The effect of fentanyl on the emergence characteristics after desflurane or sevoflurane anesthesia in children

Desflurane and sevoflurane anesthesia are associated with emergence agitation in children. In this study, we examined the effect of a single intraoperative dose of fentanyl on emergence characteristics in children undergoing adenoidectomy. One hundred children, 2-7 yr old, were randomly assigned to receive desflurane or sevoflurane for maintenance of general anesthesia after an inhaled induction with sevoflurane and a 2.5 microg/kg dose of fentanyl. An observer blind-ed to the anesthetic technique assessed the times to achieve emergence, extubation and recovery criteria, as well as emergence behaviors. The results showed a similar incidence of severe emergence agitation after general anesthesia with desflurane (24%) and sevoflurane (18%). Times to achieve extubation and postanesthesia care unit discharge criteria were shorter with desflurane than with sevoflurane. With this technique, desflurane allows for a more rapid emergence and recovery than sevoflurane. In children receiving desflurane or sevoflurane, the concurrent use of fentanyl in a dose of 2.5 microg/kg results in a small incidence of emergence agitation. IMPLICATIONS: The concurrent use of fentanyl in a dose of 2.5 microg/kg in children receiving desflurane or sevoflurane results in a low incidence of emergence agitation. Desflurane allows for a more rapid emergence and recovery than sevoflurane.     

Effects of Delayed Administration of Low-dose Lidocaine on Transient Focal Cerebral Ischemia in Rats

Background: The authors' previous study demonstrated that a clinical antiarrhythmic dose of lidocaine, when given before ischemia, is neuroprotective in a rat model of transient focal cerebral ischemia. In this study, the authors investigated whether the administration of this dose of lidocaine, when delayed until 45 min after the onset of ischemia, also reduces ischemic brain injury.

Methods: Lidocaine was administered as an intravenous bolus (1.5 mg/kg) followed by an intravenous infusion (2 mg [middle dot] kg-1 [middle dot] h-1) for 165 min, beginning 45 min after the onset of a 90-min period of transient focal cerebral ischemia. Control animals were given the same volume of saline. Focal cerebral ischemia was induced by occluding the right middle cerebral artery using an intraluminal suture. Neurologic outcome and body weight loss were quantified 7 days later. The brain was fixed 7 days after ischemia and brain sections were stained with hematoxylin and eosin for assessment of infarct size and the number of intact neurons. In separate experiments, local cerebral blood flow and the electroencephalogram were measured during ischemia and 180 min into the reperfusion period. Infarct size was assessed after 24 h.

Results: Infarct size, at either 24 h or 7 days after ischemia, was not significantly reduced in the lidocaine group. However, the number of intact neurons was significantly increased in both the ischemic penumbra and core of the lidocaine group 7 days after ischemia, compared with the vehicle group. Rats treated with lidocaine demonstrated better neurologic outcome and less weight loss (P < 0.05). Lidocaine treatment had no significant influence on local cerebral blood flow and electroencephalogram during ischemia and reperfusion.     

Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection

BACKGROUND: Chronic human lung allograft rejection, represented by bronchiolitis obliterans syndrome (BOS), is the single most important factor that limits the long-term survival following lung transplantation (LT). However, the pathogenesis of BOS remains unclear. We hypothesized that the early posttransplant inflammation would promote the development of donor anti-human leukocyte antigen (HLA) alloimmunity and predispose to BOS. METHODS: Serum levels of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, IP-10, MIG, MCP-1, MIP-1alpha, MIP-1beta, RANTES, tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-gamma, granulocyte-macrophage colony-stimulating factor, IL-1Ralpha, and IL-2R were serially analyzed in 31 BOS+ and matched 31 BOS- patients using quantitative multiplex bead immunoassays. Donor-specific HLA class II cellular immunity was analyzed using enzyme-linked immunospot (ELISPOT) by testing recipient peripheral blood mononuclear cells against mismatched donor HLA-DR peptides. Anti-HLA class II antibodies were monitored using flow panel reactive antibodies. RESULTS: There was early posttransplant elevation in basal serum levels of proinflammatory chemokines IP-10 and MCP-1 and Th1-cytokines IL-1beta, IL-2, IL-12, and IL-15 in BOS+ patients, compared to BOS- and normal subjects. In addition, a threefold decline in IL-10 levels was found during BOS development. BOS+ patients revealed increased development of HLA class II alloantibodies and Th1-predominant donor-specific cellular immunity with high frequency of IFN-gamma and low IL-5 producing T-cells. CONCLUSION: Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.     

Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer

PURPOSE: The insulin-like growth factor (IGF)-1 receptor is currently being targeted in clinical trials in prostate cancer. Despite this targeting, there are conflicting data on the presence of this receptor in human tumor samples, largely because of differences in technique. MATERIALS AND METHODS: Immunohistochemistry was used to determine the presence of IGF-1 receptor in frozen normal prostate and prostate cancer specimens. Clinical and pathologic parameters were correlated with IGF-1 receptor intensity and frequency of staining. Only 2-3+ staining on a scale of 0-3 was considered positive in this evaluation. RESULTS: IGF-1 receptor was expressed in normal prostate epithelium in 6 of 6 patients without cancer and in morphologically normal epithelium adjacent to tumor cells in 21 of 22 patients with cancer studied. IGF-1 receptor was present in the prostate tumor epithelium of 28 of 28 primary tumors, 3 of 5 locally recurrent androgen-independent tumors, and in 4 of 5 metastatic lymph nodes. Stromal staining patterns were positive in 2 of 28 specimens near benign epithelium compared to 19 of 30 specimens of stroma surrounding tumor epithelium (P < 0.0001, Fisher exact test). Stroma adjacent to Gleason grade >or=7 tumors showed higher intensity staining than that adjacent to lower grade tumors (P < 0.001). Expression of the closely related insulin receptor did not show expression in either normal or cancer epithelium, or in adjacent stroma. CONCLUSIONS: This study using frozen tissue shows widespread IGF-1 receptor expression in normal prostate, prostate cancers, and metastases. These data support investigations into IGF-1 receptor as a therapeutic target in prostate cancer.     

Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF

Human embryonic stem (hES) cells have the ability to differentiate into a variety of different cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. Here we investigated an efficient method of hepatic differentiation from hES cells. A human ES cell line, KhES-1, was used and maintained by a nonfeeder method. KhES-1 cells were cultured for 5 days in the presence of human activin A (50 ng/ml) and then treated with a deleted variant of hepatocyte growth factor (dHGF) at 0, 100, or 500 ng/ml for 7 days. The resultant cells were biologically analyzed. The expression of the endodermal genes SOX17 and FOXA2 increased in KhES-1 cells after activin A treatment. In contrast, Oct4, a self-renewal undifferentiated marker, decreased in a time-dependent manner in KhES-1 cells. Following a 7-day treatment of the resultant cells with dHGF, especially at 500 ng/ml, KhES-1 cells showed an expression of the hepatic makers albumin, AFP, and CK18. Transitional electron microscopy showed well-developed glycogen rosettes and a gap junction in KhES-1 cells treated with 500 ng/ml of dHGF. We developed an efficient method to differentiate KhES-1 cells into hepatocyte-like cells in vitro using 50 ng/ml of activin A and 500 ng/ml of dHGF.     

Effects of chronic estrogen treatment on modulating age‐related bone loss in female mice

While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age‐related bone loss, we sham‐operated, ovariectomized, or ovariectomized and estrogen‐replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin–) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six‐month‐old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham‐operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen‐treated mice did not prevent age‐related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age‐related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham‐operated mice. As compared with cells from young mice, lin– cells from aged/sham‐operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age‐related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. © 2010 American Society for Bone and Mineral Research.     

