[Reasons of changes in drug therapy after hospital discharge - a qualitative study of perception by general practitioners and patients]. / Gründe von Änderungen der medikamentösen Therapie nach Krankenhausentlassung - eine qualitative Studie aus Sichtweise von Hausärzten und Patienten.

BACKGROUND: After discharge from hospital there is often change of medication regimen. Usually, the main results of the inpatient stay and the subsequent treatment recommendations are summarised in a "discharge letter". Based on this, the general practitioner decides on how to proceed taking the individual aspects of his/her patient into consideration. The aim of the study is to trace changes of medication and suggested therapy in the discharge letter, from the GP through to the patient and the reasons/influencing factors for any changes in medication undertaken or retained. METHODS: A prospective qualitative study with successively selected patients, who were put on a new long-term medication, at discharge after a stay in a hospital internal medicine unit was undertaken. Semi-structured interviews were conducted with the patients 4-6 weeks after hospital discharge. Subsequently, interviews were conducted with the patient's GP on details of current medication. The interviews were recorded electronically, based on the consensus method and evaluated with respect to changes in medication and influencing factors. In order to detect discrepancies in drug therapy, discharge letters were included in the analysis. RESULTS: A total of 34 patients and their GPs were interviewed. Few changes of medication changes were registered; however, these were more frequent in the weeks after hospital discharge. Drug therapy recommendations were modified by GPs for different medical or non-medical reasons. Non-medical reasons identified included economic, health policy constraints, personal conviction or non-adhrence of the patient. Reasons for a change in medication by the patient included, questioning of the need for taking the drug, incompatibility, fears and a lack of knowledge about the medication. CONCLUSION: The data demonstrate that the transition from inpatient to outpatient care is a sensitive interface. The data do not allow quantitative estimation of the magnitude of this phenomenon. In this study, the reasons for the modification of the drug demonstrated that these findings could be the basis for further studies or the development of interventions for preventing unwanted medication changes.

Genetic markers in acquired haemophilia.

Acquired haemophilia (AH) is a rare autoimmune bleeding disorder, which arises as a result of the spontaneous production of autoantibodies against endogenous factor VIII. The breakdown in immune tolerance is thought to be a result of a combination of genetic and environmental factors. Both human leucocyte antigen (HLA) and cytotoxic T lymphocyte antigen 4 (CTLA-4) play an important role in the maintenance of peripheral T-cell tolerance. A higher frequency of HLA class II alleles and single nucleotide polymorphisms of the CTLA-4 gene have been observed in some autoimmune diseases and severe haemophilia A. In 57 patients with AH, significantly higher frequencies of the HLA class II alleles DRB*16 [odds ratio (OR) 10.2] and DQB1*0502 (OR 2.5) have been detected when compared with controls. The CTLA-4 + 49 G allele has also presented with a significantly higher frequency in the same cohort of patients with AH (OR 2.17). This observation was mainly because of a higher frequency of the CTLA-4 + 49 G allele in female patients. These findings suggest that immune response genes may contribute to the development of anti-factor VIII autoantibodies in AH.

The relevance of the bleeding severity in the treatment of acquired haemophilia - an update of a single-centre experience with 67 patients.

Acquired haemophilia (AH), an autoimmune disorder with clinical features ranging from harmless haematomas to life-threatening bleedings, still has a mortality rate of up to 25%. Owing to its low frequency (1-4 x 10(6)), standardized treatment protocols for its variable manifestations are not available. In case of prominent severe bleedings, the treatment should aim at rapid elimination of the antibody to protect patients from bleedings and on reinduction of long-term immune tolerance. Clinical data, short- and long-term treatment results of 67 patients diagnosed by our centre are presented. Patients were treated depending on their bleeding severity either by an immunosuppressive treatment alone, or in case of life-threatening bleedings, by a combined protocol (modified Bonn-Malmö protocol, MBMP) consisting of antibody depletion through immunoadsorption, intravenous immunoglobulin treatment, immunosuppression and high-dose factor VIII (FVIII) substitution. Mild bleedings occurred in two patients who were treated successfully alone by immunosuppression. Complete remission (CR) was achieved in 90% of the patients treated with MBMP (60). Of the six patients (10%) who achieved a partial remission (PR), four suffered from cancer. Mortality under MBMP was not seen. In contrast, five patients, in whom diagnosis of AH was delayed, experienced fatal outcome during surgical interventions before initiation of MBMP treatment. Prognosis in AH depends mainly on its prompt diagnosis. Treatment procedures should be adapted to bleeding severity and inhibitor titres. Under these conditions, AH is a potentially curable autoimmune disorder with an excellent prognosis.

