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Background: As early as 1997, the German Guideline for Guidelines laid down patient participation in guideline development as the cornerstone of good, trustworthy medical guidelines. The German Guideline Assessment Tool (DELBI) published in 2005 requires patients or relatives to be involved in the development of medical guidelines. Ideally, this should be effected through membership in the author group. The Association of the Scientific Medical Societies in Germany (AWMF) recommends this approach for the so-called S3 guidelines (systematically developed guidelines) and S2k guidelines (consensus-based guidelines). The present study addresses the question of whether and to what extent German guideline publishers adhere to these principles of patient orientation., Methods: For this purpose, a descriptive analysis of the guidelines valid at the beginning of November 2017 was carried out. All guidelines (n=520) of the AWMF member societies were assessed. We evaluated S3- and S2k guidelines only, as these are of particular importance for patient involvement due to the requirement of an interdisciplinary guideline group. Data were reported on the involvement of patients (as co-authors of medical guidelines) and on the existence of guidance documents addressing patients and the public (so-called patient information and patient guidelines)., Results: Regarding the 105 (165) S3 (S2k) guidelines, we found evidence on patient involvement in guideline development in 99 (134) cases (94 % of S3 / 81 % of S2k guidelines). In 61 (87) guidelines, authors had contributed to the authors group (58 % / 53 %) and 59 (80) guidelines with voting rights (56 % / 48 %). For 50 (15) S3 (S2k) guidelines (48 % / 9 %), the guideline report provided information on the existence or planned development of guidance documents for patients and the public (patient guidelines or patient information). Guidance-related patient information was available on the internet for only 37 (2) S3 (S2k) guidelines (35 % / 2 %)., Conclusion: A substantial gap remains between patient / public involvement standards for guideline development and practice in Germany, even 12 years after the publication of national guideline standards. This is a missed opportunity since guidelines without adequate participation of those affected by the recommendations have a problem of legitimacy and transparency. Only guidelines where patients were involved in all voting processes during development build and strengthen trust between patients and the medical profession. And only those who present the rationale for medical recommendations in a generally understandable and comprehensible manner let affected individuals make individual decisions., (Copyright © 2018. Published by Elsevier GmbH.)

The problems of national health system in the European Community member states and affiliating countries will be discussed. Particular attention will be paid to team doctor model, continuous medical education, social security system and disease management programme.

Unlabelled: PURPOSE, MATERIAL AND METHODS: The aim of this study was to investigate the influence of direct intraarterial application of the contrast agents Iodixanol-270 and Iopentol-150 on the capillary perfusion. This was accomplished through continuous recording of the capillary perfusion in the nailfold capillaries of the right hand before and after a bolus injection of 20 ml of contrast agent into the right axillary artery., Results: After injecting 20 ml of Iodixanol-270, which has a high viscosity compared to the plasma viscosity, a statistically significant decrease in the erythrocyte velocity of 60.8% from 0.439+/-0.273 mm/s to 0.172+/-0.090 mm/s was observed already 10 s after the injection (p = 0.0001). The decreased velocity was maintained until the end of the observation period of 6 min. In contrast to this finding, no change in the erythrocyte velocity was observed after injection of 20 ml of the low-viscous Iopentol-150 (p = 0.1508)., Conclusions: The erythrocyte velocity in cutaneous capillaries therefore strongly depends on the viscosity of the contrast agent.

