Prevalence and nature of side effects during clozapine maintenance treatment and the relationship with clozapine dose and plasma concentration.

Clozapine is associated with non-neurological side effects that can be subjectively unpleasant and/or clinically serious. We sought to: (i) assess the nature and prevalence of side effects experienced by patients receiving maintenance treatment with clozapine and (ii) explore the relationship between clozapine plasma concentration and side effect burden. Patients were receiving clozapine maintenance treatment.

Differential regulation of hypoxia-inducible factor-1 through receptor tyrosine kinase transactivation in vascular smooth muscle cells.

Hypoxia-inducible factor-1 (HIF-1) is a decisive element for the transcriptional regulation of many genes expressed in hypoxic conditions. In vascular smooth muscle cells, the vasoactive hormone angiotensin II (Ang II) is a very potent inducer and activator of HIF-1. As opposed to hypoxia, which induces HIF-1alpha by protein stabilization, Ang II induced HIF-1alpha through transcriptional and translational mechanisms.

Physiological approach to monitor patients in congestive heart failure: application of a new implantable device-based system to monitor daily life activity and ventilation.

Aims: We examine an expert system designed to permanently monitor patients with congestive heart failure (CHF) using data of a dual-sensor pacemaker and to allow warning of significant changes in physiological indices.

Methods And Results: This study included 67 implanted patients divided into two groups: a control group without history of CHF (n = 19) who had received DDDR pacemakers (DDD group) and a test group (n = 48) who had received cardiac resynchronization therapy systems (CRT group) for severe CHF (NYHA III or IV, LVEF <40%). The embedded monitoring system measures minute ventilation (MV) and activity (ACT) at rest and at exercise.

Photoinduced reorientation of nematic liquid crystals doped with an azo dye: a dynamic and steady-state study of reorientation and loss of liquid crystal order.

We compare photoinduced reorientation of homeotropic and planar aligned nematic liquid crystal 4-pentyl-4-cyanobiphenyl (5CB) doped with trace amounts of azo-dye disperse orange 3 (DO3) by studying the optical nonlinearities of the sample. Theoretical and experimental analyses confirm the proposal that the trans and cis isomers can be treated as independent contributors to the enhancement factor. Dynamic measurements indicate three contributions to photoinduced optical nonlinearities, two of which are isotropic and a third corresponding director reorientation.

Neutralizing antibodies to interferon beta in multiple sclerosis: analytical evaluation for validation of a cytopathic effect assay.

Background: Recent guidelines have recommended the use of validated assays for the measurement of neutralizing antibodies (NABs) to interferon beta (IFNbeta) in patients with multiple sclerosis (MS). In an attempt of validation, we studied the analytical performance of a bioassay based on antiviral cytopathic effect (CPE) using WISH cells and the vesicular stomatitis virus (WISH/VSV CPE).

Methods: NAB titres measured with the WISH/VSV CPE assay in 63 sera from IFNbeta-treated MS patients were compared to those obtained with the reference CPE method using A549 cells and the encephalomyocarditis virus.

[Drug therapy in multiple sclerosis].

For the last 10 years, three disease-modifying-therapy drugs have been approved by the French health authorities for the treatment of relapsing-remitting MS: two of them are immunomodulatory agents (interferon beta 1a or 1b and glatiramer acetate), administered by subcutaneous or intramuscular injections at different time points, reducing by about 30% the risk of relapses. The third drug approved is an immunosuppressive agent, mitoxantrone, administered intravenously at a dose of 12 mg/m2 per month up to a maximum cumulative dose of 72 mg/m2, used as a second line therapy in rapidly worsening relapsing MS non responder to immunomodulatory agents. The impact of such medications in MS patients with gradual progression of disability has not yet been established either in secondary or primary progressive MS.

Molecular structures of benzoic acid and 2-hydroxybenzoic acid, obtained by gas-phase electron diffraction and theoretical calculations.

The structures of benzoic acid (C6H5COOH) and 2-hydroxybenzoic acid (C6H4OHCOOH) have been determined in the gas phase by electron diffraction using results from quantum chemical calculations to inform restraints used on the structural parameters. Theoretical methods (HF and MP2/6-311+G(d,p)) predict two conformers for benzoic acid, one which is 25.0 kJ mol(-1) (MP2) lower in energy than the other.

Molecular structure of 2,5-dihydropyrrole (C4NH7), obtained by gas-phase electron diffraction and theoretical calculations.

The structure of 2,5-dihydropyrrole (C4NH7) has been determined by gas-phase electron diffraction (GED), augmented by the results from ab initio calculations employing third-order Møller-Plesset (MP3) level of theory and the 6-311+G(d,p) basis set. Several theoretical calculations were performed. From theoretical calculations using MP3/6-311+G(d,p) evidence was obtained for the presence of an axial (63%) (N-H bond axial to the CNC plane) and an equatorial conformer (37%) (N-H bond equatorial to the CNC plane).

Mold prevention strategies and possible health effects in the aftermath of hurricanes and major floods.

