 patients. Angiography confirmed complete nidus obliteration in 14 patients. The endovascular treatment of brain AVMs prior to radiosurgery proved safe and effective and may be considered in either high grade or incidental AVMs. AVM obliteration after embolization and radiosurgery is less frequently achieved than after stereotactic irradiation of primarily small AVMs.

Adolescent↗
PubMed1997

Identification of an active site in the antisecretory factor protein.

The antisecretory factor (AF) is a new regulatory protein, produced in the human pituitary gland, which reverses intestinal fluid secretion induced by cholera toxin. We have previously described the cDNA-cloning and characterization of the expressed gene. The aim of this study was to identify the region responsible for the antisecretory activity in the AF-molecule. The recombinant full-length AF has an increased ability to inhibit hypersecretion after treatment with trypsin, indicating that the activity of AF is achieved by smaller peptide fragments. To localize the active region of AF, we expressed truncated forms of the recombinant protein and examined their antisecretory activity against cholera toxin-induced fluid secretion in rat. Nine recombinant AF peptides and four smaller peptides made by solid phase synthesis were tested. Five of the peptides lacked all activity, whereas seven of them were highly active, a dose between 4 and 15 pmol causing a half-maximal inhibition. All the active peptides contained amino acid 36-42 of the AF sequence, whereas none of the inactive peptides contained this sequence. Our results suggest that the site of the antisecretory activity resides in a small region (I)VCHSKTR between position 35 and 42 of the AF molecule.

Amino Acid Sequence↗
PubMed1997

Interaction of earthworm hemolysin with lipid membranes requires sphingolipids.

Lytic activity in the coelomic fluid of earthworm (Eisenia fetida fetida) has been ascribed to eiseniapore, a hemolytic protein of 38 kDa. Since receptors for eiseniapore on target cell membranes are not known, we used lipid vesicles of various composition to determine whether specific lipids may serve as receptors. Lytic activity of eiseniapore was probed by the relief of fluorescence dequenching from the fluorophore 8-aminonaphthalene-1,3, 6-trisulfonic acid originally incorporated into the vesicle lumen as a complex with p-xylene-bis-pyridinium bromide. Hemolysin binds to and disturbs the lipid bilayer only when distinct sphingolipids consisting of a hydrophilic head group as phosphorylcholine or galactosyl as well as the ceramide backbone, e.g. sphingomyelin, are present. Cholesterol enhances eiseniapore lytic activity toward sphingomyelin-containing vesicles probably due to interaction with sphingomyelin. Leakage of vesicles was most efficient when the lipid composition resembled that of the outer leaflet of human erythrocytes. Presumably, an oligomeric protein pore formed by six monomers is responsible for leakage of sphingomyelin-containing vesicles. The secondary structure of eiseniapore did not change upon binding to lipid membranes. The lytic activity of eiseniapore was completely abolished after its denaturation or after preincubation with polyclonal antibodies. Our results suggest that the presence of specific sphingolipids is sufficient to mediate lytic activity of eiseniapore. This action contributes to our understanding of earthworm immune responses.

Animals↗
PubMed1997

[The concept of therapeutic equivalence].

Usually, it is the purpose of a clinical trial to demonstrate the superiority of a (new) treatment in comparison to another treatment with regard to a well-defined criterion of efficacy. However, other aspects rather than improved efficacy might be regarded as advantages of a new therapy, i.e. less or less severe adverse events, a more simple applicability, or a lower price. In this case, it may be sufficient to show a "comparable" efficacy (therapeutic equivalence). Unfortunately, equivalence studies can lead to severe problems of interpretation in case of insufficient methodological planning. In general, more detailed information must be available in advance compared to the common (superiority) trials. Very carefully designed trials are necessary to evaluate the therapeutic equivalence of treatments.

Clinical Trials as Topic↗
PubMed1997

Effect of ganglionic blocking compounds on in-vivo fluid secretion in the rat small intestine.