HLA genotype in patients with acquired haemophilia A.

Acquired haemophilia A (AH) is a rare bleeding disorder caused by an auto-antibody to coagulation factor VIII. It is associated with various autoimmune diseases, pregnancy, cancer or drug ingestion; however, in 50% of patients, no underlying disorder is found. In the present study, we investigated the association of HLA class I (A, B and Cw) and class II (DRB1 and DQB1) alleles with AH in a cohort of 57 patients. While no association with any class I allele was detected, a significantly higher frequency of DRB1*16 [odds ratio (OR) 10.2, 95%CI: 5.32-19.57, P < 0.0001] and DQB1*0502 (OR 2.2, 95%CI: 1.12-4.54, P < 0.05) was observed. In contrast, the frequency of DRB1*15 and DQB1*0602 alleles was found to be decreased in patients with AH corresponding to an OR of 0.4 for both HLA loci. Upon comparing the frequencies of these alleles with those of patients with congenital haemophilia A with inhibitors, the data demonstrate that the high risk alleles in patients with AH DRB1*16 and DQB1*0502 are found to be low risk alleles in patients with congenital haemophilia A with inhibitors (OR 1.1 and 1.5 respectively). Conversely, the alleles that exhibit low risk in AH DRB1*15 and DQB1*0602 are found to be high risk for haemophilia A inhibitor patients (OR 2.2 and 3.7 respectively). The pathophysiological reason for this finding remains unknown. It might be speculated that the presence or absence of the FVIII antigen and the various ability of HLA molecules to present the FVIII antigen to the T-cell receptor contribute to these findings.

Drug development from natural products: exploiting synergistic effects.

Drug development in phytomedicine has been focused in the past on the discovery and analysis of new structures from natural products. The search aimed at the determination of the single "active principle" in plants, based on the assumption that a plant has one or a few ingredients which determine its therapeutic effects. But traditional systems of medicines like Ayurveda, traditional Chinese medicine or the European phytotherapy generally assume that a synergy of all ingredients of the plants will bring about the maximum of therapeutic efficacy. This approach has for long been impossible to investigate since adequate methods to standardize complex plant mixtures as well as to rationalize complex mode of actions were lacking. The introduction of high throughput technologies provides the opportunity to determine profiles of plants and to systematically explore the mode of action of combinatory drug regimes. The present review highlights the concept of synergy and gives examples of synergistic effects of plant constituents. It elaborates on how the high throughput technologies can be used in drug development from natural products with the aim of creating evidence-based plant medications in prevention and treatment of different diseases in the form of new single treatments or new combinatory drug regimes while exploiting synergy-effects.

Increased frequency of the CTLA-4 49 A/G polymorphism in patients with acquired haemophilia A compared to healthy controls.

