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Refinement and interobserver agreement for the electrocardiographic Sclarovsky-Birnbaum Ischemia Grading System.

BACKGROUND: Electrocardiogram-derived grades of ischemia at the time of patient presentation with acute myocardial infarction have proved useful in predicting the salvageability by reperfusion therapy, final infarct size, severity of left ventricular dysfunction, and short- and long-term prognosis. SUBJECTS AND METHODS: The Sclarovsky-Birnbaum Ischemia Grading System based on the relation between the acute appearances of the T wave, the ST segment, and the QRS complex was considered as a means of enhanced ECG analysis in this group of patients. The evaluation of a training population (n = 46) resulted in refinement of the published description of the Sclarovsky-Birnbaum Ischemia Grading System, and a test population (n = 50) was utilized for investigating the interobserver agreement among 5 observers in determining the grade of ischemia. RESULTS: The agreement among the observers applying the "refined" Sclarovsky-Birnbaum Ischemia Grading System was 0.89. Complete agreement was found for the ECGs of 80% of the patients, and the most common reason for disagreement was the application of the terminal T-negativity criterion. CONCLUSIONS: The refined Sclarovsky-Birnbaum Ischemia Grading System can be performed manually with low interobserver variability. It has potential for support of the acute myocardial infarction triage decision as an electrocardiographic method for evaluating the level of ischemic protection at the time of either pre-hospital or emergency-department presentation.

Algorithms↗

Neonatal screening for haemoglobinopathies: the results of a 10-year programme in an English Health Region.

Neonatal identification of sickle cell disease can significantly reduce mortality and morbidity during the first 5 years of life. During a 10-year period, 414,801 neonates were screened by isoelectric focusing. The most common variants detected were haemoglobins S, C, D and E. Two hundred and fifty of the samples tested were homozygotes or compound heterozygotes, and 6554 samples were heterozygotes for the common variants. The gene frequencies in the population tested were calculated from this data for the most common variants. They were: S, 0.0057; C, 0.0014; D(Punjab(Los Angeles)), 0.0007; E, 0.0005. Additionally, 16 babies had beta thalassaemia major and 405 had rarer variants, of which six had never previously been described. Knowledge of the distribution of these inherited diseases is useful in healthcare planning and appropriate allocation of resources, while counselling targeted at appropriate couples enables informed parental choice and may prevent disease.

Anemia, Sickle Cell↗

Exercise stress testing to screen for coronary artery disease in asymptomatic persons.

Exercise testing has proven value for the diagnosis of cardiac disorders in symptomatic patients and for the objective measurement of functional capacity. Use of exercise tests to screen for cardiac disease in asymptomatic persons remains controversial because of the low prevalence of disease in the population tested, the different characteristics of the test in asymptomatic persons, and the uncertain value of the information generated. This paper addresses the use of exercise testing to screen for coronary artery disease in asymptomatic persons. The principles underlying the use of screening tests will first be presented. The epidemiological evidence concerning screening exercise tests will then be reviewed, followed by the data concerning the prognosis and treatment of asymptomatic coronary disease. Finally, possible indications for screening exercise tests in specific occupations will be addressed.

Angiography↗

Concordance of endotoxemia with gram-negative bacteremia in patients with gram-negative sepsis: a meta-analysis.

The Limulus amebocyte lysate (LAL) assay is a sensitive method for detecting endotoxin. Using gram-negative (GN) bacteremia as the basis for comparison, concordance with endotoxemia in 45 studies could be expressed as an odds ratio. Calculation of summary odds ratios by the Mantel-Haenszel-Peto method indicated that the concordance of the results was no higher by the chromogenic LAL assay than by the gelation version, and the sensitivity was improved by only 11% (62 versus 51%). Endotoxemia was detected in 77 (68%) of 114 patients with bacteremia caused by an organism that was not a member of the family Enterobacteriaceae, whereas endotoxemia was detected in only 120 (45%) of 269 patients with bacteremia caused by a member of the family Enterobacteriaceae or an anaerobe (P < 0.001). This difference was also apparent for patients with GN bacteremia for whom a fatal outcome had been recorded. The prevalence of GN bacteremia in the tested population and the type of etiological agent are critical and previously unrecognized variables which affect the interpretation of the LAL test in patients with suspected sepsis.

Bacteremia↗

Protein kinase C activation allows pulmonary artery smooth muscle cells to proliferate to hypoxia.