In this study, the regulation of mitochondrial Ca2+ transport by polyamines structurally related to spermine and by analogous polycationic compounds was characterized. Similar to spermine, a number of amino groups containing cationic compounds exerted a dual effect on Ca2+ transport of isolated rat liver mitochondria: a decrease in Ca2+ uptake velocity and an enhancement of Ca2+ accumulation. In contrast to the effects of spermine and other aliphatic polyamines, however, the accumulation-enhancing effect of aminoglucosides, basic polypeptides, and metal-amine complexes turned into an inhibition of Ca2+ accumulation at higher concentrations. Within groups of structurally related compounds, the potency to decrease Ca2+ uptake velocity and to enhance Ca2+ accumulation correlated with the number of cationic charges. The presence of multiple, distributed cationic charges was a necessary, but not sufficient criterion for effects on mitochondrial Ca2+ transport, because cationic polyamines and basic oligopeptides which did not enhance mitochondrial Ca2+ accumulation could be identified. Spermine was not able to antagonize the blocking of Ca2+ uptake by ruthenium red, but rather showed an apparent synergism, which can be explained as a displacement of membrane-bound Ca2+ by spermine. The aminoglucosides, gentamicin and neomycin, but not the inactive polyamine bis(hexamethylene)-triamine, inhibited the binding of spermine to intact mitochondria. Apparently, the binding of spermine, gentamicin, and a number of polyamine analogues to low-affinity binding sites at mitochondria, which have low, but distinct structural requirements and which may correspond to phospholipid headgroups, indirectly influences the activity state of the mitochondrial Ca2+ uniporter. The ability of aminoglucosides to displace spermine from the mitochondria and to inhibit mitochondrial Ca2+ accumulation may contribute to the mitochondrial lesions, which are known to occur early in the course of aminoglucoside-induced nephrotoxicity.

A Ca(2+)-dependent stimulation of mitochondrial phospholipase A2 is often assumed to play a role in mitochondrial Ca2+ release. We sought to clarify this relation by measuring Ca2+ transport and determining phospholipase A2 reaction products from the same sample of isolated, incubated rat liver mitochondria. When mitochondria had accumulated and spontaneously released again Ca2+, most probably by membrane permeability transition, there was no increase of phospholipase A2 reaction products. However, when the incubation was continued after Ca2+ release, significant increases of the content of lysophosphatidylcholine and unesterified fatty acids could be seen. Quinacrine, an inhibitor of phospholipase A2 activity, prevented Ca2+ release and p-hydroxymercuribenzoic acid, an inhibitor of lysophospholipid reesterification, induced a fast release of Ca2+ from isolated mitochondria. Such effects are usually taken as indirect evidence for a participation of phospholipase A2 in mitochondrial Ca2+ release, but analysis of the mitochondrial lipids revealed that no significant changes of the mass of phospholipase A2 reaction products had occurred. These experiments suggest that the accumulation of phospholipase A2 reaction products in mitochondria is the consequence rather than the cause of the membrane permeability transition. Exogenous phospholipase A2 products, lysophosphatidylcholine and arachidonic acid, induced mitochondrial Ca2+ release after a time lag, which decreased with aging of the mitochondrial preparation. The amount of lysophosphatidylcholine taken up by the mitochondria from the incubation medium during these experiments was measured and compared to the amount of lysophosphatidylcholine produced endogenously by mitochondrial phospholipase A2. From these data it appears likely that the amount of lysophosphatidylcholine generated in the mitochondria after the permeability transition is sufficient to sustain the permeable state. An accumulation of mitochondrially generated phospholipase A2 reaction products after the permeability transition could thus be a decisive factor for the limited reversibility of the membrane permeability transition.

In the period October 1993-February 1994, we performed three distal stomach resection operations laparoscopically (two Billroth-II anastomoses, one Billroth-I anastomosis combined with truncal vagotomy). The first patient, 83-year old, presented a stenosing, bleeding, prepyloric, malignant Non-Hodgkin lymphoma. The second patient, 84-year old, presented an ulcerated, non-malignant leiomyoblastoma of the antrum. Due to the histological type of the tumors a radical lymphadenectomy was not performed. The partially resected stomach (two thirds) was removed in a lap sac through a 3.5 cm infraumbilical incision. The third patient presented a persisting, prepyloric ulcer combined with an almost complete stenosis of the pylorus. In all three cases, it was possible to follow the principles of conventional open surgery. The anastomoses were all stapled intracorporally, no intraabdominal complications occurred. However, the first patient died on the 21st postoperative day from cardiopulmonary failure, the remaining two patients were discharged on day 11/day 12 postoperatively.

