Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement

Summary. Background: In patients undergoing percutaneous coronary intervention (PCI), a link between bleeding and excess mortality has been demonstrated. A potential association of platelet response to clopidogrel and bleeding has not been well established yet. Objectives: The aim of the present study was to assess the impact of clopidogrel responsiveness on the risk of bleeding in clopidogrel‐treated patients undergoing PCI. Methods: Patients (n = 2533) undergoing PCI after pretreatment with 600 mg of clopidogrel were enrolled in this study. Blood was obtained directly before PCI. Adenosine‐diphosphate (ADP)‐induced platelet aggregation was assessed on a Multiplate analyzer. The primary endpoint was the incidence of in‐hospital Thrombolysis in Myocardial Infarction (TIMI) major bleeding and the secondary endpoint was in‐hospital TIMI minor bleeding. Receiver‐operator curve (ROC) analysis was used to derive the optimal platelet aggregation value defining enhanced clopidogrel responders for the association of measurements with major bleeding. Results: Thirty‐four (1.3%) major bleeding events and 137 (5.4%) minor bleeding events were observed. The risk of a major bleeding was significantly higher in patients (n = 975) with an enhanced response to clopidogrel as compared with the remaining patients (n = 1558) (2.2 vs. 0.8%, unadjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.3–5.2, P = 0.005; adjusted OR 3.5, 95% CI 1.6–7.3, P = 0.001). No significant differences between both groups were observed for the occurrence of minor bleeding events (P = 0.68). Conclusions: Enhanced clopidogrel responsiveness is associated with a higher risk of major bleeding. Whether guidance of antiplatelet treatment based on platelet function testing proves useful for avoiding bleeding events warrants further investigation.     

In Vivo Depletion of Chicken T-Cell Subsets

In the chicken three types of T-cell receptors can be defined by monoclonal antibodies TCR1, TCR2 and TCR3, which recognize γδ T cells, and Vβ1- and Vβ2-expressing αβ T cells, respectively. In the present report we have analysed means of selectively depleting the γδ T cells and the Vβ1 ⁺αβ T cells. γδ cells, which represent up to 66% of all T cells in blood of a 6-month-old chicken, can be effectively depleted by neonatal thymectomy (Tx) to levels as low as 1%. Immunohistology demonstrates a similar depletion in lymphoid organs while intestinal epithelium-associated γδ T cells are affected by Tx to a lesser extent. Vβ1-bearing αβ T cells, which comprise about 80% of the αβ T cells, were depleted by embryonic and neonatal injection of the TCR2 antibody. In the thymus such treatment depleted only the Vβ1 ⁺αβ T cells with high density expression of T-cell receptor. Therefore, we thymectomized TCR2-treated animals in order to prevent development of mature Vβ1⁺αβ T cells from the low density immature thymocytes. Treatment of chickens with a total of 22 mg of TCR2 antibody plus Tx reduced Vβ⁺αβ T cells from an average of 65% to 10% of all T cells. In these TCR2 antibody-treated animals the Vβ2-expressing αβ T cells become the predominant type of T cell (average 85%).     

Zum Vorkommen von Chrysosporium keratinophilum (Frey) Carmichael und einer thermophilen Variante im Erdboden und bei Tieren*)

