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At least 433 records · Page 24Linked to original sources

PubMed1995

Lowering of HDL2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol Quantitative Regression Swedish Trial (PQRST) Report.

The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303) was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine (8 g BID) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic (> 6.86 mmol/L) subjects. Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery. In this report we studied in a representative subgroup (n = 72) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL particle size subclasses. Probucol lowered the relative level of HDL2b, comprising the largest HDL particles, by 53% and the protein concentration of HDL2b by 67%. The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety. The change in lumen volume correlated significantly with change in HDL, ie, HDL cholesterol (r = .34, P < .01), HDL2 cholesterol (r = .37, P < .01), HDL2b protein (r = .44, P < .001), and the relative HDL2b value (r = .51, P < .001). The corresponding values for relative HDL2b, distribution calculated on the active (n = 35) and placebo (n = 37) groups separately were also significant (r = .39 and .32, respectively; both P < .05). The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

PubMed1996

Thrombin inhibition by antithrombin III on the subendothelium is explained by the isoform AT beta.

Balloon injury of the rabbit aorta results in thrombin coagulant activity on the injured vessel wall that causes fibrin formation. The anticoagulant activity of both the intact and injured vessel wall has been partly explained by glycosaminoglycans with heparin-like activity that augment that activity of antithrombin III (AT). AT exists in two isoforms, alpha and beta, AT beta, which constitutes only 5% to 10% of AT in plasma, lacks one carbohydrate side chain, has higher affinity for glycosaminoglycans, and associates more readily with the subendothelium. This study evaluated whether AT can inhibit thrombin on the injured vessel wall and, if so, whether one of the isoforms is more effective then the other. The two isoforms were isolated from human plasma by heparin-Sepharose chromatography, and the purity was investigated by isoelectric focusing and crossed immunoelectrophoresis. Rabbits were subjected to balloon injury of the aorta; 3 hours after injury the aorta was excised. Thrombin coagulant activity on the aorta was measured by exposure to fibrinogen and thereafter by measuring the generation of fibrinopeptide A. Injured animals were treated with AT, AT alpha, or AT beta and were compared with control animals. AT was demonstrated on the injured vessel wall by using an immunohistochemical method. Animals receiving crude AT had significantly lower amounts of thrombin coagulant activity on the injured aortic wall than control animals, but AT alpha at a comparable dose had no effect. AT beta was given in the same dose as crude AT and also at a dose (10%) proportional to its presence in plasma. Animals receiving AT beta had significantly lower values of thrombin on the injured aortic wall than control animals. We conclude that the inhibitory effect of AT on thrombin coagulant activity on the injured vessel wall in explained by its AT beta content.

Animals↗

PubMed1998

Nerve growth factor gene locus explains elevated renal nerve growth factor mRNA in young spontaneously hypertensive rats.

Nerve growth factor (NGF) controls the growth of sympathetic nerves and is increased in young spontaneously hypertensive rats (SHR). The NGF gene has been linked genetically with hypertension in the SHR strain and may explain high NGF mRNA levels. To test for genetic linkage between the NGF gene and its expression in vivo, we examined renal NGF mRNA levels in male SHR, control Donryu rats (DRY), and F2 rats derived from SHR and DRY at ages 2, 4, 10, and 20 weeks. Tail-cuff blood pressure was measured at 4, 10, and 20 weeks of age. NGF mRNA levels in SHR (NGF genotype: SS) were higher than those in DRY (NGF genotype: DD) at 2, 4, and 10 weeks of age (P<0.0001) but the same at 20 weeks of age. In the F2 generation, the S allele was associated with significantly (P=0.01) higher renal NGF mRNA levels at 2 weeks of age. Mean NGF mRNA levels fell (P=0.01) with age in F2 rats, and the difference between SS and DD genotype F2 rats diminished at older ages and was not significant. In F2 rats there was a positive correlation between the number of NGF S alleles inherited and tail-cuff pressure (P<0.007). Our findings indicate that the NGF locus is an important regulator of NGF mRNA levels. It is likely that mutations in or near the NGF gene explain in part high early NGF gene expression in SHR.