The mechanism of spermine-induced enhancement of mitochondrial Ca2+ uptake was explored using the fluorescent Ca2+ indicator Fluo-3/AM to measure the free matrix Ca2+ concentration. Simultaneously, the extramitochondrial Ca2+ concentration was registered by a Ca(2+)-ion selective electrode. Spermine lowered the extramitochondrial steady state Ca2+ concentration and at the same time induced a decrease of the intramitochondrial Ca2+ concentration. However, there is a concentration-dependent reversal of the stimulatory action of spermine, which may be explained by the existence of a second, low-affinity binding site for spermine which mediates an inhibition of uptake in spite of the existence of an inwardly directed Ca2+ gradient.

Alloxan at millimolar concentrations slightly inhibited the velocity of Ca2+ uptake by isolated rat liver mitochondria irrespective of the free Ca2+ concentration between 1 and 10 microM and was an effective concentration-dependent stimulator of mitochondrial Ca2+ efflux. Ninhydrin also slightly inhibited the velocity of mitochondrial Ca2+ uptake but only at free Ca2+ concentrations above 5 microM. However, ninhydrin was a strong stimulator of mitochondrial Ca2+ efflux even at micromolar concentrations, 10-50 times more potent than alloxan. The mitochondrial membrane potential was reduced 10-20% at most by alloxan and ninhydrin. Alloxan and ninhydrin also stimulated Ca2+ efflux from isolated permeabilized liver cells. When isolated intact liver cells had been pre-incubated with alloxan or ninhydrin before permeabilization of the cells the ability of spermine to induce mitochondrial Ca2+ uptake was abolished. Glucose provided the typical protection against the effects of alloxan on mitochondrial Ca2+ transport only in experiments with intact cells but not in experiments with permeabilized cells or isolated mitochondria. Therefore glucose protection is apparently due to inhibition of alloxan uptake into the cell. Glucose provided no protection against effects of ninhydrin under any of the experimental conditions. Thus both alloxan and ninhydrin are potent stimulators of Ca2+ efflux by isolated mitochondria but very weak inhibitors of the velocity of mitochondrial Ca2+ uptake. The direct effects of ninhydrin on mitochondrial Ca2+ efflux may contribute to the cytotoxic action of this agent whereas the direct effects of alloxan on mitochondrial Ca2+ transport require concentrations which are too high to be of relevance for the induction of the typical pancreatic B-cell toxic effects of alloxan. However, the effects on mitochondrial Ca2+ transport during incubation of intact cells which may result from the generation of cytotoxic intermediates during alloxan xenobiotic metabolism may well contribute to the pancreatic B-cell toxic effect of alloxan.

1. A dual effect of the polyamine spermine on Ca2+ uptake by isolated rat liver, brain and heart mitochondria could be demonstrated by using a high-resolution system for studying mitochondrial Ca2+ transport. Depending on the experimental situation, spermine had an inhibiting or accelerating effects on mitochondrial Ca(2+)-uptake rate, but invariably increased the mitochondrial Ca2+ accumulation. 2. Both effects were concentration-dependent and clearly discernible on the basis of their different kinetic characteristics. For mitochondria from all three tissues the half-maximally effective concentration for inhibition of the initial rate of Ca2+ uptake was approx. 180 microM, whereas that for the subsequent stimulation of Ca2+ accumulation was approx. 50 microM. 3. Acceleration of the initial uptake rate could be seen when the mitochondria were preloaded with spermine during a 2 min preincubation period and thereafter incubated in a medium without spermine. 4. When such spermine-preloaded mitochondria were incubated in a spermine-containing medium, the increase in Ca(2+)-accumulation capacity was maintained in spite of an unchanged rate of Ca2+ uptake. 5. Mg2+ interacted with the effects of spermine in a differential manner, enhancing the initial inhibition of the rate of mitochondrial Ca2+ uptake and diminishing the subsequent stimulation of mitochondrial Ca2+ accumulation. 6. This dual effect of spermine on mitochondrial Ca2+ transport resolves the apparent paradox that a polycationic compound can act as a stimulator of Ca2+ uptake.

