Usefulness of transcranial magnetic stimulation to predict the development of reflex sympathetic dystrophy poststroke: a pilot study

OBJECTIVE: To investigate the predictive value of transcranial magnetic stimulation (TMS) for the development of reflex sympathetic dystrophy (RSD) poststroke. DESIGN: Blind clinical assessment of 2 groups of stroke patients defined on the basis of absent or preserved motor evoked potentials (MEPs) on the affected side. SETTING: Stroke rehabilitation center. PATIENTS: Twenty stroke patients between the ages of 41 and 85 years, undergoing rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: MEPs from upper limbs 30 days poststroke, Motricity Index, and scoring of RSD using the Enjalbert Scale 73 days poststroke. RESULTS: A good correlation was found between Motricity Index and TMS results (P<.01). Average Enjalbert scores were significantly different between the 2 groups (P=.03). No significant correlation was found between Enjalbert scores and the Motricity Index. CONCLUSIONS: Although no significant relationship was found between upper-limb motor impairment and intensity of RSD 10 weeks after stroke, the TMS responses permitted the early categorization of patients into 2 groups that developed significantly different average Enjalbert scores 1 to 2 months later when this clinical condition was fully developed.     

Leptin regulates appetite-related neuropeptides in the hypothalamus of developing rats without affecting food intake

Leptin regulates food intake in adult mammals by stimulating hypothalamic anorexigenic pathways and inhibiting orexigenic ones. In developing rodents, fat stores are low, yet circulating leptin levels are high and do not appear to regulate food intake. We determined whether two appetite-related neuropeptides [neuropeptide Y (NPY) and proopiomelanocortin (POMC)] and food intake behavior are sensitive to leptin [3 mg/kg body weight (BW), ip] in neonates. We measured the effects of 1) acute leptin administration (3 mg/kg BW, ip, 3 h before testing) on food intake on postnatal day (PND) 5, 8, and 10; and 2) chronic leptin treatment (3 mg/kg BW, ip, daily PND3-PND10) on BW gain and fat pads weight on PND10. In addition to hypothalamic POMC and NPY expression, we determined the expression of suppressor of cytokine signaling-3, all subtypes of leptin receptors, and corticotropin-releasing factor receptor-2 mRNA in PND10 pups receiving either an acute (PND10) or a chronic (PND 3-10) leptin (3 mg/kg BW, ip) or vehicle treatment. Brains were removed 30 or 120 min after the last injection. Acute leptin administration did not affect food intake at any age tested. Chronic leptin treatment did not change BW but decreased fat pad weight significantly. In the arcuate nucleus (ARC), acute leptin increased SOCS-3 and POMC mRNA levels, but decreased NPY mRNA levels in the rostral part of ARC. Chronic leptin down-regulated all subtypes of leptin receptors mRNA and decreased NPY mRNA levels in the caudal ARC but had no further effect on POMC expression. Chronic leptin increased corticotropin-releasing factor receptor-2 mRNA levels in the ventromedial hypothalamus. We conclude that despite adult-like effects of leptin on POMC, NPY, and CRFR-2 expression in neonates, leptin does not regulate food intake during early development.     

beta-Herpesvirus (human cytomegalovirus and human herpesvirus 6) reactivation in at-risk lung transplant recipients and in human immunodeficiency virus-infected patients

Human herpesvirus (HHV)-6 is a beta-herpesvirus-like human cytomegalovirus (HCMV) with the potential to reactivate in immunocompromised persons. HHV-6 and HCMV were assessed in the peripheral blood leukocytes of 26 lung transplant recipients and of 37 human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy, to determine the degree of concordance between HHV-6 and HCMV reactivation in different biologic settings. In the lung transplant recipients (145 samples), HHV-6 was not detected, even though 44 (30%) of 145 samples were from 9 HCMV DNA-positive patients (13 episodes of HCMV pneumonitis). Among the HIV-infected patients (172 samples), HCMV DNA was detected in 29 (17%) of 172 samples from 10 patients (4 episodes of HCMV disease). HHV-6 DNA was detected in 2 HIV-infected patients who did not have HCMV detected at that time. These findings suggest that the pathobiologic control mechanisms for these 2 beta-herpesviruses may be significantly different.     