Animals↗

PubMed2002

Diversity in mitochondrial function explains differences in vascular oxygen sensing.

Renal arteries (RAs) dilate in response to hypoxia, whereas the pulmonary arteries (PAs) constrict. In the PA, O2 tension is detected by an unidentified redox sensor, which controls K+ channel function and thus smooth muscle cell (SMC) membrane potential and cytosolic calcium. Mitochondria are important regulators of cellular redox status and are candidate vascular O2 sensors. Mitochondria-derived activated oxygen species (AOS), like H2O2, can diffuse to the cytoplasm and cause vasodilatation by activating sarcolemmal K+ channels. We hypothesize that mitochondrial diversity between vascular beds explains the opposing responses to hypoxia in PAs versus RAs. The effects of hypoxia and proximal electron transport chain (pETC) inhibitors (rotenone and antimycin A) were compared in rat isolated arteries, vascular SMCs, and perfused organs. Hypoxia and pETC inhibitors decrease production of AOS and outward K+ current and constrict PAs while increasing AOS production and outward K+ current and dilating RAs. At baseline, lung mitochondria have lower respiratory rates and higher rates of AOS and H2O2 production. Similarly, production of AOS and H2O2 is greater in PA versus RA rings. SMC mitochondrial membrane potential is more depolarized in PAs versus RAs. These differences relate in part to the lower expression of proximal ETC components and greater expression of mitochondrial manganese superoxide dismutase in PAs versus RAs. Differential regulation of a tonically produced, mitochondria-derived, vasodilating factor, possibly H2O2, can explain the opposing effects of hypoxia on the PAs versus RAs. We conclude that the PA and RA have different mitochondria.

Animals↗

PubMed2002

Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?

BACKGROUND: The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that pravastatin significantly reduced mortality and coronary heart disease (CHD) events in 9014 patients with known CHD and total cholesterol 4.0 to 7.0 mmol/L at baseline. Secondary objectives included assessment of CHD event reduction according to lipid levels. METHODS AND RESULTS: We investigated the relationships of baseline and on-study lipids with subsequent CHD events in separate Cox models. Treatment effect on CHD event reduction was examined by baseline lipids and after adjustment for on-study lipid levels. Baseline lipids were significant predictors of CHD events. The adjusted relative risk per mmol/L (on placebo) was 1.24 (P=0.004) for total cholesterol, 1.28 (P=0.002) for low-density lipoprotein cholesterol, and 0.52 (P=0.004) for high-density lipoprotein cholesterol. Apolipoproteins A1 and B were strong predictors (each P=0.001). Pravastatin reduced the risk of the composite outcome of fatal CHD or nonfatal myocardial infarction by 24% (95% confidence interval [CI], 15% to 32%) and the expanded end point of fatal CHD, nonfatal myocardial infarction, unstable angina, or coronary revascularization by 17% (95% CI, 10% to 24%). Similar relative effects were observed for different categories of baseline lipids. The proportion of treatment effect explained by on-study lipid levels was 67% (95% CI, 27% to 106%) for the composite and 97% (95% CI, 49% to 145%) for the expanded end point. The most important lipids associated with event reduction were apolipoprotein B, low-density lipoprotein cholesterol, and the combination of total and high-density lipoprotein cholesterol. CONCLUSIONS: Changes in lipid levels can explain all or most of the observed benefit of pravastatin. Some treatment effect may also be mediated through nonlipid changes.

Adult↗

PubMed2001

Density and kinetics of I(Kr) and I(Ks) in guinea pig and rabbit ventricular myocytes explain different efficacy of I(Ks) blockade at high heart rate in guinea pig and rabbit: implications for arrhythmogenesis in humans.

