Dyspepsie und Helicobacter-pylori-Infektion bei Besch?ftigten eines gro?en Industrieunternehmens Ergebnisse der prospektiven BASF-Helicobacter-pylori-Vorsorgeaktion

Zusammenfassung Hintergrund: Die Assoziation zwischen Helicobacter-pylori-(H.-pylori-)Infektion und Dyspepsie wird kontrovers diskutiert. Im Rahmen der BASF-H.-pylori-Vorsorgeaktion wurde u. a. die Prävalenz von Dyspepsie bei arbeitsfähigen Personen ermittelt sowie der Zusammenhang mit der H.-pylori-Infektion und der Erfolg einer Eradikationstherapie untersucht. Probanden und Methodik: 6 132 Beschäftigte der BASF wurden untersucht und im Rahmen einer standardisierten Anamnese u. a. zu dyspeptischen Beschwerden befragt. Diese wurden entsprechend der führenden Symptomatik den Dyspepsiesubtypen vom Ulkustyp, Dysmotilitätstyp, Refluxtyp und unspezifischen Typ zugeordnet. Bei allen Beschäftigten wurde die Seroprävalenz (IgG-ELISA) der H.-pylori-Infektion bestimmt. Allen H.-pylori-positiven Personen mit Dyspepsie wurde weitere Diagnostik in Form einer Ösophagogastroduodenoskopie und einer Sonographie des Abdomens bei Fachärzten empfohlen und eine H.-pylori-Eradikationstherapie (Italian-Triple-Therapie) angeboten. In einer Untergruppe endoskopisch untersuchter Beschäftigter mit peptischer Ulkuskrankheit (PUD, n = 37) bzw. Non-Ulcer-Dyspepsie (NUD; n = 39) wurde der prognostische Wert der im Western Blot ermittelten Antikörper gegen CagA und VacA untersucht. Ergebnisse: 1 255 der 6 143 Beschäftigten (20,4%) berichteten über Dyspepsie. 492 Personen mit Dyspepsie (39,2%) waren gleichzeitig H.-pylori-positiv. Bei Personen ohne dyspeptische Symptome betrug die H.-pylori-Prävalenz 35,8%. Personen mit unterschiedlichen Dyspepsiesubtypen unterschieden sich nicht hinsichtlich der H.-pylori-Prävalenz. Personen, die häufige und intensive dyspeptische Beschwerden angaben, waren allerdings signifikant häufiger H.-pylori-positiv (OR 2,09, CI 1,43-3,05). Die Seroprävalenz von CagA und VacA bei Personen mit PUD unterschied sich nicht signifikant von derjenigen bei Personen mit NUD. 458 H.-pylori-positiven Personen wurde die Eradikation empfohlen. 330 Personen (72,1%) folgten der Empfehlung. 128 (27,9%) ließen sich nicht behandeln. An der Nachkontrolle nach 12 Monaten nahmen 402 Personen (87,8%) teil, davon waren 300 behandelt, 102 nicht. Der serologisch analysierte Eradikationserfolg lag bei 81,5%. 42,8% der erfolgreich behandelten Personen berichteten über Besserung ihrer Beschwerden, 33,2% über Beschwerdefreiheit. Bei den nicht behandelten Personen war dies nur in 16,7% bzw. in 37,3% der Fall. Vermehrte Refluxbeschwerden traten nach erfolgreicher Eradikation nicht auf. Schlussfolgerung: Wir konnten keinen generellen Zusammenhang zwischen Dyspepsie und H.-pylori-Infektion in einem großen Kollektiv arbeitsfähiger Personen erkennen. Häufige und intensive dyspeptische Symptome scheinen allerdings ein prädikativer Faktor für die H.-pylori-Seropositivität zu sein. Die serologisch bestimmbaren Virulenzfaktoren tragen nicht zur Unterscheidung PUD oder NUD bei. Die Eradikationstherapie führte nach 1 Jahr zwar häufiger zur Besserung, aber nicht häufiger zu Beschwerdefreiheit bei Beschäftigten mit dyspeptischen Beschwerden im Vergleich zu unbehandelten Personen. Abstract Background: The role of Helicobacter pylori (H. pylori) infection in dyspepsia is controversial. In the course of a health initiative within a large industrial corporation, we investigated the prevalence of both dyspepsia and positive H. pylori serology and the outcome of eradication therapy in symptomatic H. pylori positive employees. Test Persons and Methods: H. pylori serology (IgG ELISA) was determined in 6,143 employees of BASF AG Ludwigshafen/Germany who were also asked to complete a standardized health history administered by a physician. Peptic ulcer disease (PUD) and dyspepsia subgroups were defined based on past medical history and symptom profiles using the criteria of Heading. Upper GI endoscopy, abdominal ultrasound and eradication therapy (Italian Triple Therapy) was recommended for symptomatic H. pylori positive individuals. The prognostic value of antibodies against CagA and VacA was evaluated in 37 and 39 employees with PUD and non-ulcer dyspepsia (NUD) confirmed by endoscopy, respectively. Results: Of 6,143 employees, 1,255 (20.4%) were classified as dyspeptic, 492 (39.2%) of whom were H. pylori positive. The seroprevalence of H. pylori in asymptomatic employees was 35.8%. There were no significant differences in H. pylori seroprevalence among dyspepsia subgroups (reflux only, dysmotility only, reflux/dysmotility, ulcer-like and non-specific). However, individuals reporting severe dyspeptic symptoms were significantly more likely to be H. pylori positive (OR 2.09, CI 1.43-3.05). The seroprevalence of CagA and VacA was not significantly different among employees with NUD compared to referents or among employees with NUD compared to those with PUD. 330 (72%) of 458 employees with dyspepsia received eradication therapy, 128 persons refused therapy. Based on a 12-month follow-up of 402 individuals (300 of whom had received therapy), eradication success was 81.5% as judged by serology. Of the successfully treated employees, 33.2% reported a total absence and 42.8% reported a decrease in symptoms. Among the employees who refused therapy, the corresponding percentages were 37.3% and 16.7%, respectively. An increase in reflux complaints was not observed among treated employees. Conclusion: In a large active employee population, at most a very weak association was observed between the prevalence of H. pylori seropositivity and dyspepsia. Frequent and severe dyspeptic symptoms were associated with an increased rate of H. pylori seropositivity. The analysis of the virulence factors is not particularly helpful in discriminating PUD or NUD. Eradication of H. pylori infection leads to a decrease in dyspeptic symptoms after 12 months, but not more often to their complete absence compared to untreated individuals.     

