Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in a pig model.

BACKGROUND: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13N-ammonia (13NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS: Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(-1). The extent of defects induced by left anterior descending coronary artery constriction measured by 18F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS: 18F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of 18F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Comparison of three instructional methods for teaching cardiopulmonary resuscitation and use of an automatic external defibrillator to high school students.

OBJECTIVE: To evaluate new instructional methods for teaching high school students cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) knowledge, actions and skills. METHODS: We conducted a cluster-controlled trial of 3 instructional interventions among Seattle area high school students, with random allocation based on classrooms, during 2003-04. We examined two new instructional methods: interactive-computer training and interactive-computer training plus instructor-led (hands-on) practice, and compared them with traditional classroom instruction that included video, teacher demonstration and instructor-led (hands-on) practice, and with a control group. We assessed CPR and AED knowledge, performance of key AED and CPR actions, and essential CPR ventilation and compressions skills 2 days and 2 months after training. All outcomes were transformed to a scale of 0-100%. RESULTS: For all outcome measures mean scores were higher in the instructional groups than in the control group. Two days after training all instructional groups had mean CPR and AED knowledge scores above 75%, with use of the computer program scores were above 80%. Mean scores for key AED actions were above 80% for all groups with training, with hands-on practice enhancing students' positive outcomes for AED pad placement. Students who received hands-on practice more successfully performed CPR actions than those in the computer program only group. In the 2 hands-on practice groups the scores for 3 of the outcomes ranged from 57 to 74%; they were 32 to 54% in the computer only group. For the outcome of continuing CPR until the AED was available scores were high, 89 to 100% in all 3 training groups. Mean CPR skill scores were low in all groups. The highest mean score for successful ventilations was 15% and for compressions, 29%. The pattern of results was similar after 2 months. CONCLUSIONS: We found evidence that interactive computer based self instruction alone was sufficient to teach CPR and AED knowledge and AED actions to high school students. All forms of instruction were highly effective in teaching AED use. In contrast to AED skills, CPR remains a set of difficult psychomotor skills that is challenging to teach to high school students as well as other members of the lay public.

Simultaneous multi-analyte determination of estrone, isoproturon and atrazine in natural waters by the RIver ANAlyser (RIANA), an optical immunosensor.

In most medical and environmental applications of biosensors, only single analytes are determined. However, the monitoring of several analytes is obviously preferable in order to gather more information about the sample under analysis. In line with this, different technologies are being developed to obtain multi-analyte sensors. In this paper, an analytical method for the simultaneous determination of three different contaminants-atrazine, isoproturon, and estrone-in natural waters by using an optical immunosensor prototype, the so-called "RIver ANAlyser" (RIANA), is described. RIANA is based on a rapid solid-phase fluoroimmunoassay that takes place at an optical transducer chip. The transducer surface is chemically modified with three analytes derivatives placed in different discrete locations. The sensor surface can be regenerated thus allowing the performance of several measurements with the same transducer. Each test cycle, including one regeneration step, is accomplished in 15 min. Detection limits achieved were 0.155, 0.046, and 0.084 microg/l, for atrazine, isoproturon, and estrone, respectively. Satisfactory repetition, with relative standard deviations between 1.06 and 6.98%, was obtained. Excluding a minor non-specifical binding of the isoproturon antibodies, no cross-reactivity effects were observed. Matrix effects were significant only in the case of wastewater samples. Biosensor measurements were validated using conventional liquid chromatography-mass spectrometry. The results obtained with both techniques were in good agreement.

Comparison of two fluorescence immunoassay methods for the detection of endocrine disrupting chemicals in water.

We describe two fluorescence immunoassays capable of detecting endocrine disrupting compounds in waste water. The first fluorescence method is a heterogeneous assay using total internal reflection fluorescence (TIRF) detection. The second method is a homogeneous assay that utilizes energy transfer (ETIA). Both fluorescence immunoassays are compared with respect to detection principle and ability to quantify the model analytes estrone, estradiol, and ethinylestradiol in a complex matrix regarding recovery rates and limits of detection. Calibrations were performed for the three analytes using both fluorescence methods. Limits of detection between 0.01 and 0.85 microg/l are achieved. In addition, measurements in synthetic waste water spiked with the analytes were performed. Both immunoassays allow the detection in waste water with recovery rates in the range of 70-112%.

Using a dual method needs assessment to evaluate the training needs of public health professionals.

A dual method research approach was used to identify the training needs of the public health professionals in Washington. A mail questionnaire was implemented, followed by focus groups with Washington State Department of Health (DOH) and local health department (LHD) professionals. Focus groups were used successfully to enhance and clarify the survey findings by identifying the specific content of the highest rated training needs (interpersonal communication, cross-culture and cross-age communication, participatory teaching/training skills, and electronic communication) and by pinpointing preference for different modes of training delivery for different training needs.

