[The effects of multimodal intervention for the primary prevention of cardiovascular diseases on depression, anxiety, and Type-D pattern: initial results of the randomized controlled PreFord trial]. / Effekte einer multimodalen Intervention zur Primärprävention kardiovaskulärer Krankheiten auf Depressivität, Angst und Typ-D-Muster: Erste Ergebnisse der randomisierten, kontrollierten PräFord-Studie.

Depression, anxiety, and Type-D pattern are associated with the earlier development and faster progression of cardiovascular disease (CVD). The aim of the randomized controlled PreFord trial was to improve multiple biological and psychosocial risk factors in the primary prevention of CVD. A total of 447 women and men with an ESC risk score >5% were randomly assigned to either multimodal or routine care groups. Somatic and psychosocial variables (HADS, DS-14) were assessed before and after the intervention, and annually for 2 years thereafter. The intervention showed no significant effects on the symptoms of depression, anxiety, and type D personality, either in the whole sample or in those with elevated scores at baseline. Thus, our study did not provide evidence that symptoms of depression, anxiety, or Type D personality can be effectively treated by multimodal behavioral interventions for the primary prevention of CVD.

Multiphase stochastic model for fluidized beds.

This article introduces a type of stochastic model, which we call a multiphase stochastic model, for the particle transport in bubbling fluidized beds, making it possible to take into account the finite velocity of fluidization bubbles and also extra particle transport due to "gulf streaming." An extended analysis of experimental results for particle transport in fluidized beds with gulf streaming is given, and results from the model are compared with the experimental results, showing that the model accounts for the effects seen.

[The PreFord Study. A prospective cohort study to evaluate the risk of a cardiovascular event (overall-collective) as well as a prospective, randomized, controlled, multicentre clinical intervention study (high-risk-collective) on primary prevention of cardiovascular diseases in the Ford Motor Company employees in Germany]. / Die PräFord-Studie. Prospektive Kohortenstudie zur Bewertung des Risikos für ein kardiovaskuläres Akutereignis (Gesamtkollektiv) sowie eine prospektive, randomisierte, kontrollierte, multizentrische klinische Interventionsstudie (Hochrisikoteilkollektiv) in der Primärprävention von Herz-Kreislauferkrankungen bei Mitarbeitern der Firma Ford in Deutschland.

The PreFord Study is a multicenter prospective cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases. Furthermore a randomised controlled trial (RCT) will be designed to analyse the effect of a special intervention program. 40,000 employees of the Ford Motor Company, Visteon Company and Deutz Company in Germany will be included, monitored for ten years and the following primary endpoints will be investigated: 1. evaluation and comparison of established and newly developed risk-scores, 2. the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases, 3. the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint: risk reduction by, 4. the influence of this intervention on secondary endpoints: death, myocardial infarction and stroke, combined appearance of angina pectoris and hospitalisation, occurrence of cerebral circulatory disorder and hospitalisation, occurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit-analysis. Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles, of anthropometric data and different lifestyle-factors. Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology (risk of a lethal primary acute cardiovascular event: I < or = 1%; II > 1-< 5% and III > or = 5%). In the following longitudinal study different strategies will be applied: Group I: low risk (< 0.5% per year): repetition of the investigation after five and ten years. Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation every two years, instruction of the patients general practitioner (GP) with respect to a risk factor oriented and evidence based treatment. Group III: high risk, (> 1.5% per year or >15% within the next 10 years) will be randomised into two interventional groups. The first one, the intervention-group "PreFord" will perform an occupational integrated rehabilitation program (2,5-3 hours twice a week, for 15 weeks according to the BAR guidelines) with a following engagement in heart-groups and an annual repetition of the check-ups. The second group, the "classic" intervention-group will be treated evidence based in cooperation with their GP. As a result of this long term interventional study efficient, area wide implementable and economically feasible prevention concepts with special regards to operational healthcare will be developed and evaluated. Core elements will be exercise- and lifestyle-oriented concepts as well as guideline-based pharmacotherapy.

Pain assessment and management in critically ill postoperative and trauma patients: a multisite study.

