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Effect of different doses of inhaled nitric oxide on pulmonary capillary pressure and on longitudinal distribution of pulmonary vascular resistance in ARDS.

Inhaled nitric oxide lowers pulmonary capillary pressure (PCP) in animals and in patients with acute respiratory distress syndrome (ARDS). A dose-response relationship in patients with ARDS has not yet been established. Therefore, we studied the effects of four concentrations of nitric oxide (1, 10, 20 and 40 volumes per million (vpm)) in random order, on PCP in 19 patients with ARDS. PCP was estimated by visual analysis of the pressure decay curve after balloon inflation of the pulmonary artery catheter. Haemodynamic and gas exchange variables were measured at each nitric oxide concentration. Patients were classified as responders when PCP decreased by at least 2 mm Hg after nitric oxide 20 vpm. In responders (n = 8), nitric oxide decreased PCP and post-capillary vascular resistance dose-dependently and changed longitudinal distribution of pulmonary vascular resistance with a maximum effect at 20 vpm. In non-responders (n = 11), PCP did not change. In both groups, the nitric oxide-induced decrease in pre-capillary vascular resistance was small with a maximum effect at 1 vpm. In ARDS, vasodilatation of pre-capillary vessels is achieved at low concentrations of nitric oxide, whereas the effect of nitric oxide on postcapillary vessels is variable. Higher concentrations may be required for optimal post-capillary vasodilatation in a subgroup of ARDS patients.

Adolescent↗

Middle cerebral artery Doppler in severe intrauterine growth restriction.

OBJECTIVE: To examine longitudinal changes in middle cerebral artery blood flow assessed by Doppler in severely growth restricted fetuses. METHODS: Eighteen structurally normal singleton pregnancies complicated by suspected intrauterine growth restriction were monitored by serial measurement of the pulsatility index of the middle cerebral artery over 7 to 72 days. Outcome measures included indication for delivery, umbilical venous pH and admission to and length of stay in neonatal intensive care. RESULTS: Thirteen fetuses demonstrated severe intrauterine growth restriction based on subsequent birth weights being below the 2.5th centile, two had intrauterine growth restriction (birth weights between the 2.5th and 5th centiles), and three had birth weights between the 5th and 50th centiles. The middle cerebral artery pulsatility index showed rapid and sharp changes between examinations in those severely growth restricted fetuses which required delivery before 34 weeks. This pattern was not obvious in severely growth restricted fetuses delivered after 34 weeks, or in those less severely growth restricted, regardless of the gestation at delivery. Changes in middle cerebral artery pulsatility index contributed to the decision to deliver in three cases. The middle cerebral artery pulsatility index demonstrated greater variation in those fetuses with cord pHs of less than 7.25. The length of stay in neonatal intensive care decreased with increasing gestational age and birth weight. CONCLUSIONS: The difference in the pattern of change in middle cerebral artery pulsatility index in intrauterine growth restricted fetuses may be a reflection of maturity in addition to the degree of fetal compromise. The decision to deliver was multifactorial. The middle cerebral artery pulsatility index only influenced the decision to deliver when changes in other parameters were evident.

Amniotic Fluid↗

Hypoadiponectinemia in lean lactating women: Prolactin inhibits adiponectin secretion from human adipocytes.

Adiponectin is an adipocyte-derived hormone involved in glucose, lipid and energy metabolism. A low plasma adiponectin concentration is associated with insulin resistance, obesity and atherosclerosis. In women, energy homeostasis is remarkably changed during gestation and lactation in order to supply sufficient nutrition for a fetus or newborn. In this study we aimed to elucidate the physiological impact of gestation and lactation on the plasma adiponectin levels and the influence of reproduction-related hormones on adiponectin secretion. We studied the longitudinal changes in plasma adiponectin concentration during pregnancy (1st, 2nd and 3rd trimester) and lactation (3 days and 1 month after the delivery) in lean healthy women (n = 22). The plasma adiponectin level declined slightly as the pregnancy advanced and reached its lowest level during lactation (12.25 +/- 0.182 microg/ml at early pregnancy vs. 6.88 +/- 0.375 microg/ml at 3 days postpartum, p < 0.001). In order to investigate the role of the lactogenic hormone prolactin in the decrease of plasma adiponectin levels during lactation, we further performed in vitro experiments using human primary cultured adipocytes. Western blotting of the adipocyte lysate and ELISA of the culture medium revealed that exogenous prolactin inhibited both production and secretion of adiponectin in a dose-dependent manner. Our results thus suggests that prolactin affects the regulation of maternal metabolism through suppression of adiponectin.