Pulmonary artery (PA) smooth muscle cell (SMC) proliferation occurs with hypoxic pulmonary hypertension in vivo. However, proliferation of cultured PA SMC to hypoxia has not been demonstrated, and thus the mechanism by which these cells respond to hypoxia is unknown. Because protein kinase C (PKC) plays a role in intracellular transduction of proliferative signals, we asked whether PKC activation 1) causes proliferation of bovine PA SMC and 2) is important in PA SMC proliferative response to hypoxia. By measuring [3H]thymidine incorporation and cell counts, we found that quiescent PA SMC from four different cows proliferated with the PKC activator, phorbol 12-myristate 13-acetate (PMA), in a concentration-dependent manner. The proliferation was blocked with a PKC inhibitor, dihydrosphingosine, or by downregulating SMC PKC. We tested whether "priming" PA SMC by PKC activation was required for in vitro SMC proliferative response to hypoxia. Each SMC population was treated with PMA and then exposed for 24 h to 20, 10, 7, 3 or 0% O2. These cells proliferated with hypoxia reaching a peak response at 3% O2. The magnitude of the response to PMA and hypoxia was different for each cell population tested. No hypoxic proliferation occurred in control cells (no PMA). Dihydrosphingosine blocked the hypoxic response to the same extent that it inhibited the initial PMA conditioning stimulus. PKC-downregulated PA SMC did not proliferate to PMA or to subsequent hypoxia. The hypoxic response was not due to a reduction in O2 radical-mediated antiproliferative effect; rather, the PMA-primed cells seemed to "acquire" the ability to directly sense hypoxia and proliferate. In summary, PKC activation caused proliferation of PA SMC in vitro and allowed an additional proliferative response to hypoxia. Activation of PKC may be a requisite step for PA SMC to respond directly to hypoxia.

Aerobiosis↗

Dihydropyrimidine dehydrogenase activity in human blood mononuclear cells.

Dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2) catalyzes the rate-limiting reaction in the catabolism of endogenous uracil and thymine and exogenous fluoropyrimidines. DPD activity was studied in human blood mononuclear cell supernatants utilizing a new and sensitive radiochromatographic assay. Total DPD activity showed a linear correlation with supernatant protein concentration. The affinity constants (Km) for NADPH and thymine were approximately 10 and 1 mumol/l, respectively. Maximal activity (Vmax) was observed at 0.25 mmol/l NADPH and 10 mumol/l thymine, respectively. DPD activity in normal individuals was 8.0 +/- (SD) 2.2 nmol/mg protein/h, and ranged from 4.4 to 12.3 nmol/mg/h (n = 25). This activity range was quite similar to values obtained in patients with metastatic solid tumors treated with fluorodeoxyuridine (FUdR; n = 33, p = 0.57). No correlation was found to exist between mononuclear leucocyte DPD activity and the observed toxicity of FUdR in the tested patients. A bimodal distribution of DPD activity was observed in the patients and in normal individuals. The entire study population tested could be divided into two groups with respect to DPD activity; one group with high (greater than 8 nmol/mg/h) activity and another with low (less than 8 nmol/mg/h) activity. The possibility that sex differences may have been responsible for this distribution of DPD activity could not be excluded. The findings of this study are relevant to the pharmacogenetics of fluoropyrimidines in humans.

Adult↗

A genome-wide approach to identify genetic loci with a signature of natural selection in the Irish population.

BACKGROUND: In this study we present a single population test (Ewens-Waterson) applied in a genomic context to investigate the presence of recent positive selection in the Irish population. The Irish population is an interesting focus for the investigation of recent selection since several lines of evidence suggest that it may have a relatively undisturbed genetic heritage. RESULTS: We first identified outlier single nucleotide polymorphisms (SNPs), from previously published genome-wide data, with high FST branch specification in a European-American population. Eight of these were chosen for further analysis. Evidence for selective history was assessed using the Ewens-Watterson's statistic calculated using Irish genotypes of microsatellites flanking the eight outlier SNPs. Evidence suggestive of selection was detected in three of these by comparison with a population-specific genome-wide empirical distribution of the Ewens-Watterson's statistic. CONCLUSION: The cystic fibrosis gene, a disease that has a world maximum frequency in Ireland, was among the genes showing evidence of selection. In addition to the demonstrated utility in detecting a signature of natural selection, this approach has the particular advantage of speed. It also illustrates concordance between results drawn from alternative methods implemented in different populations.

Cystic Fibrosis Transmembrane Conductance Regulato↗

Decontaminative effect of frozen acidic electrolyzed water on lettuce.