BACKGROUND: Pain in critically ill patients is undertreated. OBJECTIVES: To examine patients' perceptions of pain and acute pain management practices in a large metropolitan area to provide direction for improvements in pain relief. METHODS: In a descriptive, correlational study, data were collected from 213 patients in 13 hospitals. Interviews with patients, chart reviews, and interviews with nurse leaders were used to examine institutional and individual approaches to pain management. RESULTS: Twenty-eight percent of patients did not recall an explanation of a pain management plan, and 64% were often in moderate to severe pain while in the intensive care unit. High pain intensity correlated with wait for an analgesic (P < .001), expectations of less pain (P < .001), and longer stay in the intensive care unit (P < .001). Low satisfaction correlated with expectations of less pain (P < .001), often being in moderate to severe pain (P < .001), and long wait for an analgesic (P < .001). In the first 24 hours postoperatively, only 54% of patients had a numerical pain rating documented; 91% had a pain description. The amount of opioid given on postoperative day 1 was influenced by pain intensity (P < .001), the patient's age (P = .03), type of surgery (P = .002), and route of analgesic (P < .001). Only 33% of patients had nonpharmacological pain interventions documented. CONCLUSIONS: Despite moderate to severe pain, patients are generally satisfied with their pain relief. Measuring patients' satisfaction alone is not a reliable outcome for determining the effectiveness of pain management. Realistic expectations of patients about their pain may enhance coping, increase satisfaction, and decrease pain intensity after surgery.

Universal approximation in p-mean by neural networks.

A feedforward neural net with d input neurons and with a single hidden layer of n neurons is given byg(x(1), em leader,x(d))= summation operator j=1na(j)sigma,where a(j), theta(j), w(ji) in R. In this paper we study the approximation of arbitrary functions F:R(d)-->R by a neural net in an L(p)(&mgr;) norm for some finite measure &mgr; on R(d). We prove that under natural moment conditions, a neural net with non-polynomial function can approximate any given function.

Endoscopic (-ERC) fibrin sealing and histoacryl sealing of an abscess induced bilio-hepatico-cutaneous and a bilio-hepatico-phrenico-bronchial fistulous system.

We report the case of a female patient with persisting bilio-bronchial and bilio-cutaneous fistulae originating in the right liver lobe. The causative factor was a subphrenic liver abscess which had been adequately and successfully treated. No biliary obstruction was detectable on admission. Because of her previous medical history the patient was considered to be a high surgical risk. Therefore the described endoscopic (ERC) approach was chosen. Here we describe the first successful attempt to close such a fistulous system by repeated fibrin and histoacryl-sealing through an endoscopically guided catheter. The success of this innovative procedure may be helpful, in the management of similar cases in the future.

Adenocarcinoma arising from ectopic gastric pancreas: two case reports with a review of the literature.

Adenocarcinoma is a common histological diagnosis of gastric neoplasias. Only if typical elements of pancreatic structures are found nearby or in the tumor, this particular origin can be proven. The development of a carcinoma within ectopic (or heterotopic) pancreas is extremely rare. Because of the accidental observation of two of such cases this topic is discussed in the present report. There are only sporadic cases available in literature and these mostly refer to pancreatic ectopy localized in the stomach or duodenum. Due to their origin and spread, the tumors form an intramural mass with relatively late mucosal invasion. Therefore malignancy is difficult to prove by endoscopic biopsy. In general the patients' prognosis is poor, survival varying between months and many years.

Influence of cholesterol supply on cell growth and differentiation in cultured enterocytes (CaCo-2).

When used as treatment for hypercholesterolemia HMG-CoA reductase inhibitors will first pass through and act upon the gut mucosa. Although cholesterol availability is essential for cell growth of the intestinal mucosa adverse intestinal events are rare which is possibly due to hitherto undefined compensatory mechanisms. In the present work we therefore studied the long-term influence of mevinolin on proliferation and differentiation of CaCo-2 cells as an enterocyte model and their response upon the cholesterol supply of different origin. Mevinolin caused a marked and dose-dependent inhibition of cell proliferation, microvilli length and alkaline phosphatase. This parallel suppression was reversed by the addition of either exogenous free cholesterol, endogenous cholesterol from mevalonolactone or LDL but not HDL3. Surprisingly, sucrase activity reacted in an inverse fashion to alkaline phosphatase activity. Mevinolin induced enzyme activity and this was further enhanced by mevalonolactone supply, while cholesterol and LDL normalized sucrase to controls. In conclusion, the presence of luminal cholesterol as well as plasma LDL as the cholesterol source for the enterocyte may prevent mevinolin toxicity.

HDL3-mediated cholesterol efflux from cultured enterocytes: the role of apoproteins A-I and A-II.