Zwischen Dermatophyten und Chrysosporium-Arten bestehen enge Beziehungen. Wegen seiner Stoffwechselphysiologie und Griseofulvinsensibilität verdient insbesondere Chrysosporium keratinophilum verstärkte Beachtung. Aus 346 Erdproben des Leipziger Stadtgebietes züchteten wir 11mal (= 3,2%) Chrysosporium keratinophilum. Die Erdproben wiesen einen pH-Wert zwischen 6,4 und 7,6 auf. Eine Abhängigkeit des Pilzvorkommens vom Humusgehalt oder der Höhe wasserlöslicher NO₃-, P- oder K-Verbindungen war nicht festzustellen. Bei der Untersuchung von insgesamt 514 tierischen Materialien (Bürstenabstriche von Tieren des Zoologischen Gartens in Leipzig) isolierten wir weitere 28 (= 5,5%) Chrysosporium keratinophilum-Stämme; darunter befanden sich 2 atypische Varianten. Im Gegensatz zu alien anderen Chrysosporium keratinophilum-Stämmen zeigten diese Pilze gutes Wachstum bei 37° C und hohe Griseofulvinresistenz. Die Größe der Aleuriosporen lag zwischen den für Chrysosporium keratinophilum und Chrysosporium tropicum angegebenen Werten. Möglicherweise handelt es sich um den gleichen Pilz, den GARG (1966 a) aus Bodenproben in Indien isolierte und zu Chrysosporium tropicum stellte. In Deutschland sind Funde von Chrysosporium tropicum bisher nicht bekannt geworden. Für fleißige technische Mitarbeit danke ich Fräulein Ulrike Kunze     

Favorable Long‐Term Survival in Patients Undergoing Multivessel‐PCI Compared to Predicted Prognosis of CABG Estimated by EuroSCORE: Procedural and Clinical Determinants of Long‐Term Outcome

Aims/Methods: Treatment of patients with multivessel coronary artery disease (CAD) has been an ongoing focus of recent clinical studies, questioning the ideal treatment. Randomized trials comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) have so far only included a minority of screened patients. Therefore, we analyzed data from 679 consecutive “all‐comer” patients, who underwent PCI in at least two main vessels. Expected in‐hospital mortality for CABG was calculated using the EuroSCORE and compared to the observed mortality rate during in‐hospital as well as long‐term follow‐up. Results: The patients were suffering from 2.5 ± 0.6 diseased vessels, and 2.8 ± 1.0 lesions were stented (32% of patients received at least one drug‐eluting stent [DES]; 20% of lesions were treated with DES). Forty‐seven percent of patients were treated for acute coronary syndrome (ACS) ( N = 176 ST‐elevation myocardial infarction [STEMI]; N = 140 non‐ST‐elevation myocardial infarction [NSTEMI]). The EuroSCORE was significantly higher in ACS patients compared to stable patients (logistic: STEMI 16.3 ± 17.2; NSTEMI 13.6 ± 13.0; stable CAD 3.9 ± 4.2). The observed in‐hospital mortality (STEMI 13.0%; NSTEMI 2.9%; stable CAD 1.7%, P < 0.001) was far lower than the estimated 30‐day mortality. Cox regression analysis identified an elevated logistic EuroSCORE (HR per quartile 2.7, P = 0.003), severely reduced left ventricular ejection fraction (HR 2.7, P < 0.001), elevated C‐reactive protein (HR 1.8, P = 0.012), and chronic renal failure (HR 2.8, P = 0.001) as independent predictors of long‐term mortality. Conclusions: The EuroSCORE, which is routinely used to estimate the perioperative risk of patients undergoing CABG, also predicts short‐ and long‐term prognosis of patients undergoing MV‐PCI. The observed mortality of patients undergoing MV‐PCI seems to be much lower than the estimated mortality of CABG.     

The recombinant bifunctional protein αCD133–GPVI promotes repair of the infarcted myocardium in mice

Background:  Bone‐marrow‐derived progenitor cells are important in myocardial repair mechanisms following prolonged ischemia. Cell‐based therapy of diseased myocardium is limited by a low level of tissue engraftment. Objectives:  The aim of this study was the development of the bifunctional protein αCD133–glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms. Results:  We have generated and characterized a bifunctional molecule (αCD133–GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133⁺ progenitor cells with high affinity. αCD133–GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that αCD133–GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with αCD133–GPVI‐labeled progenitor cells reduces infarction size and preserves myocardial function. Conclusions:  The bifunctional trapping protein αCD133–GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.