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Value of clinical, functional, and oximetric data for the prediction of obstructive sleep apnea in obese patients.

OBJECTIVE: To evaluate the diagnostic value of clinical features, pulmonary function testing, blood gas tensions, and oximetric data for case finding of obstructive sleep apnea (OSA) before polysomnography (PSG) in a series of consecutive overweight patients. METHODS: We studied a population of 102 consecutive patients referred by an obesity clinic for suspected OSA, in whom body mass index was > or = 25 kg/m(2). The following tests were performed: clinical score (CS), pulmonary function tests (PFTs), measurement of arterial blood gas tensions, nocturnal oximetry, and full-night PSG. RESULTS: Six of 34 women and 34 of 68 men had OSA, defined by an apnea-hypopnea index > or = 15. CS and the cumulative time spent below 80% arterial oxygen saturation (SaO(2)) were higher, and PaO(2), minimal SaO(2), and mean nocturnal SaO(2) (mSaO(2)) were lower in OSA patients than in non-OSA patients. Logistic regression showed that sex, CS, and the ratio of FEV(1) over forced expiratory volume in 0.5 s (an index of upper airway obstruction on flow-volume curves) and mSaO(2), expressed as categorical variables, were independent predictors of OSA. None of these individual variables had a satisfactory diagnostic value for the diagnosis of OSA. A logistic regression model including sex and all continuous variables would have allowed us to predict the presence or absence of OSA confidently in 72.5% of the population, in whom the positive predictive value of the model was 94% and the negative predictive value was 90%. CONCLUSION: In obese patients referred to a respiratory sleep laboratory and evaluated by CS, PFTs, arterial blood gases, and oximetry, no individual sign or symptom may accurately predict the presence or absence of OSA. Provided that it is validated in prospective studies, a logistic regression model using these variables may be useful for the prediction of OSA.

Adult↗

Six-month variability of the dark-adapted pupil diameter.

PURPOSE: To determine the individual variability of the dark-adapted pupil diameter over 6 months using a standardized dark-adaptation protocol. SETTING: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: This prospective observational cohort study comprised volunteers with no history of ocular disease, surgery, or injury other than requirement for refractive correction. The right eye was tested. A standardized dark-adaptation protocol was used that controlled for accommodation and patient alertness. Infrared, still digital photographs were taken after 10 minutes of dark adaptation at 1 lux and were analyzed using digital image software. Testing was performed at baseline in the afternoon, at 3 months in the afternoon, and at 6 months in the morning. Lifestyle factors such as diet and exercise were not controlled. RESULTS: Mean intersession differences were 0.04 mm (95% confidence interval [CI]: -0.68-0.146), 0.15 mm (95% CI: -0.001-0.297), and 0.09 mm (95% CI: -0.048-0.236) for baseline-3 month, baseline-6 month, and 3 month-6 month comparisons, respectively. None of these differences was significantly different from zero (P>.05, 2-tailed Student t tests). The likelihood that the mean intersession difference was >.25 mm was negligible for all comparisons (P=.9996, .9099, and .9829 respectively, 1-tailed Student t tests). CONCLUSION: When a consistent dark-adaptation protocol that controls for alertness and accommodation is used, normal young individuals showed no significant variation in the dark-adapted pupil diameter over a 6-month period.

Accommodation, Ocular↗

Day to day variability of the dark-adapted pupil diameter.

PURPOSE: To determine the individual variability of the dark-adapted pupil diameter over 2 testing sessions using a standardized dark-adaptation protocol. SETTING: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: In this prospective observational cohort study, 40 volunteers with no history of ocular disease, surgery, or injury other than requirement for refractive correction were included. The right eye was tested. A standardized dark-adaptation protocol was used that controlled for accommodation and patient alertness. Infrared, still digital photographs were taken after 5 and 10 minutes of dark adaptation and analyzed independently by 2 investigators using digital-image software. Two test sessions were performed 1 to 7 days apart. Lifestyle factors such as sleep, diet, and exercise were not controlled. RESULTS: The mean subject age was 31.5 years (range 20 to 49 years). There were 20 men; 27 subjects wore correction for myopia, and 13 wore no correction. The mean interval between test sessions was 2 days (range 1 to 7 days). The mean difference and 95% confidence intervals for pupil diameter difference between sessions were as follows: 5-minute readings, +0.032 mm (-0.030 to +0.094); 10-minute readings, -0.006 mm (-0.059 to +0.047); mean of 5- and 10-minute readings, +0.013 mm (-0.038 to +0.064). Using the paired t test, the pupil diameter did not differ significantly between sessions in 5-minute dark adaptation (P =.2980), 10-minute dark adaptation (P =.8263), or the mean (P =.6049). CONCLUSION: Using a consistent dark-adaptation protocol that controlled for alertness, individuals aged 20 to 49 years showed no significant variation in dark-adapted pupil diameter when tested twice in 1 week.

