PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

A randomized clinical trial of ceftriaxone and teicoplanin versus ceftazidime and teicoplanin as antibiotic therapy in febrile neutropenic cancer patients and bone marrow transplant recipients

Summary A prospective, randomized clinical trial comparing combination therapy with ceftriaxone and teicoplanin versus ceftazidime and teicoplanin in the treatment of febrile episodes in neutropenic cancer patients and bone marrow transplant recipients was performed. One hundred and two patients were randomized, but two patients were considered unevaluable for efficacy, and three patients were withdrawn due to incorrect randomization. Of the remaining 97 patients, infection resolved without modification of therapy in 31/49 (63%) patients treated with ceftriaxone/teicoplanin versus 27/48 (56%) patients treated with ceftazidime/teicoplanin (P=0.48). Of all 97 patients treated therapy was modified in 18/49 (36%) with ceftriaxone/teicoplanin and 21/48 (43%) with ceftazidime/teicoplanin. Nineteen patients treated with ceftriaxone/teicoplanin received netilmicin and 21 patients treated with ceftazidime/teicoplanin also received netilmicin according to the study design (escalation therapy). When netilmicin was added infection resolved in 78% of patients treated with ceftriaxone/teicoplanin versus 84% of those treated with ceftazidime/teicoplanin. It was concluded that combination therapy with ceftriaxone/teicoplanin is an alternative to combination therapy with ceftazidime/teicoplanin, and has the advantage of once daily administration.

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Antibiotische Therapie der febrilen Neutropenie von Tumor- und Knochenmarktransplantationspatienten. Eine randomisierte Studie mit Ceftriaxon und Teicoplanin im Vergleich mit Ceftazidim und Teicoplanin

Zusammenfassung In einer prospektiven, randomisierten klinischen Studie wurde die Kombinationstherapie mit Ceftriaxon und Teicoplanin gegen die Kombinationspartner Ceftazidim und Teicoplanin bei neutropenischen Patienten oder Patienten nach Knochenmarktransplantation verglichen. Insgesamt wurden 101 Patienten in die Studie eingebracht, davon waren 97 Patienten auswertbar. In der Ceftriaxon/Teicoplanin-Gruppe waren 63% der Patienten geheilt, gegenüber 56% der Patienten in der Ceftazidim/Teicoplanin-Gruppe. Dieses Ergebnis war ohne Modifikation der Studien-Medikamente erreicht worden. Bei 18 von 49 Patienten in der Ceftriaxon/Teicoplanin-Gruppe und 21 von 48 Patienten in der Ceftazidim/Teicoplanin-Gruppe wurde von der Studienmedikation abgegangen und zusätzlich Netilmicin (Eskalationstherapie) gegeben. Durch die zusätzliche Gabe von Netilmicin waren 78% der Patienten in der Ceftriaxon/Teicoplanin-Gruppe und 84% in der Ceftazidim/Teicoplanin-Gruppe geheilt. Diese Daten deuten darauf hin, daß die Kombinationstherapie mit Ceftriaxon/Teicoplanin eine Alternative zur Kombinationstherapie mit Ceftazidim und Teicoplanin darstellt, zumal die Gabe von Ceftriaxon und Teicoplanin den Vorteil hat, daß diese Medikamente nur einmal pro Tag gegeben werden müssen.

     

Who will conceive with IVF?

When considering the chances of establishing a healthy ongoing pregnancy after in vitro fertilization (IVF), the cause of infertility plays a relatively minor role. In recent years, there has been a shift from determining the diagnosis to the individual prognosis for a given patient. A number of prognostic factors were identified, which enabled clinicians to appropriately counsel patients. Patient-determined factors are of crucial importance and some are amenable to intervention such as lifestyle and nutritional advice. However, the attention of clinicians remains on seeking adjuvant therapeutic interventions designed to improve the outcomes of IVF treatment. In this article, the patient-determined factors underlying the individual chance of conceiving and the more commonly prescribed empirical medical therapies prescribed to enhance outcomes are reviewed. It is concluded that greater attention to optimizing the health of the couple before starting IVF treatment may be more beneficial than adjuvant medical therapies during treatment.