Sodium butyrate suppresses interferon-gamma-, but not lipopolysaccharide-mediated induction of nitric oxide and tumor necrosis factor-alpha in microglia

Previously we found that in conscious, freely behaving rats chronic electric stimulation of the lateral hypothalamus (LH) caused significant augmentation of natural killer cell cytotoxicity (NKCC) and a large granular lymphocyte (LGL) number more pronounced in the spleen than in the peripheral blood. The LH belongs to the so-called "brain reward system", a collection of the central structures whose activation produce positive emotions. The midbrain ventral tegmental area (VTA) is another prominent reward-relevant structure. In the present work, chronic electric stimulation of VTA (constant current 0.1 ms duration cathodal pulses delivered at frequency 50 Hz during 60 min daily session for 14 consecutive days) caused in rats an increase in the spleen but not in the peripheral blood NKCC (chromium release assay) without simultaneous effect on the number of large granular lymphocytes (LGL) (morphological method) and plasma level of prolactin (PRL), growth hormone (GH), corticosterone (COR), and testosterone (TST). This effect was anatomically specific as no influence of analogous thalamic stimulation on immune and endocrine response was found. The results obtained indicate that both reward-related areas VTA and LH enhance the cell-mediated immune response, represented by natural killer cytotoxicity, especially in the spleen. However, the effect pronounced by VTA is weaker than that of LH, possibly due to additional connections of LH with the hormonal and/or autonomic control systems.     

Biocompatibility and charge injection property of iridium film formed by ion beam assisted deposition

Iridium thin film formed by electron-beam evaporation with simultaneous bombardment of Ar ion beam was evaluated for a stimulating neural electrode. The electrochemical behavior of as-deposited Ir film on Ni-Ti sample was almost identical to bulk Ir by producing much higher open-circuit corrosion potential and much lower anodic current density than the uncoated Ni-Ti in both 1N sulfuric acid and saline solution. The charge injection capability of Ir film was compared with that of Pt electrode currently used mostly as a stimulating neural electrode. The charge density of Pt was small and unchanged with increasing number of activating cycles in 0.1M H(2)SO(4), whilst the Ir film continuously produced increases in charge density. The charge injection density of Ir film in physiological solution was higher for the more activated sample under the identical stimulating condition. Attachment and proliferation with PC12 cells on Ir-coated CP Ti without applying electrical stimulation was similar to the polished CP Ti. A network of neurons and extending axons were formed on Ir film.     

The role of parotid biopsy in the diagnosis of pediatric Sjögren syndrome

OBJECTIVES: To describe our experience with primary and secondary Sj?gren syndrome (SS) in the pediatric population and to evaluate the effectiveness of parotid gland biopsy in the diagnosis of pediatric SS. DESIGN: Case series review of 6 pediatric patients evaluated during a 4-year period with varied head and neck manifestations of SS. SETTING: Tertiary care children's hospital. PATIENTS: Six children (4 boys and 2 girls) ranging in age from 6 to 12 years, who were diagnosed as having primary or secondary SS. INTERVENTION: Six minor salivary gland and 4 parotid gland biopsies for pathologic examination. MAIN OUTCOME MEASURES: Pathologic examination of salivary tissue consistent with SS. RESULTS: All 6 patients underwent minor salivary gland biopsy, 2 (33%) were consistent with SS, while the remaining 4 (67%) were nondiagnostic. The 4 patients with nondiagnostic minor salivary gland biopsy results went on to have parotid biopsies, of which all 4 had histologic findings consistent with SS. No complications were encountered. CONCLUSION: Parotid gland biopsy is an effective and safe means of obtaining salivary gland tissue for histologic evaluation of SS in the pediatric population.     

Alteration of biochemical profiles after high-dose intravenous immunoglobulin administration in Kawasaki disease

Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory treatment for several immune-mediated diseases. Early effects of high-dose IVIG treatment on biochemical profiles including lipids and proteins were evaluated in patients with Kawasaki disease (KD). Twelve children with KD (9 boys) were treated with IVIG at 2 g/kg over a period of 12 h. Serial sera samples were collected from the patients four times: before IVIG treatment and 2 h, 24 h and 7 d after IVIG treatment. The samples were frozen at -20°C before biochemical analysis. A significant decrease in albumin concentration was found 2 h and 24 h after IVIG treatment, but this recovered to the pretreatment level after 7 d. Total cholesterol and triglyceride increased slightly after 7 d. A significant decrease in HDL-cholesterol and C-reactive protein was seen 2 h and 24 h after IVIG treatment.

Conclusion : High-dose IVIG affects immediate changes in protein profiles and HDL-cholesterol in KD. Changes in HDL-cholesterol induced by IVIG may be the result of changes in systemic protein metabolism.     

Risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin therapy

STUDY OBJECTIVE: To evaluate risk factors for the development of arthralgias or myalgias associated with quinupristin-dalfopristin. DESIGN: Retrospective chart review and case-control analysis. SETTING: An 850-bed tertiary care medical center. PATIENTS: All adult and pediatric patients who had received quinupristin-dalfopristin through either a compassionate-use protocol (February 1996-October 1999) or in the year after quinupristin-dalfopristin was added to the hospital formulary (November 1999-October 2000) were included in this study. Case patients were those who developed arthralgias or myalgias while receiving quinupristin-dalfopristin therapy; control patients were those who received quinupristin-dalfopristin but did not develop arthralgias or myalgias. INTERVENTION: Medical records, pharmacy dispensing information, and microbiology data were reviewed by a physician and a pharmacist, both of whom specialized in infectious diseases. Presence or absence of arthralgias or myalgias was the primary outcome assessed. MEASUREMENTS AND MAIN RESULTS: Quinupristin-dalfopristin was administered to 68 patients during the period defined by the study. Arthralgias and myalgias could not be assessed in 18 of the 68 patients because they were sedated and paralyzed, or they were young children who could not communicate the presence of pain. Univariate analysis demonstrated that significant risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin were female sex, chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, major surgery, and receipt of either mycophenolate or cyclosporine. Multivariate analysis demonstrated a strong association with chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, and receipt of either cyclosporine or mycophenolate. Of 50 evaluable patients receiving quinupristin-dalfopristin, 25 had pain that may have been associated with this antimicrobial agent. CONCLUSION: The mechanism for development of arthralgias or myalgias associated with quinupristin-dalfopristin remains unknown, but these adverse events are more likely to occur in patients with chronic liver disease and those who have received a liver transplant or are receiving cyclosporine or mycophenolate.     