BACKGROUND: Class III antiarrhythmic agents commonly exhibit reverse frequency-dependent prolongation of the action potential duration (APD). This is undesirable because of the danger of bradycardia-related arrhythmias and the limited protection against ventricular tachyarrhythmias. The effects of blockade of separate components of delayed rectifier K(+) current (I(K)) may help to develop agents effective at high heart rate. METHODS AND RESULTS: We assessed the density and kinetics of the 2 components of the delayed rectifier K(+) current, I(Kr) and I(Ks), in rabbit and guinea pig ventricular myocytes. The effects of their specific blockers (chromanol 293B for I(Ks) and E-4031 for I(Kr)) on the action potential was studied at different heart rates by use of whole-cell patch-clamp techniques. In guinea pig ventricular myocytes only, blockade of I(Ks) causes APD prolongation in a frequency-independent manner, whereas blockade of I(Ks) in rabbit ventricular myocytes shows reverse frequency dependence, as does blockade of I(Kr) in both species. This result can be explained primarily by the higher density of I(Ks) in guinea pig ventricle and by its slow deactivation kinetics, which allows I(Ks) to accumulate at high heart rate because little time is available for complete deactivation of it during diastole. CONCLUSIONS: Density and kinetics of components of I(K) explain why blockade of I(Ks) is more effective at high heart rate in the guinea pig ventricle than in the rabbit ventricle, without adverse effects at low heart rate.

Action Potentials↗

PubMed1992

Are race and sex differences in lung function explained by frame size? The CARDIA Study.

Using the CARDIA cohort of 20- to 32-yr-old black and white men and women, FVC and FEV1 were standardized for standing height, sitting height, leg height, elbow breadth, and biacromial diameter in such a way that the standardized lung function showed minimal statistical dependence on these measures of frame size. Race and sex differences in lung function have been reported even after adjustment for height; however, these differences might depend on aspects of frame size other than height. We found that within this age group height2 provided robust standardization for FVC and FEV1 for all race and sex strata of the population. Height explained approximately 40% of the variance of FVC and FEV1 in whites, 30% in black women, and 20% in black men. In black men only, standardization for the combination of sitting height, leg height, elbow breadth, and biacromial diameter improved explained variance to nearly 40% for FVC and nearly 30% for FEV1. After standardization for height, FVC and FEV1 were found to be 14 to 19% higher in whites than in blacks, and in men than in women. Standardization of FVC and FEV1 for sitting height, leg height, elbow breadth, and biacromial diameter combined reduced these differences to 13-16%. Thus, race and sex differences in lung function exist even after detailed adjustment for frame size.

Adult↗

PubMed2006

Explaining the footsteps, belly dancer, Wenceslas, and kickback illusions.

The footsteps illusion (FI) demonstrates that an object's background can have a profound effect on the object's perceived speed. This illusion consists of a yellow bar and a blue bar that move over a black-and-white, striped background. Although the bars move at a constant rate, they appear to repeatedly accelerate and decelerate in antiphase with each other. Previously, this illusion has been explained in terms of the variations in contrast at the leading and trailing edges of the bars that occur as the bars traverse the striped background. Here, we show that this explanation is inadequate and instead propose that for each bar, the bar's leading edge, trailing edge, lateral edges, and the surrounding background edges all contribute to the bar's perceived speed and that the degree to which each edge contributes to the motion percept is determined by that edge's contrast. We show that this theory can explain all the data on the FI as well as the belly dancer and Wenceslas illusions. We conclude by presenting a new illusion, the kickback illusion, which, although geometrically similar to the FI, is mediated by a different mechanism, namely, reverse phi motion.

Acceleration↗

PubMed1988

Pathogenesis of Campylobacter fetus infections. Failure of encapsulated Campylobacter fetus to bind C3b explains serum and phagocytosis resistance.

