Etiologies of Acute Undifferentiated Fever and Clinical Prediction of Scrub Typhus in a Non-Tropical Endemic Area

Scrub typhus usually presents as acute undifferentiated fever. This cross-sectional study included adult patients presenting with acute undifferentiated fever defined as any febrile illness for ≤ 14 days without evidence of localized infection. Scrub typhus cases were defined by an antibody titer of a ≥ fourfold increase in paired sera, a ≥ 1:160 in a single serum using indirect immunofluorescence assay, or a positive result of the immunochromatographic test. Multiple regression analysis identified predictors associated with scrub typhus to develop a prediction rule. Of 250 cases with known etiology of acute undifferentiated fever, influenza (28.0%), hepatitis A (25.2%), and scrub typhus (16.4%) were major causes. A prediction rule for identifying suspected cases of scrub typhus consisted of age ≥ 65 years (two points), recent fieldwork/outdoor activities (one point), onset of illness during an outbreak period (two points), myalgia (one point), and eschar (two points). The c statistic was 0.977 (95% confidence interval = 0.960–0.994). At a cutoff value ≥ 4, the sensitivity and specificity were 92.7% (79.0–98.1%) and 90.9% (86.0–94.3%), respectively. Scrub typhus, the third leading cause of acute undifferentiated fever in our region, can be identified early using the prediction rule.     

Long-term behavioral and learning abnormalities produced by the irreversible cholinesterase inhibitor soman: effect of a standard pretreatment regimen and clonidine

Previous studies in this laboratory have demonstrated that the alpha 2-adrenergic agonist clonidine and related drugs can offer significant protection against both the acute and chronic toxicity to soman administration in rats and mice. The purpose of this study was to determine whether addition of clonidine to a standard pretreatment protective regimen against soman toxicity could offer added protection or benefit. The standard regimen employed was a mixture of physostigmine salicylate (150 micrograms/kg) and artane (trihexyphenidyl hydrochloride 2 mg/kg). Rats were randomly assigned to one of 4 experimental groups: (1) those receiving i.m. sterile saline injection followed 30 min later by s.c. saline injection (normal controls); (2) saline, i.m. followed 30 min later by one of several doses (60-110 micrograms/kg of soman, s.c.; (3) saline, i.m., followed 10 min later by the standard pretreatment regimen i.m., followed by one of several doses of soman (160-300 micrograms/kg), s.c.; and (4) clonidine hydrochloride (1 mg/kg) i.m., followed 10 min later by the pretreatment regimen, followed 30 min later by soman. All animals were examined acutely and survivors were examined over a 3-week period following soman administration. The following observations were made: (1) Addition of clonidine to the standard pretreatment regimen did not enhance survival rate over the standard regimen alone (unless the clonidine was administered after the regimen). (2) Of the acutely toxic behavioral signs promoted by soman, clonidine addition to the standard regimen was of benefit only in reducing soman-induced tremor. (3) Addition of clonidine to the standard regimen appeared to hasten the return to normal motor behavior after soman; however, all groups exhibited normal motor behavior in 9 days. (4) Despite apparent normal motor behavior, soman-treated animals exhibited a marked performance deficit in the passive avoidance parameter 3 weeks after injection. The standard regimen partially preserved this effect; addition of clonidine to the standard regimen completely reversed the effect. These results indicate that clonidine provides a measure of protection against chronic behavioral deficits caused by soman intoxication.     

Alcoholism-associated spinal and femoral bone loss in abstinent male alcoholics,as measured by dual X-ray absorptiometry

Although alcoholism is a known risk factor for osteoporosis, there are few published reports on alcoholism-associated bone loss. To study alcoholism-associated bone loss, this study used a dual X-ray absorptiometry (DXA) densitometer to measure lumbar and femoral bone mineral density (BMD) in a previously little-studied population: 32 relatively healthy, nonhospitalized, Caucasian, alcoholic men with a period of abstinence longer than that previously studied (median abstinence 4.0 months, range 3 days–36 months). DXA is a new, highly precise densitometric method with many advantages over the methods used in previous studies. The subjects had statistically significant bone loss at three sites: lumbar spine, femoral neck, and Ward's triangle (multiple correction adjusted two-tailed P < 0.008). Compared to the mean BMD of sex-, age-, and race-matched norms, the subjects' average femoral neck, Ward's triangle, and lumbar BMDs were, respectively, 0.56, 0.69, and 0.57 standard deviations (SDs) below the normative values.This study was partially funded by a National Institutes of Health Short Term Research Training Grant (PHSHL 07491) to K.C.     

Estimation of the bronchodilatory effect of deep inhalation after a free run in children.

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.     

Compact and accurate linear and nonlinear autoregressive moving average model parameter estimation using Laguerre functions

A linear and nonlinear autoregressive moving average (ARMA) identification algorithm is developed for modeling time series data. The algorithm uses Laguerre expansion of kernals (LEK) to estimate Volterra-Wiener kernals. However, instead of estimating linear and nonlinear system dynamics via moving average models, as is the case for the Volterra-Wiener analysis, we propose an ARMA model-based approach. The proposed algorithm is essentially the same as LEK, but this algorithm is extended to include past values of the ouput as well. Thus, all of the advantages associated with using the Laguerre function remain with our algorithm; but, by extending the algorithm to the linear and nonlinear ARMA model, a significant reduction in the number of Laguerre functions can be made, compared with the Volterra-Wiener approach. This translates into a more compact system representation and makes the physiological interpretation of higher order kernels easier. Furthermore, simulation results show better performance of the proposed approach in estimating the system dynamics than LEK in certain cases, and it remains effective in the presence of significant additive measurement noise.     

