Patient-reported health outcomes of SARS-CoV-2-tested patients presenting to emergency departments: a propensity score-matched prospective cohort study.

OBJECTIVE: This study aimed to compare the long-term physical and mental health outcomes of matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive and SARS-CoV-2-negative patients controlling for seasonal effects. STUDY DESIGN: This was a retrospective cohort study. METHODS: This study enrolled patients presenting to emergency departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network. We enrolled consecutive eligible consenting patients who presented between March 1, 2020, and July 14, 2021, and were tested for SARS-CoV-2. Research assistants randomly selected four site and date-matched SARS-CoV-2-negative controls for every SARS-CoV-2-positive patient and interviewed them at least 30 days after discharge. We used propensity scores to match patients by baseline characteristics and used linear regression to compare Veterans RAND 12-item physical health component score (PCS) and mental health component scores (MCS), with higher scores indicating better self-reported health. RESULTS: We included 1170 SARS-CoV-2-positive patients and 3716 test-negative controls. The adjusted mean difference for PCS was 0.50 (95% confidence interval [CI]: -0.36, 1.36) and -1.01 (95% CI: -1.91, -0.11) for MCS. Severe disease was strongly associated with worse PCS (ß = -7.4; 95% CI: -9.8, -5.1), whereas prior mental health illness was strongly associated with worse MCS (ß = -5.4; 95% CI: -6.3, -4.5). CONCLUSION: Physical health, assessed by PCS, was similar between matched SARS-CoV-2-positive and SARS-CoV-2-negative patients, whereas mental health, assessed by MCS, was worse during a time when the public experienced barriers to care. These results may inform the development and prioritization of support programs for patients.

Determination of cholesterol oxides by gas chromatography-flame ionization detection/mass selective detection and their occurence in lanolin-containing cosmetics and ointments.

OBJECTIVE: Cholesterol oxides (COPs) are thought to be of toxicological relevance in cholesterol-containing foods. For cholesterol-containing cosmetics and the like, no information is available up to this date. Therefore, the first of two main aims of this study was to develop and validate a method for determining COPs in lanolin-containing cosmetics such as lipsticks and fatty creams as well as in nipple ointments. The second aim was to study the occurrence of COPs and their concentration levels in the respective product classes. METHODS: The procedure is based on a published method for food comprising some necessary modifications. Sample preparation consisted of transesterfication, solid-phase extraction and silylation of target compounds. Separation of the derivatized COPs and their quantification were performed with gas chromatography (GC) using a flame ionization detector (FID) or a mass spectrometer (MS). RESULTS: The successful validation and the trouble-free application during the market survey showed that the method was fit for purpose. Total COP levels found were in the low per cent range (up to 3%) and surprisingly high, being many orders of magnitude higher than those published for foods. CONCLUSION: To our knowledge, we present for the first time a method for the determination of COPs in non-food consumer products. Furthermore, our study demonstrates that lanolin-containing cosmetics may be an additional exogenous source of COPs. We further show evidence, that at least part of the COPs are already formed on the sheep's wool.

[Pediatric bowel MRI--accelerated parallel imaging in a single breathhold]. / MRT des darms bei kindern--beschleunigte bildgebung in einem atemzug.

PURPOSE: To compare highly accelerated parallel MRI of the bowel with conventional balanced FFE sequences in children with inflammatory bowel disease (IBD). MATERIALS AND METHODS: 20 children with suspected or proven IBD underwent MRI using a 1.5 T scanner after oral administration of 700 -1000 ml of a Mannitol solution and an additional enema. The examination started with a 4-channel receiver coil and a conventional balanced FFE sequence in axial (2.5 s/slice) and coronal (4.7 s/slice) planes. Afterwards highly accelerated (R = 5) balanced FFE sequences in axial (0.5 s/slice) and coronal (0.9 s/slice) were performed using a 32-channel receiver coil and parallel imaging (SENSE). Both receiver coils achieved a resolution of 0.88 x 0.88 mm with a slice thickness of 5 mm (coronal) and 6 mm (axial) respectively. Using the conventional imaging technique, 4 - 8 breathholds were needed to cover the whole abdomen, while parallel imaging shortened the acquisition time down to a single breathhold. Two blinded radiologists did a consensus reading of the images regarding pathological findings, image quality, susceptibility to artifacts and bowel distension. The results for both coil systems were compared using the kappa-(kappa)-coefficient, differences in the susceptibility to artifacts were checked with the Wilcoxon signed rank test. Statistical significance was assumed for p = 0.05. RESULTS: 13 of the 20 children had inflammatory bowel wall changes at the time of the examination, which could be correctly diagnosed with both coil systems in 12 of 13 cases (92 %). The comparison of both coil systems showed a good agreement for pathological findings (kappa = 0.74 - 1.0) and the image quality. Using parallel imaging significantly more artifacts could be observed (kappa = 0.47) without impairing the diagnostic impact. The comparison of the bowel distension showed no significant differences. CONCLUSION: The highly accelerated parallel MRI using the SENSE technique and a 32-channel surface coil enables the examination of the entire bowel in a single breathhold without relevant restrictions in image quality and diagnostic impact.