Campylobacter fetus ssp. fetus strains causing systemic infections in humans are highly resistant to normal and immune serum, which is due to the presence of high molecular weight (100,000, 127,000, or 149,000) surface (S-layer) proteins. Using serum-resistant parental strains (82-40 LP and 23D) containing the 100,000-mol wt protein and serum-sensitive mutants (82-40 HP and 23B) differing only in that they lack the 100,000-mol wt protein capsule, we examined complement binding and activation, and opsono-phagocytosis by polymorphonuclear leukocytes. C3 consumption was similar for all four strains but C3 was not efficiently bound to 82-40 LP or 23D even in the presence of immune serum, and the small amount of C3 bound was predominently the hemolytically inactive iC3b fragment. Consumption and binding of C5 and C9 was significantly greater for the unencapsulated than the encapsulated strains. Opsonization of 82-40 HP with heat-inactivated normal human serum caused greater than 99% killing by human PMN. Similar opsonization of 82-40 LP showed no kill, but use of immune serum restored killing. Findings in a PMN chemiluminescence assay showed parallel results. Association of 32P-labeled 82-40 HP with PMN in the presence of HINHS was 19-fold that for the 82-40 LP, and electron microscopy illustrated that the difference was in uptake rather than in binding. These results indicate that presence of the 100,000-mol wt protein capsule on the surface of C. fetus leads to impaired C3b binding, thus explaining serum resistance and defective opsonization in NHS, mechanisms that explain the capacity of this enteric organism to cause systemic infections.

Blood Bactericidal Activity↗

PubMed1994

Is it true that the differences in reading performance between students with and without LD cannot be explained by IQ?

This study was designed to demonstrate whether the differences in reading between students with learning disabilities (LD) and non-learning disabled students (NLD) can be explained by IQ. A sample of 133 Spanish children (85 male, 48 female) ranging in age from 8 to 13 years were classified into four groups according to IQ as measured by the Wechsler Intelligence Scale for Children-Revised (< 80; 81-90; 91-109: 110-140) and into two groups based on reading level (LD and NLD). A lexical decision task was used and we manipulated different word parameters (length, positional syllabic frequency, and familiarity) and pseudoword parameters (length and positional syllabic frequency) to study the routes used by both groups. Our findings indicate that IQ does not explain the differences between children with LD and NLD children in lexical processing. We found that the lexical and sublexical parameters have a greater influence on students with LD than NLD students, independent of IQ. In synthesis, the LD group has more difficulty in lexical processing, which is influenced by poor phonological skills.

Adolescent↗

PubMed2003

Explaining feast or famine in randomized field trials. Medical science and criminology compared.

A feast of randomized controlled trials (RCTs) in medical science and comparative famine in criminology can be explained in terms of cultural and structural factors. Of central importance is the context in which the evaluation of interventions is done and the difference in status of situational research in the two disciplines. Evaluation of medical interventions has traditionally been led by practitioner (clinical) academics. This is not the case in criminal justice, where theory has had higher status than intervention research. Medical science has advanced in, or closely associated with, university teaching hospitals, but links between criminology and criminal justice services are far more tenuous. The late development of situational crime prevention seems extraordinary from a medical perspective, as does the absence of university police schools in the United Kingdom and elsewhere. These structural and cultural factors explain concentration of expectation, resource, and RCT productivity in medical science. The Campbell Collaboration and the Academy of Experimental Criminology are forces which are reducing this polarization of feast and famine in RCTs. But unless scientific criminology is embedded in university schools which are responsible for the education and training of law, probation, and police practitioners, convergence in terms of RCTs and implementation of findings in practice seems unlikely.

Criminology↗

PubMedDate not supplied

Surgical decisions for early stage, non-small cell lung cancer: which racially sensitive perceptions of cancer are likely to explain racial variation in surgery?

