[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.

Effect of leukotriene inhibitors on evolution of experimental brain contusions.

AIMS: Leukotriene levels increase in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) injury in rats. We investigated the impact of two different leukotriene inhibitors in the CCI model on CSF leukotriene levels, brain water content (BWC), brain swelling (BS) contusion size and cellular response. METHODS: 134 male Sprague Dawley rats were investigated at 4, 24 and 72 h after CCI for CSF leukotriene levels and BWC/BS, lesion size in T2-weighted magnetic resonance imaging and immunohistochemistry. Animals received vehicle, MK-886, an inhibitor of 5-lipoxygenase activating protein, or Boscari(®) , a mixture of boswellic acids, acting as competitive nonredox 5-lipoxygenase inhibitors before trauma and then every 8 h until sacrifice. RESULTS: The intracranial pressure (ICP) was unaffected by treatment. Boscari treatment reduced CSF leukotriene C4 increase by -45% at 4 h (P < 0.03) and increase of BWC and BS by 49% (P < 0.05) and -58% at 24 h. Treatment with both substances showed a reduction of lesion volume at 72 h by -21% (P < 0.01) in T(2) -weighted magnetic resonance imaging, which was reflected in a smaller lesion area determined from a NeuN labelled section (-17% to -20%, P < 0.05). Triple immunofluorescence and Fluoro-Jade B staining showed rarefaction of neurones, glia and vasculature in the contusion core, whereas in the pericontusional zone astro- and microglia were upregulated in the presence of dying neurones. Treatment resulted in an improved survival of NeuN labelled neurones in the pericontusional cortex (+15% to +20%, P < 0.05). CONCLUSIONS: Leukotriene inhibition should be further investigated as therapeutic option to counteract secondary growth of traumatic brain contusions and to possibly improve pericontusional neuronal survival.

[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.

[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.

Nanomaterial electronic structure investigation by valence electron energy loss spectroscopy - an example of doped ZnO nanowires.

The effects of doping (by ion implantation) on the electronic structure of ZnO nanowires, particularly on the defect states generation in the band gap of ZnO, are investigated using valence electron energy loss spectroscopy (VEELS) performed in a transmission electron microscope (TEM). The improved spectrum energy resolution via the introduction of a gun monochromator, together with the reduced intensity in the zero loss peak tail as realized by spectrum acquisition at non-zero momentum transfer, enable us to extract such electronic structure information from the very low loss region of the EEL spectra. We have compared the doping effects of several dopant elements, i.e., Er, Yb, and Co, and found that generation of the band tail states ( approximately 2-3.3eV) is a common consequence of the ion implantation process. On the other hand, specific mid-gap state(s) in the lower energy range are created only in the rare earth element doped ZnO nanowires, suggesting the dopant-sensitive nature of such state.

Rare earth doped zinc oxide nanowires.

Zinc oxide (ZnO) nanowires were grown via thermal transport and subsequently doped with different concentrations of Tm, Yb, and Eu using ion implantation and post annealing. High ion fluences lead to morphology changes due to sputtering; however, freestanding nanowires become less damaged compared to those attached to substrates. No other phases like rare earth (RE) oxides were detected, no amorphization occurs in any sample, and homogeneous doping with the desired concentrations was achieved. Photoluminescence measurements demonstrate the optical activation of trivalent RE-elements and the emission of the characteristic intra-4f-luminescence of the respective RE atoms, which could be assigned according to the Dieke-diagram. An increasing RE concentration results into decreasing luminescence intensity caused by energy transfer mechanisms to non-radiative remaining implantation defect sites. Furthermore, low thermal quenching was observed due to the considerable wide band gap of ZnO.

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.

Catalyst-nanostructure interaction in the growth of 1-D ZnO nanostructures.

Vapor-liquid-solid is a well-established process in catalyst guided growth of 1-D nanostructures, i.e., nanobelts and nanowires. The catalyst particle is generally believed to be in the liquid state during growth, and is the site for impinging molecules. The crystalline structure of the catalyst may not have any influence on the structure of the grown nanostructures. In this work, using Au guided growth of ZnO, we show that the interfaces between the catalyst droplet and the nanostructure grow in well-defined mutual crystallographic relationships. The nanostructure defines the crystallographic orientation of the solidifying Au droplet. Possible alloy, intermetallic, or eutectic phase formation during catalysis are elucidated with the help of a proposed ternary Au-Zn-O phase diagram.

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.

COX-2 and the kidneys.

The kidney is the second most frequent target of serious adverse effects of non-steroidal antiinflammatory drugs (NSAIDs). The renal side effects of NSAIDs related to inhibition of cyclooxygenase (COX) comprise reduction in renal blood flow (RBF) and glomerular filtration rate (GFR), sodium/water retention, water intoxication and hyperkalemia. The discovery of two COX-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prosta noid production, led to the development of new NSAIDs: Preferential and specific COX-2 inhibitors, promising minimal NSAID-typical toxicity with equivalent efficacy. However, we learned that there is no clear distinction in "physiologic" constitutive COX-1 and "inflammatory" inducible COX-2. This is particular true for the kidney of humans and other mammalians, where COX-2 was found constitutively in meaningful amounts. Animal experiments and clinical trials with preferential and specific COX-2 inhibitors revealed that COX-2 is the critical enzyme for sodium excretion, renin release and likely antagonism of antidiuretic hormone. Additionally, a significant role of COX-2 for nephro genesis is suggested. For renal hemodynamics the given evidence point to COX-1 as the predominant enzyme, but further investigations are required. In summary, the gain of renal safety by use of preferential or specific COX-2 inhibitors is small or negligible with respect to sodium retention, hyperkalemia and probably water intoxication. These drugs may be advantageous regarding renal perfusion, but presently the same precautions as for conventional NSAIDs must be used.

