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Biomedical subjects

J Hoekstra

Publications and source records attributed to J Hoekstra.

At least 19 recordsLinked to original sources

Current-induced embrittlement of atomic wires.

Recent experiments suggest that gold single-atom contacts and atomic chains break at applied voltages of 1 to 2 V. In order to understand why current flow affects these defect-free conductors, we have calculated the current-induced forces on atoms in a Au chain between two Au electrodes. These forces are not by themselves sufficient to rupture the chain. However, the current reduces the work to break the chain, which results in a dramatic increase in the probability of thermally activated spontaneous fracture of the chain. This current-induced embrittlement poses a fundamental limit to the current-carrying capacity of atomic wires.

Journal Article↗

Glycoprotein IIb/IIIa receptor inhibitor use in unstable angina/non-ST-segment elevation myocardial infarction: an appropriate-use model for the emergency department.

The introduction of new platelet glycoprotein (GP) IIb/IIIa receptor inhibitors has the potential to revolutionize the treatment of certain patients with unstable angina and non-ST-segment elevation myocardial infarction (MI). Treatment with these potent platelet inhibitors has been shown to improve patient outcomes prior to percutaneous intervention (PCI), following PCI, and even in the absence of PCI. In addition, there are data from clinical studies that support a time-dependence to the beneficial effects of platelet inhibitor therapy. Patients who are treated early-for example, in the emergency department (ED)-appear to have improved outcomes over those treated later. Platelet inhibitors have been used extensively in the cardiac catheterization laboratory and in the coronary care unit (CCU). In many institutions, however, their introduction and uptake in the ED has been slow. These agents are relatively expensive and have the potential to cause major bleeding complications. This review will examine the pathophysiology of acute coronary syndromes (ACS) as it relates to the mechanism of action of GPIIb/IIIa inhibitors. The available GPIIb/IIIa inhibitors will be discussed including their indications, contraindications, doses, and mechanisms of action. Data from clinical studies supporting the use of GPIIb/IIIa inhibitors will be illustrated in the context of their applications in the ED. Finally, an algorithm for GPIIb/IIIa inhibitors in the ED will be presented.

Abciximab↗

Pattern analysis of the variation in the sensitivity of aquatic species to toxicants.

Our aim in this study was to identify groups of species showing a similar pattern in their sensitivity to toxicants and to relate the patterns to the mode of toxic action and biological species characteristics. A data matrix was composed of acute toxicity data for 26 aquatic species and 21 compounds. Most of the variation in the toxicological data was due to differences in toxicity of compounds and not intrinsic differences between species, so that practically every species can be used to order compounds with respect to average toxicity. Compounds with high overall toxicity also had large interspecies variation in sensitivity. The toxicity of non-polar narcotics correlated well with the log Kow. Compounds with a specific or reactive mode of action were more than a factor 10 toxic than predicted by their log Kow. Patterns in species sensitivity were more diffuse because only part of the variance in species sensitivity could be explained. Fishes and amphibians were more sensitive to dieldrin, lindane and pentachlorophenol than were invertebrates. Among the arthropods, the Phyllopoda (daphnids) were the most sensitive species. They were very sensitive to aniline, the heavy metals, malathion and parathion.

Analysis of Variance↗

Variation in the sensitivity of aquatic species in relation to the classification of environmental pollutants.

Differences in species sensitivity to toxicants can be substantial. In this study this among-species variation in sensitivity was analyzed in relation to chemical's mode of action. Chemicals were classified as: non-polar narcotics, polar narcotics, reactive compounds and specifically acting compounds. Acute toxicity data of aquatic species were derived from the literature. Levels of enhanced toxicity, averaged over all species, and interspecies variation in sensitivity were analyzed for 35 chemicals, with data ranging from 12 to 62 aquatic species per compound. Non-polar and polar narcotic chemicals demonstrate the smallest variation in sensitivity and have levels of toxicity, which are highly predictable on the basis of their hydrophobicity. Reactive and specifically acting compounds can be much more toxic than predicted and variation in species sensitivity can be as large as 10(5) to 10(6). In general, the larger this interspecies variation the more asymmetric is the toxicity distribution due to extremely sensitive species. Reactive and specifically acting compounds pose a potentially larger risk for species in ecosystems than polar and non-polar narcotic compounds. They will need more testing to derive precisely equal estimates of safe environmental concentrations.

