Serial measurement of lymphocytotoxic antibody and response to nonmatched platelet transfusions in alloimmunized patients

Serial evaluations of lymphocytotoxic antibody (LCTAb) and responsiveness to random donor platelet transfusion were reviewed in 234 patients who had developed LCTAb at some time during their treatment course. Seventy (30%) of these patients had significant falls in antibody levels. In 44 patients these declines occurred after further antigenic exposure was reduced either because no transfusions were administered or only histocompatible platelets were transfused. Forty patients with declines in LCTAb levels who were previously refractory to platelet transfusion were rechallenged with random donor platelets. Thirty-four of 35 clinically evaluable patients had good responses to these unmatched transfusions for 2 weeks to 36 months, and in 21 patients antibody did not return despite repeated transfusions. Thus, serial LCTAb measurements are helpful in the management of alloimmunized patients. Many patients will have decreases or a loss of LCTAb, either permanently or transiently, and can be successfully supported with more easily available unmatched random donor platelet transfusions.     

Staging of head and neck squamous cell cancer with extended-field FDG-PET

BACKGROUND: Accurate baseline staging is necessary to appropriately treat head and neck squamous cell carcinoma. [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) is valuable for locoregional staging of primary head and neck disease. The effectiveness of FDG-PET for the detection of distant metastatic or synchronous disease remains unproven. OBJECTIVE: To investigate the utility of FDG-PET extended into the abdomen (extended-field FDG-PET) for wide-field staging of head and neck tumors. METHODS: This is a prospective institutional study of 35 consecutive patients diagnosed with American Joint Committee on Cancer (AJCC)-defined stage II-IV squamous cell carcinoma of the oral cavity, oropharynx, or larynx between September 2000 and June 2002. Thirty-three patients (94%) were eligible for analysis. All patients were routinely staged with chest radiography, liver function tests, and extended-field FDG-PET. Chest or abdominal computed tomographic scans were used as corroborative studies and were obtained only when one of the above tests indicated distant disease. RESULTS: Of 33 patients, 7 (21%) had evidence of distant disease by extend-field FDG-PET-4 with metastases and 3 with synchronous primary cancers of the aerodigestive tract. [F-18]-fluorodeoxyglucose PET detected hepatic, bone, gastrointestinal, and mediastinal disease not identified by chest radiography or liver function tests. Two of the 7 patients with FDG-avid distant disease had false-negative staging by all other tests, including computed tomography. CONCLUSIONS: Extended-field FDG-PET is feasible and may improve staging of primary head and neck squamous cell carcinoma. Use of staging FDG-PET must be explicitly described in reports from centers engaged in prospective research to facilitate comparison with historical results.     

脑卒中患者对负性情绪及心理治疗认知状况的调查

目的：调查甘肃省脑卒中患者对负性情绪是否影响肢体功能以及心理治疗的认知。方法：采用问卷调查方式,对甘肃省10家不同级别的省市县级医院神经内、外科2010年收治的脑卒中住院患者1 100例进行调查。结果：负性情绪对肢体功能恢复的影响占69.80%,脑卒中后心理治疗的需要占76.99%。结论：负性情绪对脑卒中患者肢体功能恢复有影响,并且非常需要心理治疗。     

Dose-response relationships for edrophonium and neostigmine as antagonists of moderate and profound atracurium blockade

To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P less than 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED80) after 10 minutes was 0.013 +/- 0.003 mg/kg (mean +/- SEM) if given at 10% recovery, and 0.032 +/- 0.004 mg/kg if given at 1% recovery. The ED80 for edrophonium was 0.22 +/- 0.04 mg/kg and 1.14 +/- 0.33 mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 16.6 +/- 3.5 and 35.3 +/- 8.9 at 90% and 99% blockade respectively (P less than 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade.     

Biologic basis for interleukin-1 in disease

To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in disease, investigators have studied how production of the different members of the IL-1 family is controlled, the various biologic activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family, and the complexity of intracellular signaling. Mice deficient in IL-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been studied. Humans have been injected with IL- 1 (either IL-1alpha or IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical trials. The topics discussed in this review include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and soluble IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokines limiting IL-1 production or activity, the effects of blocking cyclooxygenase and nitric oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special attention is paid to IL-1beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references. At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.     

Mutational analysis of CD28 in coeliac disease

BACKGROUND: Coeliac disease shows a strong genetic predisposition involving HLA-DQ2 and non-HLA components. The CD28 cell surface molecule, encoded by CD28, represents a potential candidate coeliac disease susceptibility gene. Furthermore, some studies have demonstrated linkage to the CD28/CTLA4 gene region. To investigate whether germline mutations in CD28 contribute to coeliac disease susceptibility, we have carried out a comprehensive analysis of the gene in Swedish patients with biopsy-proven disease. METHODS: Blood samples were collected from 52 children with biopsy proven coeliac disease attending one Swedish centre. DNA was extracted from lymphocytes and all exons and intron-exon boundaries of CD28 were screened for mutations. Analysis of CD28 was undertaken by a combination of conformation specific gel electrophoresis and direct sequencing. RESULTS: Three sequence variants were identified: a synonymous G-->4A substitution at position 3 of codon 35 encoding alanine, a synonymous G-->A substitution at position 3 of codon 70 encoding glycine, and a T-->C substitution at nucleotide +17 of intron 3. No pathogenic variants were detected. CONCLUSIONS: There is no evidence from this study that mutations in CD28, which lead to an altered protein, contribute to coeliac disease susceptibility.     

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.     

Persistent reversed end diastolic flow in the fetal middle cerebral artery: an ominous finding

Fetal persistent middle cerebral artery reversed end diastolic flow is a rare and ominous finding. Previous cases have been associated with intracranial hemorrhage, growth restriction, anaemia, and hepatic anomaly. Intrauterine demise or early neonatal death is a common outcome. We report the case of persistent middle cerebral artery reversed end diastolic flow in a well-grown fetus at 32 weeks’ gestation resulting from acute, severe anaemia due to a large feto-maternal hemorrhage. An emergency cesarean section was performed and the neonate required advanced resuscitation and immediate blood transfusion. Postnatal magnetic resonance imaging confirmed a hemorrhagic parietal infarct and bilateral ischaemic changes in the basal ganglia. This provides further evidence that persistent middle cerebral artery reversed end diastolic flow in any fetus is an ominous finding warranting urgent diagnostic evaluation and/or delivery.