The risk of false-positive results in orthopaedic surgical trials

The risk of concluding that the results of a particular study are true, when, in fact, they really are attributable to chance (or random sampling error) is underappreciated by investigators. This erroneous false-positive conclusion is designated as a Type I or alpha error. The extent to which randomized trials in surgery risk Type I errors is unclear. The current authors hand-searched four orthopaedic journals, six general surgery journals, and five medical journals to identify recently published randomized trials (within the past 2 years). Information on outcomes and statistical adjustment for multiple outcomes was recorded for each study. The risk of a Type I error was calculated for each study that did not explicitly state a primary outcome measure for the main statistical comparison. One hundred fifty-nine studies met the inclusion criteria for the study: 60 studies from orthopaedic journals, 49 studies from nonorthopaedic surgical journals, and 50 studies from medical journals. Of the trials that did not state a primary outcome measure, the risk of Type I errors (false-positive results) in orthopaedic and nonorthopaedic surgery journals (mean 37.3% +/- 13.3% and 37.6% +/- 10.5%, respectively) were significantly greater than medical journals (10.1% +/- 1.9%). In the current review of randomized trials in surgery and medicine, the following is reported: (1) reporting of primary outcomes in trials was inadequate; (2) one in three trials in surgery and one in 10 trials in medicine risked false-positive results; and (3) few trials in surgery and medicine considered adjustment for multiple comparisons.     

Acute cholecystitis at T2-weighted and manganese-enhanced T1-weighted MR cholangiography: preliminary study

Twelve patients with symptoms of acute cholecystitis underwent heavily T2-weighted and mangafodipir trisodium-enhanced T1-weighted magnetic resonance (MR) cholangiography and cholescintigraphy before they underwent cholecystectomy. On T2-weighted MR cholangiographic images, morphologic evidence of outflow obstruction of the gallbladder was definitive in seven patients, equivocal in one, and absent in four. In all 12 patients, biliary dynamics depicted at manganese-enhanced T1-weighted MR cholangiography agreed completely with those depicted at hepatobiliary scintigraphy. T2-weighted MR cholangiography combined with manganese-enhanced T1-weighted MR cholangiography provides not only morphologic information but also functional information about the biliary system.     

Work hours reform: perceptions and desires of contemporary surgical residents

BACKGROUND: New Accreditation Council for Graduate Medical Education (ACGME) requirements on resident duty hours are scheduled to undergo nationwide implementation in July 2003. General surgery residents, because of their long duty hours, are likely to be among those most affected by changes imposed to comply with the ACGME requirements. There are few contemporary data on their attitudes toward work hours reform. STUDY DESIGN: The study entailed a region-wide survey of residents enrolled in general surgery residencies in New England to characterize the perceptions and desires of surgical residents on the issue of work hours reform. RESULTS: Respondents reported working a mean of 105 +/- 0.7 hours per week, considerably more than the 80-hour limit stipulated by the ACGME. Of the respondents, 81% reported that sleep deprivation had negatively affected their work. A strong majority of respondents believe that work hours reform would improve their quality of life but less than one half expect it to have a positive impact on patient care. A greater percentage of senior residents than junior residents (p < 0.05) have negative perceptions of work hour limitations, particularly with respect to consequences for patient care. Other findings suggest that residents who have actually experienced work hour restrictions are less positive about such restrictions than these residents who had not yet experienced them. CONCLUSIONS: Changes imposed by residency programs to comply with work hour requirements might have detrimental effects on senior residents and patient care. The impact of such changes should be carefully monitored as the ACGME requirements are implemented.     

Indications for early postoperative intraperitoneal chemotherapy of advanced gastric cancer: results of a prospective randomized trial

Previous analysis of this prospective randomized trial and meta-analysis of published randomized trials of adjuvant intraperitoneal chemotherapy demonstrated improved survival in patients with advanced gastric cancer. Simple criteria applicable at the time of surgery for patient selection were sought in this analysis. From 1990 to 1995 a series of 248 patients with biopsy-proven gastric cancer were randomized intraoperatively to receive early postoperative intraperitoneal mitomycin C and 5-fluorouracil (125 patients) versus surgery only (123 patients). Gastric resection plus early postoperative intraperitoneal chemotherapy showed improved overall survival compared to surgery only (54% and 38%, respectively; p= 0.0278). There were statistically significant differences in patients with stage III (57% and 23%, respectively; p= 0.0024) and in those with stage IV (28% and 5%, respectively; p= 0.0098) gastric cancer. The improvement in survival rate was statistically significant for the subgroup of patients with gross serosal invasion (52% and 25%, respectively; p= 0.0004) and patients with lymph node metastasis (46% and 22%, respectively; p= 0.0027). The surgeons' impression about lymph node status was unreliable, but assessment of serosal invasion was accurate in 80% of cases. Gross serosal invasion with or without frozen section evaluation of lymph nodes can be used as the major selection criteria for early postoperative intraperitoneal chemotherapy of advanced gastric cancer.