Blood transfusion in critically injured patients: a prospective study

BACKGROUND: Despite evolving evidence that transfusion risks outweigh benefits in some patients, the critically injured continue to receive large quantities of blood. The present study evaluated patterns of red blood cell transfusions and risk factors for transfusions at various stages of admission in trauma patients. STUDY DESIGN: Prospective, observational study of transfusion practices in patients (n = 120) admitted to a single Level 1 academic trauma centre. Patients were expected to remain in the surgical intensive care unit for greater than 48 h. RESULTS: Patients had a mean age of 34.1+/- 16.0 years, a mean injury severity score (ISS) of 21.5 +/- 9.5, and were equally distributed by major injury type (48% blunt, 52% penetrating). One hundred and four patients (87%) received a total of 324 transfusions, 20 (6%) of which were given in the emergency room, 186 (57%) in the SICU, 22 (7%) post-SICU and 96 (30%) in the operating room. The mean volume of blood per patient transfused was 3144 +/- 2622 mL. One hundred and one patients received an allogeneic transfusion (mean volume 3126 +/- 2639 mL) and 10 patients received an autotransfusion (844 +/- 382 mL). The mean pre-transfusion Hb level was 9.1 +/- 1.4 g/dL. Transfusion volumes correlated with injury severity score (p = 0.011). Patients with an admission Hb < or =12 g/dL or age >55 years were at significant risk to receive increased transfusions (P < .001 and P = .035, respectively). An admission Hb < or =12 g/dL and any mention of long bone orthopedic operations or laparotomy or thoracotomy were associated with increased risk of blood transfusion during the first week of admission. Logistic regression analysis identified transfusion of >4 units of blood as a significant risk factor for SIRS. After 1 week of ICU stay, ISS > 20 and blunt injury were associated with increased risk of transfusion. CONCLUSIONS: Trauma patients are heavily transfused with allogeneic blood throughout the course of their hospital stay and transfusions are administered at relatively high pre-transfusion haemoglobin levels (mean of 9 g/dL). Transfusion of >4 units of blood is an independent risk factor for SIRS. Strategies to limit blood transfusions should be investigated in this population.     

Identifying potential germline variants from sequencing hematopoietic malignancies

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Transjugular intrahepatic portosystemic shunt for refractory ascites: an analysis of the literature on efficacy, morbidity, and mortality

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is frequently used to treat patients with refractory ascites, but its role is controversial. We sought to determine from the literature the efficacy, morbidity, and mortality associated with TIPS for refractory ascites. METHODS: We searched MEDLINE and identified studies published in English from January, 1985, to March, 2003, that evaluated the effect of TIPS in patients with refractory ascites. Outcomes that were analyzed included complete resolution of ascites, reduction in ascites, mortality, encephalopathy, stenosis, and renal function. Data were analyzed on an intention to treat basis. RESULTS: Of 25 studies identified, 16 were included in the analysis. The pooled estimate for complete response at 6 months was 45% and for any response (complete and partial) was 63%. Pooled 6-month mortality after TIPS was 36%. Risk factors for mortality included renal insufficiency (serum creatinine >1.5 mg/dl), hyperbilirubinemia (total bilirubin >3 mg/dl), advanced age (>60 yr), and poor response to TIPS. The pooled rate of new or worsening encephalopathy after TIPS was 32%. In most cases, encephalopathy was managed medically or by reduction in shunt size; however, refractory cases were associated with 100% mortality in most studies. Studies reporting the effect of TIPS on kidney function showed improvement in creatinine clearance and urinary sodium excretion. CONCLUSIONS: TIPS is effective in eliminating ascites or substantially reducing ascites in cases refractory to medical therapy. Renal insufficiency, refractory encephalopathy, and hyperbilirubinemia were consistently associated with mortality after TIPS. In individuals with risk factors for mortality, alternative strategies should be recommended.