Experimental leptospirosis in marmoset monkeys (Callithrix jacchus): a new model for studies of severe pulmonary leptospirosis

Experimental infection of marmoset monkeys (Callithrix jacchus) with Leptospira interrogans serovar Copenhageni showed microscopic patterns of tissue reactions comparable to those seen in the severe forms of human leptospirosis, including intra-alveolar hemorrhage. The most impressive microscopic changes were seen in the lung and kidney of animals killed at days 6 and 12 after inoculation. There were extensive and irregular areas of hemorrhage predominating around main bronchial branches or diffusely spread to the pulmonary parenchyma, as well as severe tubulointerstitial nephritis. Antibody response detected by the microscopic agglutination test was quantitatively similar to those seen in humans and paralleled severity of tissue lesions. The distribution of leptospires or antigenic debris in infected tissues was observed by immunofluorescence and confocal laser scanning microscopy. Large numbers of typical leptospires were seen in the lumen of proximal renal tubules. Positive reactions showing antigenic debris were closely associated with sites of tissue damage.     

Esophageal chest pain

The unequivocal diagnosis of esophageal chest pain requires the demonstration of simultaneous manometric changes and chest pain. Numerous provocative agents have been used to enhance the diagnostic value of esophageal manometry. Our aims were to: evaluate consecutively a large group of patients with proven noncardiac chest pain and normal baseline manometric studies, using edrophonium chloride, 10 mg, and determine the value of provocative testing in clinical practice. One hundred twenty patients with normal standard baseline esophageal manometries were studied using blinded testing with edrophonium chloride and followed clinically by questionnaire. A positive response of both chest pain and manometric changes was observed in 34%, a negative response in 49%, and an indeterminate response in 17% of patients. Baseline manometric features, including high-amplitude contractions, did not predict the response to edrophonium chloride. Following edrophonium chloride administration, the change in amplitude, duration, and number of repetitive contractions from baseline was significantly greater in positive responders. Edrophonium decreased the velocity of propagated contractions in positive responders (P less than 0.05), but not in nonresponders. Response to edrophonium chloride could not be predicted by patient age, sex, or clinical symptomatology. Seventy percent of patients in both groups had symptoms indistinguishable from ischemic heart disease. After making a specific diagnosis of esophageal chest pain, patients showed a marked clinical improvement, with a significant decrease in physical limitation, emergency room visits, hospital and CCU admissions, and in further cardiac testing. We conclude that provocative testing with edrophonium chloride will make it possible to definitively implicate the esophagus in over 30% of patients with normal baseline manometric findings and noncardiac chest pain.     

Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging.

AIMS: To assess the recanalization effects of post-myocardial infarction (MI) on left ventricular (LV) remodelling and contractility in relation to conservative therapy. METHODS AND RESULTS: Thirty-six patients with occluded infarct-related artery between 12 h and 14 days post-anterior MI were randomized to percutaneous coronary intervention (PCI group) or conservative therapy (no-PCI group). Magnetic resonance imaging was performed at enrollment and after 6 months. The left ventricle was divided into infarct, adjacent, and remote segments. There was no difference in relation to LV volume between groups at the 6 month follow-up. Change in LV ejection fraction was favourable to the PCI group: 5.00% vs. -0.76%, P=0.012. Change in circumferential shortening (Ecc) of the remote segments in the PCI group was significantly better than in the no-PCI group: -1.67+/-6.30% vs. 0.29+/-6.02%, P<0.001. Infarct size and LV mass were similar between groups. CONCLUSIONS: Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up, but did not change the ventricular volumes. Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infarct-related artery.     

Identification of CD8+ T cell epitopes in the immediate early 62 protein (IE62) of varicella-zoster virus,and evaluation of frequency of CD8+ T cell response to IE62, by use of IE62 peptides after varicella vaccination

Varicella-zoster virus (VZV) causes varicella, establishes neuronal latency, and can reactivate, resulting in herpes zoster. VZV-specific T cells are important for controlling infection. VZV immediate early protein 62 (IE62) is recognized by cytotoxic T cells from immune individuals, but no CD8(+) T cell epitopes have been defined for any VZV protein. CD8(+) T cell frequencies were assessed by cytokine flow cytometry (CFC), by use of synthetic-peptide pools corresponding to the IE62 sequence. IE62 peptide-specific CD8(+) T cells were below the threshold of detection, by direct CFC of either whole blood or peripheral blood mononuclear cells (PBMCs). Activated CD8(+)CD69(+) T cells that produced interferon-gamma were detectable after in vitro restimulation of PBMCs, and restricted epitopes were identified for HLA-A*0201-positive subjects. Varicella vaccination of 3 VZV-immune subjects was associated with increases in IE62 peptide-specific CD8(+) T cells, a finding indicating that in vivo re-exposure boosts memory immunity to this important viral protein.     

