Psoriatic nail involvement and its relationship with distal interphalangeal joint disease.

Psoriatic nail disease and distal interphalangeal (DIP) arthritis both are common manifestations of psoriatic arthritis (PsA). Several clinical characteristics are allegedly associated with DIP joint damage, particularly nail psoriasis. However, there is little evidence to substantiate this phenomenon. The purpose of this study is to investigate the relationship between DIP involvement, nail psoriasis and other parameters. A cross-sectional study involved 45 patients from local rheumatology clinic. Four hundred fifty psoriatic fingernails scored, and the radiographs of all these fingers were reviewed to define PsA DIP arthritic changes. 64.4 % patients had nail psoriasis and 35.6 % had DIP arthritis. Univariate analysis identified that swollen joint-count, digits with chronic dactylitis, HLA-B27 status and nail psoriasis were associated with DIP arthritis. Regression model supported that nail disease was the most significant associated factor of DIP arthritis (OR 9.7, p = 0.05). Nail psoriasis was identified in 40.2 % of digits. Pitting (29.6 %), onycholysis (15.1 %), crumbling (8.2 %), nail bed hyperkeratosis (2.0 %) were noted with the mean modified Nail Psoriasis Severity Index of 0.95 +/-1.68. Among all digits, 57 had DIP arthritis while 393 did not. Within DIP joints with PsA radiological change, 59.6 % had nail disease. Chi-square test with the Bonferroni correction further supported an association between nail psoriasis and DIP involvement with p value of 0.001. Two specific nail subtypes-crumbling and onycholysis-were found to be significantly associated with DIP disease. A significant proportion of PsA patients had nail involvement and DIP arthritis. PsA patients with nail changes may be more susceptible to DIP disease.

Effect of moisture on the extraction efficiency of polycyclic aromatic hydrocarbons from soils under atmospheric pressure by focused microwave-assisted extraction.

The effects of the moisture content in the original, air-dried and re-moistened matrices as well as solvent have been studied on the recovery of polycyclic aromatic hydrocarbons (PAHs) from soil by a focused microwave-assisted extraction (FMAE) method. Solvents selected for the extractions were cyclohexane-acetone (1:1), hexane-acetone (1:1) and dichloromethane. On the extraction of 20-day aged spiked soil, the highest recovery was found by applying hexane-acetone mixture. Spiked soil sample, quality control sample and real soil sample were used for the evaluation of moisture effect. It indicated that the presence of water in the soil is important for the recovery enhancement of PAHs and with this presence it is possible to avoid drying step with the FMAE technique. A comparison between microwave and 16-h Soxhlet methods has been made. It evidenced that the microwave-assisted extraction under ambient atmospheric pressure is a suitable alternative to Soxhlet extraction for the analysis of PAHs in soils.

One-sided tests in clinical trials with multiple endpoints.

Treatment comparisons in clinical trials often involve several endpoints. For example, one might wish to demonstrate that a new treatment is superior to the current standard for some components of the multivariate response vector and is not inferior, modulo biologically unimportant difference to the standard treatment for all other components. We introduce a new approach to multiple-endpoint testing that incorporates the essential univariate and multivariate features of the treatment effects. This approach is compared with existing methods in a simulation study and applied to data on rheumatoid arthritis patients receiving one of two treatments.

Determination of power and sample size in the design of clinical trials with failure-time endpoints and interim analyses.

An important but difficult task in the design of a clinical trial to compare time to failure between two treatment groups is determination of the number of patients required to achieve a specified power of the test. Because patients typically enter the trial serially and are followed until they fail or withdraw from the study or until the study is terminated, the power of the test depends on the accrual pattern, the noncompliance rate, and the withdrawal rate in addition to the actual survival distributions of the two groups. Incorporating interim analyses and the possibility of early stopping into the trial increases its complexity, and although normal approximations have been developed for computing the significance level of the test when the log-rank or other rank statistics are used, there are no reliable analytic approximations for evaluating the power of the test. This article presents methods, based on Monte Carlo simulations and recent advances in group sequential testing with time-to-event responses, to choose appropriate test statistics, compute power and sample size at specified alternatives, check the adequacy of commonly used normal approximations of the type I error probability, and assess the performance of different interim analysis strategies. It also presents two computer programs implementing these methods.

