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PubMed1995

Interacting roles of nitric oxide and ATP in the pulmonary circulation of the rat.

1. The potentiating effect of NG-nitro-L-arginine methyl ester, (L-NAME) a nitric oxide synthesis inhibitor, on responses of the rat pulmonary vascular pressure (PVP) to purinoceptor agonists was examined. 2. At a constant flow of 23 ml min-1 the PVP was 22.4 +/- 2.5 mmHg (n = 15), and treatment with 100 microM L-NAME for 15 min was without effect on the PVP. After the tone was raised with 28 nmol 9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U-46619), the PVP was 29.4 +/- 3.3 mmHg and treatment with 100 microM L-NAME was still without effect on the PVP. It appears that there is a graded release of nitric oxide in response to different levels of steady shear stress and in our experimental model the threshold for detection was not reached under basal conditions. 3. In contrast, when the circulation was challenged with 30 s step, additive increases in flow between 11 and 50 ml min-1 (n = 8), treatment with 100 microM L-NAME produced a significant (P < 0.05) increase in PVP suggesting that changes in flow-derived forces evoke the release of nitric oxide. This was evident for flow rates above 30 ml min-1. 4. In preparations in which tone was raised with U-46619, a dose of 1 x 10(-8) mol ATP or 2-meSATP evoked a drop in PVP while alpha,beta-meATP produced an increase in PVP under constant flow of 23 ml min-1. After treatment with 100 microM L-NAME, all three purinoceptor agonists evoked an increase in PVP. The increase in Pvp evoked by alpha, beta-meATP was not affected by L-NAME. These results suggest that P2Y-purinoceptor stimulation evokes the release of nitric oxide to produce vasodilatation.5. Under conditions of constant flow and basal pressure, 100 microM L-NAME significantly (P<0.05)potentiated the increase in Pvp evoked by 1 x 10-6 mol ATP, although the increase evoked by 1 x 10-8 mol (alpha,beta-meATP, which was of similar magnitude, was not affected. These results indicate that a blockade of evoked nitric oxide release is responsible for the potentiation of the increase in Pvp evoked by ATP.6. This study shows that, while nitric oxide does not appear to be released in the pulmonary circulation of the rat under constant flow conditions, nitric oxide release evoked by purinoceptor agonists attenuates increases in pulmonary vascular pressure.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Prenatal alcohol exposure and academic achievement at age six: a nonlinear fit.

This is a report on the effects of prenatal alcohol exposure on the academic achievement of children at 6 years of age. In this longitudinal study, women were interviewed at the end of each trimester of pregnancy, at delivery, and at 8, 18, 36, and 72 months postpartum. The women were of lower socioeconomic status, high school-educated, and moderate users of alcohol. The offspring received age-appropriate physical and developmental assessments at each follow-up. Linear regression and nonlinear curve fitting were used to investigate the nature and shape of the relationship between prenatal alcohol exposure and achievement. In addition, the role of child IQ in this relationship was explored. Alcohol exposure during the second trimester predicted deficits in each of the three subtests of the Wide Range Achievement Test-Revised (WRAT-R): reading, spelling, and arithmetic. The relationship was partially reduced by the addition of IQ to the model, but prenatal alcohol exposure still predicted significant deficits in achievement, even after controlling for IQ. Tests for the shape of the relationship demonstrated that the effect of prenatal exposure on the arithmetic subtest of the WRAT-R was a linear or dose-response relationship. By contrast, the relationships between prenatal alcohol exposure and performance on the spelling and reading subtests of the WRAT-R were better modeled as threshold effects. The thresholds for both were approximately 1 drink/day in the second trimester.

Achievement↗
PubMed1988

How do cancer risks predicted from animal bioassays compare with the epidemiologic evidence? The case of ethylene dibromide.

Cancer risks for ethylene dibromide (EDB) were estimated by fitting several linear non-threshold additive models to data from a gavage bioassay. Risks predicted by these models were compared to the observed cancer mortality among a cohort of workers occupationally exposed to the same chemical. Models that accounted for the shortened latency period in the gavaged rats predicted upper bound risks that were within a factor of 3 of the observed cancer deaths. Data from an animal inhalation study of EDB also were compatible with the epidemiologic data. These findings contradict those of Ramsey et al. (1978), who reported that extrapolation from animal data produced highly exaggerated risk estimates for EDB-exposed workers. This paper explores the reasons for these discrepant findings.

Animals↗
PubMed1998

Noninvasive rejection monitoring of cardiac transplants using high resolution intramyocardial electrograms: initial US multicenter experience.