Accommodation, Ocular↗

Early photoperiod history and short-day responsiveness in Siberian hamsters.

Siberian hamsters exhibit seasonal, photoperiod influenced cycles of reproductive activity, body size, pelage characteristics, and thermoregulatory behavior. Laboratory populations generally exhibit inter-individual variability in expression of photoperiod responsiveness, with a subset of individuals that fail to show the species typical responses to short photoperiod. This variability is partly explained by a genetic component, as it has been possible to increase the number of short-day nonresponders by artificial selection. Responsiveness to short photoperiod is also substantially influenced by photoperiod history in this species; hamsters that have been raised under long (16L) or very long (18L) day lengths are less likely to exhibit winter-type responses to short days as compared to hamsters raised under an intermediate (14L) day length. In the present experiment, we examined effects of age and early photoperiod history in a strain of Siberian hamsters that had been selected for short-day nonresponsiveness. Hamsters transferred into short photoperiod on the day of birth were uniform in exhibiting winter-type responses. However, hamsters raised until 25 days of age in either continuous illumination or in 16L exhibited variation in responsiveness when subsequently moved into short photoperiod. We conclude that virtually all hamsters of the short-day nonresponsive strain are born responsive to short days. Subsequent development of resistance to potential short day effects is dependent on age and/or photoperiod history.

Analysis of Variance↗

Medical hypophysectomy: II. Variability of ovarian response to gonadotropin therapy.

In an attempt to control individual variability of ovarian response to gonadotropin therapy, ovulatory monkeys received either "pure" follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG), with or without gonadotropin-releasing hormone (GnRH) antagonist administration. Among females that responded to gonadotropin therapy, the GnRH antagonist reduced (P less than 0.05) the variability of serum estradiol patterns. Surprisingly, after pretreatment and concurrent administration of the GnRH antagonist, FSH alone was as effective as the FSH/luteinizing hormone (LH) mixture (hMG) in stimulating follicular maturation, even when serum LH levels were at or below the limits of detection. The results indicate that in a rapidly reversible hypogonadotropic state approaching a "medical hypophysectomy," concurrent gonadotropin therapy produces a less varied ovarian response. The relative (un)importance of LH in the primate ovarian cycle seems diminished in the face of evidence that FSH alone, or in the presence of vanishingly small amounts of LH, supports follicular maturation and dynamic estrogen biosynthesis.

Animals↗

Cluster analysis: an alternative method for covariate selection in population pharmacokinetic modeling.

To be analyzed, the heterogeneity characterizing biological data calls for using appropriate models involving numerous variables. A high variable number could become problematic when one needs to determine a priori the most significant variable combination in order to reduce the inter-individual variability (IIV). Alternatively to multiple introductions of single variables, we propose a single introduction of a multivariate variable. We present cluster analysis as a stratification strategy that combines the initial single covariates to build a multivariate categorical covariate. It is an exploratory multivariate analysis that outlines homogeneous categories of individuals (clusters) according to similarities from the set of covariates. It includes many clustering techniques combining a distance measure and a linkage algorithm, and leading to various stratification patterns. The cluster analysis approach is illustrated by a case study on cortisol kinetics in 82 patients after intravenous bolus administration of synacthen (synthetic corticotropin). Using NONMEM, a basic infusion model was initially achieved for cortisol, and then a classical covariate selection was applied to improve IIV. The best fit was between the elimination rate constant k and the body mass index (BMI), which improved IIV of k. An alternative method is presented consisting in the population into homogeneous and non-overlapping groups by applying a cluster analysis. Such categorization (or clustering) was carried out using Euclidean distance and complete-linkage algorithm. This algorithm gave five dissimilar clusters that differed by increasing BMI, obesity duration, and waist-hip ratio. The dispersion of k according to the five clusters showed three distinctvariation ranges a priori, which corresponded a posteriori(after NONMEM modeling) to three sub-populations of k. After grouping the clusters that had similar variation ranges of k, we obtained three final clusters representing non-obese, intermediate, and extreme obese sub-populations. The pharmacokinetic model based on three clusters was better than the basic model, similar to the classical covariate model, but had a stronger interpretability: It showed that the stimulation and elimination of cortisol were higher in the extreme obese followed by intermediate then non-obese subjects.