Computer-based screening of patients with HIV/AIDS for clinical-trial eligibility.

OBJECTIVE: To assess the potential effect of a computer-based system on accrual to clinical trials, we have developed methodology to identify retrospectively and prospectively patients who are eligible or potentially eligible for protocols. DESIGN: Retrospective chart abstraction with computer screening of data for potential protocol eligibility. SETTING: A county-operated clinic serving human immunodeficiency virus (HIV) positive patients with or without acquired immune deficiency syndrome (AIDS). PATIENTS: A randomly selected group of 60 patients who were HIV-infected, 30 of whom had an AIDS-defining diagnosis. DESIGN: Using a computer-based eligibility screening system, for each clinic visit and hospitalization, patients were categorized as eligible, potentially eligible, or ineligible for each of the 17 protocols active during the 7-month study period. Reasons for ineligibility were categorized. RESULTS: None of the patients was enrolled on a clinical trial during the 7-month period. Thirteen patients were identified as eligible for protocol; three patients were eligible for two different protocols; and one patient was eligible for the same protocol during two different time intervals. Fifty-four patients were identified as potentially eligible for a total of 165 accrual opportunities, but important information, such as the result of a required laboratory test, was missing, so that eligibility could not be determined unequivocally. Ineligibility for protocol was determined in 414 (35%) potential opportunities based only on conditions that were amenable to modification, such as the use of concurrent medications; 194 (17%) failed only laboratory tests or subjective determinations not routinely performed; and 346 (29%) failed only routine laboratory tests. CONCLUSIONS: There are substantial numbers of eligible and potentially eligible patients who are not enrolled or evaluated for enrollment in prospective clinical trials. Computer-based eligibility screening when coupled with a computer-based medical record offers the potential to identify patients eligible or potentially eligible for clinical trial, to assist in the selection of protocol eligibility criteria, and to make accrual estimates.

Statistical analysis of ligand-binding experiments.

After a brief review of commonly used methods for parameter estimation from ligand-binding data in the biochemistry literature, we propose some diagnostic checks and statistical tests of the underlying assumptions and develop methods for evaluating the biases and variances of the estimates and for constructing confidence intervals. Examples on the analysis of data from two radioligand-binding experiments are presented to illustrate these methods.

Influence of age on gastric emptying in healthy Chinese.

Radionuclide gastric emptying studies, including solid and liquid phases, were used to evaluate the gastric motility of healthy Chinese. Forty-eight patients (18-76 years old) and 38 volunteers (27-79 years old) accepted solid or liquid food gastric emptying studies, respectively. The solid meal was two fried eggs mixed with 500 microCi Tc-99m phytate and two pieces of toast to form a sandwich. The liquid meal was 500 ml of water with 5% glucose and 500 microCi Tc-99m phytate. Studies were performed with the subjects in the supine position and a gamma camera in a left anterior oblique (LAO) position while data were collected for 90 minutes and 30 minutes after finishing the solid and liquid meal, respectively. The gastric emptying time was presented as a half-time (t1/2) of the food emptying from the stomach. The study results showed that the t1/2 is 89.0 +/- 17.8 in older patients (> 60 years old) and 88.0 +/- 18.2 in younger patients (< or = 60 years old) for the solid phase studies (P > 0.05), and that the t1/2 is 46.2 +/- 11.1 in older patients (> 60 years old) and 31.9 +/- 11.3 in younger patients (< or = 60 years old) for the liquid phase studies (P < 0.05). We concluded that the age effects of gastric emptying in healthy Chinese occurred only in the liquid phase.

Heart rate variability during respiratory pauses in puppies and dogs.

We studied the time course and change in heart rate during respiratory pauses in puppies (3-4 wk) and young adult dogs. We measured ventilation and ventilatory pattern using barometric plethysmography and recorded the respiratory rate (RR) interval using a pre-processor with an accuracy of 0.2 ms. During tidal breathing, the fluctuations in RR interval were an order of magnitude smaller in the puppy than in the dog. During respiratory pauses in dogs, the RR interval increased sharply, stabilized around the level of expiration of previous breaths, and dropped immediately with the subsequent inspiratory effort. The time course of the change in heart rate was different in the puppy: there was a gradual increase in the RR interval during the entire course of the pause and the maximum RR interval reached was substantially higher than during expiration of previous breaths. Our results suggest that 1) the change in heart rate at the outset of respiratory pauses is too fast to be related to blood gas changes in both puppies and dogs and 2) the mechanisms responsible for the vagal gating of heart rate during tidal breathing and during respiratory pauses are not well developed in early life in the puppy.