Anorectal dysfunction in systemic sclerosis.

This study was aimed to evaluate the anorectal dysfunction in systemic sclerosis (SSc) and propose the clinical significance of anorectal manometry in patients with SSc. Seven patients with SSc were evaluated with manometry for anorectal function and an additional 11 normal subjects were collected as a control group. The study group underwent esophageal manometry as well and the correlation between the degree of anorectal and esophageal dysfunction was evaluated. Patients showed a lower tolerance for balloon distention of the rectum than controls (minimal sensory volume and urgency volume, P < 0.05). The resting and squeezing pressure of the anal sphincter and the functional length of the anal canal showed no significant difference in these two groups. Rectoanal inhibitory reflex was absent in one (14%) and diminished in two (29%) of seven patients with SSc. SSc patients also showed abnormal esophageal manometry findings, notably decreased LES pressure and body amplitude of distal 2/3 esophagus. The comparison between manometric profiles of anorectum and esophagus showed no significant correlation by statistical analysis. In conclusion, our data could suggest that anorectal function may be impaired in patients with SSc which could reflect the involvement of the anorectum by the disease, and that anorectal manometric studies can be useful to detect such dysfunction in patients with SSc, even before clinical symptoms.     

A Stochastic Nonlinear Autoregressive Algorithm Reflects Nonlinear Dynamics of Heart-Rate Fluctuations

Current methods for detecting nonlinear determinism in a time series require long and stationary data records, as most of them assume that the observed dynamics arise only from the internal, deterministic workings of the system, and the stochastic portion of the signal (the noise component) is assumed to be negligible. To explicitly account for the stochastic portion of the data we recently developed a method based on a stochastic nonlinear autoregressive (SNAR) algorithm. The method iteratively estimates nonlinear autoregressive models for both the deterministic and stochastic portions of the signal. Subsequently, the Lyapunov exponents (LE) are calculated for the estimated models in order to examine if nonlinear determinism is present in the deterministic portion of the fitted model. To determine if nonlinear dynamic analysis of heart-rate fluctuations can be used to assess arrhythmia susceptibility by predicting the outcome of invasive cardiac electrophysiologic study (EPS), we applied the SNAR algorithm to noninvasively measured resting sinus-rhythm heart-rate signals obtained from 16 patients. Our analysis revealed that a positive LE was highly correlated to a patient with a positive outcome of EPS. We found that the statistical accuracy of the SNAR algorithm in predicting the outcome of EPS was 88% (sensitivity=100%, specificity=75%, positive predictive value=80%, negative predictive value=100%, p=0.0019). Our results suggest that the SNAR algorithm may serve as a noninvasive probe for screening high-risk populations for malignant cardiac arrhythmias. © 2002 Biomedical Engineering Society. PAC2002: 8719Hh, 0545Tp, 8710+e     

Differences in regional wash-in and wash-out time constants for xenon-CT ventilation studies

Xenon-enhanced computed tomography (Xe-CT) has been used to measure regional ventilation by determining the wash-in (WI) and wash-out (WO) rates of stable Xe. We tested the common assumption that WI and WO rates are equal by measuring WO-WI in different anatomic lung regions of six anesthetized, supine sheep scanned using multi-detector-row computed tomography (MDCT). We further investigated the effect of tidal volume, image gating (end-expiratory EE versus end-inspiratory EI), local perfusion, and inspired Xe concentration on this phenomenon. RESULTS: WO time constant was greater than WI in all lung regions, with the greatest differences observed in dependent base regions. WO-WI time constant difference was greater during EE imaging, smaller tidal volumes, and with higher Xe concentrations. Regional perfusion did not correlate with WI-WO. We conclude that Xe-WI rate can be significantly different from the WO rate, and the data suggest that this effect may be due to a combination of anatomic and fluid mechanical factors such as Rayleigh-Taylor instabilities set up at interfaces between two gases of different densities.     

Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

Background:This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe^®) and the conventional fixed-size ice probe.Materials and methods:We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe^® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage.Results:A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65–74 years), 7 (IQR: 6–7) and 5.9 ng/mL (IQR: 4.6–8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2–48.6 months). V-Probes^® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe^® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003).Conclusions:The use of the V-Probe^® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.     

Biomechanical assessment with electromyography of post-stroke ankle plantar flexor spasticity

Spasticity has been defined as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex (muscle tone). Muscle tone consists of mechanical-elastic characteristics, reflex muscle contraction and other elements. The aims of this study were to determine whether to assess spasticity quantitatively, and to characterize biomechanical and electromyographic spasticity assessment parameters. These assessment parameters were described by investigating the correlation between clinical measures and the response to passive sinusoidal movement with consecutive velocity increments. Twenty post-stroke hemiplegic patients and twenty normal healthy volunteers were included in the study. Five consecutive sinusoidal passive movements of the ankle were performed at specific velocities (60, 120, 180, and 240 degrees/ sec). We recorded the peak torque, work, and threshold angle using a computerized isokinetic dynamometer, and simultaneously measured the rectified integrated electromyographic activity. We compared these parameters both between groups and between different velocities. The peak torque, threshold angle, work, and rectified integrated electromyographic activity were significantly higher in the post-stroke spastic group at all angular velocities than in the normal control group. The threshold angle and integrated electromyographic activity increased significantly and linearly as angular velocity increased, but the peak torque and work were not increased in the post-stroke spastic group. Peak torque, work, and threshold angle were significantly correlated to the Modified Ashworth scale, but the integrated electromyographic activity was not. The biomechanical and electromyographic approach may be useful to quantitatively assess spasticity. However, it may also be very important to consider the different characteristics of each biomechanical parameter.