[Regression of idiopathic epiretinal membrane-Case report and consideration of the possible mechanism]. / Regression einer idiopathischen epiretinalen Gliose ­ Kasuistik und Überlegungen zum Mechanismus.

In the presence of a symptomatic epiretinal gliosis, pars plana vitrectomy with membrane peeling to remove the membrane is usually indicated in clinical practice. According to common clinical experience, almost no independent regression of such an epiretinal membrane and thus healing of the pathology alone exists. Therefore, the unusual case of bilateral independent regression of idiopathic epiretinal gliosis and formation of a lamellar macular hole in a 73-year-old male patient is described. Considerations of the possible mechanism are presented based on the existing literature. These include separation of inflammatory versus noninflammatory membranes, possible separation of individual layers depending on the status of the posterior vitreous limiting membrane and also the possible action of proteolytic systems in the posterior vitreous region. Finally, the question arises, whether patients have to be informed about this fact before possible surgery.

[The interdisciplinary orthogeriatric ward round : Recommendations for the clinical routine]. / Die interdisziplinäre alterstraumatologische Visite : Empfehlungen für den Klinikalltag.

BACKGROUND: An orthogeriatric co-management can improve the quality of care for geriatric trauma patients. OBJECTIVE: The aim of this study was the establishment of treatment recommendations for the clinical routine in order to improve the quality of care for geriatric trauma patients. MATERIAL AND METHODS: Over a period of 7 months, 226 patients were discussed and visited once a week on 29 defined days, taking into account current laboratory results, vital signs, the medication as well as the clinical assessment by the nursing personnel. Besides physicians of different medical specialties (trauma surgery, geriatrics, clinical pharmacology, microbiology), members of the nursing staff and case managers took part in the ward rounds. RESULTS: On average, three treatment recommendations were made per patient visit (two pharmacological and one non-pharmacological recommendation [e.g. concerning fluid and delirium management]). The pharmacological and non-pharmacological recommendations were divided into several subcategories. The most frequent pharmacological recommendation was the discontinuation of a drug (30.4% of all pharmacological recommendations). CONCLUSION: The pharmacotherapy of geriatric patients requires careful consideration of contraindications, adverse drug reactions, duplicate medications, circadian aspects, and renal function. Regular re-evaluation of medical equipment can prevent catheter-associated infections. Identification and management of postoperative delirium is an integral component of the interdisciplinary orthogeriatric ward round. Evaluation of anti-infective treatment regimens with the expertise of a microbiologist/infectiologist proved to be very beneficial.

[DGRh recommendations for the implementation of current security aspects in the NSAID treatment of musculoskeletal pain]. / DGRh-Empfehlungen zur Implementierung aktueller Sicherheitsaspekte in die NSAR-Therapie muskuloskelettaler Schmerzen.

NSAIDs exert their anti-inflammatory and analgesic effects by inhibition of COX­2, a key enzyme for proinflammatory prostanoid synthesis. Therapy with NSAIDs is limited by their typical gastrointestinal, cardiovascular and renal side effects, which are caused by inhibition of COX­1 (gastrointestinal toxicity), COX­2 (cardiovascular side effects) or both COX-isoenzymes (renal side effects). Appropriate prevention strategies should be employed in patients at risk. If gastrointestinal risk factors are present, co-administration of a proton pump inhibitor or misoprostol is recommended; in patients with cardiovascular risk, coxibs, diclofenac and high-dose ibuprofen should be avoided. Furthermore, drug interactions and contraindications should be considered. In patients with renal impairment (GFR < 30 ml/min) all NSAIDs must be avoided. Ulcer anamnesis is a contraindication for traditional NSAIDs. Preexisting cardio- or cerebrovascular diseases are contraindications for coxibs. Treatment decisions should be individually based with a continuous monitoring of the risk - benefit ratio and exploitation of non-pharmacological treatment options.

[Placebo therapy. Analysis of extent and expectations in a tertiary referral center]. / Placebotherapie. Analyse von Umfang und Erwartung in einer Klinik der Maximalversorgung.

BACKGROUND: The dimensions of orally administered pharmacological placebos in routine clinical practice and the attitude of the clinical staff towards placebos are widely unknown. The aim of this report was to examine the frequency, indications and the intentions of placebo use at the Medical University of Hannover (MHH). METHODS: This study was performed as an anonymous cross-sectional written survey at the MHH. Quantitative data on placebo requests registered by the dispensary were obtained in advance. RESULTS: A total of 74% of respondents reported using placebos in clinical practice, including 53% of physicians and 88% of the nursing staff. Pain (76%) and insomnia (59%) were the most frequently reported reasons for administering placebos. Placebos were considered to be highly effective by 28.5% of physicians and 63.8% of the nursing staff. CONCLUSION: The effective use of pharmacological placebos appears to be an established component of the therapeutic options of a tertiary referral center. The placebo effect seems to contain remarkable potential. While the use of pharmacological placebos is ethically problematic within the clinical context, the improvement of caregiver-patient interactions and the utilization of positive suggestion could serve as an ideal adjunct to active therapy regimes.