Determination of sleep state in infants using respiratory variability.

Sleep staging has been conventionally performed using neurophysiologic and behavioral criteria. However, these criteria may not always be available. Since it is known that cardiorespiratory variables in rapid eye movement (REM) sleep are different from those in quiet sleep, we asked whether such variables can be used for the determination of sleep state. We studied nine normal full-term infants at 1 and 4 months of life. Ventilation was measured using barometric plethysmography and the RR interval using a high accuracy R wave detector. Electroencephalogram, electrooculogram, and postural muscle electromyogram were recorded using surface electrodes and behavioral criteria applied. Means of RR interval, respiratory cycle time and tidal volume, and coefficients of variation of the same variables, were obtained for 30-s intervals throughout each sleep study. The Kolmogorov-Smirnov distances between REM and quiet sleep were larger for the coefficients of variation than for the means at both ages for all variables. Moreover, coefficient of variation of respiratory cycle time was found to provide the largest separation between REM and quiet sleep. In view of this result, we developed a statistical decision rule using coefficient of variation of respiratory cycle time for the classification of REM and quiet sleep in blocks of 5-min periods. Each study was divided into 5-min epochs and this rule was applied to each epoch. Of 85 epochs staged as quiet sleep by neurophysiologic and behavioral criteria, 79 epochs (or 93%) were classified correctly as quiet sleep using our decision rule. Of 85 epochs staged as REM sleep, 84 were classified as REM sleep and only one misclassified as quiet sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Within-breath electromyographic changes during loaded breathing in adult sheep.

To investigate the changes in diaphragm electromyogram (EMG) during the course of severe loaded breathing, we subjected five conscious adult sheep to inspiratory flow resistive breathing (resistance greater than 150 cmH2O X l-1 X s) for up to 2-3 h and studied the total EMG power per breath (iEMG) and the EMG power per unit time after dividing the duration of EMG activity within each breath into three equal parts (iEMG1, iEMG2, and iEMG3). Both total breath iEMG and transdiaphragmatic pressure (Pdi) increased, remained at a high level for a certain period of time, and then started to fall. A change in the pattern of iEMG within a breath was observed during loaded breathing. The increase in total-breath iEMG was associated mostly with an increase in iEMG3, or the last part of the EMG power within each inspiration. Similarly, the decrease in total breath iEMG was primarily due to a decrease in iEMG3. We conclude that, in sheep subjected to severe IFR loads for prolonged periods the marked increase in total-breath iEMG at the beginning of loaded breathing and the marked decrease in this iEMG at the time of decrease in Pdi are largely due to changes in iEMG that occur during the latter third of each breath. We speculate that during loaded breathing the recruitment pattern of diaphragmatic muscle fibers changes during the course of an inspiratory effort.

Effect of endorphins on heart rate and blood pressure in adult dogs.

To investigate the role of opioids in regulating cardiovascular function, we administered delta-opioid receptor agonists D-Ala-D-Leu enkephalin (DADLE) and D-Ala-Met enkephalinamide (DAME), and mu-opioid receptor agonist, a morphiceptin analogue (MA), intracisternally in 13 unanesthetized, chronically instrumented adult dogs in 2 doses (25 and 125 micrograms/kg). After an initial transient drop, the R-R interval increased (peak approximately 25-60 min) postadministration of opioids. The time course and the magnitude of the change in R-R interval depended on the agonist: delta-agonists induced a more prolonged and marked change in R-R interval than mu-agonists at both doses. Mean arterial blood pressure (MAP) increased initially but dropped toward or even below base line 30 min after opioids administration. Atropine, given intravenously or intra-arterially at peak action of agonist in relatively low doses (0.02 mg/kg), induced an AV block followed by a marked decrease in R-R interval. There was also an increase in MAP after atropine. Naloxone, given intracisternally, reversed both delta- and mu-opioid effects but did not induce changes in the R-R interval without prior administration of opioids. We conclude that in unanesthetized adult dogs 1) both mu- and delta-receptor opioid agonists prolong the R-R interval, and this depends on the type of receptor stimulated; 2) opioids induce slowing in heart rate, possibly by increasing parasympathetic activity to the heart; 3) enkephalin and morphiceptin analogues induce a biphasic response in MAP; and 4) endorphins do not modulate cardiovascular function tonically; we speculate that they can alter the R-R interval and MAP in the presence of stimuli.