Adrenocorticotropic Hormone↗

Relationships among measures of preferred tempo and motor rhythm.

Male and female subjects (Ns = 100) performed an accuracy task involving consecutive arm swings at a self-paced tempo. Following this, the subjects performed a motor rhythm task keeping in cadence with audio-visual stimuli presented at their preferred tempo. Previous findings regarding the magnitude of individual differences in preferred tempo and within-individual variability were replicated, as was the absence of sex differences for these attributes. With regard to motor rhythm, the findings indicated that (a) constant and variable error, and not absolute error, were the appropriate measures of performance, (b) there were no sex differences either in spatial or temporal accuracy or in trial-to-trial consistency of performance, (c) substantial individual differences were present in rhythmic accuracy, as were moderate individual differences in variability, (d) neither rhythmic accuracy nor variability was appreciably related to preferred tempo, and (e) spatial and temporal accuracy are relatively independent components of rhythmic accuracy.

Acoustic Stimulation↗

Repeat treadmill exercise testing: variability of results in patients with angina pectoris.

To assess the reproducibility and individual variability of ECG treadmill exercise test results, we evaluated 23 patients with coronary artery disease and stable exertional angina by means of two control exercise tests performed on different days within a 1 week period. In addition, each control test was followed on the same day by a single dose of placebo or active agent determined in a randomized double-blind manner and the exercise test was repeated. When the mean exercise test results from the control tests on days 1 and 2 were compared, there was a significant increase in exercise duration to angina (7.4 +/- 3.2 to 9.0 +/- 3.3 minutes, p less than 0.05), ST segment depression (7.8 +/- 3.9 to 9.6 +/- 3.6 minutes, p less than 0.01), and maximal exercise (9.7 +/- 3.7 to 11.0 +/- 4.1 minutes, p less than 0.01). In addition, when the mean exercise results on the control test were compared to those on the postplacebo test on the same day, similar increases in exercise duration were observed at each end point (p less than 0.01). Individual differences of more than 2 minutes in exercise duration between the two control tests and between the control and postplacebo tests in time to angina, ST segment depression, and maximal exercise were frequent (26% to 33% of patients). However, the mean rate-pressure products on the two control tests performed on days 1 and 2 and on the control and postplacebo tests performed on the same day did not differ at angina, ST segment depression, and maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Family involvement and satisfaction with community mental health care of individuals with schizophrenia.

This longitudinal study of 246 individuals with schizophrenia examined family involvement and satisfaction with outpatient care after three months of psychiatric hospital discharge. Almost 10% of the individuals reported being dissatisfied with care. Controlling for demographic variables, individuals whose family members were not helped to cope with the mental illness had almost seven times the odds of being dissatisfied. Because care disapproval increases re-hospitalization risk (Druss, Rosenheek, & Stolar, 1999), suggestions are offered for how to facilitate kin coping.

Adolescent↗

Quantitative analysis of mating behavior in aging male Drosophila melanogaster.

Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.

Aging↗

Variability of splanchnic blood flow measurements using MR velocity mapping under fasting and post-prandial conditions--comparison with echo-Doppler.