Acquired haemophilia (AH) is an autoimmune disorder characterized by autoantibodies against endogenous factor VIII (FVIII). Half of the patients present with an underlying disease known to cause the FVIII autoantibodies whereas in the other half the disease is of idiopathic nature. Recently, it has been shown that variants of the polymorphic cytotoxic T lymphocyte antigen-4 (CTLA-4) gene are associated with autoimmune diseases and also represent a risk factor for inhibitor formation in inherited haemophilia A. In the present study, we investigated whether CTLA-4 variants also play a role in the pathogenesis of AH. Therefore, we analyzed three single nucleotide polymorphisms (SNPs) of the CTLA-4 gene (-318 C/T, +49 A/G and CT60 A/G) in 57 AH patients and 98 controls. The CTLA-4 + 49 G allele occurred with a significantly higher frequency in patients with AH compared with controls [odds ratio (OR) = 2.17, 95% confidence interval (CI): 1.36-3.48, P = 0.001]. This effect was mainly caused by a higher frequency of the 49 G allele in female patients (OR = 5.1, 95% CI: 1.76-15.02, P = 0.002), whereas in males the frequencies were not significantly different (OR = 1.4, P = 0.5). A higher frequency of the G allele was also observed in the subcohort with AH and underlying autoimmune disease (OR = 3.1, P = 0.04). Our observations of a higher frequency of the CTLA-4 + 49 A/G SNP in AH patients are in concordance with findings in other autoimmune disorders. In conclusion, on the background of the CTLA-4 gene polymorphism, further genetic and/or environmental factors might contribute to and finally trigger the clinical manifestation of AH.

Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure.

OBJECTIVES: This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure. BACKGROUND: The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin-converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed. METHODS: In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol. RESULTS: Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01). CONCLUSIONS: In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin-independent actions of angiotensin-converting enzyme inhibition.

Treatment of minor severe acquired haemophilia. Is there a rationale for immunoadsorption?

OBJECTIVES: In Acquired Haemophilia (AH) autoantibodies against blood coagulation factors, mainly FVIII, inhibit the blood coagulation cascade. The clinical symptoms can vary from minor to severe life threatening bleedings. At present it is unclear if the intensity of the treatment needs to be adapted to the severity of the disease. METHODS: The clinical data and long term outcome from 20 patients suffering from minor severe AH were summarized. Bleedings requiring no blood transfusions were defined as less severe. In case of FVIII concentration <5% an immunosuppressive treatment (IT) consisting of cyclophosphamide 1-2 mg/kg BW/d and/or prednisolone 1-2 mg/kg BW/d was initiated. RESULTS: IT induced complete remission (CR) in only 40% of patients (8/20) after a mean time of 133.4 d (±90.7 d). Treatment associated severe side effects occurred in all patients. 15 patients required a factor substitution therapy due to proceeding bleedings. In 7 patients a partial remission (PR) of AH could be achieved; bleedings progressed in 5 of them and they underwent successfully second line immunoadsorption-based protocol. The inhibitor titer differed statistically significant between CR and PR with a mean of 3.7 BU vs. 16 BU. 5 patients had a fatal outcome mainly due to severe disease associated co morbidities. CONCLUSION: Immunosuppressive treatment failed in nearly a half of AH patients. Mortality was with 25% still high. The majority of patients required an intense long-term IT and developed severe treatment related side effect. Immediate start of IT did not control bleeding. In consequence, less severe AH also should be treated with a more rigorous regime because the occurrence of minors bleedings at initial presentation is not a predictive of clinical outcome. An Immunoadsorption-based protocol should be considered first line or even as a salvage strategy.

Long-term outcome of liver transplantation in HCV/HIV coinfected haemophilia patients. A single centre study of 10 patients.

UNLABELLED: The outcome and clinical features during long term follow-up of 10 haemophilia patients (haemophilia A n = 9, haemophilia B n = 1), who underwent successful orthotopic liver transplantation (OLT) due to hepatitis associated liver disease, are summarised. PATIENTS: Eight patients were HIV/HCV co-infected. Despite severe postoperative complications, which were not bleeding-associated, all patients survived OLT. RESULTS: Long-term survival was 70% after in mean 8 years follow-up. Twelve years after OLT one patient developed a cyclosporine-induced nephropathy requiring haemodialysis. HIV-HAART was initiated in all patients after OLT, and allowed a successful HCV treatment in 6 patients. Factor VIII production was sufficient in mean 72 h after OLT and remained stable at subnormal to normal FVIII levels of in median 30% (range 14-96%) also during long-term follow-up. Post-OLT spontaneous bleeding events were rare compared to pre-OLT, therefore, the performance status improved in all patients. DISCUSSION: OLT substitutes the hepatic FVIII but has no effect on the extra-hepatic endothelial FVIII production, suggesting that in case of severe tissue injury enhanced bleeding might occur. Additionally, after OLT there is no acute phase reaction of the FVIII protein. Therefore, our OLT patients received in case of a reduced FVIII activity a peri-interventional prophylactic short-term FVIII substitution in surgical and diagnostic interventions with high bleeding risk. CONCLUSION: Bleeding and wound healing disturbances were not seen.

Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies.

PURPOSE: Temporal lobe epilepsy with antibodies (abs) against the glutamic acid decarboxylase 65 isoform (GAD-TLE) is known as an immune-mediated neurological syndrome. Here we evaluate the therapy response to various immunotherapies and epilepsy surgery in this syndrome. METHOD: All patients with GAD-TLE and follow-up data and stored serum and CSF samples, identified and treated at the Bonn centre from 2002 to 2010, were studied retrospectively. Seizure freedom for ≥1 year and reduction of ≥50%, i.e. therapy response, were assessed. GAD-ab titres and neuropsychological performances were documented prior and after individual interventions. RESULTS: Thirteen patients with GAD-TLE were identified with the following seizure responses: corticosteroids (5 responders out of 11 treated patients); i.v. immunoglobulins (1/5), apheresis therapy (1/8); and natalizumab (1/1), selective amygdala-hippocampectomy (2/3). None of the patients achieved sustained seizure freedom apart from one patient. This patient was on antiepileptic drug treatment after discontinuation of immunotherapy. CONCLUSION: The seizure response to immunotherapies in patients with GAD-TLE was poor. Corticosteroids were the most effective regarding seizure response. Especially the poor effects of apheresis therapies support the idea that GAD-abs are not directly pathogenic. None of three patients was seizure-free after temporal lobe surgery suggesting that GAD-TLE patients respond worse than others to this type of intervention. Our results reflect the chronic course of the disease with low likelihood for patients with GAD-TLE to attain long-term seizure freedom.

Improving diagnostic accuracy of bacterial pharyngitis by near patient measurement of C-reactive protein (CRP)

BACKGROUND: Sore throat or pharyngitis is an extremely prevalent condition in primary care. There is a diagnostic dilemma in differentiating bacterial and non-bacterial infections for adequate use of antibiotics. Standard diagnostic procedures take too long for an immediate decision. AIM: To evaluate, if near patient C-reactive protein measurement in the general practice surgery improves diagnostic accuracy. METHOD: One hundred and seventy-nine consecutive patients with sore throat, from 15 general practitioners (GPs) in southern Germany (phase 1) and 161 consecutive patients from 14 GPs (phase 2), were examined physically and a throat-swab was taken and white blood-cell count (WBC) and CRP-measurement were performed. In phase 1, CRP was measured centrally to assess the method's diagnostic value and the adequate threshold. In the second phase, near patient CRP was measured and CRP values were used to make a diagnosis. RESULTS: Using relative operating characteristics (ROC) analysis, the diagnostic value of CRP measurement was much better than WBC count (area under curve = 0.85 versus 0.68). All diagnostic parameters improved when using the near patient CRP measurement. Sensitivity went up from 0.61 (95% confidence interval = 0.45-0.75) to 0.78 (0.61-0.90), specificity went up from 0.73 (0.65-0.81) to 0.82 (0.73-0.88). Positive and negative predictive value improved significantly as well. Diagnostic accuracy went up from 70.1% to 81.0%. Out of 1000 theoretical patients with sore throat, 109 more will be treated correctly when using CRP measurement as a diagnostic tool. CONCLUSIONS: Use of near patient CRP measurement can improve diagnostic accuracy in the differentiation of bacterial and non-bacterial pharyngitis in primary care, and potentially results in a more adequate use of antibiotics.