Adipocytes↗

The change of periapical exudate prostaglandin E2 levels during root canal treatment.

We have previously demonstrated that detectable levels of prostaglandin E2 exist in periapical exudates (PE-PGE2) from root canals of periapical periodontitis. Our data from a cross-sectional study also suggested the association of PE-PGE2 concentrations with the active phase of periapical lesions. The objective of this study was to investigate the longitudinal changes of PE-PGE2 levels during root canal treatment. Periapical exudate specimens were quantitatively sampled from root canals of 20 nonvital teeth at consecutive treatment visits to measure PGE2 concentrations. The mean PE-PGE2 levels significantly decreased following the endodontic therapy (158.0 +/- 54.1 pg/microliter in the first samples versus 48.4 +/- 37.9 pg/microliter in the second samples). A significant correlation was also found between the changes in PE-PGE2 levels and the clinical disease expression of periapical periodontitis (p < 0.01). Decreased PGE2 production is considered to reflect the remission of disease activity. These results suggest the central roles of PGE2 in regulatory mechanisms for the expression of periapical disease.

Dental Pulp Cavity↗

Longitudinal studies of inhibin B levels in boys and young adults with Klinefelter syndrome.

The aim of the study was to investigate the longitudinal changes of inhibin B in a group of patients with Klinefelter syndrome (KS; karyotype 47,XXY) progressing through puberty and to compare them to a group of age- and puberty-matched controls. Seven boys with nonmosaic KS (karyotype 47,XXY) and 11 controls were followed with longitudinal serum inhibin B measurements every 3-12 months as they approached and entered puberty. None of the boys had significant bone age delay, and all entered puberty at the normal time and progressed through it at the expected time. In addition, 15 young adults with KS, aged 16.7-29.5 yr, were studied. We found normal levels of inhibin B in prepubertal boys with KS and controls. In patients with KS as well as controls, inhibin B increased progressively before clinical pubertal onset. However, during late puberty inhibin B levels decreased gradually to the low/unmeasurable levels observed later in adult KS, while remaining unchanged in the controls.

Adolescent↗

New experiments on shear modulus of elasticity of arteries.

Although the mechanical properties of blood vessels have been studied extensively, the shear modulus of the blood vessel wall is still unknown. New data on the shear modulus of elasticity of rat arteries and its variation with axial stretch and blood pressure are presented. The data were obtained from a new instrument designed and constructed by us to perform simultaneous torsion, inflation, and longitudinal stretching tests. It was found under physiological conditions (pressure = 120 mmHg or 16 kPa; longitudinal stretch = 1.2 relative to zero-stress state), the shear modulus of normal rat thoracic aorta is G = 137 +/- 18 kPa. The difference of shear modulus at body temperature (37 degrees C) and room temperature (25 degrees C) is within 10%. The shear modulus varies significantly with changing longitudinal and circumferential strains in proportion to the strain energy due to these strains. A constitutive equation based on a pseudo strain energy function is proposed. The vessel wall is not transversely isotropic in the incremental sense. When the rat was subjected to high blood pressure due to constriction of its aorta, the shear modulus does not vary significantly with the length of time the animal was subjected to hypertension.

Animals↗

A third generation approach to detect erythropoietin abuse in athletes.

