CDR3 spectratyping analysis of the T cell receptor repertoire in Guillain-Barré and Fisher syndromes

Several autoimmune and infectious disorders show oligoclonal expansion of particular T cell phenotypes. The extent of T cell involvement in the pathogenesis of Guillain-Barré syndrome (GBS), a post-infectious autoimmune neuropathy, however, is not clear. To identify the pathogenic T cell phenotypes in GBS and Fisher syndrome (FS), variations in T cell receptor use of the V beta 1-24 and V delta 1-5 chain genes were analyzed at complementarity-determining region 3 level in 119 patients with GBS or FS. Overall, V beta and V delta spectratypes were expanded more frequently in patients with GBS (V beta in 77%, V delta in 53%) or FS (V beta in 75%, V delta in 65%) than in the healthy controls (V beta in 59%, V delta in 38%). No particular spectratype was significantly associated with GBS or FS. Subgrouping the patients by Campylobacter jejuni serology and anti-ganglioside IgG antibodies also failed to detect particular spectratype gene use. The frequency of V beta 5.2 expansion tended to be higher in patients with positive Haemophilus influenzae serology (50%) than in the controls (7%), but the difference was not significant. Our findings show that oligoclonal expansion of T cells bearing particular type T cell receptor V beta and V delta genes frequently occurs in GBS and FS, suggestive that T cells mediate the development of these neuropathies. The predominant phenotypes vary, even within subgroups of patients with a syndrome of single etiological origin or those with uniform serological features.     

Production of compound A under low-flow anesthesia is affected by type of anesthetic machine

Purpose

The purpose was to compare the concentrations of compound A in inspired gas breathed by patients produced by different types of anesthetic machines under prolonged sevoflurane low-flow anesthesia.

Methods

The anesthetic machines tested were Excel? 210 SE (Datex-Ohmeda, Louisville, CO), Cicero? (Dräger, Lübeck, Germany), and AS/3? ADU (Datex-Ohmeda, Louisville, CO). Anesthesia expected to last more than four hours was maintained with 2.0% sevoflurane and nitrous oxide (0.5 L·min^?1) / oxygen (0.5 L·min^?1). The concentrations of compound A, obtained from the inspiratory limb of the circle system, were measured using a gas Chromatograph.

Results

When Excel? and Cicero? were used, concentrations of compound A increased steadily from the baseline values to 28 and 29 (mean) ppm, respectively, at two hours after exposure to sevoflurane and became constant. There was no significant difference between the concentrations of compound A produced by these anesthetic machines. In contrast, the new anesthetic machine AS/3? was associated with lower concentrations of compound A (6 ppm at one hour, P < 0.05 compared with Excel? and Cicero?), and the concentration did not change significantly thereafter.

Conclusion

In spite of the use of a conventional carbon dioxide (CO₂) absorbent with strong bases, the anesthetic machine AS/3? with a small volume of canister/soda lime (900 ml/700 ml) produced lower concentrations of compound A than those produced by the other machines.     

Celite-activated viscometer Sonoclot can measure the suppressive effect of tranexamic acid on hyperfibrinolysis in cardiac surgery

Purpose. To investigate the usefulness of the celite-activated viscometer Sonoclot for monitoring fibrinolytic status in cardiac surgery, we demonstrated the effectiveness of high doses of tranexamic acid, an antifibrinolytic agent, in reducing postoperative bleeding. Methods. Thirty-two American Society of Anesthesiologists (ASA) physical status III patients who required cardiac surgery with cardiopulmonary bypass (CPB) were studied. Anesthesia was induced by a high dose of fentanyl and midazolam with oxygen and was maintained by the intermittent administration of these agents. Patients were divided into two groups: the control group (n = 15) and patients receiving tranexamic acid (TA; n = 17). The TA group received a high dose (50 mg/kg) of TA twice, once before and once after CPB. The percentage diminishing rate of the Sonoclot tracing 15 min after maximum clot signal (DR₁₅) and the amount of postoperative bleeding were measured. Results. After CPB, DR₁₅ in the control group (mean 28.3%) increased significantly by 45%, and the DR₁₅ in the TA group (16.1%) was significantly lower than that in the control group. The amount of postoperative bleeding in the TA group (546 ml) was significantly less, by 34%, than that in the control group (829 ml). Conclusion. Prophylactic administration of high-dose TA in cardiac surgery reduces postoperative bleeding, and this effect is consistent with changes in the diminishing rate using Sonoclot. The celite-activated viscometer Sonoclot is recommended for use in cardiac surgery for rapid assessment of fibrinolytic status. Received: May 23, 2000 / Accepted: September 26, 2000     

Management of abdominal compartment syndrome during extracorporeal life support.

OBJECTIVE: To describe the successful use of a peritoneal dialysis catheter for emergent decompression of abdominal compartment syndrome during extracorporeal life support for septic shock. DESIGN: Case report. SETTING: Pediatric intensive care unit at a freestanding tertiary children's hospital. PATIENT: Two-year-old toddler with influenza A complicated by methicillin-resistant Staphylococcus aureus pneumonia and septic shock. INTERVENTIONS: Placement of peritoneal dialysis catheter. MEASUREMENTS AND MAIN RESULTS: Changes in hemodynamic and respiratory parameters. Improvement in extracorporeal membrane oxygenation venous drainage with subsequent survival. CONCLUSIONS: Although the standard therapy for abdominal compartment syndrome is decompressive laparotomy, a minimally invasive percutaneous approach may be effective and should be considered in selected patients.     

Antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210

Background: MDX-210 is a bispecific antibody (BsAb) with specificity for both the proto-oncogene product of HER-2/neu (c-erbB-2) and FcRI (CD64). HER-2/neu is overexpressed in malignant tissue of approximately 30% of patients with breast cancer, and FcRI is expressed on human monocytes, macrophages, and IFN- activated granulocytes. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by human monocyte-derived macrophages (MDM) mediated by BsAb MDX-210, its partially humanized derivative (MDX-H210), and its parent MoAb 520C9 (anti-HER-2/neu) under various conditions.Materials and Methods: Purified monocytes were cultured with GM-CSF, M-CSF, or no cytokine for five or six days. Antibody dependent cellular phagocytosis (ADCP) and cytolysis (ADCC) assays were performed with the MDM and HER-2/neu positive target cells (SK-BR-3). ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and phycoerythrin-conjugated (red) monoclonal antibodies (MoAb) against human CD14 and CD11b. ADCC was measured with a non-radioactive LDH detection kit.Results: Both BsAb MDX-210 (via FcRI) and MoAb 520C9 (mouse IgG1, via FcRII) mediated similar levels of ADCP and ADCC. ADCP mediated by BsAb MDX-H210 was identical to that mediated by BsAb MDX-210. Confocal microscopy demonstrated that dual-labeled cells represented true phagocytosis. Both ADCP and ADCC were higher when MDM were pre-incubated with GM-CSF than when incubated with M-CSF.Conclusions: BsAb MDX-210 is as active in vitro as the parent MoAb 520C9 in inducing both phagocytosis and cytolysis of MDM. MDX-210 and its partially humanized derivative, MDX-H210, mediated similar levels of ADCP. GM-CSF appears to superior to M-CSF in inducing MDM-mediated ADCC and ADCP. These studies support the ongoing clinical investigations of BsAb MDX-210 and its partially humanized derivative.     

Discrimination of dimethylamphetamine and methamphetamine use: simultaneous determination of dimethylamphetamine-N-oxide and other metabolites in urine by high-performance liquid chromatography-electrospray ionization mass spectrometry

A simple and sensitive method by high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) has been investigated for the simultaneous determination of dimethylamphetamine (DMA), its specific yet labile main metabolite dimethylamphetamine-N-oxide (DMAO), and other metabolites, methamphetamine (MA) and amphetamine (AP), in urine. A combination of Bond Elut SCX columns for the solid-phase extraction of urine and a semi-micro SCX column for LC separations provided satisfactory results. The use of acetonitrile/5mM ammonium acetate buffer adjusted to pH 4 (65:35, v/v) as the mobile phase at a flow rate of 0.2 mL/min was found to be the most effective. The detection limits were 5 ng/mL for DMAO, 10 ng/mL for DMA and MA, and 50 ng/mL for AP in the SIM mode.     

Changes in concentrations of free propofol by modification of the solution

Because free propofol is thought to be responsible for pain on injection, we investigated the changes in concentrations of free propofol by modifying two kinds of propofol products in a medium- and long-chain triglyceride (MCT/LCT) emulsion and in an LCT emulsion. The techniques used in this study were 1) mixing 2% lidocaine (10:1), 2) mixing 5% dextrose in acetated Ringer's solution to reduce pH (10:1), and 3) changing the temperature to 4 degrees , 20 degrees , and 36 degrees C. The propofol preparations were dialyzed for 24 h, and the receptor medium was analyzed using high-performance liquid chromatography. The concentration of free propofol in propofol MCT/LCT was significantly smaller by 30% than that in propofol LCT. Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products, but the concentrations were reduced by a decrease in pH and by an increase in temperature. Because mixing lidocaine can induce instability in an emulsion of propofol and warming can rapidly induce microbial growth, injection of lidocaine before propofol administration is recommended to reduce the pain on injection. The concentrations of free propofol in propofol MCT/LCT were significantly smaller (by approximately 30%-45%) than those in propofol LCT during any situation in this study. IMPLICATIONS: Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products but the concentrations were reduced by a decrease in pH and by an increase in temperature. Propofol medium- and long-chain triglycerides had significantly smaller concentrations by approximately 30%-45% than those in propofol long-chain triglycerides during any situation in this study.     

The Relationship between Serum Insulin-Like Growth Factor-1 Levels and Body Composition Changes after Sleeve Gastrectomy

IntroductionWe previously reported that preoperative serum insulin-like growth factor-1 (IGF-1) is a predictor of total weight loss percentage (%TWL) after laparoscopic sleeve gastrectomy (LSG). IGF-1 may suppress muscle loss after surgery. IGF-1 almost accurately reflects the growth hormone (GH) secretion status, and GH has lipolytic effects. Therefore, IGF-1 may influence both the maintenance of skeletal muscle and the reduction of adipose tissue after LSG. The identification of the relationship between preoperative serum IGF-1 and body composition changes after LSG can help in understanding the pathophysiology of obesity.MethodsWe retrospectively reviewed 72 patients with obesity who underwent LSG and were followed up for 12 months. We analyzed the relationship between preoperative serum IGF-1 levels and body composition changes after LSG. A multiple regression model was used.ResultsLSG led to a significant reduction in body weight. Both body fat mass and skeletal muscle mass decreased after LSG. Preoperative serum IGF-1 levels significantly correlated with %TWL, changes in skeletal muscle mass, and body fat mass after LSG. The multiple regression model showed that preoperative serum IGF-1 levels were related to decreased body fat mass and maintaining skeletal muscle mass after LSG.Discussion/ConclusionPreoperative IGF-1 measurement helps predict not only successful weight loss but also decreases body fat mass and maintains skeletal muscle mass after LSG.