Endomyocardial biopsy (EMB) remains the mainstay for the diagnosis of acute cellular rejection in cardiac transplant patients. A noninvasive alternative that would supplant or reduce the number of EMBs would be a highly desirable and cost-effective tool. To evaluate one potential alternative, a pacemaker with high resolution telemetry capabilities and two fractally coated epimyocardial leads were implanted in 30 patients at five transplant centers during the heart transplant procedure. Ventricular electrograms were recorded during intrinsic and paced activity and digitized to a laptop-based data acquisition device. Electrograms were recorded at frequent intervals and systematically on days when EMBs were performed. The electrogram data were then transferred via the Internet to a central data processing site. Clinical patient management was blinded to the electrogram results and varied considerably among the five centers. Using EMB together with clinical assessment of the transplant revealed 18 cases of clinically significant rejection beyond postoperative day 27 that required antirejection therapy. The normalized parameter values extracted from the electrogram recordings during pacing (the ventricular evoked response) that were associated with significant rejection were statistically lower (86% +/- 16% versus 96% +/- 22%, P < 0.005). The application of a single-threshold diagnosis model to the parameter values allowed detection of significant rejection with a negative predictive value of 98%. This analysis also showed that as many as 55% of the routine surveillance EMBs could have been eliminated had the pacemaker monitoring technique been used as a screening tool prior to EMB. A prospective study should further define the role of this technique in the detection and management of cardiac transplant patients.

Electrocardiography↗
PubMed2001

Energy-independent factors influencing noise-induced hearing loss in the chinchilla model.

The effects on hearing and the sensory cell population of four continuous, non-Gaussian noise exposures each having an A-weighted L(eq)=100 dB SPL were compared to the effects of an energy-equivalent Gaussian noise. The non-Gaussian noise conditions were characterized by the statistical metric, kurtosis (beta), computed on the unfiltered, beta(t), and the filtered, beta(f), time-domain signals. The chinchilla (n=58) was used as the animal model. Hearing thresholds were estimated using auditory-evoked potentials (AEP) recorded from the inferior colliculus and sensory cell populations were obtained from surface preparation histology. Despite equivalent exposure energies, the four non-Gaussian conditions produced considerably greater hearing and sensory cell loss than did the Gaussian condition. The magnitude of this excess trauma produced by the non-Gaussian noise was dependent on the frequency content, but not on the average energy content of the impacts which gave the noise its non-Gaussian character. These results indicate that beta(t) is an appropriate index of the increased hazard of exposure to non-Gaussian noises and that beta(f) may be useful in the prediction of the place-specific additional outer hair cell loss produced by non-Gaussian exposures. The results also suggest that energy-based metrics, while necessary for the prediction of noise-induced hearing loss, are not sufficient.

Animals↗
PubMed1998

Measurements of differential scattering cross section using a ring transducer.

A procedure for the measurement of intrinsic scattering object properties is presented and used to obtain illustrative results. The procedure is based on the measurement of the scattered acoustic field as a function of scattering angle and frequency. Measurements are normalized using analytically determined expressions for emitter and detector beams resulting from a combination of unfocused linear elements arranged in a circular configuration. The spatial effects of finite emitter pulse length and detector gate length are represented by a convolution formula valid for narrow-band transmitted signals and long receiver gates. The normalization includes correction for target absorption as well as measurement of the directly transmitted acoustic power in the free field and yields the average differential scattering cross section per unit volume. Under the Born approximation, this quantity is directly proportional to the spatial-frequency spectrum of the scattering medium inhomogeneities. Measured results are reported for two phantoms consisting of glass microspheres embedded in a weakly absorbing agar background medium. For the phantoms employed, scattering effects, rather than increased absorption, are shown to account for most of the difference in transmission loss between pure agar and agar with glass spheres. The measured differential scattering cross sections are compared with theoretical cross sections for distributions of glass spheres measured experimentally. The measured values show good relative agreement with theory for varying angle, frequency, and phantom properties. The results are interpreted in terms of wave space resolution and the potential for tissue characterization using similar fixed transducer configurations.

Acoustics↗
PubMed1978

Genetics of adolescent idiopathic scoliosis.

A genetic family study was undertaken by photofluorography of the first, second, and third degree relatives of 116 index patients with adolescent idiopathic scoliosis (AIS). The index patients were ascertained in the course of an epidemiological screening. The pattern of familial clusters and the recurrence risk related to the number of affected relatives and to the severity of the disorder in the index patients support the theory of polygenic inheritance, a multifactorial-threshold aetiological model. The recurrence risk table for first degree relative, prepared by computerised data processing and analysis, may contribute to the early diagnosis and prevention of the disorder.

Adolescent↗
PubMed2004

A detection theory account of change detection.