[Computer-aided detection of small pulmonary nodules in multidetector spiral computed tomography (MSCT) in children]. / Computerassistierte Detektion (CAD) von kleinen pulmonalen Rundherden in der Mehrdetektor-Spiral-Computertomografie (MDCT) bei Kindern.

PURPOSE: Retrospective evaluation of computer-aided detection software (CAD) for automated detection (LungCAD, Siemens Medical solutions, Forchheim, Germany) and volumetry (LungCARE) of pulmonary nodules in dose-reduced pediatric MDCT. MATERIALS AND METHODS: 30 scans of 24 children (10.4+/-5.9 years, 13 girls, 11 boys, 39.7+/-29.3 kg body weight) were performed on a 16-MDCT for tumor staging (n=18), inflammation (n=9), other indications (n=3). Tube voltage 120 kVp and effective mAs were adapted to body weight. Slice thickness 2 mm, increment 1 mm. A pediatric radiologist (U1), a CAD expert (U2) and an inexperienced radiologist (U3) independently analyzed the lung window images without and with the CAD as a second reader. In a consensus decision U 1 and U 2 were the reference standard. RESULTS: Five examinations had to be excluded from the study due to other underlying lung disease. A total of 24 pulmonary nodules were found in all data sets with a minimal diameter of 0.35 mm to 3.81 mm (mean 1.7+/-0.85 mm). The sensitivities were as follows: U1 95.8% and 100% with CAD; U2 91.7% U3 66.7%. U2 and U3 did not detect further nodules with CAD. The sensitivity of CAD alone was 41.7 % with 0.32 false-positive findings per examination. Interobserver agreement between U1 / U2 regarding nodule detection with CAD was good (k=0.6500) and without CAD very good (k=0.8727). For the rest (U1 /U3; U2 / U3 with and without CAD), it was weak (k=0.0667-0.1884). Depending on the measured value (axial measurement, volume), there is a significant correlation (p=0.0026-0.0432) between nodule size and CAD detection. Undetected pulmonary nodules (mean 1.35 mm; range 0.35-2.61 mm) were smaller than the detected ones (mean 2.19 mm; range 1.35-3.81 mm). No significant correlation was found between CAD findings and patient age (p=0.9263) and body weight (p=0.9271) as well as nodule location (subpleural, intraparenchymal; p=1.0) and noise/SNR. CONCLUSION: In our study with 2 mm slice thickness and very small lesion sizes, the analyzed CAD algorithm for detection and volumetry of pulmonary nodules has limited application in pediatric dose-reduced 16-MDCTs. Determination of lesion size is possible even in the case of false-negatives.

Pediatric multidetector computed tomography using tube current modulation and a patient image gallery.