Regression Analysis of Compartmental Models.

Herein we study the problem of assessing, on the basis of noisy and incomplete observations, how much information there is in the data for model identification in compartmental systems. The underlying concept is that of an "information distance" between competing models, and estimation of this distance on the basis of the given data is discussed. Useful reduction of the dimensionality of the corresponding least squares problem is accomplished by regarding the decay rate constants as primary parameters of interest and the other parameters of the model as nuisance parameters. Estimation of the decay rate function is also discussed.

Rhythmic variations in R-R interval during sleep and wakefulness in puppies and dogs.

We studied the short-term oscillations in the R-R interval in five puppies at 4 wk of age and five adult dogs during sleep and wakefulness. The R-R interval was measured using an R-R preprocessor, and respiration was recorded using barometric plethysmography. Puppies showed much smaller fluctuations in the R-R interval (SD between 6 and 40 ms) than adult dogs (SD between 124 and 367 ms) in both rapid eye movement (REM) and quiet sleep. Spectral analysis demonstrated that these oscillations were primarily of low frequencies, and the contribution of respiratory sinus arrythmia (RSA) to total power was low. In contrast, in adult dogs during sleep, the spectral distributions were peaked in frequency bands corresponding to mean respiratory rate, and the percent contribution of low frequencies to power was small. Furthermore, the mean R-R interval was considerably larger during expiration than during inspiration in adult dogs (showing 20-140% increase), but not in puppies (showing only -0.4 to 4.4% increase). We conclude that 1) the mechanisms responsible for RSA mature postnatally in the dog; 2) the magnitude of RSA depends on the state of consciousness in the adult dog, being greater in sleep than during wakefulness; and 3) low-frequency oscillations, not related to breathing and independent of sleep state, characterize the variations in the R-R interval in early life but are insignificant in the adult dog.

Optimal sequential sampling from two populations.

Given two statistical populations with unknown means, we consider the problem of sampling chi 1, chi 2, ... sequentially from these populations so as to achieve the greatest possible expected value of the sum Sn = chi 1 + ... + chi n. In particular, for normal populations, we obtain the optimal rule and study its properties when the average of the two population means is assumed known, and exhibit an asymptotically optimal rule without assuming any prior knowledge about the population means.

Enkephalin-induced changes in ventilation and ventilatory pattern in adult dogs.

We studied the changes in ventilation induced by intracisternal administration of enkephalins in four unanesthetized adult dogs. Instantaneous minute ventilation (VT/TT) decreased markedly after D-Ala-Met-enkephalinamide (DAME). Mean VT/TT decreased maximally by 20-50 min after DAME and lasted an additional 15-60 min; by 2 h, VT/TT had returned to base line. Four doses (5, 25, 60, and 125 micrograms/kg) of DAME were used, and the ventilatory response depended on the dose. Mean inspiratory time decreased but mean expiratory time and mean TT showed a marked prolongation. Periodic breathing (2-3 breaths separated by long apneic pauses) occurred in every study and the frequency of sighs increased considerably. All these ventilatory changes were reversed by low doses of naloxone or naltrexone; in addition, VT/TT increased well above base line after the administration of these antagonists. However, naloxone did not increase VT/TT when injected without prior administration of DAME. We conclude that 1) the decrease in VT/TT is due to a decrease in respiratory duty cycle; 2) periodic breathing and increased frequency of sighs constitute part of the changes in the ventilatory pattern induced by DAME; 3) a ventilatory withdrawal reaction may occur after a receptor-agonist interaction of short duration; and 4) although enkephalins can modulate ventilation and the breathing pattern in a major way, these data provide no evidence suggesting that this modulation is tonic.

Adaptive choice of mean or median in estimating the center of a symmetric distribution.

