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.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

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.     

Viral infections in the mouth

Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein–Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via non-glossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis.     

Endoscopic-assisted sciatic nerve exploration.

A sciatic nerve lesion is uncommon. We report the utility of the endoscope in an 18-year-old female with multiple lesions of her sciatic nerve. Somatosensory evoked potentials and MRI were indicative of a sciatic nerve lesion. We describe a simple technique of endoscopic exploration of the sciatic nerve to assist intraoperative decision making.     

Cardiac rehabilitation referral and attendance: not one and the same.

Despite empirical evidence that cardiac rehabilitation programs can play a significant role in enhancing recovery following a primary cardiac event and in enacting secondary prevention measures, attendance rates remain remarkably low. Referral and attendance at cardiac rehabilitation programs are not one and the same. Recognizing this, issues related to the referral of eligible patients to cardiac rehabilitation and factors that affect patients' decisions regarding attendance must be identified and addressed. This article presents an overview of the potential benefits of cardiac rehabilitation programs, describes salient issues related to referral and attendance, and identifies directions for future research.