We investigated the effects of frozen acidic electrolyzed water (AcEW) on lettuce during storage in a styrene-foam container. The lettuce was kept at 2 to 3 degrees C for 24 h. Populations of aerobic bacteria associated with lettuce packed in frozen AcEW were reduced by 1.5 log CFU/g after storage for 24 h. With frozen tap water, no microorganism populations tested in this study were reduced. A frozen mixture of AcEW and alkaline electrolyzed water (AlEW) also failed to reduce populations of microorganisms associated with lettuce. Although chlorine gas was produced by frozen AcEW, it was not produced by the AcEW-AlEW mixture. This result indicates that the main factor in the decontaminative effect of frozen AcEW was the production of chlorine gas. Accordingly, low-temperature storage and decontamination could be achieved simultaneously with frozen AcEW during distribution.

Bacteria, Aerobic↗

Apolipoprotein E gene polymorphism and allele frequencies in the Lebanese population.

Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence in the Lebanese population and compare it with other populations. DNA from 160 unrelated healthy donors from our HLA-bank was used. ApoE genotype was determined using the CardioVascular Disease (CVD) StripAssay (this assay is based on a Polymerase Chain Reaction-Reverse Hybridization technique). The prevalence of genotypes E3/3, E3/4, and E2/3 was found to be 69%, 26%, and 22%, respectively, and 0.6% for each of E2/4 and E4/4 genotypes. The Lebanese population tested showed similarities to earlier reported ApoE genotypic distributions (high E3 allele frequency) but also peculiar differences especially to some Arabic countries (total absence of E2 allele among Saudis) and other populations. This is the first report from Lebanon that will serve as a template for future investigations of the prevalence of ApoE alleles in association with various clinical entities.

Apolipoproteins E↗

Volatile organic compound testing of a population living near a hazardous waste site.

Accurate measures of individual exposure are critical in reducing misclassification and establishing scientifically valid associations between health outcomes and exposures to environmental contaminants. As part of a community health study, the Agency for Toxic Substances and Disease Registry conducted exposure testing for volatile organic compounds (VOCs) in the blood of people residing near an industrial complex. The purposes of the study were to assess recent exposures to VOCs in this community and to assess the utility of conducting blood VOC testing on populations near hazardous waste sites. One hundred blood specimens from the target area and 106 blood specimens from the control area were collected for analysis. The blood VOC levels in the target-area participants were compared to those in the control area and to a national reference population. Of the 31 separate VOCs for which testing was done, only acetone was statistically significantly (p < 0.05) higher in target-area participants (1,636 parts per billion [ppb]) than in control-area participants (1,353 ppb). 1,1,1-Trichloroethane was found at higher geometric mean levels in the control group (0.169 ppb) than in the target group (0.115 ppb) (p = 0.01). Median blood levels of 2-butanone and 1,4-dichlorobenzene were slightly higher in both target- and control-area groups than in the national reference population, but neither area was statistically significantly higher than the national reference population for any contaminant measured. Overall, there appeared to be no association between residing in the target area and elevated blood VOC levels. Based on the results of this study, blood VOC testing should be limited to populations living near sites where environmental testing has shown recent, elevated VOC exposure, or where unusual circumstances of illness may be attributed to VOC exposure.

Acetone↗

Infection of Gammarus duebeni populations by two vertically transmitted microsporidia; parasite detection and discrimination by PCR-RFLP.

We screened a population of the brackish water crustacean Gammarus duebeni from the Isle of Cumbrae for the presence of vertically transmitted microsporidia. We compared 2 screening techniques; light microscopy and PCR-based detection using generic 16S rDNA microsporidian primers. Fifty percent of females from this population tested positive for vertically transmitted microsporidia. The PCR screen was 100% efficient in comparison with existing LM based screening. In addition, the PCR screen produced bands of 2 sizes suggesting that more than 1 species of microsporidian was present. Sequencing revealed 2 distinct species of vertically transmitted microsporidia; 33% of females were infected with the feminizer Nosema granulosis and 17% were infected with a new species which we provisionally designate Microsporidium sp. On the basis of sequence information, we developed a discriminatory PCR-RFLP test based on MspI and HaeIII digests. This screen allows rapid detection and discrimination of vertically transmitted microsporidia in natural field populations. We applied the PCR-RFLP screen to a second G. duebeni population from the Isle of Man. This population also hosted these 2 parasite species. In total 45% of females harboured N. granulosis and 10% harboured Microsporidium sp. No dual-infected individuals were found in either population. The occurrence of 2 vertically transmitted parasites within a population has implications for our understanding of parasite-host relationships in the field and we discuss factors affecting the dynamics of parasite-parasite competition and coexistence.