BACKGROUND/AIMS: The aim was to study the reproducibility of magnetic resonance velocity mapping, when measuring portal vein and superior mesenteric artery blood flow, under fasting and post-prandial conditions. Magnetic resonance flow measurements for the portal vein were compared with echo-Doppler measurements in the right portal vein. METHODS: Eight healthy volunteers were studied on two occasions, separated by 1 week. Blood flow in the portal vein and superior mesenteric artery was measured repeatedly under basal fasting conditions. On one occasion measurements were also made after a meal. Every magnetic resonance measurement was followed by an echo-Doppler measurement in the right portal vein. Correlations between flow values were calculated using Pearson's r. Variability components were assessed using ANOVA. RESULTS: Intra-individual variability was approximately 7% for portal vein flow measurements using magnetic resonance velocity mapping. This variability did not increase after 1 h, 1 week and after a meal. Values of flow measured in the portal vein and superior mesenteric artery using magnetic resonance velocity mapping correlated well (r = 0.80, p < 0.001). Fasting portal flow as measured with magnetic resonance velocity mapping was 1.2 l/min (range 0.96-1.6 l/min). Variability in echo-Doppler measurements was comparable to the variability of magnetic resonance velocity mapping, and flow measurements obtained with the two techniques correlated well (r = 0.74; p < 0.001). CONCLUSIONS: Magnetic resonance velocity mapping accurately measures blood flow in the portal vein with low variability and should be preferred when absolute flow values are necessary. Echo-Doppler measurement of the right portal vein has a low variability and can be used to study changes in flow.

Adult↗

Abnormal thallium kinetics in postoperative coarctation of the aorta: evidence for diffuse hypertension-induced vascular pathology.

After operative correction of congenital coarctation of the aorta, patients continue to have excess cardiovascular mortality, including manifestations of ischemic heart disease. Previous morphologic studies support the concept of direct hypertensive vascular injury in these patients. To determine whether abnormalities of myocardial perfusion were present in an asymptomatic group of patients with coarctation repair, 18 men and 9 women with a mean age of 26 years (range 19 to 41) were studied between 2 and 25 years after operative correction. Stress electrocardiography and quantitative thallium imaging by a circumferential profile technique were used. These patients were compared with a normal group, statistically defined as having a less than 1% prevalence of significant obstructive coronary artery disease. The postoperative coarctation group demonstrated a reduction in global thallium redistribution in each view analyzed. As compared with findings in the control subjects, thallium washout in the anterior view (41.9 versus 48.6%, p = 0.02) and left anterior oblique projection (40.5 versus 48.2%, p = 0.007) was significantly diminished. Although the postoperative coarctation group had a lower thallium redistribution rate in the lateral view (41.4 versus 46.3%, p = 0.09) this difference did not reach statistical significance because of the intrinsic variability of this projection. Plots of the median percent thallium washout revealed independence from circumferential profile angle, indicating global abnormalities in perfusion. No correlation between clinical variables and thallium kinetics could be established, suggesting marked individual variability in the development of this vascular lesion. The observation of abnormal thallium kinetics in patients with coarctation repair may have consequences for long-term follow-up and therapy.

Adult↗

Risks factors for highly unstable response to oral anticoagulation: a case-control study.

The factors associated with persistent instability of oral anticoagulant treatment (OAT) were investigated in a case-control study. The most unstable patients from 35 Italian anticoagulation clinics were matched with stable controls, for gender, age and OAT indication. Socio-demographic data, medical history, dietary and life habits, cytochrome P450 CYP2C9 variants, blood cell count, liver and renal functions were investigated. An 'Abbreviated Mental Test' (AMT) and a questionnaire to assess patient compliance to, and comprehension of, OAT indications and mechanisms were administered. An International Normalized Ratio (INR) above 4.5 was more frequently found in cases (n = 77) than controls (n = 80) (12.3% vs. 0.4%; P < 0.0001). The odds ratio for instability was significantly higher for: people who worked versus pensioners, acenocoumarol versus warfarin, and an insufficient score in the AMT and/or in the questionnaire. Cytochrome P450 CYP2C9 variants *1/*3 or *2/*3 or *3/*3 were more frequent among cases than controls (29.9% vs.15.0%; P = 0.042). No differences were observed as regards the other variables. In conclusion, we found that high intra-individual variability in OAT control was multifactorial, but poor OAT comprehension was prevalent.

Acenocoumarol↗

Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide.

