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Urinary kallikrein: assay validation and physiological variability.

Decreased urinary kallikrein (UK) output has been suggested as a preclinical indicator of essential hypertension. In preparation for UK studies in hypertension prone Utah kindreds, we assessed selected UK assay parameters and physiological variability. Precision for the colorimetric kallikrein assay was quite acceptable, coefficient of variation (CV) less than 5% within run and 14% day-to-day at a concentration of 9.5 TU/l. The mean recovery was 105% and assay results were correlated with results from the 3H-TAME esterase method, r = 0.990. Urine specimens were stable at room temperature for up to 4 days, frozen at -20 degrees C for 6 weeks, or frozen at -80 degrees C after Sephadex treatment for a year. UK output varied significantly throughout the day with excretion highest in the morning. Urine collections at 10.00, 12.00 and 14.00 had significantly (p less than 0.05) more UK than the overnight collection. Intra- and inter-individual variations were of the same magnitude, mean 20%. In children UK output increased with age until the adult levels were reached at age 15. Male and female values were similar. Smoking; consumption of alcohol, coffee, tea, cola of chocolate; and female hormone medications did not significantly influence the 12-hour UK output in the 1110 caucasian subjects.

Adolescent↗

Short term variation of human immunoglobulin levels with an estimation of the day to day physiological variability.

In this work serum Ig levels were determined daily for 14 days in 12 subjects, every two days for 14 days in 19 subjects, every week for 1 month in 11 subjects and fortnightly in 11 subjects for 6 months. The serum IgG, IgM and IgA levels were quantitated by the linear plate method. The day-to-day reproducibility of the technique was checked for a period of one months on seven different samples. The mean coefficient of variation in the reproducibility experiments was found to be 4.8% for IgG, 8.2% for IgM and 5.2% for IgA. Since the observed variation in all groups of subjects was found to be higher than the methodological variation, it appears that physiological variability occurs in the serum Ig levels of an individual. No difference was found between the physiological variances of IgG, IgM and IgA observed in the group with daily analysis and those with determinations every two days. The physiological variations increase when longer periods are considered between consecutive determinations, but the variability of IgG and IgA in the group with fortnightly determinations is less important than that observed in the group with weekly analyses. Some evidence is presented indicating a periodic fluctuation of serum IgG and IgA levels with an amplitude of nearly 20% and with a recurrence rate of two weeks.

Adolescent↗

Normal plasma free amino acid values in adults: the influence of some common physiological variables.

We measured plasma free amino acids in ten healthy adults (five males, five females, ages 26 to 54 years), at four times of day, under two dietary protocols. The design allowed us to measure the effects of some common physiological variables on the metrical distributions (mean, SD, skewness, kurtosis) of 80 values (in most cases), for each of 20 amino acids. Analysis of variance indicates that individuals in a "public" population possess "private" phenotypes for 18 plasma amino acids under typical external experiences; the exceptions were aspartate and taurine. The collective infradiem variation rarely exceeded 50% of the nadir value for any amino acid. We conclude that genotype is an important determinant of plasma amino acid phenotype in normal persons, and that there is striking homeostasis of plasma amino acid values in human adults adapted to normal daily activity.

Adult↗

The VITA Project: population-based distributions of protein C, antithrombin III, heparin-cofactor II and plasminogen--relationship with physiological variables and establishment of reference ranges.

A proper laboratory diagnosis of inherited thrombophilia due to defects of the coagulation system may be obtained only by a stringent definition of the diagnostic reference ranges taking into account the influence exerted by major physiological variables. To this purpose, we analyzed the data for Protein C, Antithrombin III, Heparin-Cofactor II and plasminogen coming from the first 4,000 subjects enrolled in the VITA Project. This is the first study that allows the establishment of reference ranges in a non-selected, active population using stringent standardization of clinical and laboratory measurements and multivariable regression techniques for data analysis. Serum triglycerides and total cholesterol, together with plasma fibrinogen were found to influence the functional plasma level of the four considered proteins. Menopause increased AT-III concentration, while pill use increased Heparin-Cofactor II and plasminogen. PT and PTT ratio, gender, age, smoking, body-mass index, HDL cholesterol and blood group had minor effects. The effect of these variables should be taken into account for both clinical and epidemiologic purposes, using appropriate reference ranges or covariance analysis for adjustment.

Adolescent↗

Use of physiologic variables to predict milk yield after clinical mastitis in dairy cattle.