Effects of combined supplementation with B vitamins and antioxidants on plasma levels of asymmetric dimethylarginine (ADMA) in subjects with elevated risk for cardiovascular disease.

Elevated plasma asymmetric dimethylarginine (ADMA) concentrations have been suggested as a potential risk factor for cardiovascular disease (CVD). Studies indicate a linkage between hyperhomocysteinemia, oxidative stress and ADMA metabolism. We tested the hypothesis that combined supplementation of B vitamins and antioxidants reduces ADMA concentrations in subjects with at least two CVD risk factors. A total of 123 men and women (58+/-8.1 years) were randomly assigned to take either a preparation including B vitamins and antioxidants (verum) or placebo for 6 months in a double-blind design. Blood concentrations of ADMA, symmetric dimethylarginine (SDMA), L-arginine, B vitamins, total homocysteine (tHcy), alpha-tocopherol, antioxidant capacity (TEAC), and oxLDL were measured pre- and post-intervention. Treatment with verum significantly decreased tHcy (-2.14 micromol/L; P<0.001) and significantly increased TEAC values (+39.3 microM; P<0.022), but no effect on ADMA was observed. OxLDL was significantly reduced in verum (-7.3 U/L; P=0.001) and placebo (-9.2U/L; P<0.001). At baseline, significant correlations were found only between ADMA and SDMA (r=0.281; P=0.002), L-arginine/ADMA and SDMA (r=-0.294; P<0.001), L-arginine/ADMA and oxLDL (r=-0.281; P=0.016), and L-arginine/ADMA and age (r=-0.231; P=0.010). Our results indicate that combined supplementation of B vitamins and antioxidants is not an adequate strategy to reduce ADMA plasma levels in subjects with elevated CVD risk.

Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2.

BACKGROUND: According to previous studies, cinnamon may have a positive effect on the glycaemic control and the lipid profile in patients with diabetes mellitus type 2. The aim of this trial was to determine whether an aqueous cinnamon purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2 diabetes. METHODS: A total of 79 patients with diagnosed diabetes mellitus type 2 not on insulin therapy but treated with oral antidiabetics or diet were randomly assigned to take either a cinnamon extract or a placebo capsule three times a day for 4 months in a double-blind study. The amount of aqueous cinnamon extract corresponded to 3 g of cinnamon powder per day. RESULTS: The mean absolute and percentage differences between the pre- and post-intervention fasting plasma glucose level of the cinnamon and placebo groups were significantly different. There was a significantly higher reduction in the cinnamon group (10.3%) than in the placebo group (3.4%). No significant intragroup or intergroup differences were observed regarding HbA1c, lipid profiles or differences between the pre- and postintervention levels of these variables. The decrease in plasma glucose correlated significantly with the baseline concentrations, indicating that subjects with a higher initial plasma glucose level may benefit more from cinnamon intake. No adverse effects were observed. CONCLUSIONS: The cinnamon extract seems to have a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.

The second generation of COX-2 inhibitors: clinical pharmacological point of view.

Valdecoxib, parecoxib, etoricoxib and lumiracoxib represent the second generation of selective COX-2 inhibitors. In comparison to the first generation, they show an at least equivalent efficacy in the treatment of pain and inflammation. However, the postulated gain of safety is yet difficult to determine and seems to be, if any, small.

Elevated nitric oxide levels in patients with chronic liver disease and cirrhosis correlate with disease stage and parameters of hyperdynamic circulation.

Chronic liver diseases are accompanied by changes in splanchnic and systemic circulation. These changes are characterised by a reduction in peripheral vascular resistance and an increased cardiac output at rest. An increased release of nitric oxide (NO) has been proposed to play a role in the pathogenesis of vasodilatation and vascular hypocontractility. This study was designed to determine the nitric oxide metabolism measured as circulating nitrate levels in serum/urine in patients with chronic liver disease and cirrhosis. The nitrate concentrations were significantly increased in advanced degrees in cirrhosis Child B and C, and normal or even reduced in patients with chronic active hepatitis and early cirrhosis. In our study the connections between the extent of portal hypertension and nitrate levels were evident. The presence of ascites as well as the the progression of oesophageal varices were associated with higher circulating nitrate levels. The connection between increased nitric oxide production and the haemodynamic sequelae of portal hypertension is also apparent in the significant correlation between plasma renin and serum nitrate levels. Circulating nitrate levels also correlated to the serum interleukin-6 levels. This study demonstrated that the increased nitric oxide metabolism is associated with the haemodynamic alterations induced by portal hypertension.

