Efficacy and safety of fluticasone propionate 250 microg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids.

BACKGROUND: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. OBJECTIVE: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). METHODS: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. RESULTS: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). CONCLUSIONS: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.     

A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-Hooded rats

Vigabatrin (gamma-vinyl GABA), an enzyme-activated, irreversible inhibitor of GABA transaminase, was administered orally to albino Sprague Dawley and pigmented Lister-Hooded rats. A dose-dependent retinal lesion characterized histologically by disruption of the outer nuclear layer was observed in the Sprague Dawley rat but not in Lister-Hooded rats, indicating that this alteration is related to the absence of pigment. The lesion is similar to that induced in albino rats by light and certain drugs. In addition, myelin vacuolation of the brain was observed in both rat strains, consistent with the findings of other toxicity studies with vigabatrin. In all cases, the vacuolation was limited to myelinated tracts and resulted from separation of the myelin sheath at the intraperiod line. There was no evidence of demyelination, axonal degeneration or damage to contiguous structures in the affected areas. The vacuolation is histologically similar to that induced in rats by certain other compounds such as isoniazid, hexachlorophene, and triethyltin, but differs in that it is focal in distribution, it is limited to the brain, and is reversible upon cessation of treatment.     

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma involving bone marrow with an interfollicular pattern

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) may involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns. However, B-cell CLL/SLL associated with large reactive germinal centers (the so-called interfollicular pattern) involving the bone marrow is not reported. We describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow with an interfollicular pattern. In both cases, the neoplasms were composed of small round lymphoid cells; proliferation centers also were present. The neoplasms surrounded large reactive germinal centers that were devoid of peripheral mantle zones. The germinal centers were paratrabecular and nonparatrabecular in case 1 and nonparatrabecular in case 2. Flow cytometry immunophenotypic studies done on bone marrow aspiration samples of both cases showed a uniform population of neoplastic cells positive for pan-B-cell antigens and the CD5 and CD23 antigens. Immunohistochemical studies done on bone marrow biopsy sections supported the flow cytometry results and demonstrated that the germinal centers were negative for BCL-2. B-cell CLL/SLL may rarely involve the bone marrow with an interfollicular pattern. Knowledge of this pattern will prevent confusion with follicle center lymphoma and large cell transformation, both of which initially were considered in the differential diagnosis of these cases.     

Standardization of rye-grass pollen (Lolium perenne) extract. An immunochemical and physicochemical assessment of six candidate international reference preparations

Six candidate extracts of Lolium perenne (rye-grass) pollen have been studied in 6 laboratories using a variety of immunochemical and physicochemical techniques. Radioallergosorbent test inhibition, crossed immunoelectrophoresis, crossed radio-immunoelectrophoresis, sodium dodecyl sulphate-polyacrylamide gel electrophoresis combined with immunoblot, thin-layer isoelectric focusing and enzyme-linked immunosorbent assay inhibition were used to evaluate each of the coded extracts. The source materials were also studied for identity and possible contamination by light microscopy. On the basis of these data, the Rye-Grass Working Party recommended to the Steering Committee of the Allergen Standardization Subcommittee of the International Union of Immunological Societies that the extract coded C be chosen as the candidate international reference preparation.     

A reversed-phase high-performance liquid chromatographic assay for the determination of N-acetylcysteine in aqueous formulations

A stability-indicating assay is described for the determination of N-acetylcysteine in aqueous pharmaceutical formulations. The sample is diluted to an appropriate concentration with dilute aqueous orthophosphoric acid. An aliquot of the solution, containing added l-tyrosine as an internal standard, is chromatographed using a 10-mum C(18) stationary phase with dilute orthophosphoric acid (pH 2.0) containing 0.5% w/v of sodium perchlorate as the mobile phase. The assay, which has a relative standard deviation of about 0.8%, can also be used as a test for related impurities in N-acetylcysteine. It is also suitable for determining the N-acetylcysteine content of the drug substance.     

Primary prevention: Key issues and a competence perspective

At a superficial level, one might characterize the primary prevention debate as centering on the question of whether primary prevention has been demonstrated to be an effective means of promoting mental health. This interpretation is supported by the clarity and strength of the confident generalizations of primary prevention proponents such as Dr. Albee (We have a lot of evidence on the effectiveness of primary prevention ... it is available in the literature for all to read) and primary prevention critics such as Dr. Lamb (... The major functional mental illnesses, as well as the frequently occurring diagnosable minor illnesses, remain untouched by efforts to strengthen mental health.). However, it seems clear that the disagreement is not primarily a matter of differences in data interpretation (although this is clearly a part of the problem). Rather, it seems to be mostly a function of differences at the level of basic assumptions about the nature of mental illness and the appropriate scope of activity for mental health professionals.     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...