OBJECTIVE: To determine the association between intramammary infections caused by various bacteria and hepatic damage, as measured by serum sorbitol dehydrogenase (SDH) activity, WBC counts, and PCV and the association of clinical variables with milk production after a case of clinical mastitis. DESIGN: Prospective, cohort study. ANIMALS: 82 cows with clinical mastitis. PROCEDURE: Information on milk production, mastitis status, and selected physiologic variables was collected during a 1-year period. Milk samples for bacteriologic evaluation were collected on day 1 of an episode of clinical mastitis. Physical examination was performed and blood samples for laboratory evaluation were collected on days 1, 5, and 9. Primary outcome was mature equivalent 305-day (ME305) milk production. Correlations were assessed using a multiple regression model. RESULTS: Higher WBC counts were associated with higher ME305 values. For cows with coliform mastitis, increases in SDH values were associated with higher ME305 values. For cows with coliform and streptococci/staphylococci mastitis, PCV was associated with ME305 values. Higher PCV values were associated with lower ME305 values for streptococci/ staphylococci and coliform infections. CLINICAL IMPLICATIONS: The association between milk production and WBC count indicated that cows mobilizing WBC were better able to neutralize mammary gland infections, which may result in better milk production. The association between milk production and PCV suggested that maintaining hydration in cows with clinical mastitis may be a critical aspect of treating all cows with mastitis.

Animals↗

Prospectively validated prediction of physiologic variables and organ failure in septic patients: The Systemic Mediator Associated Response Test (SMART).

OBJECTIVE: Conventional outcomes research provides only percentage risk of such end points as mortality rate, utilization of resources, and/or broad groupings of multiple organ system dysfunction. These prognostications generally are not applicable to individual patients. The purpose of the present study was to determine whether the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic variables, standard hospital laboratory tests, and circulating cytokine concentrations that predicted continuous and dichotomous dependent clinical variables, in advance, in individual patients with severe sepsis and septic shock, and whether these independent variables could be integrated into prospectively validated predictive models. DESIGN: Data review and multivariate stepwise logistic regression. SETTING: University research laboratory. PATIENTS: Three hundred three patients with severe sepsis or septic shock who comprised the placebo arm of a multiple-institution clinical trial, who were randomly separated into a model building training cohort (n = 200) and a predictive cohort (n = 103). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From baseline data and baseline plus serial input, including patient demographics, hospital laboratory tests, and plasma concentrations of interleukin-6, interleukin-8, and granulocyte colony stimulating factor, multiple regression models were developed that predicted clinically important continuous dependent variables quantitatively, in individual patients. Multivariate stepwise logistic regression was used to develop models that prognosticated dichotomous dependent end points. Data from individual patients in the predictive cohort were inserted into each predictive model for each day, with prospective validation accomplished by simple linear regression of individual predicted vs. observed values for continuous dependent variables, and by establishing the receiver operator characteristics area under the curve for logistic regression models that predicted dichotomous end points. Of SMART models for continuous dependent variables, 100 of 143 (70%) were validated at r values >.7 through day 3, and 184 of 259 (71%) above r =.5 through day 5. SMART predictions of dichotomous end points achieved receiver operator characteristics areas under the curve >.7 for up to 84% of the equations in the first week. Many SMART models for both continuous and dichotomous dependent variables were validated at clinically useful levels of accuracy as far as 28 days after baseline. CONCLUSIONS: SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with severe sepsis and septic shock.

Clinical Laboratory Techniques↗

Physiologic variability during transition to extrauterine life.

The first 24 hours of life can be the most precarious in a person's lifespan. Physical changes occur so quickly during the transformation from fetus to neonate that any deviations from the expected need to be identified and acted on immediately to assist the baby toward successful adaptation to extrauterine life. Newborns respond to physiologic stress by becoming less responsive, often giving few cues that a problem is arising. Transition and physiologic stability have traditionally been measured in the time domain. However, heart beat or respiratory rate per minute are gross measures that do not reliably alert the health care provider to subtle signs of stress. Physiologic variability is mainly due to the interaction of the sympathetic and parasympathetic nervous systems. Patterns in the variability may be used as indexing variables for the assessment of neurophysiologic status. Linear and non-linear analysis of the variability promises to provide a sensitive, noninvasive measure for the identification of neurophysiologic stress that can better inform the health care provider of the fetal and neonatal response to stress.

Adaptation, Physiological↗

Physiologic variables affecting thromboxane B2 production in human whole blood.

