Clinical trial outcome of anti-tumour necrosis factor alpha therapy in rheumatic arthritis.

Rheumatoid arthritis is a common debilitating disease. Chronic joint inflammation leads to irreversible joint damage. Disability is a common sequel, therefore it is a major healthcare burden.

Drug treatment of essential hypertension: the case for initial combination therapy.

Essential hypertension is a major cause of cardiovascular morbidity and mortality in the Western world, yet it remains poorly controlled. Single drug-antihypertensive therapy is unsuccessful in up to half of all patients with hypertension; although lack of adherence may account for a proportion of this, there is evidence of considerable variation in the response of different hypertensive patients to different drug classes. A number of algorithms have been proposed in the literature, with a view to predicting an individual's response to different antihypertensive agents.

Use of imaging to assess patients with muscle disease.

Purpose Of Review: A variety of imaging modalities can be used in muscle diseases. These range from plain x-rays to conventional magnetic resonance imaging (MRI) and phosphate magnetic resonance spectroscopy (MRS). This review places these imaging methods into their relevant clinical contexts on the basis of the best available research evidence.

Identification of a naturally processed cytotoxic CD8 T-cell epitope of coxsackievirus B4, presented by HLA-A2.1 and located in the PEVKEK region of the P2C nonstructural protein.

The adaptive immune system generates CD8 cytotoxic T lymphocytes (CTLs) as a major component of the protective response against viruses. Knowledge regarding the nature of the peptide sequences presented by HLA class I molecules and recognized by CTLs is thus important for understanding host-pathogen interactions. In this study, we focused on identification of a CTL epitope generated from coxsackievirus B4 (CVB4), a member of the enterovirus group responsible for several inflammatory diseases in humans and often implicated in the triggering and/or acceleration of the autoimmune disease type 1 diabetes.

Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting.

There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise.

Older stroke patients in Europe: stroke care and determinants of outcome.

Background: in order to implement cost-effective stroke services for older patients, it is necessary to identify how stroke care is currently provided for these patients and how provision relates to outcome.

Objectives: to estimate the structure and process of care, and identify independent factors associated with 3 month mortality and functional outcome in patients aged over 75 years compared with younger stroke patients across Europe.

Setting: 13 hospitals in 10 European countries.

Microalbuminuria and cardiovascular risk.

Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits.

Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology.

The endothelial generation of reactive oxygen species (ROS) is important both physiologically and in the pathogenesis of many cardiovascular disorders. ROS generated by endothelial cells include superoxide (O2-*), hydrogen peroxide (H2O2), peroxynitrite (ONOO-*), nitric oxide (NO), and hydroxyl (*OH) radicals. The O2-* radical, the focus of the current review, may have several effects either directly or through the generation of other radicals, e.

[Arthritides in the elderly].

The arthritides of the elderly comprise a fairly heterogeneous group of diseases. They include conditions that affect exclusively or predominantly the elderly (such as, for instance, remitting seronegative symmetric synovitis with pitting edema) and conditions affecting any age group, but which can present with peculiar features in the elderly, like rheumatoid arthritis and the seronegative arthropathies. Therefore, in order to arrive at a correct diagnosis, a knowledge of the specific features of these disorders is required.

Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series.

Huntington's disease (HD) is a late-onset neurodegenerative disorder that is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (htt). The normal function of htt, and the molecular mechanisms that contribute to the disease pathogenesis, are in the process of being elucidated. In this review, we outline the potential functions of htt as defined by the proteins with which it has been found to interact.

Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate.

IL-18, an immunoregulatory and proinflammatory cytokine, has been shown to play an important pathogenic role in Th1-driven autoimmune disorders. In this study, we evaluated the circulating levels and salivary-gland expression of IL-18 in patients with Sjögren's syndrome (SS), a mainly Th1-mediated disease. IL-18 serum levels were measured by ELISA in 37 patients with primary SS, 42 with rheumatoid arthritis, and 21 normal controls.

Nitric oxide-dependent beta2-adrenergic dilatation of rat aorta is mediated through activation of both protein kinase A and Akt.