This study examined the effect of high, normal, and uncontrolled end-tidal Pco(2) (Pet(CO(2))) on the ventilatory, peak cerebral blood flow velocity (V(p)), and mean arterial blood pressure (MAP) responses to acute hypoxia. Nine healthy subjects undertook, in random order, three hypoxic protocols (end-tidal Po(2) was held at eight steps between 300 and 45 Torr) in conditions of hypercapnia, isocapnia, or poikilocapnia (Pet(CO(2)) +7.5 Torr, +1.0 Torr, or uncontrolled, respectively). Transcranial Doppler ultrasound was used to measure V(p) in the middle cerebral artery. The slopes of the linear regressions of ventilation, V(p), and MAP with arterial O(2) saturation were significantly greater in hypercapnia than in both isocapnia and poikilocapnia (P < 0.05). Strong, significant correlations were observed between ventilation, V(p), and MAP with each Pet(CO(2)) condition. These data suggest that 1). a high acute hypoxic ventilatory response (AHVR) decreases the acute hypoxic cerebral blood flow responses during poikilocapnia hypoxia, due to hypocapnic-induced cerebral vasoconstriction; and 2). in hypercapnic hypoxia, a high AHVR is associated with a high acute hypoxic cerebral blood flow response, demonstrating a linkage of individual sensitivities of ventilation and cerebral blood flow to the interaction of Pet(CO(2)) and hypoxia. In summary, the between-individual variability in AHVR is shown to be firmly linked to the variability in V(p) and MAP responses to hypoxia. Individuals with a high AHVR are found also to have high V(p) and MAP responses to hypoxia.

Acute Disease↗

Hierarchy of different muscles in postural control.

The effects of muscle spindle activation on different postural muscles were examined in eight volunteers, using a force platform technique. Small electrical vibrators were placed symmetrically over the muscles concerned and the effects of vibration frequencies of 20, 40, 60, 80 and 100 Hz were studied at a constant amplitude of 0.4 mm (peak-to-peak). Significant responses were observed in most muscles. The responses were observed (in maximum response order) from: the neck, triceps surae, gluteus, abdominal, hamstring, quadriceps, lumbar and tibialis anterior muscles. The response direction did not follow anatomical gonistic vis-à-vis antagonistic distribution of the muscles studied, indicating that it is the functional properties of the muscles that determine posture stabilization. The large inter-individual variability in responses, but the consistency in intra-individual muscle responses indicates that the subjects used afferent muscles to a varying extent in postural control. The vibration-induced activation of the muscles was presumably derived by activation of stretch-sensitive secondary endings of muscle spindles that control postural stability.

Adult↗

IgG serology pattern in long-term follow-up of patients successfully treated for Helicobacter pylori eradication.

A long-term specific IgG serology pattern after successful eradication of Helicobacter pylori using Pyloriset EIA-G with acid-glycine extracted antigen is shown. A total of 214 HP-seropositive dyspeptic patients, mean age 51, were included. Despite individual variability among patients, calculation of antibody decline in each individual, 2, 4, 6, 12, 18, and 24 months after treatment, the authors observed that overall mean decline in the group as a whole was 49%, 67%, 78% 87%, 91%, and 93%, respectively. Unlike Cutler and coworkers, the authors found a regular constant IgG-decline in successfully treated patients until seroconversion. The time to reach seroconversion was found to depend on the pretreatment level of specific IgG. In the groups of patients with baseline IgG less than 1300, 42/44 (95%) seroconverted within the first year of monitoring. When long-term monitoring is needed, unnecessary multiple biopsies can be avoided by use of quantitative IgG serology.

Adult↗

The prediction of radiological destruction during the early stage of rheumatoid arthritis.

A total of 107 patients with definite rheumatoid arthritis of no longer than six months' duration were observed for three years. The radiological destruction of the hand and foot joints after the follow-up time was compared with 65 anamnestic, clinical, laboratory and radiological variables at the onset of the disease. Of the individual variables, early radiological changes in the joints showed the best correlation with the progress of joint destruction. Grip strength, ESR, serum iron, serum C1 esterase inhibitor, rheumatoid factor and old age also had prognostic value. In multiple regression analysis 15 variables explained about 50% of the variance in the progress of joint destruction.

Arthritis, Rheumatoid↗

A method for the assessment of fitness in aerobically taxing occupations.

A good level of physical fitness is a fundamental prerequisite of many occupations, hence the importance of valid methods of fitness assessment. A method, using submaximal treadmill exercise, was tested in a group of Urban Police Officers. Physiology variables and subjective perceptions were monitored. The trend of individual variables provided a means to define the "critical" capacity which corresponded to a mean value of 6.8 MET (a "heavy activity" according to Haskell's classification). This level is proposed as a predictor of endurance and could be used in follow-up fitness assessments.

Adult↗