Immunomodulation during prolonged treatment with combined interleukin-2 and interferon-alpha in patients with advanced malignancy.

Treatment with combined IL-2 and alpha-IFN has resulted in synergistic antitumour efficacy in animal studies. The mechanisms responsible for this synergy remain unclear. In this study, several immune parameters which might be involved in mediating antitumour activity have been monitored serially in 15 patients with advanced malignant melanoma or renal cell cancer during treatment with concurrent IL-2 and alpha-IFN. Both drugs were given subcutaneously in low to moderate (outpatient) dosages but for a prolonged duration. This treatment resulted in remarkable immunomodulation. In vivo induction of cytotoxicity against K562 and Daudi target cells was consistently seen, and percentages of peripheral blood cells expressing CD 25 (IL-2 receptor) and CD 56 (Leu-19) increased. In vitro proliferation of lymphocytes in response to IL-2 was enhanced during the treatment periods, whereas spontaneous proliferation was inhibited. Moreover, correlations between immune parameters and subsequent clinical responses were present in the early phase of the study. Cytotoxicity levels generated in vivo as well as the percentage of CD 56+ lymphocytes were higher in patients who responded to treatment than in non-responders. In contrast, responders had lower levels of CD 25+ cells. These findings indicate that it might be possible to select patients who are likely to benefit from prolonged immunotherapy.     

P2-purinoceptor-mediated inhibition of noradrenaline release in rat atria.

1. We looked for P2-purinoceptors modulating noradrenaline release in rat heart atria. Segments of the atria were preincubated with [3H]-noradrenaline and then superfused with medium containing desipramine (1 microM) and yohimbine (1 microM) and stimulated electrically, by 30 pulses/1 Hz unless stated otherwise. 2. The adenosine A1-receptor agonist, N6-cyclopentyl-adenosine (CPA; EC50 9.7 nM) and the nucleotides, ATP (EC50 6.6 microM) and adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S; EC50 4.8 microM), decreased the evoked overflow of tritium. The adenosine A2a-agonist, 2-p-(2-carbonylethyl)-phenethylamino-5'-N-ethylcarboxamido-a denosine (CGS-21680; 0.03-0.3 microM) and the P2x-purinoceptor agonist beta, gamma-methylene-L-ATP (30 microM) caused no change. 3. The concentration-response curve of CPA was shifted to the right by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX; 3 nM; apparent pKB value 9.7) but hardly affected by the P2-purinoceptor antagonist, cibacron blue 3GA (30 microM). In contrast, the concentration-response curves of ATP and ATP gamma S were shifted to the right by DPCPX (3 nM; apparent pKB values 9.3 and 9.4, respectively) as well as by cibacron blue 3GA (30 microM; apparent pKB values 5.0 and 5.1, respectively). Combined administration of DPCPX and cibacron blue 3GA caused a much greater shift of the concentration-response curve of ATP than either antagonist alone. The concentration-response curve of ATP was not changed by indomethacin, atropine or the 5'-nucleotidase blocker alpha, beta-methylene-ADP. 4. Cibacron blue 3GA (30 microM) increased the evoked overflow of tritium by about 70%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pericarditis constrictiva after aortic valve replacement simulating tricuspid stenosis.

Pericarditis constrictiva after cardiac surgery is rare and may occasionally lead to congestive heart failure. The case of a 29-year-old patient is described who presented with pericarditis constrictiva after aortic valve replacement with localized tamponade, causing functional tricuspid stenosis. Pericardiectomy as the treatment of choice was curative.     

Kryokonservierung und Transplantation von Ovarialgewebe

There are relatively few effective clinical options for preserving female fertility, particularly following aggressive chemotherapy and/or radiotherapy treatment protocols. This document reviews scientific background, current technology, clinical results, and potential future applications of ovarian tissue cryopreservation and transplantation. The technology is investigational although rapidly evolving, and the list of appropriate indications may be expanded in the future. Germany stays abreast of these rapid worldwide developments by having founded the first German network of experts for fertility preservation in patients undergoing chemotherapy and/or radiotherapy.     

Problems and needs for improving primary care of osteoarthritis patients: the views of patients, general practitioners and practice nurses

Background  

Osteoarthritis (OA) is highly prevalent and has substantial impact on quality of life as well as on healthcare costs. The general practitioner (GP) often is the first care provider for patients with this chronic disease. The aim of this study was to identify health care needs of patients with OA and to reveal possible obstacles for improvements in primary care management of OA patients.     

Orale Zytologie

Zusammenfassung Die orale Zytologie erf?hrt eine Renaissance, die durch die Einführung der Bürste als Entnahmetr?ger und durch die Anwendung zus?tzlicher moderner Verfahren bedingt ist. Die Bürste kann tiefe Schichten der oralen Mukosa erfassen, in denen die squam?se intraepitheliale Neoplasie (SIN) beginnt. Zus?tzliche Verfahren zur Bewertung der biologischen Potenz der gewonnenen oralen Epithelzellen sind: die computerunterstützte Bildanalyse (OralCDx^?), die DNA-Zytometrie, die Immunzytochemie, die Dünnschichtzytologie und molekularbiologische Analysen. Alle genannten Verfahren sind geeignet, die Sensitivit?t (bis zu 100%) und Spezifit?t (bis zu 100%) der oralen Zytologie zu erh?hen. Dennoch gibt es Berichte über orale Plattenepithelkarzinome, die mithilfe der Bürstenbiopsie nicht erkannt wurden. Die Wertigkeit der einzelnen Verfahren kann aktuell aufgrund fehlender vergleichender Studien nicht abschlie?end beurteilt werden. Die Immunzytochemie mit kommerziellen Antik?rpern gegen Laminin 5 ist allseits verfügbar und methodisch einfach. Das nichtinvasive diagnostische Verfahren der methodisch unterstützten oralen Bürstenbiopsie kann einen Beitrag zur frühen Erkennung ausgew?hlter Mundschleimhautl?sionen leisten. Ein positiver Befund oder eine Progression der L?sion bei negativem Befund sind Indikationen zur überweisung des Patienten an Fachkliniken und zur dort durchgeführten Skalpellbiopsie mit histopathologischer Untersuchung. Die histopathologische Begutachtung bleibt der Goldstandard in der definitiven Diagnostik maligner oraler L?sionen.      

Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review.

OBJECTIVE: To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. METHODS: A systematic review of randomized controlled trials (RCTs), observational studies (N >/= 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% CI. RESULTS: Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); 1 study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (- 0.06, 0.11); chi2 = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% CI (0.49, 1.07); chi2 = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% CI (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26). CONCLUSIONS: Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease.