Pharmacologic treatment of fibromyalgia

Fibromyalgia is a syndrome of widespread pain, nonrestorative sleep, disturbed mood, and fatigue. Optimal treatment involves a multidisciplinary approach with a team of health care providers using pharmacologic and nonpharmacologic treatment. Because of the heterogeneity of the illness, management should be individualized for the patient. Pharmacologic treatment should address issues of pain control, sleep disturbance, fatigue, and any underlying coexisting mood disorder. Nonpharmacologic treatment should include patient education, a regular exercise and stretching program, and cognitive behavioral therapy. All of these are essential to improving functional capacity and quality of life. This review provides general guidelines in initiating a successful pharmacologic treatment program for patients with fibromyalgia.     

Haloperidol impairs classically conditioned nictitating membrane responses and conditioning-related cerebellar interpositus nucleus activity in rabbits

Rabbits, chronically implanted with recording electrodes in the cerebellar interpositus nucleus and following acquisition of a classically conditioned eyelid response, were injected with haloperidol (HAL, 250 micrograms/kg). HAL significantly reduced the number of conditioned responses when a 75 and 85 dB tone conditioned stimulus (CS) was presented but not when a 95 dB tone CS was used. There was a corresponding decrease in interpositus activity at the 75 and 85 dB CS intensities but not at the 95 dB intensity. HAL appeared to disrupt CRs and interpositus activity by increasing the intensity threshold of the tone CS for eliciting conditioned responses. Possible mechanisms for the effect of HAL on neural circuitry involved in classical eyelid conditioning are discussed.     

Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma.

PURPOSE: Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown. Materials and METHODS: We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation. RESULTS: Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P =.007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P =.009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P =.03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV. CONCLUSION: Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.     

Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.     

Conventional versus digital radiographs for intraoperative cervical spine-level localization: a prospective time and cost analysis

BackgroundIn today's health-care environment, operational efficiency is intrinsic to balancing the need for increased productivity driven by rising costs and potentially decreasing reimbursement. Other operational factors kept constant, decreasing the time for a procedure can be viewed as one marker for increased efficiency.PurposeTo prospectively evaluate the time and operating room efficiency differences between the two methods for intraoperative level localization.Stydy designProspective nonrandomized study.Patient sampleProspective consecutive patients undergoing a single-level anterior cervical discectomy and fusion (ACDF) with plate and allograft.Outcomes measuresTime for performance and interpretation of intraoperative localization radiograph.MethodsThis is a prospective nonrandomized study of patients treated consecutively with a single-level ACDF with allograft and plating. All the patients underwent a conventional approach to the cervical spine. After exposure, a spinal needle was placed in the exposed intervertebral disc and a radiography was performed. Either a conventional or a digital radiography was used in each case.ResultsEighteen patients were enrolled in this study. Ten patients underwent localization with conventional radiography, whereas eight patients underwent localization with digital imaging. The mean time for conventional radiography was 823 seconds (standard deviation [SD], 159), and for digital, it was 100 seconds (SD, 34; p<.001).ConclusionsCurrent technology provides options for level localization. Digital imaging provides equally accurate information as conventional radiography in a significantly reduced amount of time. Image quality, ease or archival, and manipulation provided by digital radiography are superior to those by provided fluoroscopy. Keeping operational factors constant, decreasing the time for a procedure, and increasing the efficiency of the environment may be viewed as a surrogate for improving the cost basis for a procedure.     

Immunoassays for proteins alkylated by nicotine-derived N-nitrosamines

Polyclonal antibodies recognizing the pyridyloxobutyl (POB) moiety of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were produced in rabbits immunized either with POB-bovine albumin or POB-Sepharose. The POB intermediates necessary to modify the protein were generated by alkaline (pH 9.0) treatment of the synthetic precursor 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone. In a competitive enzyme linked immunoabsorbent assay (ELISA), 70 pmole NNK inhibited 50% of the binding of the anti-POB antibodies to POB-protein absorbed on microtiterplates. This 50% inhibition varied from 70 pmole to 200 nmole using a series of NNK analogues, depending on the integrity of the POB moiety. Immunological techniques initiated in this study detect NNK-protein conjugates or measure the quantity of POB groups liberated upon alkaline or acid treatment of NNK modified protein.