Animals↗

Variation in the degree and costs of adaptive phenotypic plasticity among Rana temporaria populations.

Adaptive phenotypic plasticity in the form of capacity to accelerate development as a response to pond drying risk is known from many amphibian species. However, very little is known about factors that might constrain the evolution of this type of plasticity, and few studies have explored to what degree plasticity might be constrained by trade-offs dictated by adaptation to different environmental conditions. We compared the ability of southern and northern Scandinavian common frog (Rana temporaria) larvae originating from 10 different populations to accelerate their development in response to simulated pond drying risk and the resulting costs in metamorphic size in a factorial laboratory experiment. We found that (i) northern larvae developed faster than the southern larvae in all treatments, (ii) a capacity to accelerate the response was present in all five southern and all five northern populations tested, but that the magnitude of the response was much larger (and less variable) in the southern than in the northern populations, and that (iii) significant plasticity costs in metamorphic size were present in the southern populations, the plastic genotypes having smaller metamorphic size in the absence of desiccation risk, but no evidence for plasticity costs was found in the northern populations. We suggest that the weaker response to pond drying risk in the northern populations is due to stronger selection on large metamorphic size as compared with southern populations. In other words, seasonal time constraints that have selected the northern larvae to be fast growing and developing, may also constrain their innate ability for adaptive phenotypic plasticity.

Adaptation, Physiological↗

Habitat specialization and adaptive phenotypic divergence of anuran populations.

We tested for adaptive population structure in the frog Rana temporaria by rearing tadpoles from 23 populations in a common garden experiment, with and without larval dragonfly predators. The goal was to compare tadpole phenotypes with the habitats of their source ponds. The choice of traits and habitat variables was guided by prior information about phenotypic function. There were large differences among populations in life history, behaviour, morphological shape, and the predator-induced plasticities in most of these. Body size and behaviour were correlated with predation risk in the source pond, in agreement with adaptive population divergence. Tadpoles from large sunny ponds were morphologically distinct from those inhabiting small woodland ponds, although here an adaptive explanation was unclear. There was no evidence that plasticity evolves in populations exposed to more variable environments. Much among-population variation in phenotype and plasticity was not associated with habitat, perhaps reflecting rapid changes in wetland habitats.

Adaptation, Physiological↗

Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer.

PURPOSE: To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer. METHODS: In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue. RESULTS: while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the activated form of Akt in the tumors. CONCLUSION: This study demonstrates a good correlation between the degree of inhibition of EGFR in skin and in breast tumors. The lack of significant clinical activity of gefitinib in our study population is not due to lack of receptor inhibition in these tumors but rather to lack of EGFR dependence in the tested population.

Adult↗

[Clinical and electrophysiological studies of the organ of hearing of newborn infants. III. Evaluation of the organ of hearing of newborn infants from high risk pregnancy using brain stem evoked response audiometry (ABR)].

In a group of 130 tested newborns, pathological brain stem responses derived from acoustic stimulus was achieved in 28 cases (21.5%). 85.2% of newborns in this group of birthed babies comprised a high-risk pregnancy group. Based on criteria evaluating monitoring and parameters achieved ABR responses: conduction hearing disorders were found in 7 newborns, sensori-neural in 12 cases, and neurological dysfunction was observed in 9 cases. Control testing was carried through for three months following the initial evaluation allowing for the elimination of 12 children in a group of 19 for further testing and observation. This represents 42.85% of children initially evaluated as possessing a hearing disorder and 9.2% from the total of those tested. Results obtained during successive control testing were carried-out in a 3-6 month period following the initial examination and allowed for decisions to be made. Conforming to: 4 children (3.07%) were supplied with hearing aids and hearing rehabilitation begun, 1 child (0.76%) was referred to rehabilitation the deaf, whereas the 2 remaining children (1.53%) are currently under neurological observation. Nonetheless, testing older children eliminates cases that present with lack of success at the initial evaluation or transitory hearing impairment that is self-limited, although ABR testing, while the child is on the unit, allows for the introduction of hearing-organ controls of newborns based on population testing.

Audiometry, Evoked Response↗

[Investigation of the immunity status towards tetanus of a population of mechanics at the car-factory "Renault" (author's transl)].