Thrombin-induced thromboxane (TX) A2 production in whole blood, as reflected by serum TXB2 measurements, has proven to be a simple and reproducible capacity-related index of platelet TXA2 production ex vivo. In the present study we have determined the influence of a number of physiologic variables on serum TXB2 measurements performed by radioimmunoassay in a group of 177 subjects undergoing evaluation for atherosclerosis risk factors. Serum TXB2 averaged 300 +/- 108 ng/ml in the whole group, with a normal distribution. No statistically significant correlation was found between serum TXB2 and the continuous variables examined (age, BMI, blood pressure, cigarettes, serum cholesterol, triglyceride, glucose and wine consumption) except for the number of platelets. Platelet TXB2 production did not differ between men and women (296 +/- 119 vs 302 +/- 100 ng/ml). We conclude that, within the limits of the examined variables, serum TXB2 is an easily measurable and highly reproducible capacity index primarily related to platelet cyclooxygenase and TX-synthase activity, which can be used for monitoring drug- or disease-induced changes of these enzyme activities.

Adolescent↗

Physiological variables and mortality in patients with various categories of chronic respiratory disease.

As an introduction to a prospective study on the complex non-invasive estimation of pulmonary arterial pressure, the mortality experience of 834 patients with chronic respiratory disease was analysed historically. In patients with chronic obstructive lung disease, chronic fibrosing alveolitis and pulmonary tuberculosis, the relationships between mortality and values of ten physiological variables were examined. The most important variable as regards mortality in chronic obstructive lung disease was FEV1.0; after controlling for FEV1.0, pulmonary arterial pressure, arterial oxygen and carbon dioxide pressures were all strongly related to mortality. By contrast, in fibrosing alveolitis, values of FEV1.0 had little relation to mortality, and pulmonary arterial pressure was the most important variable, followed by FVC and FEV/VC. In patients with tuberculosis, arterial oxygen and pulmonary arterial pressure had the strongest relationship with mortality. Pulmonary arterial pressure was therefore strongly related to mortality in all three conditions; FEV1.0 had its highest predictive power in chronic obstructive lung disease and arterial oxygen saturation in tuberculosis. In chronic obstructive lung disease, pulmonary arterial pressure had a stronger influence in relation to mortality of younger than of older patients.

Blood Pressure↗

Further evaluation of the basic nature of the human biological aging process based on a factor analysis of age-related physiological variables.

This study aimed to reexamine whether there exists a primary aging process that controls the rate of aging in a number of different functions. Eighty-six adult males who successively received a 2-day routine health checkup test for 7 years from 1992 to 1998 at the Kyoto Red Cross Hospital were selected as subjects. Nine candidate biomarkers of aging were selected from the 25 physiological variables based on the investigation of age-related changes. A principal factor analysis was applied to the partial correlation matrix for 9 selected biomarkers calculated by controlling for age. Furthermore, a confirmatory factor analysis in testing first- and second-order factor models was applied to the covariance matrix for 9 biomarkers. The results of these factor analyses revealed that there existed one general factor and three system-specific factors. Therefore, biological age changes can be viewed as a time-dependent complex integration of the primary and secondary aging processes.

Adult↗

Physiological variability arising from in vitro propagation of Nothofagus obliqua.

As with cuttings, the microcuttings produced from in vitro generated shoots could be affected by topophysis. Very little research has been done about such in vitro effect. This paper reports the influence of the topophysis on the regeneration response (shoot multiplication, microcutting rooting and plantlet acclimation) of explants on the in vitro culture of juvenile N. obliqua trees. The results showed that the main responsible of the physiological variability arising from all the in vitro propagation stages is topophysis. This influence was found in the first culture and can be extended to the next subculture (multiplication stage). Growth of the obtained plants was also affected (rooting of microcuttings and plantlet acclimation). The multiplication rate was lower in apical portion (1:3.66) than basal portion (1:5.8) while rooting was 48.6% and 27.0% respectively. By the way, length of acclimated explants was 52.4 mm in the apical rooted explants and 28.7 mm in the basal ones at the 30th day. In order to reduce such variability, it is necessary to take into account the initial position of the explants during the establishment and multiplication stages of micropropagation of forest trees.

Culture Techniques↗

Patterns of menopause: a study of certain medical and physiological variables among Caucasian and Japanese women living in Hawaii.