Comparison of different activity parameters in atopic dermatitis: correlation with clinical scores.

BACKGROUND: Several laboratory markers have been described to correlate positively with disease activity of atopic dermatitis (AD). These include soluble adhesion molecules and eosinophil granular proteins. Although the correlation of these parameters with the severity and extent of skin involvement has been repeatedly studied in the past, no systematic investigation has been performed over a lengthy period of time. In addition, no subjective disease parameters recorded by the patient have been included in studies dealing with disease activity. OBJECTIVES: To assess the validity of different objective and subjective parameters [soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), eosinophil cationic protein (ECP), urinary nitrate excretion (reflecting endogenous nitric oxide formation) and the patients' impressions of pruritus, sleeplessness and skin status] as markers of AD disease activity. METHODS: Twenty patients were examined for 1 year and their skin status was evaluated by an established score (SCORAD). sE-selectin, sVCAM-1 and ECP were analysed by commercial test kits. Urinary nitrate concentration was measured by gas chromatography-mass spectrometry. The subjective parameters, pruritus, sleeplessness and impression of skin status, were recorded by the patients on a visual analogue scale. RESULTS: In this long-term trial, only sE-selectin and the subjective parameters showed a statistically significant correlation with the SCORAD score. CONCLUSIONS: Our data indicate that basic clinical scoring remains a most effective and relevant method of recording skin disease activity in AD.

Knowledge on drug dosages of ward physicians.

OBJECTIVE: Dosing errors are a common source for preventable adverse drug events. This study evaluated the knowledge of German hospital physicians with respect to the daily dosage of frequently used drugs. METHODS: A questionnaire survey was carried out among 168 ward physicians from three university and four municipal hospital departments of internal medicine asking for the daily dosage of 17 frequently used drugs. RESULTS: One hundred twenty-seven of 168 physicians returned a completed questionnaire, a response rate of 75.6%. Only 50% of the dose estimates were within the therapeutic range. Even in cases of frequent prescription 7% of the stated doses were overdosed and 15% were underdosed. CONCLUSIONS: The results of this survey suggest that adverse drug events and the lack of therapeutic effect due to dosing errors could be prevented by an improved knowledge of daily dosages.

Effects of intravenous oxygen on prostacyclin and thromboxane formation in patients with peripheral occlusive arterial disease.

Oxygen infusion is used in complementary medicine for treatment of peripheral occlusive arterial disease. The mechanism of action is unknown. Thus, we determined the effects of oxygen infusion on prostacyclin, thromboxane and nitric oxide synthesis. Twelve patients with peripheral occlusive arterial disease received oxygen 40 ml/d intravenously for 3 weeks. Study parameters, analyzed by gas chromatography-mass spectrometry on day 1, 3, 10, 16, 21: 2,3-dinor-6-oxo-PGF(1alpha), colour invisible 2,3-dinor-TXB2 and nitrate in one-hour-urine before and after oxygen infusion, reflecting prostacyclin, thromboxane and nitric oxide synthesis. Urinary 8-iso-PGF2alpha, indicating oxidative stress, was assessed in one patient. Urinary 2,3-dinor-6-oxo-PGF1alpha rose from baseline more than 4-fold after oxygen infusion. In contrast, urinary 2,3-dinor-TXB2 excretion remained unchanged. Oxygen infusion had no effect on urinary nitrate excretion. Urinary 8-iso-PGF(2alpha) was not influenced by oxygen infusion with and without diclofenac pretreatment. Our data demonstrate a shift of the prostacyclin/thromboxane ratio toward prostacyclin by oxygen infusion. Thus, a mechanism of action is provided and clinical trials with intravenous oxygen find a rational basis.

Blood donors on medication. Are deferral periods necessary?