L-arginine supplementation accelerates renal fibrosis and shortens life span in experimental lupus nephritis

BACKGROUND: Inducible, high-output nitric oxide (NO) production has been identified as a central mediator of cell injury in immune-mediated renal disease. In acute anti-thy-1 glomerulonephritis prefeeding with the NO precursor L-arginine increases mesangial cell injury and the subsequent fibrosis. The present study tested the hypothesis that L-arginine supplementation may also be detrimental in chronic, NO-mediated murine lupus nephritis. METHODS: Groups (N = 18) of female MRL/lpr mice with lupus nephritis were fed the following diets: (1) normal protein (22% casein); (2) normal protein and 1.0% L-arginine in the drinking water; (3) low protein (6% casein); (4) low protein + 0.4%l-arginine; and (5) low protein + 1.0% L-arginine. After 40 days mouse survival, albuminuria, matrix accumulation, inflammatory cell infiltration, immunoglobulin G (IgG) deposition, expression of transforming growth factor-beta 1 (TGF-beta 1), fibronectin and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein, anti-DNA antibody titer, inducible nitric oxide synthase (iNOS) mRNA expression, blood amino acid levels, blood urea nitrogen (BUN) concentrations and blood and urinary NOx (nitrite + nitrate) levels were assessed. RESULTS: L-Arginine supplementation increased mortality significantly (P < 0.02). The death rate increased from 0% in the lowest to 50% in the highest L-arginine intake group (normal protein + 1.0% L-arginine). L-Arginine administration increased albuminuria, renal matrix accumulation, TGF-beta 1, fibronectin, PAI-1, blood L-arginine, L-citrulline, BUN and blood and urine NOx levels, while protein restriction reduced these parameters. Renal cell infiltration and iNOS mRNA expression were decreased in the low protein group only. Anti-ds DNA-IgG and renal IgG deposition were comparable in all groups CONCLUSIONS: Increasing L-arginine intake increases the severity of renal fibrosis and the likelihood of death in MRL/lpr mice. The results appear to be at least in part mediated through enhanced cytotoxic NO generation via iNOS. The data suggest that L-arginine restriction should be considered in human immune-mediated renal diseases.     

Age-dependent differences in glutathione peroxidase activity after traumatic brain injury

Children younger than 4 years old have worse outcome after traumatic brain injury (TBI) compared to older children and adults. This increased susceptibility may in part be due to differences in the response to oxidative stress. We hypothesized that the immature brain does not have an adequate compensatory response to injury from oxidative stress. To begin to address this hypothesis, we first compared the general dimensions and water content in postnatal day 21 (P21) and adult murine brain in the naive state as well as after injury (edema). We examined glutathione peroxidase (GPx ) activity in cortical and subcortical regions in P21 and adult murine brain following a controlled cortical impact. Brain dimensions including areas of the mantle and hemispheres were similar in each of these groups. The thickness of the cortical mantle was significantly greater in the immature brain as compared to the mature brain (p = 0.01, respectively). Brain edema was assessed through changes in water content, and the response to oxidative challenge was identified by changes in GPx activity. The P21 brain was similar in vulnerability to posttraumatic brain edema when compared to adult. GPx activity in the adult brain was increased within 24 h post-injury in the cortex, thalamus and hippocampus (ANOVA, p < 0.05), whereas there was no compensatory increase in GPx activity in P21 brain, although baseline levels had reached adult levels developmentally. These findings support our hypothesis and illuminate the important role of oxidative stress after TBI in the immature brain that warrants further study.     

Gastroesophageal reflux disease in lung transplant recipients

BACKGROUND: Chronic allograft dysfunction after lung transplantation contributes to poor long-term survival. A link between gastric aspiration and post-transplant lung dysfunction has been suggested, but little is known about the significance of gastroesophageal reflux disease (GERD) after lung transplantation. METHODS: A retrospective study was performed to determine the prevalence of GERD in lung transplant recipients. Patients who underwent lung transplantation at Duke University, survived at least 6 months and had post-transplant 24-h pH studies were included in the analysis. Antireflux medications were discontinued prior to the pH study. Demographic data, pH study date and results, FEV1 at the time of the pH study, confirmed acute rejection episodes, and current medications were collected. The FEV1 ratio was calculated at the time of pH study (current FEV1/best post-transplant FEV1). RESULTS: Forty-three patients met entry criteria. Studies were performed at a median of 558 d post-transplant. Thirty of forty-three (69.8%) patients tested had abnormal total acid contact times (normal: <5%). The mean acid contact times for all patients were 10% total, 11.8% upright and 7.9% supine. A negative correlation was found between total or upright acid reflux and FEV1 ratio at the time of studies (-0.341 and -0.419; p = 0.025 and p = 0.005, respectively). The effect of acid reflux on FEV1 ratio remained significant after multivariable analysis. CONCLUSIONS: There is a high prevalence of GERD among selected lung transplant recipients who had pH studies performed and its presence is associated with worse pulmonary function. Future studies are needed to assess whether GERD contributes to the pathogenesis of bronchiolitis obliterans syndrome (BOS).     

