Evidence for activation of cellular immune responses in patients with acute hepatitis E.

INTRODUCTION: Although acute hepatitis E virus (HEV) infection is known to induce IgM and IgG humoral host immune responses, little is known about occurrence of cellular responses in this infection. We looked for evidence of lymphocyte sensitization to HEV peptides in patients with acute HEV infection. METHODS: peripheral blood lymphocytes were obtained from patients with acute hepatitis E and healthy controls. Proliferation of these lymphocytes in the presence of each of seven peptides with amino acid sequences corresponding to open reading frames 2 and 3 proteins of HEV (3 and 4 peptides, respectively) were studied; no peptide was added to control wells. Proliferative responses with stimulation indices exceeding 3.0 were taken as positive. RESULTS: More patients showed reactivity to two or more HEV peptides than did controls (11/21 vs 5/22, p<0.05). Reactivity to one peptide corresponding to open reading frame 2 of HEV was more frequent in patients than in controls (7/21 vs 1/22, p<0.05). CONCLUSION: Our results show that lymphocytes of patients with acute hepatitis E show sensitization to HEV peptides. This may have significance in understanding the pathogenetic mechanisms of liver injury in this infection.     

Evidence for functional presynaptic alpha-2 adrenoceptors and their down-regulation in human heart failure

OBJECTIVES: The aim of this study was to investigate the role of peripheral presynaptic alpha-2 adrenergic receptors in modulating norepinephrine (NE) release in congestive heart failure (CHF). BACKGROUND: Activation of the sympathetic nervous system is a hallmark of CHF. Clonidine, an imidazoline and adrenergic agonist with high selectivity for the alpha-2 adrenoceptor, has been shown to reduce generalized sympathetic activity in heart failure after parenteral administration. If it could be shown that peripheral presynaptic alpha-2 adrenoceptors are inhibitory to NE release, then they could be targeted for future therapy, and as a corollary, potentially circumvent unwanted side effects arising from stimulation of alpha-2 adrenoceptors in the brain. Additionally, it could be concluded that these receptors form the basis for an auto-inhibitory feedback to further NE release. METHODS: Fifteen healthy volunteers and 10 patients with heart failure received intra-arterial clonidine via the brachial artery (0.05 microg and 0.48 microg/100 ml forearm/min). Radio-tracer techniques were employed for studying NE kinetics. RESULTS: Intra-arterial clonidine caused a dose-dependent decrease in forearm spillover of NE in healthy individuals (low dose, high dose: 26%, 49%: p < 0.05, p < 0.001, respectively). In the patient group, no decrease in forearm spillover was demonstrated after local administration. The difference in response between the two groups was statistically significant (p = 0.004). CONCLUSIONS: Peripheral sympathoneural alpha-2 adrenoceptors are functionally important in inhibiting NE release in the healthy human. In heart failure, this function is lost. This finding offers further insights into the mechanisms responsible for high circulating levels of NE in patients with heart failure. In addition, it suggests that selective targeting of peripheral presynaptic alpha-2 adrenoceptors will not achieve sympathoinhibition in heart failure.     

Aortoarteritis presenting with hypoparathyroidism

Clinical manifestations of aortoarteritis (Takayasu's arteritis) are varied, depending on the involved segment of the aorta and its branches. A case of a young Indian woman with aortoarteritis presenting primarily with hypoparathyroidism is reported. Aortogram showed total occlusion of the arch arteries. To the best of our knowledge, the occurrence of hypoparathyroidism in aortoarteritis has not been reported. Possible mechanisms of such an involvement are discussed.     

Intrapericardial benign teratoma with unusual presentation

Benign teratoma, also referred as dermoid cyst, do occur in the mediastinum. However, their intrapericardial location has been reported very occasionally. This case of intrapericardial benign solid teratoma is being presented because of its rarity and its unusual presentation as a case of empyema, with features of cardiac compression and pericardial effusion.     