It is reported on the practicability and the results of therapeutic embolizations in 7 patients with pulmonary av-malformations. The embolizations were carried out by detachable balloons. In all cases there were immediate and well-defined occlusions. In direct fistulas the embolization represents a curative procedure. However, in cases of angiomatous malformations with slow flow character, only a reduction of shunt or decreasing of size is obtained.

Imaging procedures in patients suffering from portal hypertension and the problems arising from this condition are limited to the demonstration of the morphology of the collateral circulation towards the superior and the inferior vena cava. Imaging is essential prior to elective and emergency treatment of bleeding varices. Non-invasive and invasive imaging procedures are available. Acute hemorrhage of varices usually can not be demonstrated with any of the methods. Important is the preoperative evaluation of the portal system and the angiographic demonstration of the anatomy.

After application of various ionic and non-ionic contrast media in the myocardium and intestine of rats, significant changes of flow conditions in the terminal vascular bed were observed with intravital microscopy: Amidotrizoate causes severe disorder in microcirculation distribution (heterogeneous perfusion, functional shunts), while Ioxaglate, Iopromide, Iohexol, Iotrolan cause significantly less microcirculation reactions.

The case of a 6-year-old girl is reported with severe hemorrhage and "false aneurysm" in the left hepatic lobe due to polytrauma. The diagnosis of the haemobilia which developed 6 weeks after the accident was established by arteriography and scintigraphy. Despite only conservative treatment no further bleeding recurred. Spontaneous restitution was controlled by arteriography and scintigraphy. A long-term follow-up after hepatic trauma is necessary because the haemobiliary syndrome may develop after an asymptomatic interval of several years.

Importance of atrial septostomia in newborns with complete transposition of the great heart vessels was to be proved in 75 children, 27 of them with an atrial shunt and 48 without additional shunt. Arterial oxygen-tension while breathing roomair rose from 19 Torr without shunt to 29 Torr after septostomia. Corresponding values while breathing oxygen are 23 Torr before and 40 Torr after septostomia. In 14 children 2-5 years after septostomia control-values of oxygen-tension were 42 Torr in aorta (ventr. dext.), 34 Torr in v. cava, 67 Torr in a. pulm. (ventr. sin.) and 104 Torr in v. pulm. Differences of oxygen-content were 2,97 vol.% between aorta and v. cava, 2.83 vol.% between v. pulm. and a. pulm., 7.46 vol.% between v. pulm. and aorta and 10.34 vol.% between v. pulm. and v. cava.

Within one year 15 women suffering from unexplained abdominal pain in the right upper quadrant were examined by sonography and hepatic arteriography. Ten benign liver tumours were detected. Symptoms, diagnostics and therapy are dealt with.

Colicky pain in the gallbladder region, hematemesis, melena and jaundice are symptoms of hemobilia. The underlying cause can be an arterio-biliary or a porto-biliary fistula, resulting in hemorrhage into the duodenum. Shunting may be intra- or extrahepatic and may originate from trauma, or from biliary, pancreatic or vascular lesions. Since 1976 liver biopsies were done in 2221 patients; in 3 of these hemobilia occurred. In one case the artery involved could be obturated by transarterial placement of Ivalon particles; the two other cases recovered without special treatment. A review is given of 23 cases of hemobilia after liver biopsy, and treatment is discussed.

A baby of 5 months had an incomplete aortic ring (arcus aortae circumflexus) in combination with a ligamentum arteriosum. Even in infancy specific symptoms may occur. Carefull angiographic investigation can avoid misjudging the symptoms (stridor, dysphagia) and can contribute to an exact diagnosis thus preventing unnecessary operation.

Report on the application of a new (valve equipped) detachable balloon for percutaneous transvasal embolization therapy in 372 patients with (noncerebral) curative preoperative and palliative indications.