OBJECTIVES: Drugs and their metabolites in transfused blood components may cause effects in the recipient. If the treated disorder is not to be regarded as an exclusion criterion from blood donation, donors on medication should be deferred for a period consistent with the drug's pharmacokinetics. GENERAL PRINCIPLES AND METHODS: Peak plasma drug concentrations of 3% or less of the therapeutic concentration were regarded to be safe for the recipient of a blood product. For teratogenic drugs a much lower safety level of less than 0.000001% has been proposed. For the calculation of deferral periods, both the type of blood component to be prepared and the drug's pharmacokinetics for a given formulation were considered. SUGGESTED WAITING PERIODS: For drugs with known teratogenic risks, we suggest a deferral period of 28 plasma-elimination half-lives. For non-teratogenic drugs, a simple, conservative approach could be based on waiting for five plasma-elimination half-lives, thus reaching the required 3% safety level already in any donor. If, however, the type of blood component to be prepared is also considered, a more differentiated approach appears to be appropriate: for blood components containing 50 ml or less plasma from a single donor, donor medication may be disregarded because of the high dilution in the recipient's plasma volume, whereas for blood components with higher plasma contents (250 ml on average) from a single donor on medication the 3% safety level will be achieved by observing the deferral period of five plasma-elimination half-lives mentioned. A guideline for 191 drugs and drug classes has been elaborated accordingly.

Microsomal prostaglandin E synthase is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells.

The selective induction of PGE(2) synthesis in inflammation suggests that a PGE synthase may be linked to an inducible pathway for PG synthesis. We examined the expression of the recently cloned inducible microsomal PGE synthase (mPGES) in synoviocytes from patients with rheumatoid arthritis, its modulation by cytokines and dexamethasone, and its linkage to the inducible cyclooxygenase-2. Northern blot analysis showed that IL-1beta or TNF-alpha treatment induces mPGES mRNA from very low levels at baseline to maximum levels at 24 h. IL-1beta-induced mPGES mRNA was inhibited by dexamethasone in a dose-dependent fashion. Western blot analysis demonstrated that mPGES protein was induced by IL-1beta, and maximum expression was sustained for up to 72 h. There was a coordinated up-regulation of cyclooxygenase-2 protein, although peak expression was earlier. Differential Western blot analysis of the microsomal and the cytosolic fractions revealed that the induced expression of mPGES protein was limited to the microsomal fraction. The detected mPGES protein was catalytically functional as indicated by a 3-fold increase of PGES activity in synoviocytes following treatment with IL-1beta; this increased synthase activity was limited to the microsomal fraction. In summary, these data demonstrate an induction of mPGES in rheumatoid synoviocytes by proinflammatory cytokines. This novel pathway may be a target for therapeutic intervention for patients with arthritis.

Drug expenditure in hospitals: what do German ward physicians know?

AIMS: Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs. METHODS: A questionnaire survey was carried out among 168 ward physicians from university and municipal hospital departments of internal medicine. RESULTS: One hundred and twenty-seven physicians returned a completed questionnaire, a response rate of 75.6%. On average the physicians successfully identified both low cost and expensive drugs. The prices of inexpensive and moderately expensive drugs were generally overestimated whereas those for the expensive and highly expensive drugs were underestimated in 35% and 68% of respondents, respectively. CONCLUSIONS: The results of this survey of German hospital physicians suggest that a more economically efficient use of drugs could be achieved by an improved knowledge of daily therapeutic costs.

S-Transnitrosylation of albumin in human plasma and blood in vitro and in vivo in the rat.

S-Nitrosoalbumin (SNOALB) is the most abundant physiological circulating nitric oxide (NO) carrier regulating NO-dependent biological actions in humans. The mechanisms of its formation and biological actions are still incompletely understood. Nitrosation by authentic NO and S-transnitrosylation of the single sulfhydryl group located at Cys-34 of human albumin by the physiological S-nitroso compounds S-nitrosocysteine (SNOC) and S-nitrosoglutathione (GSNO) are two possible mechanisms. On a quantitative basis, we investigated by gas chromatography-mass spectrometry the contribution of these two mechanisms to SNOALB formation in human plasma and blood in vitro. GSNO and SNOC (0-100 microM) rapidly and efficiently (recovery=35%) S-transnitrosylated albumin to form SNOALB. NO (100 microM) S-nitrosated albumin to SNOALB at a considerably lower extent (recovery=5%). The putative NO-donating drugs glyceryl trinitrate and sodium nitroprusside (each 100 microM) failed completely in S-nitrosating albumin. Bubbling NO into human plasma and blood resulted in formation of SNOALB that inhibited ADP-induced platelet aggregation. Infusion of GS(15)NO in the rat resulted in formation of S(15)NOALB, [(15)N]nitrate and [(15)N]nitrite. Our results suggest that S-transnitrosylation of albumin by SNOC and GSNO could be a more favored mechanism for the formation of SNOALB in the circulation in vivo than S-nitrosation of albumin by NO itself.