OBJECTIVES: Twenty-three percent of white and 36% of African American patients who suffer from early stage non-small cell lung cancer do not undergo potentially curative surgery A simple decision model is presented to probe for elements of surgical decision making that could explain decisions against lung cancer surgery and racial variation in these decisions. METHODS: A survey of 181 diverse individuals to measure health utility scores for conditions relevant to lung cancer surgery was performed. These scores were inserted into a simple model that calculates quality-adjusted survival related to decisions for and against cancer surgery RESULTS: The health utility score (HUS) for progressive lung cancer, as determined by a survey using the standard gamble approach, is nearly twice as high in African Americans as whites (0.32 v. 0.18). However, in a model incorporating African American utility data, lung cancer surgery remains heavily favored compared to the no-surgery decision (2.32 v. 0.48 quality-adjusted life years). Sensitivity analysis shows that factors that lead to a belief of cancer "cure" in the absence of surgical intervention are much more important than variations of HUS in directing model results away from surgery. CONCLUSION: This analysis illustrates that racial differences in quality-of-life ratings of progressive lung cancer as measured by HUS exist but may not explain decisions against surgery as much as other elements of patient care.

Black or African American↗

PubMedDate not supplied

Use of clinical judgment analysis to explain regional variations in physicians' accuracies in diagnosing pneumonia.

The authors sought to explain regional differences in physicians' accuracies in diagnosing pneumonia by prospectively studying emergency department patients at three sites and analyzing differences in physicians' diagnostic strategies and patient characteristics. They enrolled 1,119 Illinois patients, 150 Nebraska patients, and 142 Virginia patients presenting with fever or respiratory symptoms for whom physicians ordered a chest radiograph because of suspicion of pneumonia. Emergency department physicians recorded patients' clinical findings and estimated the probability that a chest radiograph would show pneumonia. A measure of accuracy, the correlation between physicians' probability estimates and actual outcomes, was 0.41 (95% CI 0.36-0.46) at Illinois, 0.66 (95% CI 0.54-0.75) at Nebraska, and 0.55 (95% CI 0.42-0.65) at Virginia. Physicians' strategies at the three sites differed markedly in their weightings of asthma, signs of consolidation, cough, tachypnea, age, and gender. These differences in weighting paralleled differences in the optimal clinical strategies derived from patient data at the three sites. Differences in diagnostic accuracy were best explained by differences in the difficulties of diagnosing pneumonia in the populations. Physicians at each site used clinical findings in a way that was close to optimal for their location. This type of analysis provides a new tool for understanding the sources of regional variations in clinical practice.

Adult↗

PubMedDate not supplied

An educational model for explaining hospice services.

Explaining the concept and philosophy of hospice can be difficult. There is a reluctance in our society to openly address dying/death issues; there is a reluctance on the part of many health-care professionals to look beyond physical issues. The following model has been used successfully to explain hospice to both the general public and health care professionals. It is not intended to introduce hospice to a patient/family during the initial referral/assessment visit.

Health Education↗

PubMed1996

Does severity explain differences in hospital length of stay for pneumonia patients?

OBJECTIVES: In the USA, the role of patient severity in determining hospital resource use has been questioned since Medicare adopted prospective hospital payment based on diagnosis-related groups (DRGs). Exactly how to measure severity, however, remains unclear. We examined whether assessments of severity-adjusted hospital lengths of stay (LOS) varied when different measures were used for severity adjustment. METHODS: The complete study sample included 18,016 patients receiving medical treatment for pneumonia at 105 acute care hospitals. We studied 11 severity measures, nine based on patient demographic and diagnosis and procedure code information and two derived from clinical findings from the medical record. For each severity measure, LOS was regressed on patient age, sex, DRG, and severity score. Analyses were performed on trimmed and untrimmed data. Trimming eliminated cases with LOS more than three standard deviations from the mean on a log scale. RESULTS: The trimmed data set contained 17,976 admissions with a mean (S.D.) LOS of 8.9 (6.1) days. Average LOS ranged from 5.0-11.8 days among the 105 hospitals. Using trimmed data, the 11 severity measures produced R-squared values ranging from 0.098-0.169 for explaining LOS for individual patients. Across all severity measures, predicted average hospital LOS varied much less than the observed LOS, with predicted mean hospital LOS ranging from about 8.4-9.8 days. DISCUSSION: No severity measure explained the two-fold differences among hospitals in average LOS. Other patient characteristics, practice patterns, or institutional factors may cause the wide differences across hospitals in LOS.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed2003

Can early infection explain the sibling effect in adult atopy?