A novel predictor of clinical response to methotrexate in patients with rheumatoid arthritis: a pilot study of in vitro T cell cytokine suppression

OBJECTIVE: Methotrexate (MTX) is an important drug for treatment of rheumatoid arthritis; however, there is variation in the clinical response. MTX inhibits T cell cytokine production, with significant interindividual variability in the dose required. We investigated if the variability in clinical response was related to variability in the in vitro assay. METHODS:Patients with disease modifying antirheumatic drug-naive, active RA [1982 American College of Rheumatology (ACR) criteria] seen from September 2005 through January 2006 were enrolled. MTX was started at 10 mg/week and increased monthly by 2.5 mg/week. Baseline whole-blood cultures were set up with anti-CD3, anti-CD28, and increasing doses of MTX. Supernatants were harvested at 96 hours and tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 10 (IL-10) concentrations were estimated by ELISA. The dose of MTX (ID50) required for 50% suppression of production of cytokines and the change in Disease Activity Score-28 (DeltaDAS) at 4 months were noted. RESULTS: T cell stimulation resulted in significant increase in cytokine release, and addition of MTX led to a dose-dependent suppression of all 3 cytokines. There was significant negative correlation of DeltaDAS with ID50 values for TNF-alpha (R = -0.62, p < 0.01) and IFN-gamma (R = -0.43, p = 0.04). At 4 months, EULAR moderate and ACR 20% responses were achieved by 13 and 16 patients, respectively. EULAR moderate response could be predicted using ROC curves for TNF-alpha (sensitivity 93%, specificity 86%) and IFN-gamma (60% specificity, 71% sensitivity). ACR response was correctly predicted in 14 of 16 ACR 20% responders and in all ACR 50% and ACR 70% responders. CONCLUSION: An in vitro TNF-alpha suppression assay may help predict clinical response to MTX in RA.     

Hepatitis E

Hepatitis E, previously known as enterically transmitted non-A, non-B hepatitis, is an infectious viral disease with clinical and morphologic features of acute hepatitis. Its causative agent, hepatitis E virus, consists of small, 32- to 34-nm diameter, icosahedral, nonenveloped particles with a single-stranded, positive-sense, 7.5-kb RNA. The virus has two main geographically distinct strains, Asian and Mexican; recently, novel isolates from nonendemic areas and a genetically related swine HEV have been described. HEV is responsible for large epidemics of acute hepatitis and a proportion of sporadic hepatitis cases in the Indian subcontinent, southeast and central Asia, the Middle East, parts of Africa, and Mexico. The virus is excreted in feces and is transmitted predominantly by fecal-oral route, usually through contaminated water. Person-to-person transmission is uncommon. Clinical attack rates are the highest among young adults. Recent evidence suggests that humans with subclinical HEV infection and animals may represent reservoirs of HEV; however, further data are needed. Diagnosis of hepatitis E is usually made by detection of specific IgM antibody, which disappears rapidly over a few months; IgG anti-HEV persists for at least a few years. Clinical illness is similar to other forms of acute viral hepatitis except in pregnant women, in whom illness is particularly severe with a high mortality rate. Subclinical and unapparent infections may occur; however, chronic infection is unknown. No specific treatment is yet available. Use of clean drinking water and proper sanitation is currently the most effective method of prevention. Passive immunization has not been proved to be effective, and recombinant vaccines for travelers to disease-endemic areas and for pregnant women currently are being developed.     

Molecular identification of enteroviruses associated with aseptic meningitis in children from India

We identified and characterized enteroviruses associated with aseptic meningitis in children between April 2009 and March 2010. Enterovirus RNA was detected in 51 (45.5 %) of 112 CSF samples. Molecular typing by RT-PCR and sequencing of a partial VP1 region revealed the predominance of echovirus (ECV) 32 (n = 20), followed by ECV 11 (n = 10), ECV 13 and ECV 14 (n = 5 each), coxsackievirus (CV) B3 and CV B6 (n = 3 each), CV A2, CV A10 and ECV 30 (n = 1 each). Phylogenetic analysis of ECV 32 showed 0 to 4 % sequence divergence among strains of the present study and 20-23 % from the prototype Puerto Rico strain at the nucleotide level. This is the first report of ECV 32 associated with an aseptic meningitis epidemic and identification of seven different enterovirus serotypes (CV A2, CV A10, CV B3, CV B6, ECV 13, ECV 14 and ECV 32) in meningitis cases from India.