Comparisons were made between menopausal women and nonmenopausal controls among Caucasians and Japanese living in Honolulu, to investigate the extent of physical changes and clinical symptoms associated with menopause. The analysis was conducted using the multiphasic screening records of 170 menopausal cases and 162 nonmenopausal controls in Caucasians, and of 159 menopausal women and 187 nonmenopausal controls in Japanese. Discriminant function analysis was employed with relevant anthropometric, medical, and physiological variables. After adjusting for the linear and non-linear effects of age, only surgery and medication were retained as significant discriminant variables. Discriminant functions for Caucasian and Japanese groups were not found to be significantly heterogeneous. With regard to the discrimination of the menopausal and nonmenopausal groups, the data suggested that, while no clinical conditions other than those attributable to the effects of aging were significantly associated with the menopausal state, medication and surgical procedures for female disorders were significantly related to menopause.

Adult↗

Physiological variables at lactate threshold under-represent cycling time-trial intensity.

BACKGROUND: The importance of lactate threshold (LT) as a determinant of performance in endurance sports has been established. In addition, it has been shown that during running and selected other endurance competitions, athletes perform at a velocity and VO2 slightly above LT for the duration of the event. Prior work indicates however, that this may not be true during a cycling time-trial (TT). This investigation sought to compare physiological variables during a 20-k TT with those corresponding to the athlete's LT. METHODS: Thirteen male cyclists (22.7+/-0.8 yrs; 180.6+/-8.0 cm; 77.1+/-10.0 kg; 8.3+/-2.5% fat; 4.9+/-2.2 l x min(-1), VO2max) participated in the study. Subjects performed a graded protocol starting at 150 Watts (W) to determine LT (2 mmol x L(-1) above baseline) which consisted of 20 W increases every 4-min. Following an 8 min-recovery, subjects cycled at the wattage corresponding to LT-20 W for 1 min and then workload increased 20 W every minute until volitional exhaustion to determine VO2max x On a separate occasion a self-paced, 20-k TT was completed. RESULTS: Mean values of blood lactate, HR and % HRmax, VO2 and % VO2max, and power output throughout the 20-k TT were greater (p<0.01) than those at LT. During the TT these cyclists performed at an intensity well above LT (blood lactate=252.0+/-0.1%, HR=9.4+/-0.03%, %HRmax=9.2+/-0.15%, VO2=26.5+/-0.7%, %VO2max=17.2+/-0.08% and power out-put=14.8+/-0.14% above LT) for over 30 min. CONCLUSIONS: Therefore, while LT may be highly correlated to performance, it may not be representative of race pace for a cycling TT, and may be questionable as a benchmark used to prescribe training intensity for competitive TT-cycling.

Adult↗

[Reactions of dairy calves exposed to transport stress at 60 days of age. Effects of various rearing conditions in the developmental quality of calves on physiological variables and their changes].

Dairy calves reared in groups of constant (Gk, N = 16, m 8, w 8) and changing composition (Gw, N = 16, m 8, w 8) and single box reared calves (E, N = 15, m 8, w 7) were exposed to transport stress lasting around 60 minutes at 60 days of age. Long term measurements of heart rate (HF) were combined with blood sampling (V. jugularis) before and immediately after transport and at the following day as well. Mean differences of HF, Hb, Hk, lactate and blood urea between groups were found at all sampling points. After transport mean values of HF, MetHb, pO2, O2SAT and O2CONT were increased in all calves and such of HHb were decreased. Measures of acid-base balance and lactate changed differently in calves of the three rearing groups concerning direction and degree. Changing of the variables after transport comparing the starting values was different between rearing groups in 16 out of 25 possible cases. Changing of variables immediately after transport showed strong negative correlations with starting values in case of pH, HCO3, base excess, COHb, total protein, albumin, lactate, glucose and Ca in all groups, in all other cases not in all groups. Strong correlations between sampling points of Hb, Hk, MCHC, O2CONT, O2CAP, creatinine, blood urea and of the minerals indicate a high individual specificity of these measures. Results proof variation components of physiological variables in calves caused by husbandry conditions and their effects on reactions of animals in case of transport stress.

Animal Husbandry↗

Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin.

Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under strong genetic influence. To ascertain whether variability in circulating osteocalcin levels may reflect allelic variation in the vitamin D receptor gene, we have analyzed the relationship between frequent restriction fragment length polymorphisms (RFLPs, detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91 Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating osteocalcin levels (P less than 0.0001) independent of age or menopause effects. Since the osteocalcin gene and the vitamin D receptor gene are encoded on different chromosomes, the interaction between these two genes occurs in trans. Thus, common alleles of this trans-acting factor, the vitamin D receptor, are functionally different and contribute to "normal" physiological variability in osteocalcin levels. Preliminary analysis in monozygotic and dizygotic twin pairs indicates that the greater diversity in lumbar spine density between the dizygotic pairs can be explained by divergence in vitamin D receptor alleles. Variations in this receptor and other transacting factor genes may confound physiological studies of regulation of target genes and will need to be considered in future human and animal studies. This approach to genetic analysis provides a paradigm for the study of functional variation in trans-acting factors and the role such variation may play in the generation and evolution of physiological diversity.

Alleles↗

Relationships between physiological variables and race performance in French standardbred trotters.

The relationships between V4 (the velocity for a blood lactate concentration of 4 mmol/litre) and V200 (the velocity for a heart rate of 200 bpm) and the performance indices of 223 healthy French trotters were analysed. They were divided into four age groups of three, four, five and six years and over, and into three performance groups (good, intermediate and poor performers) defined by the index of trot (ITR), an annual index of performance calculated by the national stud. V4 and V200 were assessed during the performance of a three-step standardised field exercise test, and four performance indexes (ITR, earnings, best time and the number of starts) were calculated for each group. An analysis of variance showed that V4 and V200 were highly correlated with the horses' age and level of performance (P<0.05). The correlation between the physiological variables and ITR was better for the three- and four-year-old horses than for the older horses.

Age Factors↗

Evolution of physiological variables in patients with chronic obstructive pulmonary disease before and during long-term oxygen therapy.

In 24 patients with severe chronic obstructive pulmonary disease (COPD), we investigated the evolution of pulmonary volumes, arterial blood gases (ABG) and mean pulmonary artery pressure (PAP), before (T0-T1) and during (T1-T2) long-term oxygen therapy (LTO). LTO was initiated at T1 on usual criteria (PaO2 persistently less than or equal to 55 mm Hg) and was given during greater than or equal to 16 h/day. The T0-T1 period ranged from 12 to 186 months (mean 53 +/- 41 months) and the T1-T2 period from 12 to 120 months (mean 44 +/- 30 months). There was a significant worsening of the obstructive pattern (FEV1 decreasing from 1,084 +/- 326 to 879 +/- 318 ml, p less than 0.005) and of ABG (PaO2 decreasing from 58.2 +/- 9.2 to 51.6 +/- 6.5 mm Hg, p less than 0.01) before the onset of LTO, whereas there was a rather good stability of ABG during LTO and the changes in pulmonary volumes were modest and statistically nonsignificant (FEV1 decreased from 879 +/- 318 to 809 +/- 247 ml). PAP tended to increase from T0 to T1 and to decrease from T1 to T2, but these changes only reached the level of statistical significance when they were expressed as changes per year (+1.0 +/- 2.7 vs. -1.3 +/- 4.5 mm Hg, p less than 0.05). The evolution of physiological variables was nearly identical in subgroups of patients who had died (n = 13) or were still alive (n = 11) at the time of data collection (T3) and this held particularly true for PAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

A method for quantitative analysis of spatially variable physiological processes across leaf surfaces.

Many physiological processes are spatially variable across leaf surfaces. While maps of photosynthesis, stomatal conductance, gene expression, water transport, and the production of reactive oxygen species (ROS) for individual leaves are readily obtained, analytical methods for quantifying spatial heterogeneity and combining information gathered from the same leaf but with different instruments are not widely used. We present a novel application of tools from the field of geographical imaging to the multivariate analysis of physiological images. Procedures for registration and resampling, cluster analysis, and classification provide a general framework for the analysis of spatially resolved physiological data. Two experiments were conducted to illustrate the utility of this approach. Quantitative analysis of images of chlorophyll fluorescence and the production of ROS following simultaneous exposure of soybean leaves to atmospheric O3 and soybean mosaic virus revealed that areas of the leaf where the operating quantum efficiency of PSII was depressed also experienced an accumulation of ROS. This correlation suggests a causal relationship between oxidative stress and inhibition of photosynthesis. Overlaying maps of leaf surface temperature and chlorophyll fluorescence following a photoinhibition treatment indicated that areas with low operating quantum efficiency of PSII also experienced reduced stomatal conductance (high temperature). While each of these experiments explored the covariance of two processes by overlaying independent images gathered with different instruments, the same procedures can be used to analyze the covariance of information from multiple images. The application of tools from geographic image analysis to physiological processes occurring over small spatial scales will help reveal the mechanisms generating spatial variation across leaves.

Algorithms↗