High density lipoproteins (HDL) were recently demonstrated in an enterocyte model (CaCo-2 cells) to mediate reverse cholesterol transport by retroendocytosis. The present study was carried out to define the role of the major HDL apoproteins (apo) A-I and apo A-II in this pathway. HDL3 was fractionated by heparin affinity chromatography into the two main fractions containing either apo A-I only (fraction A) or both apo A-I and apo A-II (fraction B). In addition, liposomes were reconstituted from purified apo A-I or apo A-II and dimyristoyl phosphatidylcholine. The cell binding properties and cholesterol efflux potential were studied in the lipoprotein fractions and the liposomes. Both fractions exhibited similar maximal binding capacities of 4427 (A) and 5041 (B) ng/mg cell protein, but their dissociation constants differed (40.5 and 167.7 micrograms/mL, respectively). Fraction A induced cholesterol efflux and stimulated cholesterol synthesis more than did fraction B. Fraction A mobilized both cellular free and esterified cholesterol, whereas fraction B preferentially mobilized cholesteryl esters. Liposomes, containing either apo A-I or apo A-II, showed specific binding, endocytosis and endosomal transport, and were released as intact particles. Apo A-I liposomes also mediated cholesterol efflux. In conclusion, there is evidence that the HDL3 subfractions A and B, as well as reconstituted liposomes containing either apo A-I or apo A-II, were specifically bound and entered a retroendocytosis pathway which was directly linked to cholesterol efflux. Quantitatively, the apo A-I subfraction appeared to play the dominant role in normal enterocytes. The apo A-II content of fraction B was related to the mobilization of cholesteryl esters.

Gastroduodenal ulcer hemorrhage: endoscopic injection therapy using a fibrin sealant.

In a retrospective analysis of bleeding upper gastrointestinal ulcers we examined the clinical outcome of the patients observed during the period 1989-1991. Out of 452 patients with benign gastric or duodenal ulcers, 85 patients exhibited stigmata of fresh bleeding (5.9% Forrest Ia, 24.7% Ib, 45.9% IIa and 23.5 IIb) and were treated endoscopically by the injection of fibrin sealant with or without additional hypertonic saline plus epinephrine. The endoscopic therapy was repeated until Forrest grade III was reached. Initial endoscopic hemostasis was achieved in all, permanent hemostasis in 85.9%, of the patients treated. The overall bleeding-associated mortality was 7.0%, in 9.4% continued bleeding required surgery. No therapy-associated complications were seen. Interestingly, the fibrin clot appeared to induce rapid healing of ulcers. It may be concluded that fibrin sealing is a complication-free, highly effective endoscopic therapy.

Polyamine deficiency impairs proliferation and differentiation of cultured enterocytes (CaCo-2).

The polyamine dependence of enterocyte growth and differentiation was studied in the human intestinal cell line CaCo-2 using a specific inhibitor of the key enzyme ornithine decarboxylase (ODC), difluoromethylornithine (DFMO). ODC was highest during the initial phase of rapid growth and was inhibited in a dose dependent fashion by DFMO at 0.06-2 mM. At low levels DFMO only delayed cell replication without affecting final cell count whereas at concentrations of 0.125 mM and above the final cell number was diminished by at least 53% compared to controls. In contrast, DFMO even at 0.03 mM reduced sucrase activity to 44% of controls when added at day 2 but was ineffective when supplemented at day 7 of culture or later. The inhibitor also diminished the number and length of microvilli in a dose dependent fashion, although this effect required higher DFMO levels than the reduction of sucrase activity. The DFMO mediated suppression of cell replication, enzymatic and morphologic differentiation was reversible in the presence of the ODC product putrescine. Putrescine alone did not affect any of the above parameters. In conclusion, the present data suggest that ODC and polyamines are involved both in enterocyte growth and differentiation.

[Idiopathic ulcer of the small intestine]. / Idiopathisches Dünndarmulcus.

The authors report on a female patient, 32 years old, suffering for eight years from recurrent and progressive abdominal pain, combined with chronic anemia, due to iron deficiency. Neither anamnesis and clinical course, nor technical examinations elucidated the etiology. Finally an explorative laparotomy with segmental resection of the small intestine led to diagnosis and healing of the rare "idiopathic small bowel ulcer". Possible differential diagnoses were lacking. This case report demonstrates the need of an invasive and aggressive diagnostic approach after excluding all common causes of disease, related to the symptoms, in order to prevent patients from suffering for years.

[Bilateral rupture of the quadriceps tendon--case report and review of the literature]. / Die beidseitige Quadricepssehnenruptur--Fallbeschreibung und Literaturübersicht.

We report a very rare case of bilateral simultaneous rupture of the quadriceps tendons in a 64-year-old patient following a minor trauma. The reconstruction of the ruptured tendons was achieved by intertwined PDS-sutures which were supportively fixed in the patellae. After wound healing, the patient was mobilized in his two casts which were applied for 6 weeks. After the period of one year, a satisfactory result could be seen. We report the etiology, pathogenesis, diagnosis, therapy and postoperative treatment which are described in the literature.

Mevinolin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, suppresses enterocyte esterification of exogenous but not endogenous cholesterol.