BACKGROUND AND OBJECTIVES: Information derived from blood analyses can assist in the detection and/or deterrence of blood doping in sport. We investigated whether comparing an athlete's hematologic values against his or her own historical baseline rather than population-derived thresholds enhanced the ability to detect blood doping. DESIGN AND METHODS: We developed an approach whereby an athlete's true baseline value could be estimated with just one prior blood test. We also estimated a universal value for within-subject variability for key hematologic parameters using the highest value obtained among four separate cohorts of male athletes including 80 elite rowers, 124 endurance-trained or team-sport subjects, 288 professional football players and 630 athletes competing at national or international level. The (individual) baseline and (universal) variability were then incorporated so as to define expected thresholds for subsequent blood tests. The sensitivity of our approach was obtained by analyzing data from 49 recreational athletes administered either recombinant human erythropoietin (n=37) or placebo (n=12). RESULTS: We found that removing within-subject variability by comparing new results against an historical baseline heightened the capacity to detect blood doping. It was possible to delineate the longitudinal changes in either hemoglobin (Hb) or the OFF-hr model score (an algorithm using both Hb and percent reticulocytes) caused by recombinant human erythropoietin treatment from the natural biological fluctuations found in subjects treated with placebo. INTERPRETATION AND CONCLUSIONS: Our objective data supported the intuitive belief that longitudinal monitoring of athletes' blood profiles will help detect blood doping. This information could be used to instigate target-testing of suspicious athletes, or even warrant the exclusion from competition of athletes with aberrant variations in key hematologic values.

Cohort Studies↗

Genetic analysis of drinking behavior in World War II veteran twins.

The objective of the present study was to investigate longitudinal changes in drinking behaviors of adult male twins and model these changes as a function of genetic and environmental influences. Alcohol data available for World War II veteran twins, first surveyed in 1967-69 and followed up during 1983-85, were used to examine components of variability in measures of alcohol consumption. Multivariate biometric analysis of these data indicated 1) longitudinal stability of drinking behaviors in this cohort, 2) a significant contribution of genetic factors to the observed stability that accounted for more than 80% of the stable variation in frequency and in quantity of alcohol consumed per drinking occasion, and 3) evidence for a significant contribution of shared environmental influences to drinking of specific beverages (e.g., wine). The implications of these results for issues of health in the elderly are considered.

Aging↗

Dietary change in an intervention trial of wheat bran fiber and colorectal adenoma recurrence.

PURPOSE: The objectives of this study were to determine whether participants in the Wheat Bran Fiber (WBF) trial exhibited changes in diet over time, and whether these changes were differential by assigned treatment group. METHODS: The WBF trial was a randomized trial with participants assigned to one of two groups: a low-fiber (2.0 g/d) or high-fiber (13.5 g/d) wheat bran fiber cereal supplement. A total of 685 participants from both treatment groups completed the Arizona Food Frequency Questionnaire (AFFQ) at baseline, year one, and year three of the trial. Means were calculated for nutrient intake, change in nutrient intake, number of food group servings, and change in number of food group servings. RESULTS: For both treatment groups combined, significant increases were observed for most micronutrients and vitamins at years one and three, while fat intake significantly decreased. Participants from both groups significantly increased their consumption of cereals, breads, and crackers, but decreased the number of servings from the meat, poultry, and egg group, the fats group, and the salty snacks group. The only differential changes in intake between the treatment groups were for sugar and iron, which increased to a lesser extent among those assigned to the high-fiber treatment as compared with the low-fiber group. CONCLUSIONS: Although differential dietary intake was not appreciable in the WBF trial, participants exhibited longitudinal changes. Future intervention studies should carefully monitor dietary changes during the trial with multiple dietary assessment tools to assess potential secular and treatment-related diet changes.

Adenoma↗

Relationship of menopause to skeletal and muscle mass.

Cross-sectional and longitudinal changes in body composition with age were examined in white women to determine the relationship of body cell mass to menopause and of body fat to bone mass. There was statistical evidence for a curvilinear component to loss of total body potassium with negligible rates of loss before menopause. Longitudinal measurements also indicated a relationship between the proximity to menopause and the rate of loss of potassium. Total body potassium was significantly related to total body calcium and bone density of the spine, radius, and femoral neck. Total body fat was not related to any of these measurements. We found no evidence that adiposity plays a major role in protecting against bone loss.

Adipose Tissue↗

The distribution of structural neuropathology in pre-clinical Huntington's disease.

