Experimental determination of pCo perturbation factors for plane-parallel chambers

For plane-parallel chambers used in electron dosimetry, modern dosimetry protocols recommend a cross-calibration against a calibrated cylindrical chamber. The rationale for this is the unacceptably large (up to 3-4%) chamber-to-chamber variations of the perturbation factors (pwall)Co, which have been reported for plane-parallel chambers of a given type. In some recent publications, it was shown that this is no longer the case for modern plane-parallel chambers. The aims of the present study are to obtain reliable information about the variation of the perturbation factors for modern types of plane-parallel chambers, and-if this variation is found to be acceptably small-to determine type-specific mean values for these perturbation factors which can be used for absorbed dose measurements in electron beams using plane-parallel chambers. In an extensive multi-center study, the individual perturbation factors pCo (which are usually assumed to be equal to (pwall)Co) for a total of 35 plane-parallel chambers of the Roos type, 15 chambers of the Markus type and 12 chambers of the Advanced Markus type were determined. From a total of 188 cross-calibration measurements, variations of the pCo values for different chambers of the same type of at most 1.0%, 0.9% and 0.6% were found for the chambers of the Roos, Markus and Advanced Markus types, respectively. The mean pCo values obtained from all measurements are [Formula: see text] and [Formula: see text]; the relative experimental standard deviation of the individual pCo values is less than 0.24% for all chamber types; the relative standard uncertainty of the mean pCo values is 1.1%.     

Significant improvement of the quality of bystander first aid using an expert system with a mobile multimedia device

OBJECTIVE: Better quality bystander first-aid could improve outcome rates for emergency victims significantly. In this case-control study, we hypothesised that expert knowledge presented step-by-step to untrained helpers using a personal digital assistant (PDA), would improve the quality of bystanders basic life support. METHOD: We confronted 101 lay-helpers with two standard emergency situations. (1) An unconscious trauma victim with severe bleeding. (2) Cardiopulmonary resuscitation (CPR). Performance was assessed using an Objective Structured Clinical Examination (OSCE). One group was supported by a PDA providing visual and audio instructions, whereas the control group acted only with their current knowledge. The expert system was programmed in HTML-code and displayed on the PDA's Internet browser. RESULTS: The maximum score obtainable was 24 points corresponding to optimal treatment. The control group without the PDA reached 14.8+/-3.5 (mean value+/-standard deviation), whereas the PDA supported group scored significantly higher (21.9+/-2.7, p<0.01). The difference in performance was measurable in all criteria tested and particularly notable in the items: placing in recovery position, airway management and quality of CPR. CONCLUSION: The PDA based expert system increased the performance of untrained helpers supplying emergency care significantly. Since Internet compatible mobile devices have become widely available, a significant quality improvement in bystander first-aid seems possible.     

Abnorme Verkürzung der linksventrikul?ren Diastolendauer unter k?rperlicher Belastung bei Patienten mit dilatativer Kardiomyopathie

BACKGROUND AND PURPOSE: Cardiac performance can be characterized in terms of the relative duration of systole and diastole. In pediatric patients with dilated cardiomyopathy (DCM), a disproportionate shortening of left ventricular diastole was observed. The present study was intended to reproduce these findings in an adult patient group and to evaluate exercise-related changes of both time intervals. PATIENTS AND METHODS: Exercise radionuclide angiography was used in 61 patients with DCM NYHA (New York Heart Association) stage II-III. The phases of the cardiac cycle were derived from a radionuclide time-activity curve with high temporal resolution. The control group consisted of 26 patients referred for ventricular function assessment with radionuclide angiography before cardiotoxic cancer treatment. RESULTS: When the duration of systole was expressed as the product of systolic time and heart rate, DCM patients exhibited a significant increase in left ventricular systolic time at rest (23.9 vs. 21.5 s/min; p = 0.006) and during peak exercise (29.2 vs. 26.7 s/min; p = 0.01). The prolongation of left ventricular systole at peak exercise was evident, although the peak heart rate was significantly lower in the patient group than in the control group (118 vs. 127/min; p = 0.04). In DCM patients the diastolic time loss per beat was further quantified using a regression equation obtained from the healthy control group. A significant shortening of left ventricular diastolic time was confirmed during peak exercise. Furthermore, a progressive loss in diastolic time per beat from rest to peak exercise was noted. CONCLUSION: Cardiac cycle abnormalities of patients with DCM are characterized by a prolongation of left ventricular systole and an abnormal shortening of left ventricular diastole. The systolic-diastolic mismatch is accentuated during exercise and has the potential to impair the cardiac reserve in these patients by restricting ventricular filling and perfusion.     

