Immune monitoring in a phase 1 trial of a PSA DNA vaccine in patients with hormone-refractory prostate cancer

Prostate cancer remains a leading cause of cancer illness and death among men in Europe. No curative treatment exists when the disease has spread beyond the prostate. Immunotherapy with DNA vaccines has emerged as a potential therapeutic approach for the induction of antitumor specific cytotoxic T lymphocytes. In this study six patients with hormone-refractory prostate cancer were monitored for their ability to mount PSA-specific cellular responses after receiving a pVAX/PSA DNA vaccine (patients 1-3, 100 microg; patients 7-9, 900 microg) with recombinant GM-CSF and IL-2 as adjuvants. IFNgamma ELISPOT showed that naturally processed PSA protein and PSA peptides are recognized by T cells in the blood of some prostate cancer patients after a PSA DNA vaccine. Analysis of other cytokines showed the production of IL-4 and IL-6 but importantly did not show an increase in the number of IL-10-producing cells after vaccination in any of the patients. The authors conclude that a pVAX/PSA DNA vaccine can induce PSA-specific cellular immune responses in patients with hormone-refractory prostate cancer, thus emphasizing the potential for PSA as a target molecule for the immunotherapy of prostate cancer.     

Craniomandibular Pain,Bite Force,and Oral Health-Related Quality of Life in Patients with Jaw Resection

The present study evaluated the connection between temporomandibular disorders (TMD), maximum voluntary bite force and oral health-related quality of life (OHRQoL) in patients with oral cancer. Twenty-six prosthetically rehabilitated patients with partial resection of the upper and/or lower jaw with segmental mandibulectomy, with and without reconstruction, were examined. The examination comprised the Research Diagnostic Criteria for TMD (RDC/TMD), determination of the individual pain threshold, evaluation of the maximum voluntary bite force, and OHRQoL according to the Oral Health Impact Profile (OHIP) questionnaire. Male pain thresholds were significantly higher than female pain thresholds (P = 0.003). Patients with maxillary resection showed higher pain threshold values than patients with (segmental) mandibulectomy. Bite force was significantly (P = 0.000014) lower in resected jaw areas than in healthy ones. Patients with resections of the maxilla showed higher voluntary bite forces than patients with resections of the mandible; males showed higher bite forces than females. The prevalence of negative responses (“often”—2 and “very often”—1) on the OHIP items was 10.39%, whereas the prevalence of positive responses (“from time to time”—3, “seldom”—4, and “never”—5) was 89.60%. The prevalence for negative responses was 2.46% in male patients and 8.07% in female patients. Patients with resections in the maxilla suffered from negative responses of 3.92%, patients with resection of the mandible of 6.64%. According to the OHIP, the psychological disposition of these patients clearly referred to coping mechanisms.     

Improved response to cardiac resynchronization therapy through optimization of atrioventricular and interventricular delays using acoustic cardiography: a pilot study

BackgroundThe purpose of this pilot study was to determine the utility of acoustic cardiography for the optimization of atrioventricular (AV) and interventricular (VV) delays in cardiac resynchronization therapy (CRT).Methods and ResultsWe evaluated 14 patients (86% male, mean age 64 ± 9 years, mean time since implant 15 ± 18 months). Subjects were enrolled >10 weeks after CRT implant. Spiroergometry and 2-dimensional/3-dimensional echocardiography were used to assess cardiac performance for “out-of-the-box” settings (baseline settings: AV 120 ms, VV 0 ms) versus optimal settings (determined by acoustic cardiography). Cardiac performance measurements were performed 6 weeks after settings were modified. Optimal AV/VV settings were determined based on the lowest electromechanical activation time (EMAT, the time from the onset of QRS to the mitral valve component of the first heart sound). Statistical analysis was performed using a paired 2-tailed Student's t-test. In comparison to “out-of-the-box” settings, AV/VV delay optimization with acoustic cardiography improved cardiac performance as indicated by significant changes in work capacity, maximum oxygen uptake, oxygen pulse, ejection fraction, end-systolic volume, and velocity-time integral in left ventricular outflow tract.ConclusionsAV and VV optimization by acoustic cardiography produces significant improvements in objective clinical and hemodynamic parameters in comparison to typical “out-of-the-box” settings.     

Die chronische idiopathische eosinophile Pneumonie – eine diagnostische Herausforderung

Zusammenfassung Fallbeschreibung:   Eine 43-j?hrige Patientin mit den klinischen Zeichen eines fieberhaften respiratorischen Infekts wurde trotz mehrfacher Antibiotikatherapie mit persistierenden beidseitigen pulmonalen Infiltraten station?r eingewiesen. Diagnostik, Therapie und Verlauf:   In der weiteren Diagnostik fiel im Diffentialblutbild eine Eosinophilie von 31% auf. In der Bronchoskopie mit bronchoalveol?rer Lavage wurde ebenfalls eine Eosinophilie gesehen. Nach Ausschluss bekannter Ursachen einer pulmonalen Eosinophilie wurde die Diagnose einer chronischen idiopathischen eosinophilen Pneumonie gestellt. Unter alleiniger Therapie mit hochdosierten Kortikosteroiden normalisierten sich die pathologischen Laborwerte, die klinischen und die radiologischen Befunde innerhalb 1 Woche ann?hernd vollst?ndig. Schlussfolgerung:   Bei therapierefrakt?ren pulmonalen Infiltraten sollten die Diagnose einer akuten oder chronischen eosinophilen Pneumonie in Betracht gezogen und eine Bronchoskopie mit bronchoalveol?rer Lavage veranlasst werden. Differentialdiagnostisch muss aus prognostischen und therapeutischen Gründen zwischen einer akuten und chronischen idiopathischen eosinophilen Pneumonie unterschieden werden. Ein rasches Ansprechen auf Kortikosteroide unterstützt die Diagnose. Bei einer chronischen idiopathischen eosinophilen Pneumonie ist auf eine Therapiedauer von etwa 6 Monaten zur Vermeidung von Rezidiven zu achten.      