Putative neuroprotective agents in Huntington's disease may have particular application before brain pathology becomes manifest clinically. If these agents were to be tested in clinical trials, a reliable marker of the burden and rate of progression of pathological change in the pre-clinical group would be needed. The present study investigates whether the Huntington's disease genotype is associated with regional differences in brain structure, particularly differences that could not be predicted from clinical or neuropsychological assessment. A secondary aim is to seek indirect evidence of pathological progression in the form of changes in local tissue volume with age, specific to the Huntington's disease genotype. Formal motor examination, neuropsychological assessment, and T(1)-weighted cerebral MRI were performed in 34 subjects who had undergone predictive genetic testing for Huntington's disease. Clinical and cognitive testing were performed blinded to gene status. A linear discriminant analysis revealed the combination of test scores (the 'optimal clinical score') which best differentiated 18 subjects carrying the Huntington's disease gene mutation (the 'gene-positive' group). Voxel-based morphometry (VBM) was used to identify regions of significant main effect of Huntington's disease gene status on grey and white matter volume and regions of significant interaction of gene status with age. In the gene-positive group, there was significant reduction in grey matter volume in the left striatum, bilateral insula, dorsal midbrain and bilateral intra-parietal sulcus relative to 'gene-negative' controls. There was a significant reduction of periventricular white matter volume with age bilaterally in the gene-positive relative to the gene-negative group. Changes remained significant when controlled for differences in optimal clinical score between subjects. This study provides evidence of distributed grey matter pathology and progressive white matter atrophy with age before clinical onset of Huntington's disease. This suggests that VBM may be useful in monitoring cross-sectional and longitudinal changes in brain structure in pre-clinical Huntington's disease and for determining the efficacy of neuroprotective agents.

Adult↗

Pressure and flow changes in the pulmonary circulation in exercising sheep: evidence for elevated microvascular pressure.

The purpose of this study was to measure hemodynamic and transvascular filtration changes in the lung during strenuous exercise in sheep. The specific goals were (1) to determine the nature of the reduction in pulmonary arterial pressure (Ppa) after its initial peak rise with onset of exercise; (2) to use a pulmonary artery catheter distal wedge technique ("microwedge") to better assess longitudinal changes in resistance in the pulmonary circulation with exercise; and (3) to compare lung lymph flow and protein concentration changes at comparable estimated microvascular pressure (Pmv) (mean Ppa - mean left atrial pressure) (Pla) x 0.4 + mean Pla) during exercise versus passive left atrial hypertension to determine whether exercise causes a higher than expected lymph flow. We found that cardiac output rises quickly and thereafter remains constant with constant-rate exercise, and, thus, the secondary reduction in Ppa was due to vasodilation and/or recruitment. The microwedge pressure rose more than did Pla, suggesting that actual Pmv was probably higher than that estimated. With hypoxia, most of the change in pulmonary vascular resistance was in upstream vessels (arteries and capillaries), as was most of the exercise-induced vasodilation. Lymph flow rose more quickly and was much higher during brief exercise than during left atrial hypertension at a comparable calculated Pmv, and lymph protein content decreased more quickly. The data point to a Pmv with strenuous exercise that is higher than expected.

Animals↗

Community integration in spinal cord injury of long duration.

OBJECTIVE: to examine longitudinal changes in community reintegration among people aging with spinal cord injury, and to determine if these changes are related to demographic variables and scores on psychosocial measures of stress, life satisfaction, depression, psychological well-being, and perceived quality of life. DESIGN: 178 members of a British population-based study of outcomes after spinal cord injury were evaluated at three-year intervals from 1990 to 1999. Participants responded to a questionnaire that included measures of community integration and perceived psychosocial status. Scores and results were analyzed to identify changes over time in community reintegration. RESULTS: The findings indicate a general decline in community reintegration over time in terms of physical independence, mobility, occupation and social integration. However, economic self-sufficiency appears to steadily improve as time passes. Life satisfaction also declined over time and was related to community reintegration. Measures of emotional distress were not important predictors of community reintegration. CONCLUSIONS: Community reintegration declined over time in this sample of British individuals aging with SCI. Although there were concurrent relationships between demographic variables of age and neurologic group, neither these factors nor duration of injury appeared to impact change in community reintegration. More significant was the relationship between perceived life satisfaction and community integration.

Adaptation, Psychological↗

PSA velocity for the diagnosis of early prostate cancer. A new concept.