It is well-known that enteric, secreto-motor nerves mediate cholera toxin-induced fluid secretion in the rat small intestine. This notion is, in part, derived from experiments on anaesthetized animals in which the response to cholera toxin was antagonized by the ganglionic nicotinic receptor antagonist, hexamethonium. In the current study, such anti-secretory action of ganglionic blocking compounds was analysed in an experiment designed to minimize any possible negative effect of general anaesthesia on intestinal secretion. Rats were anaesthetized with ether for 5-10 min, during which time a jejunal loop (10-12 cm) was constructed. The loop was challenged with one of the secretagogues, cholera toxin, prostaglandin E1 (PGE1) or okadaic acid. Saline (control) or either of the ganglionic blockers, hexamethonium and chlorisondamine, was administered intravenously. The rats were killed 5 h (cholera toxin) or 1.5 h (PGE1 and okadaic acid) after challenge, and the amount of fluid accumulated in the loops was determined. Cholera toxin-induced secretion was unchanged by hexamethonium but reduced by approximately 80% by chlorisondamine. The difference in effect between the two blockers might relate to the duration of ganglionic blockade. Chlorisondamine blocked secretion induced by either PGE1 or okadaic acid by approximately 60%. It is suggested that the anti-secretory effect of ganglionic blocking compounds might be a result of blockade of secreto-motor nerves but other mechanisms, for example interference with haemodynamic factors, cannot be ruled out.

Alprostadil↗
PubMed1997

Antisecretory factor suppresses intestinal inflammation and hypersecretion.

BACKGROUND: Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin. AIMS: To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A from Clostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa. METHODS: Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 microgram of toxin A or 3 micrograms of okadaic acid administered before or after injection of 0.1 microgram of recombinant AF (rAF). RESULTS: The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55-80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF. CONCLUSION: Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system.

Animals↗
PubMed1997

High Pressure Coronary Stenting: Efficacy and Safety of Aspirin Versus Coumadin Plus Aspirin Ñ Preliminary Results of a Randomized Study.

The efficacy and safety of treatment after coronary stenting was examined with aspirin alone, 100 mg daily, as compared to coumadin plus aspirin. Data from the first 101 patients, 73 men and 28 women, aged 59.2 +/- 9.3 years, of a prospective randomized study are presented in this preliminary report. Forty-eight patients suffered from one-vessel disease, 32 had two- and 21 three-vessel disease. Indications for stenting were stable angina in 65 patients, unstable angina in 16, threatening myocardial infarction in 4 and restenosis in 16 patients. The stents were implanted by high pressure balloon inflation (14.5 +/- 2.2 atm), 55 of them were Palmaz-Schatz, 31 Micro, 10 Gianturco-Roubin, 2 Wiktor and 3 combined stents. Intravascular ultrasonographic guidance was not performed. The primary end point was defined as the absence of the following events: death, subacute coronary artery closure, acute myocardial infarction, emergency coronary bypass surgery, repeated PTCA, major bleeding or arterio-venous aneurysms needing transfusion or surgery. Eighty out of 101 patients (79.2%), 41 out of 47 (87.2%) in the aspirin group and 39 out of 54 (72.2%) in the coumadin plus aspirin group (p = 0.06) were free of events during hospitalization (9.5 +/- 5.7 days, median: 8 days). Forty-five out of 47 patients (95.7%) in the aspirin and 51 out of 54 (94.4%) in the coumadin plus aspirin group (p = 0.8) were without subacute closure. One death occurred in the aspirin group due to stent abscess two weeks after an angiographically successful stent recanalization. All 7 arterio-venous aneurysms with surgical interventions occurred in the coumadin group (p = 0.01). No emergency bypass surgery had to be performed. If these preliminary results will be confirmed by the final analysis, the combination of coumadin with aspirin does not show more efficacy or safety as compared with aspirin alone in the treatment after high-pressure coronary stenting during the hospital stay.

Journal Article↗
PubMed1997

[Penile metastasis of recto-sigmoid adenocarcinoma. Apropos of a case].

Metastases to the penis from rectocolic adenocarcinoma are extremely uncommon with 50 cases reported; the diagnosis is often delayed and the prognosis is very poor. The choice between an aggressive surgical approach and a palliative treatment is difficult, but surgery seems to give the best results in limited penile lesions. The authors report a case of metastatic involvement of the penis by a recurrent rectocolic adenocarcinoma in a 42 year old patient. A MR scan was performed before surgical treatment of both lesions.

Adenocarcinoma↗