Angiotensin I conversion and coronary constriction by angiotensin II in ischemic and hypoxic isolated rat hearts.

Dose-response curves of angiotensin I (AI, 1.0-1000.0 pmol) and angiotensin II (AII, 1.25-1250.00 pmol) were obtained in isolated rat hearts subjected to control conditions, mild hypoxia (PO2 = 145 mm Hg), reoxygenation, ischemic (perfusion pressure = 35 mm Hg) and reperfusion. Both AI and AII caused dose-dependent coronary flow (CF) of 26 +/- 3 and 27 +/- 2%, respectively. The effects of both AI and AII were substantially attenuated during hypoxia, but were fully restored upon reoxygenation. During ischemia, the effect of AII was unaltered while the effect of AI was enhanced compared to the control (P less than 0.05). This enhancement was reversible on reperfusion. Cardiac conversion of AI, calculated from ED50 values for AI and AII, was significantly increased during ischemia (P less than 0.05). Infusion of saralasin (0.5-5.0 micrograms/min) did not increase CF in any of the groups. We conclude that (1) the coronary vasoconstrictive effect of AII is preserved in ischemia but attenuated in hypoxia and (2) cardiac conversion of AI to AII is enhanced in hearts injured by ischemia.     

Experimental and clinical possibilities of MR spectroscopy of the heart

MR-spectroscopy of the heart is a relatively new technique for the study of various aspects of cardiac metabolism. The majority of results has so far been obtained with the isolated perfused heart. Here, 31P-MR spectroscopy can be employed to measure high-energy phosphate metabolism and intracellular pH repeatedly and non-invasively. Using a technique called saturation transfer, velocities of enzymatic reactions, such as the creatine kinase reaction, can be measured. Intra- and extracellular Na+ and K+ concentrations can be registered with 23Na- and 39K-MR in conjunction with shift reagent. 13C-MR can be used to tackle carbohydrate metabolism. In-situ-R-spectroscopy allows determination of high-energy phosphates in intact large mammals. Clinical applications of MR-spectroscopy remain to be defined; preliminary results indicate high diagnostic and prognostic potential for patients with coronary artery disease and congestive heart failure.     

Epilepsie im Kindesalter: Wann kann die antiepileptische Therapie abgesetzt werden?

Zusammenfassung Der richtige Zeitpunkt für das Absetzen der Antiepileptika (AE) im Kindesalter ist unbekannt. Anl?sslich ihrer Jahrestagung haben die Mitglieder des K?nigsteiner Arbeitskreises (KA) eigene und publizierte Absetzstrategien diskutiert. Da Studien zu diesem Thema rar und widersprüchlich sind, wurde beschlossen, die Diskussionsergebnisse im Sinne einer Meinungs?u?erung zu publizieren. Bei Neugeborenen besteht übereinstimmung, AE innerhalb von 2 bis 12 Wochen nach dem letzten Anfall abzusetzen. Bei BNS-Epilepsie wird Vigabatrin nach 6 bis 12 und Sultiam nach 6 bis 36 Monaten abgesetzt. Nach erfolgreicher Steroidtherapie setzt die Mehrheit des KA die AE-Therapie für zwei Jahre fort. Für die Rolando-Epilepsie sind 1 bis 3 Jahre Anfallsfreiheit ausreichend, auch wenn fokale Spike-Waves persistieren. Im Falle einer symptomatisch fokalen Epilepsie ist die Grunderkrankung mitentscheidend für das Absetzen. Die Behandlung der Absencen-Epilepsie kann nach zwei Jahren beendet werden, w?hrend bei myoklonisch- astatischer Epilepsie meist eine 2- bis 5-j?hrige Anfallsfreiheit vorausgesetzt wird. Konsens besteht darüber, dass die Juvenile- Myoklonus-Epilepsie ein sehr hohes Rückfallrisiko birgt. Dennoch ziehen einzelne neurop?diatrische Mitglieder einen Absetzversuch nach 2- bis 3-j?hriger Anfallsfreiheit in Betracht. Die überwiegende Mehrheit des KA führt aber bei gesicherter Diagnose keinen Absetzversuch durch. Bezüglich der Absetzgeschwindigkeit wird ein langsames (3 bis 12 Monate) Ausschleichen favorisiert. Nur zwei Mitglieder praktizieren ein rascheres Absetzen (<3 Monaten). Das EEG spielt für die Entscheidung eine untergeordnete Rolle und bleibt auf bestimmte Epilepsieformen (z. B. Absencen-Epilepsie) beschr?nkt. Das vorliegende Papier gibt die Meinung des KA wieder und eignet sich nicht im Sinne einer Leitlinie. Für die Entscheidung AE abzusetzen, ist immer eine individuelle Abw?gung von Grunderkrankung, Epilepsieform und psychosozialen Umst?nde erforderlich.      

Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma.

The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p-hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate.     

Human imaging of phosphorus in cortical and trabecular bone in vivo.

Phosphorus was imaged in vivo in human cortical and trabecular bone and the T(1) and T(2) (*) were measured. An ultrashort TE (UTE) pulse sequence (TE = 70 microm) was used with half pulse excitation and radial mapping of k-space from the center out. T(2) (*) was measured using multiple echo times and T(1) was measured both by saturation recovery and by a method using different RF pulse amplitudes. Seven normal subjects (32-85 years) were examined. Phosphorus was imaged, with a true in-plane resolution of 2.9 x 2.9 mm and a signal-to-noise ratio (SNR) of 19:1, in both cortical and trabecular bone. The mean T(2) (*) value was 207 +/- 12 micros, and the mean T(1) value was 8.6 +/- 3.0 sec. Images and measurements were obtained in realistic times on a clinical MR system. This may provide a new approach to characterizing disease of bone.     

The association between daytime sleepiness and sleep-disordered breathing in NREM and REM sleep

BACKGROUND: Daytime sleepiness is common in patients with sleep-disordered breathing. Although respiratory events during sleep are associated with the occurrence of daytime sleepiness, the differential impact of these events during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep on daytime sleepiness has not been well characterized. STUDY OBJECTIVES: To determine the effect of respiratory events during REM sleep and NREM sleep on daytime sleepiness, as assessed by the multiple sleep latency test (MSLT). DESIGN: Cross-sectional study. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: Patients referred for polysomnography and daytime MSLT (n=1,821). INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: The study sample was initially divided into quartiles based on the level of the apnea-hypopnea index (AHI) during NREM sleep. Within the first NREM-AHI quartile (NREM-AHI < 8.3 events/hr), the association between REM-related respiratory events and daytime sleepiness was examined using the method of Kaplan-Meier analysis and Cox proportional hazards regression. After adjusting for age, gender, body mass index, and the duration of NREM and REM sleep, REM-AHI was not associated with daytime sleepiness (Relative Risk: 1.01; 95%CI: 0.94-1.10). Similarly, no significant association was observed between REM-AHI and the MSLT in patients within the second through fourth NREM-AHI quartiles. In contrast, increasing severity of disordered breathing during NREM sleep was associated with daytime sleepiness. For a 10-point increase in NREM-AHI, the adjusted relative risks for daytime sleepiness in the second through fourth NREM-AHI quartile were 1.21 (95%CI: 1.01-1.46), 1.20 (95%CI: 1.05-1.37), and 1.10 (95%CI: 1.04-1.16), respectively. CONCLUSION: Sleep-disordered breathing during NREM sleep, but not REM sleep, is associated with increased risk of daytime sleepiness.