Effect of anti-interferon-γ and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE.     

Rizatriptan in the treatment of migraine

Migraine is a common, disabling disorder associated with considerable personal and societal burden. Current guidelines recommend triptans for the acute treatment of migraine unlikely to respond to less effective therapies. Rizatriptan is a second-generation triptan available in tablet or orally disintegrating tablet (wafer) formulations that offers several advantages over other members of its class. Rizatriptan is rapidly absorbed from the gastrointestinal tract and achieves maximum plasma concentrations more quickly than other triptans, providing rapid pain relief. Clinical trials have shown that rizatriptan is at least as effective or superior to other oral migraine-specific agents in the acute treatment of migraine, and has more consistent long-term efficacy across multiple migraine attacks. Rizatriptan has a favorable tolerability profile, and patients have reported greater satisfaction and a preference for rizatriptan over other migraine-specific agents. Improvements in quality of life reported with rizatriptan are consistent with its favorable efficacy and tolerability profiles. Notably, multi-attribute decision models that combine clinical data with patient- and physician-reported treatment preferences have identified rizatriptan as one of three triptans closest to a hypothetical “ideal”. The efficacy and tolerability of rizatriptan for the acute treatment of migraine have thus been well established.     

Intraoperative Awareness in a Regional Medical System: A Review of 3 Years' Data

Background: Intraoperative awareness in patients undergoing general anesthesia is an infrequent but well-described adverse outcome. The reported incidence of this phenomenon is between 0.1% and 0.9%.

Methods: With institutional review board approval, the authors reviewed continuous quality improvement data from 3 yr (2002-2004) at the locations where the physician group provided anesthesia. Board-certified anesthesiologists supervising certified registered nurse anesthetists in the anesthesia care team model of practice delivered all anesthetics. Brain function monitors were not used in the operating room setting. Patients were interviewed twice during a 48-h postoperative period and, as part of that process, underwent a modified Brice interview to determine intraoperative awareness. All cases that met the criteria for awareness were examined by the continuous quality improvement committee to modify anesthetic practice and were included in this study.

Results: Data from 211,842 patients undergoing anesthesia were considered. Of these, the continuous quality improvement process followed up 177,468 (83.1%). Cases were not included in the study if the patient was younger than 18 yr, did not have a general anesthetic, or had a terminal event during the hospital course. By these criteria, a total of 87,361 patients followed by the continuous quality improvement process were at risk for awareness. Six patients reported instances of recall.     

Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes.

Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 microM) known to activate GR. In contrast, treatment with 0.1 microM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human (h)GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor (hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor.     

Aerotitis: cause, prevention, and treatment

Aerotitis, an acute inflammation of the middle ear caused by the difference in air pressure between the airplane cabin and the middle-ear space, is becoming more common in the United States as our society becomes increasingly mobile. We describe a case in which a 33-year-old woman with a resolving upper respiratory tract infection and mildly blocked eustachian tubes flew on a business trip. During ascent, her ears became blocked. This blockage was partially alleviated by a Valsalva's maneuver. On descent, however, her ears became severely blocked, she experienced intense pain, and her tympanic membranes ruptured. She became nauseated and vomited. Her hearing became significantly diminished and she experienced vertigo. On landing, she was taken to a local emergency room and treated with penicillin and antivertiginous medication. Subsequent otologic evaluation revealed severe permanent sensorineural hearing loss. The vestibular symptoms lasted several months. She now requires hearing aids on a permanent basis. Suggestions are presented for prevention and treatment of aerotitis.     

Terra es animata On Having a Life

To live the risen life with God is, presumably, to be what we are meant to be. What can we conclude about our duties to the dying from the medieval belief that we join the hosts of heaven as “animated earth”?     

Effect of middle ear effusion on the vestibular labyrinth.

Although middle ear effusion was once described as the most common cause of vestibular disturbance in children, the association between glue ear and symptoms of dysequilibrium has never been quantified objectively. In this study the effect of middle ear effusion on the vestibular system of the inner ear was studied in a select group of children suffering from long lasting effusion in the middle ear with no evidence of infection at least one year prior to the study. The results were compared with results obtained from otitis free children, as well as from examinations of children after the insertion of ventilating tubes. The results of this study confirm the assumption that middle ear effusion has an adverse effect on the vestibular system, which can be resolved following the insertion of ventilation tubes. This effect may also contribute to the adverse effect that otitis media has on a child's development.     

Sclerosing epithelioid fiberosarcoma: short T2 on MR imaging

A case of sclerosing epithelioid fibrosarcoma and its appearance on MRI is presented. The tumor showed a zonal architecture on MRI with a large central core of very low signal intensity and a peripheral rim of intermediate to high signal intensity on T1- and T2-weighted spin echo pulse sequences. The core showed decreased cellularity with dense collagen deposition on histologic examination, and the peripheral zone increased cellularity with increased nuclear atypia. The presence of a prominent region of very low signal intensity on T1- and T2-weighted images can be seen with neural tumors, giant cell tumor of the tendon sheath, aggressive fibromatosis, and, in rare instances, with soft tissue sarcomas rich in collagen.