Atopy is strongly and inversely related to family size, a pattern which is plausibly assumed to reflect a protective effect of early infection. The current study tested this hypothesis by case-referent analysis of an adult cohort in the UK. The study established that atopy, defined by prick tests to common aeroallergens, was less common among those from larger families after adjustment for potentially confounding factors. In particular, a higher number of brothers appeared to offer protection. The current authors attempted to explain this distribution by examining contemporary family-doctor records of early childhood infections; and by a number of other indirect indices of early-life "hygiene". The sibling effect was unexplained by evidence of infection with either hepatitis A or Helicobacter pylori, or by counts of infections or antibiotic prescriptions in early life. There was a significant and independent negative association between the number of gastrointestinal infections before the age of 5 yrs and the odds of atopy. Dog ownership and home moving in early life also displayed potentially protective associations. Although the current study replicates the finding that atopy is inversely associated with family size this could not be explained by documentary or serological evidence of early infection. The findings support the suggestion that the "sibling effect" in atopy may not simply reflect protection by early infection.

Adult↗

PubMed2005

Differences in codon bias cannot explain differences in translational power among microbes.

BACKGROUND: Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level and degree of codon bias among genes of Escherichia coli and other bacteria capable of rapid growth is commonly attributed to selection for high translational power. Conversely, the absence of such a correlation in some slowly growing microbes has been interpreted as the absence of selection for translational power. Because codon bias caused by translational selection varies between rapidly growing and slowly growing microbes, we investigated whether observed differences in translational power among microbes could be explained entirely by differences in the degree of codon bias. Although the data are not available to estimate the effect of codon bias in other species, we developed an empirically-based mathematical model to compare the translation rate of E. coli to the translation rate of a hypothetical strain which differs from E. coli only by lacking codon bias. RESULTS: Our reanalysis of data from the scientific literature suggests that translational power can differ by a factor of 5 or more between E. coli and slowly growing microbial species. Using empirical codon-specific in vivo translation rates for 29 codons, and several scenarios for extrapolating from these data to estimates over all codons, we find that codon bias cannot account for more than a doubling of the translation rate in E. coli, even with unrealistic simplifying assumptions that exaggerate the effect of codon bias. With more realistic assumptions, our best estimate is that codon bias accelerates translation in E. coli by no more than 60% in comparison to microbes with very little codon bias. CONCLUSIONS: While codon bias confers a substantial benefit of faster translation and hence greater translational power, the magnitude of this effect is insufficient to explain observed differences in translational power among bacterial and archaeal species, particularly the differences between slowly growing and rapidly growing species. Hence, large differences in translational power suggest that the translational apparatus itself differs among microbes in ways that influence translational performance.

Bacterial Physiological Phenomena↗

PubMed1999

Explaining illness to children: advancing theory and research by determining message content.

Numerous scholars have suggested the importance of explaining illness to children and empirical efforts have been made to determine effective illness explanation strategies. However, the studies have been few and provide little advancement of theory and practical advice for health practitioners. Much, if not all, of the theory and research in this area focuses on explaining the etiology and biology of illness to children. This practice, as argued here, may be the central factor inhibiting theory, research, and understanding of effective illness explanation to children. Specifically, children may find this knowledge of little use and may prefer explanations that adhere to psychosocial concerns. As such, suggestions for future research are offered.

Journal Article↗