Mevinolin (lovastatin), a competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase, directly inhibited acyl-CoA cholesteryl acyltransferase in rabbit intestinal microsomes at a dose of 20 micrograms/ml or more. Lineweaver-Burk analysis showed a competitive type of inhibition with respect to oleoyl-CoA. In cultured intestinal Caco-2 cells, mevinolin reduced [14C]oleate incorporation into cholesteryl-esters by 86% of controls at doses as low as 0.1 micrograms/ml. However, in cells whose activity of acyl-CoA cholesteryl acyltransferase was stimulated 7-fold by 10 mM mevalonolactone, a significant inhibitory effect on cholesteryl-ester formation could not be detected, even at 40 micrograms/ml of mevinolin. In contrast, cells supplied with liposomal cholesterol or cholesterol derived from low-density lipoproteins showed a marked reduction of cholesteryl-ester formation in the presence of 10 or 0.1 micrograms/ml of mevinolin, respectively. It is concluded that the observed suppressive effects of mevinolin on cholesterol esterification in cultured Caco-2 cells are indirect and possibly caused by changes in the acyl-CoA cholesteryl acyltransferase substrate pool or intracellular cholesterol transport.

High-density lipoprotein 3 retroendocytosis: a new lipoprotein pathway in the enterocyte (Caco-2).

The present study in Caco-2 cells, derived from a human colon carcinoma and capable of enterocyte differentiation in culture, describes a retroendocytotic pathway for high-density lipoprotein 3 (HDL3). These cells exhibit specific binding of apolipoprotein E-free HDL3 which was competed for by HDL3 but not by low-density lipoproteins. At 37 degrees C, degradation was negligible and intact particles were internalized and resecreted into the medium within 2 hours. Electron microscopy showed binding and internalization of gold-labeled HDL3 in coated pit regions and transport in endosomes distinct from lysosomes to lipid droplets. The fusion of these endosomes with lipid droplets was followed by their dissolution and the subsequent extrusion of HDL particles from the cells. Fluorescence labeling studies of HDL3 supported cytosolic transport in vesicles. Specific binding showed negative feedback regulation by HDL3, was modulated by alterations in cellular cholesterol content, and increased with the cellular state of differentiation. HDL3 mediated efflux of endogenously labeled cholesterol. It is concluded that intact HDL3 is bound specifically by Caco-2 cells, leading to a subsequent intracellular passage and resecretion through a process of retroendocytosis effecting the efflux of cellular cholesterol.

Regulation of cholesterol metabolism and low-density lipoprotein binding in human intestinal Caco-2 cells.

In the present paper, the regulation of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, acylcoenzyme A cholesterol acyltransferase (ACAT) and low-density lipoprotein (LDL) binding was studied in the human colon cancer carcinoma cell line Caco-2. LDL down-regulated HMG-CoA reductase activity in a dose-dependent fashion to a minimum of 28% of control at 200 micrograms/ml and LDL binding to 52% of control. The activity of ACAT was stimulated by LDL. High-density lipoprotein 3 (HDL3) increased HMG-CoA reductase activity, whereas cholesteryl ester formation was slightly decreased. Inhibition of the endogenous cholesterol biosynthesis by mevinolin increased both LDL binding and activity of HMG-CoA reductase. This effect was reversed by the addition of mevalonolactone but not by LDL. It is concluded that regulation of HMG-CoA reductase and LDL binding is subject to the availability of non-sterol products of mevalonic acid and of exogenous cholesterol. ACAT is regulated mainly by the level of its substrate cholesterol.

Compartmentalization of cholesterol metabolism and cellular growth in cultured intestinal crypt cells.

Growth of rat intestinal crypt derived cells IEC-6 ceased when the key enzyme of cholesterol synthesis, hydroxymethylglutaryl-CoA reductase, was blocked by the competitive inhibitor mevinolin. This effect was reversed by the addition of mevalonolactone. LDL suppressed reductase activity as well as cholesterol synthesis from [14C]octanoate and stimulated acyl-CoA cholesterol acyltransferase, but failed to support cell growth despite rapid receptor mediated degradation even in the presence of low mevalonolactone concentrations. Inhibition of cholesterol esterification by Sandoz-Compound 58-035 enhanced cell growth in the presence of mevinolin, but did not promote proliferation in the additional presence of low-density lipoproteins. HDL3 but not HDL2 or tetranitromethane-modified HDL3 totally reversed the mevinolin induced inhibition of cell growth. This rescue by HDL3 was overcome by an increased dose of mevinolin. HDL3 derepressed reductase, stimulated cholesterol synthesis and reduced cholesterol esterification, but did not reverse the cholesterol synthesis inhibition by mevinolin. It is concluded that IEC-6 cells preferentially use endogenously synthesized cholesterol for membrane formation rather than low-density lipoprotein cholesterol. High-density lipoproteins appear to normalize cell growth in the presence of mevinolin by inhibition of cholesterol esterification and probably by inducing the formation of non sterol products of mevalonate.