An evaluation of longitudinal changes in PSA in men with and without prostate disease revealed that with age, the development of prostate disease is the most important factor influencing changes in PSA. Furthermore, the PSA changes with age are significantly different in men with and without prostate disease. The PSA velocity is greater in men with prostate cancer than in men with BPH and greater in men with prostate cancer and BPH than in men without any prostate disease. Thus, evaluation of PSA changes may help distinguish between men with prostate cancer and those without the disease. This idea will need to be confirmed prospectively. Finally, estimation of PSA doubling time from changes in PSA suggests that changes reflect prostatic growth. Therefore, PSA velocity could be of benefit in identifying men with prostate cancer that is destined to progress.

Adult↗

Precision in assessment of osteoporosis from spine radiographs.

Inter- and intra-observer variation in spine radiographs of 100 osteoporotic women and longitudinal change in roentgenologic status after 1 year of antiosteoporotic treatment were assessed. The method applied was naked eye inspection, and a score system estimating severity of fractures - vertebral deformation score (VDS). Agreement was assessed by the Kappa coefficient corrected for agreement by change. The results showed a satisfactory inter- and intraobserver agreement for wedge (Kappa = 0.72 and 0.90) and compression fractures (Kappa = 0.60 and 0.92). The method proved less reliable for endplate fractures (Kappa = 0.39 and 0.73). We think that the method of investigation is well suited for monitoring treatment effects in longitudinal studies.

Aged↗

Relationship of severity of dementia to caregiving stressors.

In studies of individual differences and longitudinal changes in stress and coping among dementia caregivers, assessing severity of patient impairment is critically important. It is proposed that with the progression of dementia, cognitive impairment may steadily increase, but other stressful behavioral symptoms peak at various stages of dementia. Cross-sectional data from 49 caregiving families and longitudinal follow-up data from 48 families suggest that instrumental self-care deficits begin early in dementia, and basic self-care deficits increase with dementia severity, but that many distressing behavioral symptoms decrease in late dementia. Assessments of dementia patient severity should be multidimensional, and increases and decreases in various dementia patient stressors over time should be considered as factors influencing caregiver coping.

Activities of Daily Living↗

Periodontal changes by HIV serostatus in a cohort of homosexual and bisexual men.

UNLABELLED: These data represent 20 months of follow-up on 114 homo/bisexual men. Periodontal changes were analyzed in relation to HIV-1 serostatus, immune status, age and plaque. Gingival index (GI), plaque index (PI), and relative attachment levels recorded by the computerized Florida disk probe were performed every 4 months. A threshold of > or = 3.0 mm of relative attachment loss (RAL) was selected as a significant longitudinal change. RAL > or = 3 mm occurred 6.16 times (95% CI = 1.95, 19.40) more frequently among subjects with T4 counts < 200 compared to subjects with counts of 200 or more. Among older subjects (age > or = 35 years), the incidence (33%) of RAL > or = 3 mm was significantly higher (p = 0.004) in more immunosuppressed subjects (T4 < 200) compared to the incidence (5%) in less immunosuppressed subjects (T4 > or = 200); this association was not significant in younger subjects less than 35 years old (p = 0.55). In 78 subjects present at all follow-up visits, averaged GI increased and were significantly higher in the seropositive subjects compared to seronegative subjects, but, GI was not related to T4 cell counts within the seropositive group. Separate linear regression of GI by PI by HIV serostatus revealed a significantly higher slope in the seropositive group compared to the seronegative group (p = 0.04), suggesting greater sensitivity to plaque in the seropositive group. CONCLUSION: immunosuppression, especially in combination with older age, may be a risk factor for attachment loss, and HIV seropositivity, independent of T4 cell counts, may be a risk factor for gingival inflammation.

Adult↗

Changes in functional competency in the oldest old. A longitudinal study.

Changes in everyday functioning and cognitive abilities are studied longitudinally in a representative sample of the oldest old. Respondents were selected by using census records from all people aged 84, 86, 88, and 90 years old living in an area of South Central Sweden, and then were assessed at 2-year intervals. The findings show high base rates for disabilities and high incidence of cognitive and functional deficits among survivors. Mortality is associated with higher rates of disability at the previous time of assessment. Because of this increased mortality rate among disabled individuals, prevalence does not rise as much as would be expected from the high incidence. Instead, new cases of disabled are partly replacing disabled individuals who died since the previous evaluation.

Activities of Daily Living↗