MRI of breast cancer: influence of chemotherapy on sensitivity.

MR mammography (MRM) seems to be a sensitive method for detection of breast cancer. The effect of cytotoxic agents on the dynamics of contrast medium uptake in primary breast carcinoma or recurrent disease is not known. This study addresses this question and evaluates MRM as a method of monitoring therapeutic success. A total of 13 patients (age range 34-62 years) with histologically confirmed breast cancer were investigated. The patients received neoadjuvant intravenous (iv) chemotherapy. MRM and interpretation of the dynamic measurements were performed in a standardized manner after positioning the patient in a double breast coil. A gradient echo sequence (Flash 3D, TE 5 ms, TR 12 ms, flip angle 25 degrees) was acquired before and 1, 2, 3 and 8 min after intravenous injection of Gd-DTPA 0.15 mmol kg-1 body weight. A T2 weighted SE sequence (TE 103 ms, TR 6900 ms, 4 mm, field of view 350 mm) was also obtained. MRM was performed prior to histological evaluation and after chemotherapy. All cases of malignancy were correctly diagnosed with MRM. Based on MR findings, eight patients were classified as "responders" and the remaining as "non-responders". In the "responders" a flattening of the Gd-DTPA uptake curve after the first cycle of chemotherapy of complete absence of Gd-DTPA uptake after the fourth cycle was observed. The change in Gd-DTPA uptake behaviour led to an underestimation of the extent of tumour in two patients and false negative findings in four patients. MRM provides information regarding response to therapy following the first cycle. MRM does not provide information regarding invasive tumour tissue in "responders".

[Dynamic arthro-CT in the diagnosis of recurrent shoulder dislocations]. / Dynamisches Arthro-CT in der Diagnostik rezidivierender Schulterluxationen.

"Dynamic" double contrast arthro-CT in internal and external rotation was performed on 42 patients with recurrent subluxation of the shoulder. The differential distribution of contrast and air caused by the rotation resulted in optimal demonstration of the capsulo-labrale components responsible for joint stability. In 22 patients there appeared to be an indication for arthroscopy; this confirmed the previous findings. In all cases the anterior part of the capsule and the middle and lower labrum were seen best during internal rotation. In this way all the 15 anterior capsule lesions could be seen, as well as 16 out of 17 Bankart lesions; it also showed one lesion of the middle labrum which had been masked by a haemarthrosis during external rotation. The study also defined lesions of the upper labrum caused by a different pathological mechanism which was present in 7 patients (6 Andrews and 1 S.L.A.P. lesion). These and 2 posterior labrum tears could be diagnosed during external rotation. Sensitivity for lesions of the anterior labrum was 95%.

[The place of portangiography in the follow-up control of locoregional chemotherapy]. / Stellenwert der Portangiographie bei der Verlaufskontrolle der lokoregionären Chemotherapie.

101 portangiographies in patients with liver metastases from colorectal primaries who underwent hepatic intraarterial or intraperitoneal chemotherapy were performed and studied between January 1991 and February 1992. 81% of the examinations did not involve complications. In 19% of the angiographies abnormalities of the arterial perfusion of the liver, like occlusion, dissection or narrowing of hepatic arteries, were found. We conclude that portangiography is a very important investigation before regional chemotherapy.

[The value of MR-mammography at 1.5 tesla in the differential diagnosis of non-puerperal mastitis and inflammatory breast carcinoma]. / Der Wert der MR-Mammographie in der Differentialdiagnostik von non-puerperaler Mastitis und inflammatorischem Mammakarzinom bei 1,5 Tesla.

