Evaluation of Differences Between Fan-Beam and Pencil-Beam Densitometers

We compared the bone and body composition results in vivo on two bone densitometers using fan-beam geometry (EXPERT and PRODIGY) with those using pencil-beam geometry (DPX). Measurements were made on large groups of adults ranging in weight from about 50 to 120 kg. Both spine and femur neck BMD on the fan-beam densitometers averaged within 1% of the pencil-beam results, and there was no magnitude dependence of the results by Bland-Altman analysis. Total body BMC and BMD on the PRODIGY and DPX were congruent, but on the EXPERT, BMC was about 2% lower and BMD 2% higher than corresponding values on the DPX. Soft-tissue composition was closely congruent for the PRODIGY and DPX; the comparable EXPERT-DPX differences showed greater scatter but no significant magnitude dependence. The smaller fan-angle of the PRODIGY (4°) probably contributed to its better congruence to pencil-beam results compared with the EXPERT (12°). Received: 23 February 2000 / Accepted: 14 April 2000 / Online publication: 27 July 2000     

Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international normalized ratio (INR) of 2.5–6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5–2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation. Received: 1 September 1999/Received in revised form: 28 October 1999/Accepted: 19 November 1999     

The influence of bile salts and mixed micelles on the pharmacokinetics of quinine in rabbits.

The bioavailability of orally administered drugs can be influenced by interactions with food components and by physico-chemical conditions in the upper gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic drugs across mucosal membranes. Bile salts are able to form stable mixed micelles consisting of fatty acids and phospholipids. Conventional micellar systems are known to solubilize lipophilic drugs having a low bioavailability. The influence of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug quinine was investigated in rabbits. Female rabbits were given intraduadenally quinine (5 mg/kg body weight) without and with incorporation into the micellar or mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma, concentration of quinine was measured using HPLC. The plasma concentration-time profiles of quinine were significantly lower within the first 2 h after administration in presence of both the sodium salt of glycodeoxycholic acid (above the critical micellar concentration) as well as of mixed micellar systems consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The pharmacokinetic parameters AUC (relative bioavailability) and c(max) of quinine were significantly decreased by micellar systems in rabbits. These mixed micellar systems lower and not as expected, increase the absorption of quinine in vivo. Therefore, quinine should be orally administered at least 1h before food intake, particularly before fat intake.     

Empfehlungen und Standards für die Analgosedierung kinderkardiologischer Patienten

Monatsschrift Kinderheilkunde - Bei kinderkardiologischen Patienten bzw. Kindern mit angeborenen Herzfehlern werden häufig diagnostische oder therapeutische Prozeduren durchgeführt, die...     

Distinguishing true from false positives in genomic studies: p values

Distinguishing true from false positive findings is a major challenge in human genetic epidemiology. Several strategies have been devised to facilitate this, including the positive predictive value (PPV) and a set of epidemiological criteria, known as the “Venice” criteria. The PPV measures the probability of a true association, given a statistically significant finding, while the Venice criteria grade the credibility based on the amount of evidence, consistency of replication and protection from bias. A vast majority of journals use significance thresholds to identify the true positive findings. We studied the effect of p value thresholds on the PPV and used the PPV and Venice criteria to define usable thresholds of statistical significance. Theoretical and empirical analyses of data published on AlzGene show that at a nominal p value threshold of 0.05 most “positive” findings will turn out to be false if the prior probability of association is below 0.10 even if the statistical power of the study is higher than 0.80. However, in underpowered studies (0.25) with a low prior probability of 1 × 10^?3, a p value of 1 × 10^?5 yields a high PPV (>96 %). Here we have shown that the p value threshold of 1 × 10^?5 gives a very strong evidence of association in almost all studies. However, in the case of a very high prior probability of association (0.50) a p value threshold of 0.05 may be sufficient, while for studies with very low prior probability of association (1 × 10^?4; genome-wide association studies for instance) 1 × 10^?7 may serve as a useful threshold to declare significance.     

Total elbow arthroplasty is moving forward: Review on past,present and future

The elbow joint is a complex joint, which, when impaired in function, leads to severe disability. In some cases however, an arthroplasty might be an appropriate treatment. In the past four decades, large steps havebeen taken to optimize this treatment in order to achieve better post-operative outcomes. To understand these progresses and to discover aspects for upcoming improvements, we present a review on the past developments, the present state of affairs and future developments which may improve patient care further.