Carvedilol induces greater control of β2- than β1-adrenoceptor-mediated inotropic and lusitropic effects by PDE3, while PDE4 has no effect in human failing myocardium

The β-blockers carvedilol and metoprolol provide important therapeutic strategies for heart failure treatment. Therapy with metoprolol facilitates the control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of catecholamines in human failing ventricle. However, it is not known whether carvedilol has the same effect. We investigated whether the PDE3-selective inhibitor cilostamide (0.3 μM) or PDE4-selective inhibitor rolipram (1 μM) modified the positive inotropic and lusitropic effects of catecholamines in ventricular myocardium of heart failure patients treated with carvedilol. Right ventricular trabeculae from explanted hearts of nine carvedilol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β₁-adrenoceptors (β₂-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β₂-adrenoceptors (β₁-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of the PDE inhibitors. The inotropic potency, estimated from –logEC₅₀s, was unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in carvedilol-treated compared to non-β-blocker-treated patients, consistent with the previously reported β₂-adrenoceptor-selectivity of carvedilol. Cilostamide caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in trabeculae from carvedilol-treated patients. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline. Treatment of heart failure patients with carvedilol induces PDE3 to selectively control the positive inotropic and lusitropic effects mediated through ventricular β₂-adrenoceptors compared to β₁-adrenoceptors. The β₂-adrenoceptor-selectivity of carvedilol may provide protection against β₂-adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated patients. PDE4 does not control β₁- and β₂-adrenoceptor-mediated inotropic and lusitropic effects in carvedilol-treated patients.     

Interaction of Fibronectin and Aggregation Substance Promotes Adherence of Enterococcus faecalis to Human Colon

This in vitro study investigates the interaction between aggregation substance (AS), a virulence factor of Enterococcus faecalis, and colonic mucosal fibronectin in normal colon and colon from patients with Crohn's disease. Fibronectin was found to be overexpressed in Crohn's disease compared to normal colon. Compared to E. faecalis OG1X:pAM944 (AS-negative), E. faecalis OG1X:pAM721 (expressing AS) showed a significantly enhanced adhesion to human colonic mucosa in normal colon and in colon from patients with Crohn's disease. Double-staining of fibronectin and AS-positive enterococci showed that colocalization of bacteria and fibronectin was significantly more frequent in Crohn's disease than in normal colon. Preincubation of bacteria with soluble fibronectin caused a significant reduction in the adherence to fibronectin. In conclusion, the interaction between AS and fibronectin plays is an important factor that mediates adhesion of Enterococcus faecalis to colonic mucosa. This might be one of the mechanisms responsible for bacterial translocation of Enterococcus faecalis.     

Novel pathogenic EIF2S3 missense variants causing clinically variable MEHMO syndrome with impaired eIF2γ translational function,and literature review

Rare pathogenic EIF2S3 missense and terminal deletion variants cause the X-linked intellectual disability (ID) syndrome MEHMO, or a milder phenotype including pancreatic dysfunction and hypopituitarism. We present two unrelated male patients who carry novel EIF2S3 pathogenic missense variants (p.(Thr144Ile) and p.(Ile159Leu)) thereby broadening the limited genetic spectrum and underscoring clinically variable expressivity of MEHMO. While the affected male with p.(Thr144Ile) presented with severe motor delay, severe microcephaly, moderate ID, epileptic seizures responsive to treatments, hypogenitalism, central obesity, facial features, and diabetes, the affected male with p.(Ile159Leu) presented with moderate ID, mild motor delay, microcephaly, epileptic seizures resistant to treatment, central obesity, and mild facial features. Both variants are located in the highly conserved guanine nucleotide binding domain of the EIF2S3 encoded eIF2γ subunit of the heterotrimeric translation initiation factor 2 (eIF2) complex. Further, we investigated both variants in a structural model and in yeast. The reduced growth rates and lowered fidelity of translation with increased initiation at non-AUG codons observed for both mutants in these studies strongly support pathogenicity of the variants.