Extensive water damage after major hurricanes and floods increases the likelihood of mold contamination in buildings. This report provides information on how to limit exposure to mold and how to identify and prevent mold-related health effects. Where uncertainties in scientific knowledge exist, practical applications designed to be protective of a person's health are presented.

[Mitoxantrone as induction therapy in aggressive relapsing remitting multiple sclerosis: a descriptive analysis of 100 consecutive patients].

Introduction: On the basis of the French and British (FB) MS Trial, Mitoxantrone (MITOX) was approved by the AFSAPPS in October 2003 in patients with aggressive multiple sclerosis (MS), given as induction therapy monthly for 6 months (ELSEP). We report an observational study of 100 aggressive relapsing remitting (RR) MS patients treated by induction therapy with MITOX and followed up to 5 years.

Methods: One hundred patients with aggressive RR MS received an induction therapy with MITOX 20 mg monthly combined with methylprednisolone 1 g for 6 months.

Eye and respiratory symptoms in poultry processing workers exposed to chlorine by-products.

Background: CDC/NIOSH responded to a request to investigate complaints of eye and respiratory irritation among workers in a poultry processing facility's evisceration department.

Methods: Investigators administered symptom questionnaires and sampled for chlorine and chloramines. Spirometry was performed on workers before and after their work shift.

Mitoxantrone in the treatment of multiple sclerosis.

Mitoxantrone is useful for the treatment of cancer and MS and, as with other chemotherapeutic agents, many studies have examined its tolerability. The suitability of mitoxantrone in MS is particularly interesting because of its role in treating various stages of the disease. Evidence shows that mitoxantrone could be a first-line treatment for malignant forms of MS, and a second-line drug in relapsing-remitting or secondary progressive MS that is unresponsive to interferon beta-1a, -1b or glatiramer acetate.

Storage lipid accumulation and acyltransferase action in developing flaxseed.

Investigations of storage lipid synthesis in developing flaxseed (Linum usitatissimum) provide useful information for designing strategies to enhance the oil content and nutritional value of this crop. Lipid content and changes in the FA composition during seed development were examined in two cultivars of flax (AC Emerson and Vimy). The oil content on a dry weight basis increased steadily until about 20 d after flowering (DAF).

The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy.

From 1991-2002, we treated 58 patients with multiple sclerosis (MS) using the humanised monoclonal antibody, Campath-1H, which causes prolonged T lymphocyte depletion. Clinical and surrogate markers of inflammation were suppressed. In both the relapsing-remitting (RR) and secondary progressive (SP) stages of the illness, Campath-1H reduced the annual relapse rate (from 2.

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease.

Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS.

Attitudes to atypical and conventional antipsychotic drug treatment in clinicians participating in the cutlass study.

Objectives To examine clinicians' attitudes regarding the relative benefits and risks of conventional and atypical antipsychotic medication, and the perceived validity of the CUtLASS study. To examine the attitudes of participant clinicians' regarding the operation and administration, and the potential clinical impact of the findings. Method Two hundred and sixty-two clinicians were each sent an anonymous questionnaire, and invited to indicate whether they agreed or disagreed with each of to nine statements (from agree to disagree).

Imaging of congenital coronary anomalies with multislice computed tomography.

Objective: To describe a single-center experience of using retrospectively gated multislice computed tomographic (MSCT) coronary angiography for imaging congenital coronary anomalies.

Patients And Methods: We retrospectively reviewed the clinical information and imaging studies for 9 patients diagnosed as having congenital coronary anomalies on invasive, selective coronary angiography between February 2001 and October 2003 at the Mayo Clinic in Jacksonville, Fla. Two experienced observers classified by consensus the origin and proximal course of the abnormal coronary arteries as seen on MSCT.

Rationale for the use of mitoxantrone in multiple sclerosis.

Mitoxantrone is a member of the anthracendione family developed to treat malignancies and increasingly used to treat multiple sclerosis (MS). It has been studied as a treatment for MS since the late 1980s, and is licensed in a number of countries for progressive and worsening MS. Review of the published earlier open-label, and more recently of controlled trials suggests that mitoxantrone is efficacious in cases of worsening MS that have an inflammatory component as evidenced by progression with or without superimposed relapses and/or gadolinium (Gd) enhancing magnetic resonance (MR) lesions.

Determination of serum IgG antibodies to Bacillus anthracis protective antigen in environmental sampling workers using a fluorescent covalent microsphere immunoassay.

Aims: To evaluate potential exposure to Bacillis anthracis (Ba) spores in sampling/decontamination workers in the aftermath of an anthrax terror attack.

Methods: Fifty six serum samples were obtained from workers involved in environmental sampling for Ba spores at the American Media, Inc. (AMI) building in Boca Raton, FL after the anthrax attack there in October 2001.

Clinical use of immunoassays in assessing exposure to fungi and potential health effects related to fungal exposure.

Objective: To review and summarize current evidence regarding the proper role of immunoassays in clinical assessments of exposure to fungi and health effects related to fungal exposure.

Data Sources: We reviewed relevant scientific investigations and previously published reviews concerning this topic.

Study Selection: The authors' clinical, laboratory, and public health experiences were used to evaluate relevant data for scientific merit.