Previous studies have suggested that visual short-term memory (VSTM) has a storage limit of approximately four items. However, the type of high-threshold (HT) model used to derive this estimate is based on a number of assumptions that have been criticized in other experimental paradigms (e.g., visual search). Here we report findings from nine experiments in which VSTM for color, spatial frequency, and orientation was modeled using a signal detection theory (SDT) approach. In Experiments 1-6, two arrays composed of multiple stimulus elements were presented for 100 ms with a 1500 ms ISI. Observers were asked to report in a yes/no fashion whether there was any difference between the first and second arrays, and to rate their confidence in their response on a 1-4 scale. In Experiments 1-3, only one stimulus element difference could occur (T = 1) while set size was varied. In Experiments 4-6, set size was fixed while the number of stimuli that might change was varied (T = 1, 2, 3, and 4). Three general models were tested against the receiver operating characteristics generated by the six experiments. In addition to the HT model, two SDT models were tried: one assuming summation of signals prior to a decision, the other using a max rule. In Experiments 7-9, observers were asked to directly report the relevant feature attribute of a stimulus presented 1500 ms previously, from an array of varying set size. Overall, the results suggest that observers encode stimuli independently and in parallel, and that performance is limited by internal noise, which is a function of set size.

Adolescent↗
PubMed2005

Predictors of use of services among dementia caregivers.

Caregivers of persons with dementia do not use community resources until late in the disease process, despite the fact that judicious use of community resources can delay nursing home admission. Data from the National Caregiver Training Project, based on Hall and Buckwalter's (1987) progressively lowered stress threshold (PLST) model, were used to examine variables related to use of community resources. Spouse and adult child caregivers were divided into two groups based on amount of community resources used per week. Within this geographically diverse sample of caregivers, 64% did not use professional services, 79% did not use respite services, and 65% did not use other services. Being a spouse decreased the odds that the caregiver would use community resources. Resource use was also related to the care recipient's problems with activities of daily living and the increase in frequency of memory and behavioral problems.

Aged↗
PubMed2004

Health risks of low dose ionizing radiation in humans: a review.

Radiobiologists have been struggling to estimate the health risks from low doses of radiation in humans for decades. Health risks involve not only neoplastic diseases but also somatic mutations that may contribute to other illnesses (including birth defects and ocular maladies) and heritable mutations that may increase the risk of diseases in future generations. Low dose radiation-induced cancer in humans depends on several variables, and most of these variables are not possible to correct for in any epidemiologic study. Some of the confounding factors include (i) interaction of radiation with other physical (UV light), chemical, and biological mutagens and carcinogens in a synergistic manner; (ii) variation in repair mechanisms that depend on dose; (iii) variation in sensitivity of bystander cells to subsequent radiation exposure that depends on whether they have been pre- or postirradiated; and (iv) variation in adaptive response that depends on radiation doses and protective substances (antioxidants). In our opinion, both the linear no-threshold-response and the threshold-response models might not be suitable in predicting cancer risk at low radiation doses in a quantitative sense. Low doses of ionizing radiation should not be considered insignificant for risks of somatic and heritable mutations and neoplastic and nonneoplastic diseases in humans.

Child↗
PubMed2003

Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure.

BACKGROUND: Genetic studies of complex disorders such as hypertension often utilize families selected for this outcome, usually with information obtained at a single time point. Since age-at-onset for diagnosed hypertension can vary substantially between individuals, a phenotype based on long-term follow up in unselected families can yield valuable insights into this disorder for the general population. METHODS: Genetic analyses were conducted using 2884 individuals from the largest 330 families of the Framingham Heart Study. A longitudinal phenotype was constructed using the age at an examination when systolic blood pressure (SBP) first exceeds 139 mm Hg. An interval for age-at-onset was created, since the exact time of onset was unknown. Time-fixed (sex, study cohort) and time-varying (body mass index, daily cigarette and alcohol consumption) explanatory variables were included. RESULTS: Segregation analysis for a major gene effect demonstrated that the major gene effect parameter was sensitive to the choice for age-at-onset. Linkage analyses for age-at-onset were conducted using 1537 individuals in 52 families. Evidence for putative genes identified on chromosome 17 in a previous linkage study using a quantitative SBP phenotype for these data was not confirmed. CONCLUSIONS: Interval censoring for age-at-onset should not be ignored. Further research is needed to explain the inconsistent segregation results between the different age-at-onset models (regressive threshold and proportional hazards) as well as the inconsistent linkage results between the longitudinal phenotypes (age-at-onset and quantitative).

Adolescent↗
PubMed1997

Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis.

From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95 % CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%. The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.

Adult↗