BACKGROUND: Dose reduction is crucial in pediatric multidetector computed tomography (MDCT). PURPOSE: To perform pediatric 16-slice MDCT using tube current modulations and to adjust prospectively the tube current using a patient image gallery (IG) providing simulated dose-reduced protocols; and to evaluate and compare the image quality of the IG and the clinical MDCT. MATERIAL AND METHODS: 30 examinations (thorax, n = 15; abdomen, n = 8; pelvis, n = 7) in 20 patients (nine male, age 8.05 +/- 7.33 years, weight 29.8 +/- 24.02 kg) were performed according to an IG on a 16-slice MDCT with additional use of online tube current modulation (CARE Dose). Three radiologists visually assessed image quality from the IG and actual 16-slice MDCT scans. For objective analysis, image noise was determined. RESULTS: Statistical analysis showed moderate concordance in objective (K = 0.68-0.78) and subjective (K = 0.33-0.64) image assessment between the IG and clinical 16-slice MDCT scans. Depending on the weight group and clinical question, no or only minor dose reductions in the chest, but moderate to considerable reductions in the abdominal/pelvic 16-slice MDCT scans compared to previously used pediatric protocols were achieved. Extra dose reduction was achieved due to additional use of CARE Dose depending on age group and scan region (mean 8.6-23.9%). CONCLUSION: The IG enabled us to prospectively reduce the tube current and adapt the required image quality to the clinical question. Additional dose reduction was achieved with application of CARE Dose; nevertheless, the images are comparable to the simulated images of the IG.

[Bowel imaging--a reevaluation. Part 1: Conventional techniques and ultrasonography]. / Bildgebende Diagnostik des Darms--eine Neubewertung. Teil 1: Konventionelle Techniken und Ultraschall.

For decades fluoroscopy was the only adequate imaging modality in the diagnostic evaluation of the bowel. In the 1980 s new techniques such as MRI, CT and flexible fiber-optic endoscopy were introduced into the daily routine and revolutionized bowel imaging. Wireless capsule endoscopy (WCE) is the latest technical innovation for visualizing the bowel. Today a broad range of different imaging methods is available. This article provides a review of state-of-the-art bowel imaging and is divided into two parts. The first part addresses conventional X-ray techniques and ultrasonography and the second part discusses bowel imaging with computed tomography (CT) and magnetic resonance imaging (MRI). The goal of this article is to present the imaging techniques and to discuss them in the context of competitive methods.

[Bowel imaging: a reassessment. Part 2: CT and MRI]. / Bildgebende Diagnostik des Darms--eine Neubewertung. Teil 2: CT und MRT.

This is the second part of a review of bowel imaging. While the first part addressed conventional X-ray techniques and ultrasonography, the second part discusses the diagnostic features of computed tomography (CT) and magnetic resonance imaging (MRI) including virtual colonography and PET-CT in the diagnosis of bowel disorders. Indications, performance and the diagnostic impact of the different methods are presented and discussed in the context of competitive methods such as (capsule-)endoscopy.

[CT-guided interventions in children]. / Computertomografisch gesteuerte Interventionen bei Kindern.

In pediatric CT-guided interventions specific features have to be taken into account. Due to a lack of cooperation or limited ability to cooperate, procedures are often performed using analgosedation or general anesthesia. To provide radiation protection, justified indication for CT-guided intervention is necessary and sonography and MRI are to be preferred whenever possible. CT examinations also need to be dose-adapted with sequential scanning and a tube voltage and tube current reduction compared to pediatric diagnostic CT studies must be ensured. Gonad shields are recommended for male patients. Biopsy device selection depends on the assumed tumor entity since histology and also immunohistochemical, molecular pathological and cytogenetical analysis are necessary to differentiate pediatric tumors (small, round, blue cell tumors). In addition to diagnostic procedures, therapeutic interventions (drainage, injection therapies, neurolysis, and radiofrequency ablation) can also be used in children and can provide an alternative to surgery in selected cases. With justified indications and precise performance, CT-guided interventions can be successful in pediatric patients with limited risks.

Initial and mid-term results of a 4F compatible self-expanding low strut profile nitinol stent in the superficial femoral artery.