PURPOSE: The distinction between mastitis and inflammatory breast carcinoma is an important one. Current methods of evaluation including mammography, ultrasound and clinical examination do not enable this distinction. Dynamic magnetic resonance mammography (MRM) is a study with potential in this regard. MATERIAL AND METHODS: 12 patients, in whom clinical examination, mammography and ultrasound could not distinguish between both diseases, were reviewed retrospectively by means of MRM using a 1.5 T Siemens Magnetom SP and a circular mamma coil. We used dynamic 3-D gradient echo sequences with a duration of one minute. RESULTS: At present MRM cannot definitely distinguish between mastitis and inflammatory carcinoma, 80% of the inflammatory carcinomas were found to enhance more than 100% in the first minute, compared to 43% for mastitis. No other differences were seen. CONCLUSION: MRM proved useful in the follow-up of treated mastitis to demonstrate the success of antibiotic treatment of mastitis and to diagnose a histologically unconfirmed inflammatory carcinoma by means of a different follow-up.

[MR enteroclysis for nuclear spin tomographic diagnosis of inflammatory bowel diseases with contrast enhancement]. / MR-Enteroklyse zur kernspintomographischen Diagnostik entzündlicher Darmerkrankungen mit verbesserter Darmkontrastierung.

PURPOSE: To evaluate MRI for effectiveness in assessment of intra- and extramural changes in the small intestine. METHODS: 40 patients with known or suspected small bowel disease underwent MR imaging immediately after conventional enteroclysis with barium and a mixture of methyl cellulose and gadolinium-DTPA. RESULTS: In 6 of 24 patients with no pathological findings in conventional enteroclysis, intraabdominal pathology such as thickening of the intestinal wall and an abscess were identified. In the remaining patients, MRI showed good correlation with conventionally obtained data and provided important additional information regarding extraluminal involvement such as enlargement of mesenterial lymph nodes and fistulas as well as abscesses. CONCLUSIONS: MRI, carried out using this technique, provides important additional information regarding intra- and extraluminal changes with good image quality.

[Doubtful mammographic findings: the value of negative MR mammography for tumor exclusion]. / Der unklare Mammabefund--Wert der negativen MR-Mammographie zum Tumorausschluss.

PURPOSE: To determine whether the addition of MR mammography (MRM) is useful in excluding malignant lesions and how reliable negative MRM findings are. METHODS: Amongst 694 MRM's, those originally regarded as normal were retrospectively reappraised. 239 female patients were involved. In all these patients there were clinical, sonographic and/or mammographic findings which were not entirely normal but there was no urgent indication for histological clarification. In 46 patients there were, however, histological examinations since the patients themselves insisted on it. In the remaining patients there was clinical, sonographic, mammographic and/or MRM follow-up after 12 to 18 months. RESULTS: In 95.4% (200/239) a carcinoma could be excluded by means of MRM, in 7 patients a carcinoma in situ and in two patients an invasive carcinoma was demonstrated histologically which had not been demonstrated by MRM. Even in retrospect, no abnormality could be found. CONCLUSION: Because of the only moderate sensitivity of MRM in the recognition of carcinoma in situ, doubtful lesions which can be localised, should be biopsied by a stereotactic method. In cases where evaluation is difficult on clinical, sonographic and mammographic findings, MRM is of value in excluding tumours, particularly in patients with increased carcinoma risk.

[The value of tumor volumetry as opposed to bidimensional determination of tumor size during follow-up of hepatic metastases from colorectal carcinoma]. / Wertigkeit der Tumorvolumetrie gegenüber der zweidimensionalen Tumorgrössenbestimmung bei der Verlaufskontrolle hepatischer Filiae von kolorektalen Karzinomen.

36 patients with liver metastases due to colorectal carcinoma under treatment with arterial perfusion chemotherapy of the liver with 5-fluoro-2-desoxyuridine (FUDR) via a subcutaneous pump were investigated by axial liver CT at 6-monthly intervals. In all examinations a dynamic CT scan with intravenous bolus injection of contrast medium was carried out following a native scan. Changes in tumour size were documented by means of 1. volumetry and 2. bidimensional measurement according to WHO criteria. Since we were not able to assess small newly developing lesions within the liver using the volumetric classification, the WHO-classification showed much higher sensitivity in cases of progressive disease. In addition, volumetric determination of tumour size by means of region-of-interest technique proved to be rather impracticable in clinical routine compared to bidimensional measurement.

