Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

用于鼻腔测量的声反射技术——应用与进展

本文综述了声反射鼻腔测量（acoustic rhinometry,AR）近年来在临床中的应用和研究。主要阐述了声反射测量的工作原理,在鼻周期以及正常人鼻腔测量相关参数建立等基础研究,在耳鼻喉科疾病诊断和药物作用等临床研究中的进展。     

Providing monovalent oral polio vaccine type 1 to newborns: findings from a pilot birth-dose project in Moradabad district, India

Problem

Poliovirus transmission remained a public health challenge in western Uttar Pradesh, India in late 2005 and early 2006. In 2006, the India Expert Advisory Group for Polio Eradication concluded that, given the peak incidence of polio among children 6 to 12 months of age, a targeted birth dose of oral polio vaccine may be necessary to interrupt intense poliovirus transmission in high risk areas.

Approach

The Government of Uttar Pradesh, the National Polio Surveillance Project and the United Nations Children’s Fund (UNICEF) implemented a pilot birth-dose project aimed at identifying and vaccinating all newborns with a dose of oral polio vaccine within 72 hours of birth in an effort to evaluate operational feasibility and potential impact on population immunity.

Local setting

The project was piloted in Moradabad district: zone 7 in Moradabad City (urban setting), Kunderki block (rural setting) and in select birthing hospitals.

Relevant changes

Between July 2006 and February 2007, 9740 newborns were identified, of which 6369 (65%) were vaccinated by project personnel within 72 hours of birth. Project coverage (for total newborns vaccinated) ranged from 39% (in zone 7) to 76% (in Kunderki block) of the estimated number of newborns vaccinated during previous supplemental immunization activities.

Lessons learned

Birth-dose coverage among newborns was lower than expected. Expansion costs were estimated to be high, with marginal impact. The project, however, provided opportunities to strengthen newborn tracking systems which have increased the number of newborns and young infants vaccinated during supplemental immunization activities and enrolled in routine programmes.     

Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually transmitted viruses: evidence of sexual and parenteral transmission

BACKGROUND: The first epidemiologic evidence of GB virus type C (GBV- C)/hepatitis G virus (HGV) infection showed a high prevalence of asymptomatic carriers in blood donors and in populations at risk for blood-borne viruses. However, by using only viral RNA polymerase chain reaction, those studies underestimated the true spread of GBV-C/HGV infection. The combined detection of GBV-C/HGV RNA and of anti-E2 (which reflects recovery from infection) is necessary to define accurately the prevalence of GBV-C/HGV. STUDY DESIGN AND METHODS: The presence of both anti-E2 and GBV-C/HGV RNA was searched for in 1438 serum samples collected from various groups of individuals at low or high risk for blood-borne or sexually transmitted viruses (blood donors, organ donors, unselected pregnant women, immunocompetent or immunodepressed multiply transfused patients, HIV-positive or HIV- negative homosexual men, intravenous drug addicts). RESULTS: The presence of GBV-C/HGV RNA and/or anti-E2 (exposure to GBV-C/HGV) was frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV appeared also to be sexually transmitted, with transmission from male to female more efficient than vice versa. A particularly elevated level of exposure to GBV-C/HGV was observed in homosexual men. In immunocompetent individuals, the prevalence of anti- E2 was about twice that of GBV-C/HGV RNA, which suggests the frequency of recovery from GBV-C/HGV infection. Most of the GBV-C/HGV RNA- positive individuals had no biochemical evidence of liver damage. CONCLUSIONS: GBV-C/HGV is frequent in populations at risk for blood- borne or sexually transmitted viruses. GBV-C/HGV is not a hepatitis virus, and it seems appropriate to rename it.     

The final destiny of acantholytic cells in pemphigus is Fas mediated

Background  Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective  This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods  Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results  All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4⁺CD69⁺ cells. Additionally, CD19⁺ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion  This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

Conflicts of interest

None declared.     

ROLE OF NITRIC OXIDE IN THE DEVELOPMENT OF CORTICOTROPIN-INDUCED HYPERTENSION IN SHEEP

1. The possibility that altered synthesis of vascular nitric oxide (NO) plays a role in the development of corticotropin-induced hypertension in sheep was examined by determining the effect of concomitant infusion of L-arginine, a precursor of NO, on the development of the hypertension. 2. Corticotropin (5 μg/kg per h) infused over 2 days increased mean arterial pressure (MAP) from 83 ± 4 to 99 ± 4 mmHg in five conscious sheep. Concomitant infusion of L-arginine (60 mg/kg per h) did not alter this response; infusion of L-arginine alone had no effect on blood pressure. 3. The dose of L-arginine (60 mg/kg per h) used blocked the rise in MAP (+16 mmHg) in response to a 5 h infusion of N-nitro-L-arginine (1 mg/kg per h). 4. These findings suggest that disruption of NO synthesis does not play a role in the development of corticotropin hypertension in sheep.     

A reversible monoamine oxidase inhibitor, toloxatone: Structural and electronic properties

Toloxatone is a reversible MAO_A-inhibitor, marketed as antidepressant (Humoryl^®), with an original chemical structure. It differs from first generation irreversible MAOIs, known to induce covalent bonds with the enzyme active site. In order to understand the mechanism of the reversible inactivation of the MAO, as a first step, a detailed structural and electronic analysis was undertaken. An X-ray diffraction-crystallographic study showed that toloxatone is a planar molecule and brought to light hydrogen bonds and π-π interactions. MO calculations confirmed the planar structure as energetically favoured. Electronic analysis demonstrated a delocalization of both ring systems. The combined results give evidence for the potential of toloxatone to participate in reversible, long distance interactions with an appropriate partner.