Virtual real-time digital processing of hemodynamic data

At present, the majority of cardiac catheterization laboratories acquire and store hemo-dynamic data in analog form. To examine the possibility of performing complex analysis of digital data during the catheterization procedure, we examined whether virtual realtime digital (fast Fourier) analysis improves the accuracy of clinical data. We compared digital filtering of fluid manometry during right heart catheterization with 10-Hz and 250-Hz analog filters. Using the simultaneously acquired micromanometry as the “gold standard,” we found that analog filtering is associated with a greater error and time delay than digital filtering. This study demonstrates that digital hemodynamic data analysis performed during cardiac catheterization can improve the quality of data obtained during right heart catheterization, with the results available within seconds. More extensive use of computers in the cardiac catheterization laboratory may be useful for both clinical and research purposes. © 1992 Wiley-Liss, Inc.     

Early pathological changes in progressive multifocal leukoencephalopathy: a report of two asymptomatic cases occurring prior to the AIDS epidemic

Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

Structure function interface with sequential shortening of basal and apical components of the myocardial band

Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30–85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18±3%, with endocardial exceeding epicardial shortening by 5±1%. Epicardial segment crystal displacement followed endocardial shortening by 82±23 ms in the anterior wall, and finished 92±33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation–contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed ‘isovolumetric relaxation’.     

Penile rehabilitation following treatment for prostate cancer: an analysis of the current state of the art

Despite recent advances in surgical technique using laparoscopic and robotic approaches for the management of early organ-confined prostate cancer, most contemporary reports demonstrate significant rates of erectile dysfunction comparable to standard open approaches. Controversy remains related to many of the pre-and postoperative management strategies, including agents to enhance nerve recovery, erectogenic drugs, antioxidants, vasoactive injectables, vacuum erection devices and nerve grafting procedures. Additionally, the optimal timing of these interventions and their duration, dose, frequency and outcome thresholds remain ill-defined. In our paper, we provide a comprehensive literature review involving both the basic and clinical data surrounding rehabilitative approaches.     

Laparoscopic bilateral nephrectomy for renin-mediated hypertension

Hypertension arising from retained native kidneys complicates the management of recipients of renal transplants. Reluctance to administer angiontensin-converting enzyme inhibitor (ACEI) drugs to patients taking cyclosporine has reopened the question of performing native nephrectomies for poorly controlled, renin-dependent hypertension. We report the first published cases of simultaneous bilateral laparoscopic nephrectomies in 2 patients: 1 in preparation for living-related donor transplantation and the other ten months following cadaver transplantation in a patient whose end-stage renal disease was from malignant nephrosclerosis. Both had very severe hypertension resistant to multiple drugs and both became normotensive with little or no antihypertensive medication following nephrectomies. A bilateral nephrectomy is currently feasible using a laparoscopic approach.     

Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors

Summary Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastromestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.This investigation was supported by Pfizer Inc.