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.

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.

Effect of selective inhibition of the inducible cyclooxygenase on renin release in healthy volunteers.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) can block renin release via inhibition of cyclooxygenase (COX). The responsible COX-isoenzyme in man is unknown. Therefore, we assessed the effects of meloxicam, a selective inhibitor of COX-2, and indomethacin, an unselective inhibitor of COX-1 and COX-2, on furosemide stimulated plasma renin activity (PRA). METHODS: In a randomized cross-over design 15 healthy female volunteers received no NSAID or meloxicam 7.5 mg/d for 6 days or indomethacin 25 mg tid for 2 days and 25 mg on the 3rd day. On the control day and on the last day of each treatment the following parameters were evaluated before and after furosemide 20 mg i.v.: PRA measured by RIA, urinary excretion of prostaglandin E2 (PGE2) assessed by gas chromatography-tandem mass spectrometry, urine volume and urinary excretion of sodium, potassium, and creatinine, and serum concentrations of sodium, potassium, and creatinine. RESULTS: Furosemide led to a more than two-fold rise of PRA. Indomethacin as well as meloxicam had no significant effect on basal PRA but inhibited the furosemide-stimulated PRA increase. PGE2 excretion on the control day rose two-fold after furosemide. Meloxicam had no effect on basal PGE2 excretion, whereas indomethacin reduced this parameter by 30%. Both drugs inhibited the increase of urinary PGE2 after furosemide. No drug effects on urine flow nor on electrolytes and creatinine in serum and urine could be observed. CONCLUSION: Meloxicam inhibited furosemide stimulated renin release, suggesting that in man COX-2 is responsible for prostaglandin synthesis mediating renin release.

Effects of meloxicam and indomethacin on cyclooxygenase pathways in healthy volunteers.

BACKGROUND: Meloxicam is a new NSAID with selectivity for the inducible cyclooxygenase (COX-2) in vitro. We compared the effects of therapeutically equivalent doses of meloxicam and indomethacin, a preferential inhibitor of the constitutive cyclooxygenase (COX-1), on platelet aggregation and platelet thromboxane formation, which are exclusively COX-1 dependent, physiological renal, and total body prostaglandin E2 (PGE2) production. METHODS: In a randomized cross-over design, 14 healthy female volunteers received meloxicam 7.5 mg per day for 6 days or indomethacin 25 mg three times per day for 3 days; the wash-out period was 5 days, and drug intake was adapted to the menstrual cycle. On the day before treatment and on the last day of each treatment period the following parameters were evaluated: maximum platelet aggregation and thromboxane B2 (TXB2) formation in response to 1.0 mmol/L arachidonic acid; 24-hour urinary excretion of PGE2 and 7 alpha-hydroxy-5, 11-diketo-tetranor-prosta-1, 16-dionic acid (PGE-M), the index metabolites of renal and total body PGE2 synthesis, respectively, were assessed by gas chromatography/tandem mass spectrometry. RESULTS: Maximum platelet aggregation and TXB2 formation were almost completely inhibited by indomethacin (-87% and -99%, respectively; p < 0.001, each) as compared to control (100%), but remained unaffected by meloxicam (-1% and +4%, respectively). Meloxicam showed no significant effects on urinary PGE2 excretion (-13%) and only slight effects on PGE-M excretion (-22%; p < 0.05), whereas indomethacin reduced urinary PGE2 excretion (-43%; p < 0.05) as well as PGE-M excretion (-36%; p < 0.001). CONCLUSIONS: Our data show, that meloxicam 7.5 mg per day is COX-1 sparing in humans in vivo.

[New non-steroidal anti-rheumatic drugs: selective inhibitors of inducible cyclooxygenase]. / Neue nichtsteroidale Antirheumatika: Selektive Hemmstoffe der induzierbaren Cyclooxygenase.

UNLABELLED: MODE OF ACTION OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: Non-steroidal anti-inflammatory drugs (NSAID) exert their major therapeutic and adverse effects by inhibition of prostanoid synthesis. Also the interactions with antihypertensive drugs and lithium are caused by this mechanism of action. Cyclooxygenation is a key enzymatic step in the synthesis of prostanoids. 1990 2 isoforms of the enzyme cyclooxygenase have been identified: Prostanoids synthesized by the constitutive cyclooxygenase (COX-1) are involved in physiological homeostasis. In contrast, the inducible cyclooxygenase (COX-2) produces large amounts of prostanoids, mainly contributing to the pathophysiological process of inflammation. COX-2 SELECTIVE NSAID: The discovery of the cyclooxgenase-isoenzymes ushered in a new generation of NSAID: A drug with selectivity for COX-2 would inhibit proinflammatory prostanoid synthesis while sparing physiologic prostanoid synthesis. Thus, a selective COX-2 inhibitor should be anti-inflammatory with less or no gastrointestinal or other NSAID-typical adverse effects. The experiences with currently used NSAID, which show an increasing incidence of side effects as COX-1 inhibition increases, and studies with the COX-2 selective NSAID salsalate and meloxicam, which have less adverse effects than nonselective COX inhibitors in equivalent antiphlogistic dosage, prove the concept of selective COX-2 inhibition to avoid the NSAID typical side effects. Newly developed drugs with a very high selectivity for COX-2 are now tested in clinical trials. CONCLUSION: So far the results suggest, that selective and highly selective COX-2 inhibitors have significantly fewer gastrointestinal and renal adverse effects and do not inhibit platelet aggregation.

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.