Tetanus immunity has been studied in a population of mechanics working at the car-factory "Renault". For the study, 283 individuals were divided into 3 groups. The first group consisted of non-vaccined individuals, the second of vaccinated individuals and the third of individuals who had been boostered. The influence of different parameters on tetanus immunity status was considered, i. e. the age of the subjects, the time at which boostering was given, the serotherapy (when it was administered) and the contact with machine lubricating and cooling fluids. Clostridium tetani bacilli and spores were frequently found in aqueous machine fluids. Their presence is a potential hazard for non-vaccinated mechanics coming to contact with the fluids. Tetanus antibody levels in the sera of the tested population were determined in vivo by the toxin neutralization test. The influence on tetanus immunity of the different parameters considered in this paper was subjected to statistical analysis. From the whole population, 27% of the individuals were found to have no protection against tetanus. When age was taken into account, 53% of the individuals over 45 years old and 10% of those under 45 years old were shown to be devoid of tetanus immunity. It could be shown that younger individuals were better protected than older ones, because the formers had been immunized with adsorbed tetanus toxoid and most of the latters with fluid toxoid. Of the individuals in the third group who had received a booster injection within 15 years after primo-vaccination, 98% showed protective tetanus antibody levels in their sera in contrast to 25% when boostering had occurred more than 15 years after primo-vaccination. Contact with machine fluids was found to influence the degree of immunity of only those individuals whose boostering dated back to more than 25 years. Unexpectedly, 3 mechanics seemed to develop immunity after coming into contact with machine fluids. From the results reported here, it is concluded that tetanus immunity in vaccinated individuals should be renewed by a compulsory booster injection given every 5, 10 or, at the minimum, 15 years. Moreover, high-risk populations such as that represented by the mechanics should be immunized or boostered on commencing employment.

Adult↗

Postsynaptic action potentials do not alter short-term potentiation in the dentate gyrus.

The dendrites of neocortical neurons have been shown to support active action potentials which back-propagate from the soma after an output spike has been initiated. This observation has led to speculation that dendritic action potentials may participate in various forms of synaptic plasticity. The contribution of dendritic spikes to paired-pulse facilitation (PPF), a form of short-term plasticity, was investigated in the dentate gyrus of hippocampal slices. Paired orthodromic stimulation of the perforant path produced an average facilitation of the test population spike (PS) amplitude of 167% (n = 16, conditioning response = 100%). There was also a small but significant increase in slope of the field EPSP (fEPSP) of 108%. To determine whether increased presynaptic drive could account for this facilitation, the relationship between fEPSP slope and spike amplitude (I-O) was determined for a range of stimulus intensities. An increase in fEPSP slope of 171% was associated with an increase in PS amplitude equal to the facilitation produced by paired-pulse stimulation (167%), suggesting a postsynaptic component in PPF. Electric field effects were then used as a tool to alter the excitability of granule cells during the conditioning response without changing synaptic drive. Any change in the test response associated with manipulation of the conditioning population spike amplitude would suggest that dendritic spikes may contribute to the postsynaptic component of PPF. Surprisingly, altering the number of neurons responding to the conditioning stimulus with an action potential had no effect on the test response, suggesting that dendritic action potentials do not participate in this form of short-term synaptic plasticity.

Action Potentials↗

Acaricide resistance profiles of single- and multi-host ticks from communal and commercial farming areas in the Eastern Cape and North-West Provinces of South Africa.

A field study (February 2000 to August 2001) was conducted on communal and commercial farms in the Eastern Cape and North-West Provinces of South Africa to detect the levels of tick resistance to commonly used acaricides. The larvae obtained from engorged females of the one-host tick Boophilus decoloratus, the two-host tick Rhipicepalus evertsi evertsi and the three-host ticks Amblyomma hebraeum and Rhipicephalus appendiculatus were tested against various concentrations of amitraz, chlorfenvinphos and cypermethrin using the Shaw Larval Immersion Test method. Ticks from the communal farms showed higher levels of resistance to cypermethrin and some resistance to chlorfenvinphos whilst no resistance was detected against amitraz. However, ticks from commercial farms were equally resistant to amitraz, chlorfenvinphos and cypermethrin. The B. decoloratus populations tested were considerably more resistant to all the acaricides tested than the R. evertsi evertsi, A. hebraeum and R. appendiculatus populations. This supports the hypothesis that single-host ticks develop resistance faster than multi-host ticks. This trend was recorded on most of the farms where single- and multi-host ticks co-existed. It was concluded that the use of acaricides at high frequencies and high concentrations was one of the main causes of tick resistance in the study areas. Possible factors which caused the resistance problems are discussed and acaricide management strategies recommended.

Animals↗