PURPOSE: To evaluate the initial and mid-term results of a new self-expanding low strut profile nitinol stent for treatment of atherosclerotic lesions stenoses and occlusions in the superficial femoral artery (SFA). MATERIALS AND METHODS: In 8 patients (4 male, 4 female, mean age 74.8 +/- 8.8 years) with SFA lesions and non-satisfying results after PTA treatment alone, 10 self-expanding nitinol Xpert stents were deployed via a 4 F sheath. Stent characteristics and handling were graded by the interventionalist. Fontaine classification, duplex flow measurements and ankle brachial index (ABI) at rest and stress were taken prior and one day after stent placement. Patients were followed 3, 6 and 12 months after the procedure obtaining the same parameters at each appointment. RESULTS: Initial stent treatment was successful in all patients. Stent handling and positioning were rated very good and safe. All patients improved clinically by at least one Fontaine stage (range before treatment: stage IIb to IV). The mean ABI at rest (stress) improved initially from 0.68 (0.70) to 1.07 (0.99). During a mean follow-up period of 8.3 months no case of clinically relevant in-stent stenosis was observed with stable values of ABI at rest and stress. CONCLUSION: Treatment of SFA lesions using the 4F-compatible self-expanding nitinol Xpert stent is technically simple, safe and shows good initial and mid-term results.

[Dose-reduced 16-slice multidetector-row spiral computed tomography in children with bronchoscopically suspected vascular tracheal stenosis -- initial results]. / Dosisreduzierte 16-Schicht-Multidetektor-Spiralcomputertomographie bei Säuglingen und Kleinkindern mit bronchoskopischem Verdacht auf vaskulär bedingte Trachealstenosen -- erste klinische Ergebnisse.

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced dose-reduced 16-slice multidetector-row CT (MDCT) in newborns and infants with fiberoptic bronchoscopically suspected vascular-induced tracheal stenosis. MATERIALS AND METHODS: 12 children (4 days to 3 years, 1.2 - 13.5 kg body weight) were examined using i. v. contrast-enhanced 16-slice MDCT (SOMATOM Sensation 16, Forchheim, Germany) without breath-hold and under sedation (11/12). All MDCTs were performed with a dose reduction. The beam collimation was 16 x 0.75 mm, except in the case of one child. MPRs along the tracheal axis in the x-, y- and z-directions and volume-rendering-reconstructions (VRTs) were calculated based on a secondary raw data set in addition to conventional axial slices. 2 radiologists used a three-point grade scale to evaluate the image quality, motion, and contrast media artifacts as well as the usefulness of the 2D- and 3D-reconstructions for determining the diagnosis. Statistical analysis was performed on the basis of a Kappa test. RESULTS: In all cases the cause of the fiberoptic bronchoscopically suspected tracheal stenosis was revealed: compression due to the brachiocephalic trunk (n = 7), double aortic arch (n = 2), lusorian artery (n = 1), vascular compression of the left main bronchus (n = 2). In 3 patients further thoracic anomalies, such as tracheobronchial (n = 2), and vascular (n = 2) and vertebral (n = 1) anomalies were found. The attenuation in the anomalous vessels was 307 +/- 140 HU. The image noise was 9.8 +/- 1.9 HU. The mean dose reduction was 82.7 +/- 3.2 % compared to a standard adult thoracic CT. All examinations were rated as diagnostically good (median 1, range 1, k = 1). 3D images did not show any stair artifacts (median 2, range 1 - 2, k = 1). The image noise was minor to moderate and hardly any motion artifacts were seen (median 1, range 1 - 2, k = 0.8). Contrast media artifacts were rated zero to minor (median 1.5, range 1 - 2, k = 0.676). MPRs (median 1, range 1, k = 1) and VRTs (median 1, range 1, k = 1) were found to be useful for diagnosis. Subsequent vascular surgery was performed on 8 patients. CONCLUSION: Contrast-enhanced dose-reduced 16-slice MDCT is effective for demonstrating the cause of fiberoptic bronchoscopically suspected vascular-induced tracheal stenosis even in very small and severely ill children despite the small contrast media amount and free breathing.

Oxysterols in cosmetics-Determination by planar solid phase extraction and gas chromatography-mass spectrometry.

Sterol oxidation products (SOPs) are linked to several toxicological effects. Therefore, investigation of potential dietary uptake sources particularly food of animal origin has been a key issue for these compounds. For the simultaneous determination of oxysterols from cholesterol, phytosterols, dihydrolanosterol and lanosterol in complex cosmetic matrices, planar solid phase extraction (pSPE) was applied as clean-up tool. SOPs were first separated from more non-polar and polar matrix constituents by normal phase thin-layer chromatography and then focussed into one target zone. Zone extraction was performed with the TLC-MS interface, followed by gas chromatography-mass spectrometry analysis. pSPE showed to be effective for cleaning up cosmetic samples as sample extracts were free of interferences, and gas chromatographic columns did not show any signs of overloading. Recoveries were between 86 and 113% with relative standard deviations of below 10% (n=6). Results of our market survey in 2016 showed that some cosmetics with ingredients of plant origin contained phytosterol oxidation products (POPs) in the low ppm range and therefore in line with levels reported for food. In lanolin containing products, total SOPs levels (cholesterol oxidation products (COPs), lanosterol oxidation products (LOPs), dihydrolanosterol oxidation products (DOPs)) being in the low percent range exceeded reported levels for food by several orders of magnitudes.

The role of arachidonic acid in rat heart cell metabolism.

Although it is known that arachidonic acid accumulates in the ischemic myocardium and that cardiac prostaglandin formation from the precursor arachidonic acid is altered during disease states, the role of arachidonic acid in the myocyte itself is not yet clear. Using isolated Ca-tolerant adult rat heart muscle cells, we were able to study cardiac metabolism of arachidonic acid without the effects induced by endothelial or other non-muscle tissue. Myocytes rapidly incorporate arachidonic acid as well as other fatty acids into their lipid pools, the predominant acceptor being the triacylglycerols at an extracellular fatty acid concentration of 20 microM. As exogenous arachidonic acid is decreased, the distribution pattern shifts to favor phospholipid esterification. Cardiocyte prostaglandin production from arachidonic acid added to the incubation medium was limited (less than 1% conversion of added arachidonic acid) and lipoxygenase pathway activity was not detected. Oxidation rates of arachidonic acid were 3-fold lower than for palmitic acid, indicating that it is of secondary importance in energy-yielding reactions. Our results suggest that arachidonic acid serves primarily as a structural component of myocardial membranes and that its release during ischemia would permit its use as a substrate for prostaglandin production by coronary vascular tissue.

[Diagnostic evaluation of chronic inflammatory intestinal diseases in children and adolescents: MRI with true-FISP as new gold standard?]. / Diagnostik chronisch entzündlicher Darmerkrankungen bei Kindern und Jugendlichen: MRT mit True-FISP als neuer Goldstandard?

PURPOSE: To evaluate the impact of magnetic resonance imaging (MRI) with use of True-FISP sequences in the evaluation of inflammatory bowel-wall changes in children and adolescents with Crohn's disease. Furthermore, the diagnostic procedure in children and adolescents with chronic inflammatory bowel disease (IBD) will be discussed in light of the relevant literature. MATERIAL AND METHODS: Twenty-four children and adolescents aged between 7 and 21 years with suspected or known IBD underwent MRI on a 1.5 T-scanner (Philips ACS-NT, Best, Netherlands). One hour after 1 l of a 2.5 % mannitol solution was given orally, MR imaging was performed using coronal HASTE-M2D, coronal fat-suppressed T2-TSE, axial dynamic T1-weighted GE-sequences before and after i. v.-contrast material injection (0.1 mmol/kg Gd-DTPA) and using a 2D-balanced-FFE-sequence (True-FISP) before and after i. v.-contrast material injection in coronal and axial planes. The MR-images were correlated with endoscopy and the clinical findings. In 14 patients, a recently performed conventional radiographic enteroclysis was available. Each performed MRI sequence was evaluated by three experienced radiologists regarding the sensitivity and specificity of each sequence in the detection of inflammatory bowel wall changes. In addition, the image quality was assessed regarding the different tissue contrasts and the susceptibility to artifacts. The distension of the bowel wall and the patients' acceptance of the MRI examination were recorded. RESULTS: With a sensitivity in detecting inflammatory small bowel changes of 93.3 % (axial pre-contrast, coronal post-contrast) and 100 % (axial post-contrast, coronal pre-contrast), the True-FISP outnumbers the other performed sequences (T1 = 80 %, HASTE = 13.3 % and T2-TSE = 53.3 %). The difference between True-FISP and contrast-enhanced T1 was not statistically significant, whereas the difference between True-FISP and HASTE and T2-TSE, respectively, was statistically significant. The True-FISP sequences revealed a statistically significant superiority regarding the soft-tissue differentiation in comparison to all other performed MR-sequences. The distension of the bowel wall was good in all patients. The patients' acceptance of the MRI examination was excellent. CONCLUSION: The described small bowel MRI examination is appropriate for children and adolescents. With the use of True-FISP sequences, it is a convincing method with an outstanding sensitivity in the diagnosis of IBD. Not least because of the lack of radiation exposure, small bowel MRI ought to replace conventional enteroclysis as a gold standard for IBD diagnosis in children and adolescents.