Elevated serum concentrations of soluble adhesion molecules in coronary artery disease and acute myocardial infarction.

OBJECTIVES: Adhesion molecules are involved in a number of chronic conditions and diseases like rheumatoid arthritis, tumor growth and wound repair. Soluble adhesion molecules (SAM) play an important role in angiogenesis which is a common aspect of the conditions mentioned above and atherosclerosis. The aim of the present study was to assess the prevalence and the impact of elevated soluble adhesive molecule plasma concentrations in patients with atherosclerosis. DESIGN AND SUBJECTS: In this study, we measured the soluble forms of intercellular adhesive molecule (sICAM), endothelial adhesive molecule (sELAM) and vascular adhesive molecule (sVCAM) using a sandwich ELISA technique in plasma of patients with acute myocardial infarction (AMI), coronary heart disease (CHD) and in healthy subjects (HS). RESULTS: Patients suffering from CHD and AMI showed significant higher plasma concentrations of sICAM (p <0. 05 and p <0.005), sELAM (p <0.01 and p <0.001) and sVCAM (p <0.001 and p <0.005) than HS. In patients with fatal outcome of myocardial infarction the plasma concentrations of sICAM, sELAM and sVCAM were significantly elevated compared to surviving patients (p <0.005; p <0.005; p <0.05). In patients undergoing thrombolytic therapy there were no significant differences of plasma adhesive molecule concentrations. The levels of SAM were not related to other risk factors like diabetes, nicotin abuse, hyperlipidemia, hypertension and a familiary history of cardiovascular disease. CONCLUSIONS: Elevated levels of SAMs are found in patients with coronary heart disease. High SAM levels in plasma seem to be a prognostic factor in acute myocardial infarction. This effect is independent from other concomitant risk factors. Our results suggest that SAMs are involved both in acute phase of myocardial infarction and chronic process of atherosclerosis. It seems that similiar to other chronic inflammatory diseases, atherosclerosis seems to be modulated by soluble forms of adhesive molecules.

[The DEGAM guidelines "Dysuria" by the German Society of General Practice and Family Medicine (DEGAM)--possible consequences of the implementation in general practice]. / Die DEGAM-Leitlinie "Brennen beim Wasserlassen"--mögliche Konsequenzen der Umsetzung in der allgemeinärztlichen Praxis.

INTRODUCTION: In Germany, there are hardly any reliable data on patient care in the primary care setting which warrant the development and implementation of clinical guidelines. In this paper, data generated by a prospective observational study of patients with urinary tract symptoms are compared to the recommendations of an evidence-based clinical guideline. PATIENTS AND METHODOLOGY: Over a period of 6 months all patients consulting one of 6 General Practitioners in southern Germany with symptoms of dysuria have been documented on a standardised patient record. Data were compared to the recommendations of the guideline "Dysuria" by the German Society of General Practice and Family Medicine (DEGAM) to assess the relevance and feasibility of the guideline. In a scenario, compliance with the guideline is extrapolated to the realm of primary care. RESULTS: Basic demographic and epidemiological data agree with basic assumptions of the guideline. As far as diagnostic and therapeutic strategies are concerned there are significant discrepancies between the recommendations and the realm of primary care. Microbiologic cultures are ordered far less then recommended, second line drugs are prescribed far more often then recommended, macroscopic urinoscopy is performed widely but not covered by the guideline at all. If GPs complied completely with the guideline, many more diagnostic procedures would be performed and a different palette of antimicrobial drugs would be prescribed. CONCLUSION AND OUTLOOK: The "Dysuria-Guideline" of DEGAM was developed for a prevalent and relevant topic in primary care in Germany. There are significant discrepancies between the recommendations and the realm of primary care. Post-hoc-analysis is an informative and feasible tool to identify potential obstacles against implementation of guidelines.