Animals↗

Effect of ambient oxygen concentration upon the acute toxicity of chlorophenols and heavy metals to the groundwater copepod Parastenocaris germanica (Crustacea).

Acute static toxicity experiments have been performed under normoxic and hypoxic conditions. The test animals used were adults of the groundwater-adapted copepod Parastenocaris germanica. The animals originated from a sandy, gravelly phreatic aquifer of the Meuse valley in The Netherlands. Toxicants applied were pentachlorophenol, 3,4-dichlorophenol, zinc, and cadmium. The results were statistically evaluated by a log-logistic model. LC50 and LC5 values with 95% confidence limits were calculated. Response models of application under both oxygen conditions were compared. The influence of ambient oxygen concentration on sensitivity appeared to be very small; only in the case of pentachlorophenol were hypoxic and normoxic models slightly but significantly different. Comparisons with the sensitivity of other organisms are made and the results are discussed against the specific physiological adaptations of the organisms to groundwater conditions.

Animals↗

Regional cerebral blood flow with manual internal cardiac massage versus direct mechanical ventricular assistance.

STUDY HYPOTHESIS: Previous studies have not discerned the best method for generating regional cerebral blood flow during internal cardiac massage. We hypothesized that regional cerebral blood flow generated by a mechanical method--direct mechanical ventricular assistance (DMVA)--would be superior to manual internal cardiac massage (MAN). STUDY POPULATION: Twelve adult Yucatan minipigs weighing more than 44 kg each were studied. METHODS: Swine were instrumented for regional cerebral blood flow measurements using tracer microspheres. After 15 minutes of ventricular fibrillation, swine were randomized to receive either MAN or DMVA. Regional cerebral blood flow was measured during normal sinus rhythm and at one minute (VF-1) and six minutes (VF-2) after initiation of circulatory support. Regional cerebral blood flow values were compared using a Wilcoxon rank sum test. RESULTS: During VF-1, there was a tendency for DMVA to produce greater regional cerebral blood flow than MAN, although these differences were not statistically significant (DMVA vs MAN as mL/min/100 g): cerebral cortex, 28 versus 11; cerebellum, 49 versus 22; midbrain, 43 versus 16; pons, 55 versus 18; medulla, 55 versus 19; and spinal cord, 33 versus 10. During VF-2, DMVA produced greater regional cerebral blood flows than were produced by MAN: cerebral cortex, 39 versus 12 (P less than .06); cerebellum, 58 versus 20 (P less than 0.5); midbrain, 50 versus 18 (P less than .05); pons, 52 versus 22 (P less than .06); medulla, 53 versus 20 (P less than .05); and spinal cord, 31 versus 12 (P less than .05). CONCLUSION: DMVA produces greater regional cerebral blood flow than is produced during MAN after 15 minutes of ventricular fibrillation. DMVA is effective at maintaining regional cerebral blood flow after a prolonged cardiac arrest.

Animals↗

Collaborative study on the use of motility enrichment on modified semisolid Rappaport-Vassiliadis medium for the detection of Salmonella from foods.

A collaborative study was performed in 15 laboratories to evaluate the use of motility enrichment on modified semisolid Rappaport-Vassiliadis (MSRV) medium for rapid Salmonella detection in a variety of food products. The results of this procedure were compared with those obtained by the cultural procedure using Rappaport-Vassiliadis (RV) broth as selective enrichment and modified brilliant green agar for selective plating. The tests were performed with Salmonella reference samples (SRS) as well as with naturally contaminated food products. When SRS were used without added food the productivity of both MSRV and RV was 96%. When SRS were combined with reference samples containing competitive bacteria the productivity was 98% for MSRV and 95% for RV. In the tests with food samples the productivity of MSRV was 92% with SRS added to food and 96% with naturally contaminated samples, while the productivity of RV was 88% and 90%, respectively. Statistical analysis showed that there was no significant difference between the procedures.

Culture Media↗

Median frequency--a new parameter for predicting defibrillation success rate.

