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.     

Lifetime and six-month prevalence of mental disorders in the Munich follow-up study

Summary The Lifetime and 6 month DSM-III prevalence rates of mental disorders from an adult general population sample of former West Germany are reported. The most frequent mental disorders (lifetime) from the Munich Follow-up Study were anxiety disorders (13.87%), followed by substance (13.51%) and affective (12.90%) disorders. Within anxiety disorders, simple and social phobia (8.01%) were the most common, followed by agoraphobia (5.47%) and panic disorder (2.39%). Females had about twice the rates of males for affective (18.68% versus 6.42%), anxiety (18.13% versus 9.07%), and somatization disorders (1.60% versus 0.00%); males had about three times the rates of substance disorders (21.23% versus 6.11%) of females. Being widowed and separated/divorced was associated with high rates of major depression. Most disordered subjects had at least two diagnoses (69%). The most frequent comorbidity pattern was anxietyand affective disorders. Simple and social phobia began mostly in childhood or early adolescence, whereas agoraphobia and panic disorder had a later average age of onset. The majority of the cases with both anxiety and depression had depression clearly after the occurrence of anxiety. The DIS-DSM-III findings of our study have been compared with both ICD-9 diagnoses assigned by clinicians independently as well as other epidemiological studies conducted with a comparable methodology.     

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.     

Unterschenkel-Muskelatrophie bei Arthrose des oberen Sprunggelenks und deren Rehabilitation nach Implantation einer Sprunggelenksprothese

The aim of this orthopaedic-biomechanical study was to evaluate lower leg muscle function in ankle osteoarthritis (OA) patients and muscle rehabilitation after the implantation of a total ankle replacement (TAR). Patients with a severe unilateral ankle OA were assessed with an orthopaedic and biomechanical examination before and one year after TAR surgery. Visual analogue pain score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle score, ankle range of motion for dorsi- and plantar flexion (ROM DF/PF), and calf circumference difference between affected and contralateral healthy leg were measured. Isometric maximal voluntary torque for ankle dorsiflexion and plantar flexion were measured simultaneously with surface electromyography (EMG; mean frequency and intensity) of the anterior tibial, medial gastrocnemius, soleus, and peroneus longus muscle. Data were compared to a group of age- and gender-matched normal subjects. The mean calf circumference difference between legs did not significantly decrease from preoperative to one year follow-up. The mean dorsiflexion torque and plantar flexion torque of the affected ankle increased significantly. The atrophic muscles were characterized by a reduction of the mean EMG intensity and mean EMG frequency. In the rehabilitation process, the mean EMG intensity recovered and was not significantly different for all muscles, however, not for EMG frequency, which remained low and unchanged. This study reports for the first time in the literature the clinical and biomechanical facts of lower leg muscle atrophy in ankle OA as well as the amount of the muscle rehabilitation after a total ankle replacement. Patients with a symptomatic ankle OA achieve better function with a total ankle replacement; however, one year after the operation neuromuscular and biomechanical deficits may still be present.     

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.