Effects of obesity and hypertension on ventricular myocytes: comparison of cells from adult SHHF/Mcc-cp and JCR:LA-cp rats.

OBJECTIVE: The aim was to compare beta adrenergic receptors, cAMP production, and Ca2+ accumulation by the sarcoplasmic reticulum in ventricular cardiomyocytes from female SHHF/Mcc-cp and JCR:LA-cp rats. Whereas rats from both strains exhibit gross obesity when the animals are homozygous for the recessive "corpulent" gene, the SHHF rats, which are hypertensive, all develop heart failure during their second year of life. The normotensive JCR:LA-cp animals do not. METHODS: beta Adrenergic receptor number, ligand affinity, isoprenaline and forskolin stimulated cyclic AMP production, and ATP dependent, phosphate supported 45Ca2+ uptake by the sarcoplasmic reticulum were compared in ventricular cardiomyocytes isolated from 6 months old obese female SHHF/Mcc-cp and obese and lean female JCR:LA-cp rats. RESULTS: Bmax and Kd for (-)-[125iodo]-cyanopindolol (125ICYP) binding were each approximately 50% lower in SHHF/Mcc-cp v JCR:LA-cp myocytes. Cyclic AMP production in response to isoprenaline, isoprenaline plus isobutylmethylxanthine (IBMX), and forskolin plus IBMX was also significantly depressed in the SHHF/Mcc-cp cells. In addition, sarcoplasmic reticular 45Ca2+ uptake by SHHF/Mcc-cp cells was 35% lower than in lean or obese JCR:LA-cp myocytes. Isoprenaline stimulated cAMP production and sarcoplasmic reticular Ca2+ uptake by the lean JCR:LA-cp cells were comparable to that described previously for myocytes from normal Sprague-Dawley rats. By contrast, Bmax and Kd for 125ICYP binding by the JCR myocytes differed substantially from previously described results for normal Sprague-Dawley rats, whereas values for the SHHF cells did not. CONCLUSIONS: Declines in Ca sequestration by the sarcoplasmic reticulum of ventricular cardiomyocytes from obese, hypertensive SHHF rats are not related to their obesity. However, obesity may contribute to the decline in cAMP production. This may account, in part, for the exacerbation by obesity of cardiac dysfunction in essential hypertension.

The relationship between cutaneous cellular immune responsiveness and mortality in a nursing home population.

The survival over 18 months of 29 nursing home residents was compared with results of cutaneous testing of cell-mediated immunity at the start of the period of observation. Eight antigens were used to evaluate immunity by intradermal injection of each antigen and measurement of the areas of induration at 48 and 72 hours. A difference in responses was seen between the survivors and those who died, although this difference was statistically significant at 72 hours only. As expected, survivors had more (3.1, compared with 1.47) and larger (8.6 mm, compared with 3.2 mm) reactions at 72 hours than those who died.

Persistent cutaneous cellular immune responsiveness in a nursing home population.

Mantoux-type skin tests were applied to 29 elderly residents of an intermediate care floor of a nursing home. Eight antigens were used with each resident, and the size of the reactions was measured at 6, 24, 48, and 72 hours. All but one resident had at least one response greater than or equal to 3 mm at 48 or 72 hours, and most had more than one response of that size. At 48 compared with 72 hours, there was one more responder and the mean size of the reactions to each antigen was greatest. However, there were two responders at 72 hours who did not react at 48 hours, and the total number of reactions in the group was greater at the later reading. Only one resident did not produce any response at either 48 or 74 hours. The minimum number of antigens needed to identify all responsive subjects was five (PPD-Avian, coccidioidin, histoplasmin, streptokinase-streptodornase, and trychophytin). The purified protein derivative of tuberculin skin test was repeated on subjects who had an initial response less than 10 mm, and one increase of more than 6 mm was observed in a resident who was initially unresponsive to that antigen.

Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia.

Murine spinal cord primary mixed cultures were treated with the respiratory inhibitor, rotenone, to mimic hypoxic conditions. Under these conditions neurons rapidly underwent oncosis (necrosis) with a complete loss in viability occurring within 260 min; however, astrocytes, which accounted for most of the cell population, died more slowly with 50% viability occurring at 565 min. Inosine preserved both total cell and neuronal viability in a concentration-dependent manner. The time of inosine addition relative to hypoxic insult was critical with the most effective protection occurring when inosine was added just prior to or within 5 min after insult. Inosine was ineffective when added 30 min after hypoxic insult. The effect of guanosine was similar to that of inosine. Treatment of cultures with BCX-34, a purine nucleoside phosphorylase inhibitor, prevented protection by inosine or guanosine, suggesting involvement of a purine nucleoside phosphorylase in the nucleoside protective effect.

Effects of amiloride on calcium uptake by myocytes isolated from adult rat hearts.

Amiloride at high concentrations inhibits the uptake of Ca by rat heart myocytes containing elevated levels of intracellular Na and retards the development of Ca-dependent hypercontracture in these cells. In contrast, amiloride enhances the net uptake of Ca in Ca-tolerant myocytes containing normal levels of Na. The results suggest that amiloride may inhibit Na-Ca exchange across the sarcolemma of cardiac myocytes.

Vascular and contractile responses to extracellular ATP: studies in the isolated rat heart.

The dose-response characteristics for the effect of ATP upon cardiac function and vascular tone have been investigated in the isolated perfused rat heart. Vasodilation was observed with low ATP concentrations (0.01-0.1 mM) whereas severe vasoconstriction occurred with high concentrations (1.0-10.0 mM). At all doses studied, heart rate and pressure-rate product were reduced in a dose-dependent manner, with 10 mM ATP almost complete cardiac arrest was observed. Analysis of epicardial electrograms revealed that ATP induced arrhythmias, prolonged the P-R interval and induced partial blockade of S-A nodal activity and A-V conduction. Investigating possible mechanisms for the vascular and contractile effects of ATP, it was possible to exclude the calcium chelating properties of ATP and the effects of coincident ischemia arising as a consequence of ATP-induced vasoconstriction. Pharmacological studies revealed the ATP-induced vasoconstriction to be unresponsive to a range of coronary vasodilators and also allowed exclusion of prostaglandins, catecholamines and adrenergic receptors in the mediation of ATP effects. Investigations with acetylcholine revealed remarkably similar effects upon both contractile and vascular activity but studies with atropine suggested that the muscarinic receptor was not involved. Studies with theophylline allowed a dissociation of the vascular and contractile effects of ATP and indicated a possible involvement of the adenosine receptor in the cellular response to both high and low concentrations of ATP.

Investigation of the aluminium biokinetics in humans: a 26Al tracer study.

Despite the well-known toxicity of aluminium in chronic renal failure, a solid database on its biokinetics has been difficult to establish. A highly sensitive method using (26)Al as tracer and accelerator mass spectrometry (AMS) for detection was used. No perturbing background and saturation effects were taken into account using a delta function input of aluminium in time. Aluminium absorption, distribution, speciation and excretion in six healthy volunteers and in two patients with chronic renal failure were investigated following administration of a single oral or i.v. dose of (26)Al. Serial samples of blood and urine were taken. In a speciation study, the time dependence of the binding of (26)Al to low-molecular weight molecules in serum was investigated. The measured data were compared and interpreted with simulations in an open compartmental model. Fractional absorption, distribution, excretion and time constants for the aluminium transport were determined. Typical intestinal absorption rates for AlCl(3) were found to be in the range of 10(-3). The ultrafiltrable percentage of aluminium in serum of one volunteer was estimated to be 5.6+/-0.8%. Differences between healthy volunteers and patients with chronic renal failure were deduced. The employed method using (26)Al and ams has proven to be highly sensitive for investigations of aluminium biokinetics at the ultra-trace element level. With the model, the measured values of (26)Al in serum and urine were used to precisely determine absorption, speciation, distribution, retention and excretion of aluminium in humans.