An adaptive choice of the sample mean x(n) or the sample median m(n) is proposed for estimating the center of a symmetric distribution. This choice becomes correct as n --> infinity, and in simulation results for finite n it is almost as good as the better of x(n) and m(n).

Heart rate pattern during sleep in an infant with congenital prolongation of the Q-T interval (Romano-Ward syndrome).

Heart rate and the variability of the heart rate, indices of autonomic control, were studied during sleep in an infant with prolonged Q-T interval (Romano-Ward syndrome) and were compared to the heart rate and variability of heart rate in 18 normal infants studied at monthly intervals during the first four months of life. The overall variability and beat-to-beat variability in the infant with Romano-Ward syndrome were significantly below the median in the normal infants at each age and sleep state. This decrease in overall and beat-to-beat variability persisted after normalization by the absolute heart rate; however, the heart rate in the infant with Romano-Ward syndrome was not different from those in normal infants. These data suggest that the presence of a normal heart rate does not exclude abnormal autonomic activity; and in certain clinical situations, the variability of heart rate may be a more sensitive index of abnormal autonomic function than the heart rate itself.

Determination of ventilatory pattern in REM sleep in normal infants.

Using methods that we devised for detecting and counting eye movements on the electrooculogram (EOG), we studied tidal volume (VT) and total respiratory cycle time (Ttot) as a function of the frequency of rapid eye movements (REM) during REM sleep in nine normal infants at 1 mo of age. In each of the nine infants, the mean VT and mean Ttot decreased with increasing frequency of eye movements. Instantaneous minute ventilation (VT/Ttot or V), however, did not change with the frequency of eye movements. In addition, there was no consistent change in the variability of VT, Ttot, or V when studied as a function of the frequency of eye movements. Our data support the notion that the ventilatory pattern in REM sleep depends in part on mechanisms that are inherent to REM sleep.

Breath-to-breath variations in rate and depth of ventilation in sleeping infants.

Ventilatory measurements were made noninvasively over 2- to 3-h periods during sleep in each of nine normal infants at 1 mo of age. To assess the changes that occur in ventilation on a breath-to-breath basis, we 1) examined the variations of each of tidal volume (VT), respiratory cycle time (Ttot), expiratory time (TE), and inspiratory time (TI) and 2) studied their interrelationships. We found that the variations of VT, Ttot, and TE but not of TI were significantly greater in rapid-eye-movement (REM) than in quiet sleep. In addition, on a breath-to-breath basis, VT had a positive linear relationship and strong correlation with TI; however, the correlation between VT and TE was weak in both sleep states. VT/Ttot was found to be moderately and negatively correlated with Ttot in both REM and quiet sleep. VT was weakly correlated with Ttot in REM sleep and was, on the average, more correlated with Ttot in quiet sleep. We suggest that in infants 1) on a breath-to-breath basis, VT/Ttot is likely to drop if respiratory frequency is decreased and 2) VT is nonlinearly related to Ttot during sleep; this lack of linearity depends on the lack of constancy of VT/Ttot, which is in turn closely related to the variability of the "on-switching" of inspiratory activity.

Ventilation and ventilatory pattern during sleep in aborted sudden infant death syndrome.

To assess ventilatory control during sleep in infants at risk for the sudden infant death syndrome (SIDS), we made serial measurements of resting tidal volume (Vt), respiratory cycle time (Ttot), and the ventilatory changes resulting from inhalation of 2% CO2 in aborted SIDS infants in rapid eye movement and quiet sleep and compared them to a group of normal infants during the first 4 months of life. Ventilation was measured by the barometric method, and sleep was staged using electroencephalogram, electrooculogram, and electromyogram and behavioral criteria. Although resting instantaneous minute ventilation (Vt/Ttot) was virtually the same in both groups of infants, Vt tended to be smaller (by up to 50% in the first 2 months) and Ttot tended to be shorter in aborted SIDS than in normal infants in both rapid eye movement and quiet sleep. The increase in the mean Vt/Ttot with 2% CO2 is greater by about 5 to 20% in aborted SIDS than in normal infants at 3 and 4 months of age in both sleep states. These findings, together with our previous findings that aborted SIDS infants have an increase in heart rate and a shortening of the QT interval, provide indirect evidence that infants at high risk for SIDS may have increased sympathoadrenal activity.