Vasorelaxation to beta(2)-adrenoceptor stimulation occurs through both endothelium-dependent and endothelium-independent mechanisms, and the former is mediated through Ca(2+)-independent activation of endothelial-type nitric oxide synthase (NOS-3). Since Ca(2+)-independent NOS-3 activation may occur through its serine phosphorylation via protein kinase A (PKA) or Akt, we determined the PKA and Akt dependency of beta(2)-adrenergic relaxation of rat aorta. Rat aortic rings were pre-incubated with the PKA inhibitor H-89 (10(-7) m), the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (5 x 10(-7) m), Akt inhibitor (10(-5) m), or vehicle, in the absence or presence of the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 10(-4) m).

Antibody response to the human stress protein BiP in rheumatoid arthritis.

Objectives: The human stress protein BiP (immunoglobulin binding protein) has been implicated in the pathogenesis of rheumatoid arthritis (RA) since BiP was found to stimulate synovial T-cell proliferation and anti-BiP antibodies are present in the serum of RA patients. The aim of this study was the development of a rapid and reproducible enzyme-linked immunosorbent assay (ELISA) to determine the specificity and sensitivity of anti-BiP antibodies in RA.

Methods: An ELISA was developed that detected antibodies to BiP.

Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure.

It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rh-Epo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of <10.7 g/dl for 6 mo before treatment and a rh-Epo dose of > or =12,000 IU/wk, were recruited.

Glycoform composition profiling of O-glycopeptides derived from human serum IgA1 by matrix-assisted laser desorption ionization-time of flight-mass spectrometry.

Pools of O-glycopeptides prepared from trypsin-digested reduced and alkylated human serum IgA1 have been analyzed using matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-ToF-MS) in the positive-ion mode, using 2,4,6-trihydroxy acetophenone-ammonium citrate matrix. Dozens of such pools prepared from normal serum IgA1 and from serum of patients with a number of different medical conditions have been routinely analyzed in this manner. The glycopeptides present in these pools possess identical amino acid sequences but are substituted with a variety of neutral and sialylated glycans and the spectra obtained were such that individual compositional glycoforms were baseline resolved.

Prognostic indicators for early discontinuation of risperidone long-acting injection.

Although efficacy trials have been conducted on risperidone long-acting injection (RLAI), its most appropriate utilization in clinical practice remains unclear. This 6-month, follow-up study investigated prognostic indicators for early discontinuation of RLAI. Consecutive sampling was conducted for adult patients with a psychotic disorder commenced on RLAI, whose injection was dispensed by one of three South London psychiatric hospital pharmacies.

Monitoring aggregate formation in organotypic slice cultures from transgenic mice.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the HD gene. It encodes a protein known as huntingtin, which aggregates in the nuclei of affected neurons. These aggregates are an obvious therapeutic target, thus an organotypic slice culture assay has been designed to screen potential antiaggregation compounds using the R6/2 mouse model of HD.

Mouse models of triplet repeat diseases.

Since their discovery in 1991, triplet repeat mutations have been found to be the cause of genomic fragile sites, two of which are linked to mental retardation, myotonic dystrophy, and several late-onset neurodegenerative diseases. In all cases, these mutations exhibit gametic and/or somatic instability once they have expanded into the mutant range. The mutations are located in coding and noncoding gene regions and have been found to act by dominant and recessive mechanisms.

NOX-2S is a new member of the NOX family of NADPH oxidases.

A novel isoform of the NOX-2 subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has been identified using expressed sequence tag (EST) database mining. The novel isoform, NOX-2S, is a splice variant of NOX-2 and includes a previously unidentified exon, mapped 6.4 kb downstream of exon III, and encodes an in-frame stop codon generating a predicted truncated protein of approximately 12.

Analysis of ex vivo left ventricular pressure-volume relations in the isolated murine ejecting heart.

The development of microconductance technology to study cardiac pressure-volume relations in mice in vivo has significantly advanced the haemodynamic assessment of gene-modified models of cardiovascular disease. In this study, we describe the application of microconductance analysis of cardiac function to the isolated murine ejecting heart. This ex vivo model is complementary to the previously described in vivo preparation, allows assessment without confounding effects of anaesthetic or neurohumoral influences and enables careful control of cardiac loading (particularly preload).