STUDY HYPOTHESIS: Current American Heart Association guidelines recommend immediate defibrillation of ventricular fibrillation. When this is unsuccessful, there are no guidelines to help determine the optimum time at which to defibrillate after the administration of an alpha-adrenergic agonist. Previous studies have shown that the median frequency of the ventricular fibrillation ECG signal correlates with myocardial perfusion during CPR. We hypothesized that median frequency could predict the success of defibrillation and thus accurately determine the most appropriate time at which to defibrillate during ventricular fibrillation. STUDY POPULATION: Twenty-two mixed-breed swine weighing more than 15 kg were studied. METHODS: Ventricular fibrillation was induced electrically, and the ventricular fibrillation ECG signal was analyzed using fast Fourier analysis. After ten minutes of ventricular fibrillation, mechanical CPR was begun. After three minutes of CPR, the animals received one of three alpha-adrenergic agonists and CPR was continued. Defibrillation was attempted three and one-half minutes after drug administration. The average median frequency 20 seconds before defibrillation was calculated. Sensitivity and specificity of median frequency with respect to defibrillation success were determined. RESULTS: A median frequency of 9.14 Hz had a sensitivity of 100% and a specificity of 92.31% in predicting the results of defibrillation in this model. CONCLUSION: The median frequency may serve as a valuable parameter to guide defibrillation therapy during ventricular fibrillation.

Animals↗

Estimation of myocardial ischemic injury during ventricular fibrillation with total circulatory arrest using high-energy phosphates and lactate as metabolic markers.

STUDY OBJECTIVE: To define the time course of myocardial ischemic injury using high-energy phosphate (HEP) depletion and the cessation of lactate production as metabolic markers. SETTING: Data were collected in a laboratory animal model. TYPE OF PARTICIPANTS: Ten immature mixed breed swine weighing 23.2 +/- 3.5 kg. DESIGN: After thoracotomy, transmural myocardial biopsies were taken in vivo during normal sinus rhythm and at designated times during ventricular fibrillation with total circulatory arrest (VF-TCA). MEASUREMENTS AND MAIN RESULTS: Frozen tissue samples were analyzed for adenine nucleotides, by high-performance liquid chromatography, and lactate by enzymatic assay. At five minutes of VF-TCA, myocardial adenosine triphosphate averaged 50% of control. At 15 minutes of VF-TCA, 89% of animals had myocardial adenosine triphosphate levels above 20% of control and adenylate charge ratio above 0.60. With more than 30 minutes of VF-TCA, all animals had adenosine triphosphate levels below 10% of control and adenylate charge ratio below 0.30. In addition, myocardial lactate levels plateaued after 30 minutes of VF-TCA, indicating the cessation of lactate production. CONCLUSION: These results suggest that the myocardium can tolerate VF-TCA for as long as 15 minutes without irreversible injury; however, post-ischemic myocardial dysfunction may occur after as little as five minutes of VF-TCA. With more than 30 minutes of VF-TCA, myocardial injury is likely to be irreversible.

Adenosine Diphosphate↗

Hemodynamic effects of 1-[3,4-dihydroxyphenyl]-1,2-diaminoethane versus norepinephrine during ventricular fibrillation and cardiopulmonary resuscitation.

We hypothesized that substitution of the hydroxyl group (OH) on the beta carbon of norepinephrine (NE) with an amino group would yield a compound, 1-(3,4-dihydroxyphenyl)-1,2-diaminoethane (DHPDAE), that would maintain the hemodynamic properties of NE during CPR, but would decrease the rate of post-defibrillation dysrhythmias. Six mixed breed swine weighing greater than 28 kg were studied. The animals were instrumented for cerebral (CBF) and myocardial blood flow (MBF) measurements. Ventricular fibrillation (VF) was induced. After 10 min of VF, CPR was begun. After 3 min of CPR, 2.5 mg/kg of DHPDAE was administered and CPR continued. Defibrillation was attempted 3.5 min after drug administration. CBF, MBF and defibrillation rates were compared to an historical control group receiving 0.16 mg/kg of NE. Outcome variables were compared using a Wilcoxon Rank Sum test and Fisher-exact test. NE significantly improved CBF and MBF compared to DHPDAE. All the animals in the NE group were successfully defibrillated into a perfusing rhythm. Sixty percent of the NE treated animals experienced post-defibrillation ventricular dysrhythmias. None of the animals in the DHPDAE were successfully defibrillated into a perfusing rhythm. Substitution of the hydroxyl group on the beta-carbon of NE with an amino group significantly decreases the hemodynamic properties of the parent molecule.

Animals↗