[Effects of dehydration on functional parameters of fluid balance as well as effectiveness of rehydration using crystalline or colloidal infusion drips in calves]. / Einfluss von Dehydratationen auf funktionelle Parameter des Flüssigkeitshaushaltes sowie Wirksamkeit einer Rehydratation mit kristalliner oder kolloidaler Infusionslösung bei Kälbern.

Studies were conducted on 57 calves (aged 3-23 d) to elucidate the effects of diarrhoeal and experimentally induced dehydration upon functional parameters of the fluid balance and of renal functionality. Aggravating intensity and length of diarrhoea was found to be accompanied by decline in intravasal and extracellular fluid compartments. Ante mortem dehydration of the animals with diarrhoea was close to 20% relative to body weight. This was paralleled by life-threatening drop of glomerular filtration rates to < 10% of original physiological values. Administration of a diuretic, associated with reduction by 50% of daily liquid uptake, proved helpful in generating dehydration of 5 to 6% relative to body weight. Evidence was provided to the effect that isooncotic colloid-electrolyte solution was superior to pure isotonic electrolyte solution for rehydration of calves dehydrated in the first place in the way described. Colloidal infusion, in particular, produced favourable therapeutic effects in terms of optimization of blood plasma volume and renal ultrafiltration.

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals]. / Diagnostische und pathophysiologische Aspekte der Nieren-funktionsbestimmung bei Tieren.

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals]. / Diagnostische und pathophysiologische Aspekte der Nierenfunktionsbestimmung bei Tieren.

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

Regulation of the beta-adrenoceptor-cAMP-system during dynamic exercise in patients with primary hypertension after acute beta-blockade.

Beta-adrenoceptors on lymphocytes are acutely increased after dynamic exercise in normotensive subjects, but not in hypertensives. It was thus of interest to evaluate the acute regulation of the lymphocyte beta-adrenoceptor-adenylate-cyclase-cAMP-system (BAAS) in patients with primary hypertension during dynamic stress after acute beta-blockade. Density and affinity of beta 2-adrenoceptors, and intracellular cAMP concentrations (baseline and isoprenaline stimulated values) were measured on the peripheral mononuclear cells in 8 male patients with primary hypertension before and immediately after dynamic exercise on a bicycle (50-200 W) at baseline and after acute beta-blockade (2 h following 100 mg atenolol). Dynamic exercise causes no significant changes in receptor density and affinity, nor in basal cAMP values. After acute beta-blockade the dynamic stress-induced rise in mean arterial blood pressure was significantly (p < 0.01) reduced from 33 to 24 mmHg, and beta-adrenoceptor density significantly (p < 0.05) increased from 1320 to 2102 molecules/cell, whereas affinity remained unchanged. Baseline and stimulated cAMP concentrations increased significantly (p < 0.05) from 5.3 to 7.0 and from 2.1 to 3.5 pmol/10(6) cells, respectively. These findings suggest that in primary hypertension the regulation of the beta 2-adrenoceptor-adenylate-cyclase-cAMP-system is impaired on exercise and can be normalised by acute beta-blockade. Since atenolol predominantly blocks beta 1-adrenoceptors, the observed normalisation of the lymphocyte BAAS may reflect only an unspecific effect of antihypertensive therapy per se.

Beta-adrenergic blood pressure regulation in Shy-Drager syndrome and pheochromocytoma.

Both Shy-Drager syndrome and pheochromocytoma are characterized by an abnormal catecholamine secretion, e.g. a reduced secretion in Shy-Drager syndrome, and an excessive stimulation in pheochromocytoma resulting in adrenergic dysfunction and in adrenergic hyperactivity, respectively. The relationship between extreme variations in circulating catecholamines and beta-adrenergic receptor activity was studied in two patients with severe orthostatic hypotension (Shy-Drager syndrome) and in a patient with pheochromocytoma with excessive spontaneous catecholamine increases using the lymphocyte beta 2-adrenoceptor assay. In both patients with Shy-Drager syndrome, basal plasma concentrations of epinephrine and dopamine were low under resting conditions and could not be stimulated in the upright position. Norepinephrine was low in the first patient, and could not be stimulated; whereas the second patient had a normal basal concentration of norepinephrine, which could be moderately stimulated. There was no beta-adrenoceptor abnormality in the first patient: however, in the second patient, there were no measurable beta-adrenoceptors on membrane fractions, whereas a population of receptors only in the low affinity state could be identified on intact cells. Alpha-adrenoceptor density on thrombocyte membranes was slightly increased in both patients with Shy-Drager syndrome and showed no substantial change during upright posture. Catecholamine increases in the pheochromocytoma patient were accompanied by a rise in blood pressure, bradycardia, and an acute up-regulation of beta-adrenoceptors. Plasma concentrations of cAMP paralleled the increase in receptor density and blood pressure. The findings in pheochromocytoma add support to the theory that an acute catecholamine stimulation gives rise to an acute beta-adrenergic sensitization leading to blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)