Long‐Term Survival of Routine Implantable Cardioverter/Defibrillator Recipients Appears to be Significantly Impaired with Concomitant Diuretics and Improved with Aldosterone Antagonists

Evidence‐based treatment for heart failure (HF) comprises beta‐blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists (ARA). Diuretics (DR) are prescribed in acute and chronic HF, but their impact on survival and ventricular tachyarrhythmias (VT/VF) is unclear. The present observational study aims to examine the influence of DR and ARA on survival and appropriate cardioverter/defibrillator (ICD) treatment episodes in routine ICD patients. In 352 consecutive ICD patients (291 men, 60 ± 12 years, LVEF 34 ± 15%, follow‐up 37 ± 19 months) overall survival and the time to a first appropriate VT/VF episode were assessed. Electrograms were validated. Potassium and creatinine serum levels and the medical treatment regimen for heart failure were documented at baseline. Multivariate Cox regression analyses revealed significantly worse survival for patients with DR compared to those without DR (OR 0.24, CI 0.08–0.76, P= 0.016), whereas the group with ARA had better survival compared to patients without (OR 2.05, CI 1.02–4.10, P= 0.04). Patient groups did not differ regarding survival without incident VT/VF (DR+ vs. DR– OR 1.10, CI 0.67–1.83, P= 0.70; OR 0.66, CI 0.40–1.09, P= 0.10). Long‐term survival appears to be compromised in ICD patients receiving concomitant DR, but is favorably influenced by ARA, although VT/VF incidence does not differ. Randomized analyses are warranted to assess long‐term prognostic effects of DR in HF.     

Metabolic rates in small brain nuclei determined by high-resolution PET.

Identification of small nuclei in the brain by PET has been limited by the spatial resolution of conventional scanners. The new detector technology and advanced signal analysis of a high-resolution research tomograph (HRRT) has improved 3-dimensional spatial resolution to 2.2 mm at sufficient efficiency and permitted the quantification of tracer concentrations in small volumes. METHODS: In 9 healthy volunteers, cerebral glucose metabolism was investigated after intravenous injection of 370 MBq of (18)F-FDG, and regional cerebral metabolic rates for glucose (rCMRGlc) were determined in various structures of the brain identified on coregistered MR images using stereotactic and topographic anatomic information. RESULTS: rCMRGlc values (in mumol/100 g/min) were higher in the cerebral cortex (33.5 +/- 2.98), the basal ganglia (32.6 +/- 3.04 in the nucleus caudatus and 40.2 +/- 3.50 in the putamen), the thalamus (36.6 +/- 4.72), and the cerebellum (29.8 +/- 2.20) and were lower in the cerebral white matter (12.3 +/- 1.45) than those reported previously with conventional scanners. This resulted in an increased ratio of cortical values to white-matter values. Various nuclei in the basal frontal lobe (21.4 +/- 3.19 in the basal forebrain and 32.3 +/- 2.39 in the nucleus accumbens), the temporal lobe (22.2 +/- 1.74 in the corpus amygdalae), the hippocampus (25.7 +/- 2.11), the diencephalon (23.1 +/- 3.33 in the corpus geniculatum laterale, 20.2 +/- 2.87 in the corpus geniculatum mediale, and 25.2 +/- 3.29 in the nucleus subthalamicus), and the brain stem (24.4 +/- 2.47 in the colliculus superior, 31.4 +/- 3.63 in the colliculus inferior, 31.0 +/- 3.10 in the nucleus ruber, and 22.8 +/- 2.35 in the substantia nigra) could be identified, and the metabolic rate was assessed in these structures. The effect of improved spatial resolution on quantified metabolic rates could directly be demonstrated in a few cases investigated on scanners of different generations. CONCLUSION: The improved spatial resolution of the HRRT decreased partial-volume effects in the quantification of metabolic rates in the brain and increased the accuracy of rCMRGlc values in large structures. For the first time, this scanner has permitted the determination of metabolic rates in small nuclei that are involved in various neurodegenerative disorders.     

Kardiovasculäre Fehlbildungen mit konstitutionellen Charakteristika und Debilität

Zusammenfassung Das erst in den letzten Jahren erkannte Syndrom mit supravalvulärer Aortenstenose, ähnlichen facialen Merkmalen, Zahnanomalien, Minderwuchs und Debilität hat durch den Nachweis einer zusätzlichen Störung im Vitamin D-Stoffwechsel im Sinne einer Überempfindlichkeit eine aktuelle Bedeutung bekommen.Diese Annahme — und nicht die allein exogene Verursachung durch eine Überdosierung — wird durch die Mitteilung einer Halbgeschwisterbeobachtung unterstrichen; daneben wird vergleichsweise über einen typischen Einzelfall berichtet.In Verbindung mit gefundenen Halswirbelanomalien wird außerdem die Frage aufgeworfen, ob die oft beobachtete Ptose der Kinder damit in Zusammenhang steht, evtl. auch die tiefe rauhe Stimme auf der Grundlage einer Kehlkopfentwicklungsstörung.

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Summary The diagnosis in recent years of syndrome together with supravalvular aortic stenosis, facial resemblance, dental abnormalities, impaired growth and mental deficiency has gained actual significance because proof has been found of an additional error of vitamine D-metabolism being expressed in hypersensitiveness.This assumption — and not alone the exogenetic cause through a hyperdosage — is being underlined by the information regarding the observation on half-brothers; along with that a typical singular case has been reported in comparison. In connection with the findings of malformations of cervical vertebral column the question also arises whether the ptosis often observed on these children has any relevance to it, possibly the deep hoarse voice too, caused through a maldevelopment of the larynx.

     

Cranial morphology in the 18p- syndrome

Three of four recently described children with the 18p^- syndrome were reinvestigated using cranial computerized tomography (CCT). More severe deformities were found in the cases with severe cerebral malformation, but there was no correlation with the degree of mental retardation.     

Absorption kinetics of dihydroergotoxine following oral administration to man.

The absorption characteristics of dihydroergotoxine administered as an oral solution, tablet and retard capsule have been determined in a randomised cross-over investigation in 12 healthy males. The plasma concentrations of dihydroergotoxine produced by the three preparations, measured using a specific and sensitive radioimmuno-assay method over 24 h, exceeded 200 pg ml-1 for approximately 5 h and decayed in a biphasic manner with a slowest measured half-life of 12-14 h. The retard capsule differs from the other two preparations in having a low Cmax (50% of that recorded for the solution) and a clearly defined plateau. The bioavailability of the retard capsule was similar to that for the solution indicating that first-pass metabolism is not significantly increased following a three-fold prolongation in the absorption rate constant. The 20-40% greater bioavailability of dihydroergotoxine solution and retard capsule in comparison with the standard tablet may be due to a reduced contact time with gastric secretions achieved by means of rapid absorption from the stomach (solution) or delayed release at pH 1.5 (retard capsule).     

Sonstige Körperverletzungen. Gewaltsamer Tod

Ohne Zusammenfassung     

Pathologische Anatomie (Sektionstechnik) und Physiologie

Ohne Zusammenfassung     

The ergoloid mesylate dihydroergotoxine: radioimmunoassay measurements on plasma and blood-pressure-lowering activity

Dihydroergotoxine plasma concentrations determined using a newly developed radioimmunoassay method and corresponding blood-pressure-lowering effects have been measured in normotensive subjects after intravenous injection (0.6 mg) and administration of an oral solution (4.5 mg). Plasma concentrations in the range 0.2-1 ng/ml dihydroergotoxine produced clinically significant reductions of up to 15% in systolic and diastolic standing and supine blood pressures, while no significant changes occurred in pulse rate.