Low-dose unenhanced multidetector CT of patients with suspected renal colic

OBJECTIVE: This study is designed to assess the intraobserver and interobserver agreements and the diagnostic performances of low-dose unenhanced multidetector CT (MDCT) in patients with suspected renal colic. SUBJECTS AND METHODS: The study included 106 patients who underwent unenhanced MDCT with 4 x 2.5 mm collimation, 120 kVp, 30 mAs, and, if necessary, additional focused acquisitions at 60 or 120 mAs on areas with an equivocal ureteral stone or with significant image noise. The effective radiation dose was computer-simulated with software based on the Monte Carlo model and International Commission on Radiological Protection recommendations. CT scans were archived and independently reviewed by three radiologists during two interpretation sessions on a workstation with three dimensions functions. Intraobserver and interobserver agreements were calculated with the kappa statistics. Accuracy for detection of ureteral stone on low-dose MDCT was calculated by comparison with combined clinical (stone passage), surgical (stone retrieval, extracorporeal shock wave lithotripsy), biologic (urinalysis, urine culture), and other imaging (excretory urography, standard-dose MDCT, follow-up sonography, and abdominal radiography) findings or by evidence for an alternative diagnosis. RESULTS: Ureteral stones were present in 38 (36%) of 106 patients. Thirty-six of 38 ureteral stones were detected by low-dose MDCT. From reviewer to reviewer, the number of true-positive, false-positive, true-negative, and false-negative findings ranged, respectively, from 34 to 36, 1 to 4, 64 to 68, and 2 to 4. The corresponding sensitivity, specificity, and accuracy ranged from 89.5% to 94.7%, from 94.1% to 100%, and from 93.4% to 98.1%, respectively. The intraobserver and interobserver agreements were excellent, with kappa values ranging from 0.87 to 0.98. In 13 patients, an alternative diagnosis explaining the patient's symptoms was proposed by all reviewers using images obtained at 30 mAs. No additional or alternative diagnosis was found at standard dose. At 30 mAs, the mean effective dose was 1.2 mSv in men and 1.9 mSv in women. Additional acquisitions at 60 mAs, all focused on the lower pelvis, were acquired in 20 patients, but the corresponding images were needed by the reviewers for only six of them. The acquisitions at 60 mAs were responsible for an additional mean effective dose of 0.5 in men and 0.8 mSv in women. CONCLUSION: Our study shows that low-dose unenhanced MDCT is appropriate for the diagnosis of ureteral stones, and that it provides excellent intraobserver and interobserver agreements and does not obscure alternative diagnoses.     

Tolerance to acute isovolemic hemodilution. Effect of anesthetic depth

BACKGROUND: Acceptance of a lower transfusion trigger in the perioperative period requires study of the effects of anesthetic depth on the tolerance to acute isovolemic anemia. Anesthetic agents with negative effects on the cardiovascular system may exert proportionately greater depressant effects on cardiac output response than on tissue oxygen demand, reducing tolerance to acute isovolemic anemia. METHODS: In the first study, animals were anesthetized with halothane (n = 14; 23.8 +/- 4.8 kg, mean +/- SD). In a second study, animals were anesthetized with ketamine (n = 14; 24.3 +/- 4.7 kg). In each study, dogs were randomly allocated to receive either low or high concentrations of anesthetic. Oxygen delivery and oxygen consumption were determined from independent measurements during a stepwise isovolemic hemodilution protocol. In each dog, critical oxygen delivery was determined from a plot of oxygen consumption versus oxygen delivery using a least-sum-of-squares technique. Critical hemoglobin (hemoglobin) was determined from a plot of hemoglobin versus oxygen consumption using the same method. RESULTS: With both agents, the higher anesthetic concentration was associated with decreased oxygen consumption, resulting in a lower critical oxygen delivery. However, critical hemoglobin was significantly higher in the animals receiving the higher anesthetic dosage (1.5 vs. 1.0 minimum alveolar concentration of halothane: 4.1 +/- 1.3 vs. 2.3 +/- 0.5 g/dl, P < 0.05; high- vs. low-dose ketamine: 3.7 +/- 1.4 vs. 2.5 +/- 0.6 g/dl, P < 0.05). This was related to a marked blunting of the cardiac output response to hemodilution in the animals receiving the higher anesthetic dosage. CONCLUSIONS: Increased anesthetic depth with halothane or ketamine resulted in a decreased tolerance to acute anemia, as reflected by a significant increase in critical hemoglobin concentration.