Non-fluoroscopic catheter visualization using MediGuide™ technology: experience from the first 600 procedures

A novel cardiovascular navigation system known as MediGuide? (MG) which allows non-fluoroscopic catheter tracking over a background of pre-recorded cine loops was recently introduced. This system allows significant reduction of fluoroscopy exposure which is one of the potentially harmful aspects of today's electrophysiological procedures such as ablations or device implantations. We provide a summary of recently published studies related to this new technological platform and describe our experience from the first 600 MG procedures at our institution. After reviewing the currently available publications in the field of MG-supported EP procedures, we describe the workflows for (1) ablation of supraventricular tachycardia (SVT), atrial fibrillation (AF), and ventricular tachycardia using MG-enabled diagnostic and ablation catheters, as well as (2) implant of cardiac resynchronization therapy (CRT) devices using sensor-equipped delivery tools including sheaths, sub-selectors, and guidewires. As shown in several studies [5–9], MG procedures resulted in similar efficacy as conventional cases but with a significant reduction in fluoroscopy time and dose. In particular, for SVT ablations, the median fluoroscopy time using the MG technology was 0.5?±?1.4 min compared to 10.2?±?9.6 min in conventional fluoroscopic settings. Similar reductions were demonstrated for AF ablation procedures from 25 min in conventional settings with electroanatomical mapping systems and live x-ray to 4.6 min with the addition of the MG technology. Recently, it was demonstrated that the application of MG for CRT device implants could successfully result in a median fluoroscopy time of 2.6 min for LV lead deployment. In summary, the first measurable clinical impact of the MG technology on a daily clinical routine is the reduction of fluoroscopy time and radiation exposure for various EP indications. These beneficial effects were achieved without negative consequences on procedural efficacy, complications, or time in more than 600 EP procedures.     

Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice

BACKGROUND & AIMS: Three pathways control gastric acid secretion: the gastrin-enterochromaffin-like (ECL) cell axis, the vagus-parietal cell axis, and the cholecystokinin (CCK)-D cell axis. Mice lacking gastrin or both gastrin and CCK were examined to determine the role of the hormones. METHODS: Acid was measured after pylorus ligation, and biopsies from gastrin knockout (KO), gastrin-CCK double-KO, and wild-type (WT) mice were collected for biochemical, immunocytochemical, and electron-microscopic examination. RESULTS: The ECL cells were inactive in both groups of mutant mice but the cell number was unaffected. Both parietal cell number and level of H(+)/K(+)-ATPase messenger RNA (mRNA) were reduced in the mutant strains, but gastrin-CCK double-KO mice displayed more active parietal cells and larger acid output than the gastrin KO mice. The acid response to histamine in double-KO mice was unchanged whereas that to gastrin was diminished, but it could be restored by infusion of gastrin. Oxyntic D-cell density was the same in both mutant strains, but the D cells were more active in the gastrin KO than in the double-KO mice. CCK infusion in gastrin-CCK double-KO mice raised the somatostatin mRNA level and inhibited acid secretion to the level seen in gastrin KO mice. Vagotomy and atropine abolished acid secretion in all 3 groups of mice. CONCLUSIONS: Lack of gastrin impairs the gastrin-ECL axis, whereas lack of gastrin and CCK impairs both hormonal pathways. In the gastrin-CCK double-KO mice, acid secretion is only controlled by cholinergic vagal stimulation, which normalizes the acid output.     

Effects of fucosylated milk of goat and mouse on Helicobacter pylori binding to Lewis b antigen

AIM:To evaluate the effects of animal milk containing fucosylated antigens on Helicobacter pylori (H pylon) binding to Lewis b antigen.METHODS:A mammary gland expression vector containing human α1-3/4-fucosyltransferase cDNA sequences was constructed. Transient expression of human(α1-3/4-fucosyltransferase cDNA in goat mammary cell and establishment of transgenic mice were performed. The adhesion inhibitory properties of milk samples were analyzed by using Hpylori.RESULTS: Goat milk samples were found to inhibit bacterial binding to Lewis b antigen. The highest inhibition was observed 42 h after injection of the plasmid. The binding activity of Hpylori to Lewis b antigen reduced mostly, by 83%, however milk samples from transgenic mice did not inhibit Hpylori binding to Lewis b antigen.CONCLUSION: The use of “humanized“ animal milk produced by the transgenic introduction of fucosylated antigen can perhaps provide an alternative therapy and preventive measure for Hpylori infection.