For 50 sucklings and small infants with cyanotic and acyanotic heart defects the non-ionic contrast medium Iopromide was tested against the ionic contrast medium Amidotrizoate in angiography. With consideration to the applied method the tested cardiospecific enzymes (CK MB, alpha-HBDH, lactate) as well as hematocrit, oxygen content of central venous blood, heart rate, systolic pressures in both ventricles and ECG showed no significant differences. The different end-diastolic pressures in both ventricles and the average pressure in the right atrium, however, showed the cardiotoxicity of Amidotrizoate. Conclusively the use of Iopromide is demanded for infants, small infants and sucklings.

In 15 patients with extensive malignant renal tumours before operation the artery of the kidney concerned was closed by foam substance particles (ivalon) after percutaneous selective catheterisation. The occurring ischaemic pain was controllable by medicaments and eased off after hours. In most cases the nephrectomy followed on the same day, but it can be performed also on the following day. The operation was principally performed from the transverse flank cut in practically bloodless kidney. Compared with the major interventions (transthoraco-abdominal or transabdominal) of the tumour nephrectomy the procedure described in this paper as a more careful one which at the same time meets the principles of modern surgery of cancer and which can also suggested to patients suffering from a severe disease.

In a retrospective study of 303 patients with renal cell carcinomas the prognostic influence of the percutaneous transvasal embolization of the renal artery was demonstrated. In form of the life-table-method we compared statistically the survival rates of preoperatively or palliatively embolized patients with such ones who were only nephrectomized or treated only symptomatically. In the tumour stages T2 and T3 the preoperative percutaneous transvasal embolization leads to a clearly higher survival rate; in stage T2 statistically significant. After palliative embolization the improvement of the prognosis is evident compared with the inoperable patients who were treated only symptomatically. The prognosis after palliative preoperative percutaneous transvasal embolization and retarded nephrectomy is not worse than after preoperative percutaneous transvasal embolization and immediate nephrectomy. The effect of the preoperative and palliative embolization improving the prognosis should incite all partners who up to now objected to this therapeutic method to reconsider their therapy concept.

In vivo microscopic (video) investigations on the variability of flow conditions in the myocardium and intestines of anaesthesized normal tension rats after application of various ionic and non-ionic contrast media (Amidotrizoate, Ioxaglate, Iopromide, Iohexol, Iotrolan). Amidotrizoate causes heterogeneous microperfusion and functional shunt vessels (distribution disorder) with the typical symptoms of disturbed microcirculation. Ioxaglate, Iopromide, Iohexol and Iotrolan influence microcirculation differently but always to a far less degree.

Analysis of 1,104 non-surgical biliary drainages (600 ERCD, 531 PTCD) from 1983 to 1988 concerning changing frequency, indications and success rates. With a continuous increase of the total numbers, the fraction of percutaneous-transhepatic drainages has decreased to 28%. With increasing degree of difficulty and risk PTCD (90.9% success) is indicated primarily in case of impossible ERCD (85.9% success) and hilar benign and malign biliary obstruction for temporary or permanent biliary drainage. Both methods are complementary and are increasingly used for combined palliative drainage.

To assess changes in resting left ventricular function after reestablishment of myocardial perfusion, echocardiographic studies were performed before, at three resp. six days after as well as three months after successful PTCA in 19 patients and after coronary artery bypass grafting in 20 patients. Reference data were obtained from analog processing of values from 20 healthy control subjects. Baseline values (in addition to primary morphologic criteria) were indicative of a clearly functional selection pattern. As compared with those undergoing PTCA, patients who underwent bypass surgery had more unfavorable values for ejection fraction at rest. Immediately after the intervention, there was a consistent tendency to transiently reduced resting pump function. At three months, however, in both groups, cardiac performance had returned to control values and the global and regional parameters of contractility had either reached or exceeded the preoperative values. The mean values showed more improvement in the PTCA group, a finding most probably attributable to the more favorable baseline situation. Paradoxic septum motion was found frequently in those who had undergone bypass surgery. All patients with grafting to the right coronary artery were included in the latter group. Whether perioperative injury, the varying perfusion conditions or the pericardiotomy is responsible for this phenomenon, remains to be established.