Post-cholecystectomy amputation neuroma of the common bile duct with obstructive jaundice

Amputation neuroma of the common bile duct after surgery is a rare and mostly asymptomatic lesion. A 60-year old patient presented with obstructive jaundice three months after a cholecystectomy for symptomatic gallstones. Imaging investigations showed common extrahepatic bile duct stenosis. Surgical resection of the stricture with biliodigestive anastomosis was performed. Histological examination of the surgical specimen revealed an amputation neuroma. Despite its rarity, amputation neuroma of the common bile duct should be considered in patients with post-cholecystectomy syndrome following liver or extrahepatic bile duct surgical procedures.     

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

BACKGROUND: We previously demonstrated that short-cycle structured intermittent therapy (SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum levels of lipids. Adherence to such a regimen may be problematic for certain patients. METHODS: Eight patients with a history of receiving combination ART that maintained suppression of plasma HIV RNA to <50 copies/mL received a once-daily SIT regimen of didanosine, lamivudine, and efavirenz. RESULTS: For 7 patients, suppression of plasma HIV RNA to <50 copies/mL was maintained for 60-84 weeks. Four patients with adequate samples had no evidence for an increase in plasma viremia for up to 72 weeks, by use of an assay with a limit of detection of <1 copy/mL. The lack of rebound viremia may be the result of the persistence of efavirenz in plasma on day 7 of the no-therapy period, as was detected in 7 of 7 patients. There was no significant change in CD4(+) T cell counts or serum hepatic transaminase or lipid levels. CONCLUSION: A once-daily short-cycle SIT regimen maintained suppression of plasma HIV RNA while preserving CD4(+) T cell counts. Such a regimen may have importance in resource-limited settings where the monetary cost of continuous ART is prohibitive.     

The first record of American visceral leishmaniasis in domestic cats from Rio de Janeiro, Brazil

This paper is the first to report visceral leishmaniasis in domestic cats (Felis catus domesticus) from an endemic area in Rio de Janeiro state, Brazil. A relatively high seroprevalence of 25% was observed although none of them have presented any symptom. Our results support the observation of previous authors, suggesting that cats may be considered as alternative domestic hosts of visceral leishmaniasis and should be included in serological investigations performed in endemic areas.     

Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial.

BACKGROUND: Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging. METHODS AND RESULTS: This multicenter, double-blinded phase 3 trial involved 784 patients at 54 sites. Each patient underwent 2 sets of gated single photon emission computed tomography myocardial perfusion imaging studies: an initial qualifying study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine. Regadenoson was administered as a rapid bolus (<10 seconds) of 400 mug. The primary endpoint was to demonstrate noninferiority by showing that the difference in the strength of agreement in detecting reversible defects, based on blinded reading, between sequential adenosine-regadenoson images and adenosine-adenosine images, lay above a prespecified noninferiority margin. Other prospectively defined safety and tolerability comparisons and supporting analyses were also performed. The average agreement rate based on the median of 3 independent blinded readers was 0.63 +/- 0.03 for regadenoson-adenosine and 0.64 +/- 0.04 for adenosine-adenosine-a 1% absolute difference with the lower limit of the 95% confidence interval lying above the prespecified noninferiority margin. Side-by-side interpretation of regadenoson and adenosine images provided comparable results for detecting reversible defects. The peak increase in heart rate was greater with regadenoson than adenosine, but the blood pressure nadir was similar. A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than adenosine (P = .013). CONCLUSIONS: This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.     

Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand mRNA expression in patients with rheumatoid arthritis and healthy controls

OBJECTIVE: To further understand the role of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANK-L) in rheumatoid arthritis (RA), we studied the levels of RANK-L and OPG mRNA in peripheral blood mononuclear cells (PBMC) and synovial tissue of patients with RA and controls. METHODS: RANK-L and OPG mRNA levels were measured in PBMC and CD4+/CD8+ T cell subsets of patients with chronic RA, osteoarthritis (OA), and healthy controls, using quantitative real-time polymerase chain reaction. OPG and RANK-L mRNA levels were measured in paired blood and synovial tissue samples of patients with early, untreated RA at 2 timepoints with an interval of 16 weeks. RESULTS: RANK-L mRNA levels were significantly higher in PBMC of patients with early and chronic RA compared to healthy controls. Contrary to healthy controls, RANK-L mRNA levels in patients with chronic RA were mainly of CD4+ T cell origin. OPG mRNA was observed in the blood of all (17/17) early RA patients, but could not be detected in chronic RA patients (0/14) or in patients with OA (0/8). Three out of 17 healthy controls showed measurable levels of OPG mRNA. The OPG/RANK-L ratio tended to be higher in the synovium than in the PBMC of early RA patients. RANK-L mRNA in synovial tissue was mainly of non-T cell origin. CONCLUSION: Since RANK-L and OPG mRNA levels are elevated in PBMC of RA patients, and CD4+ T cells are the major contributors to RANK-L mRNA expression, mononuclear cells in patients with RA may be involved in the pathways that regulate bone metabolism.     

Integrating the Accreditation Council for Graduate Medical Education Core competencies into the model of the clinical practice of emergency medicine

In response to public pressure for greater accountability from the medical profession, a transformation is occurring in the approach to medical education and assessment of physician competency. Over the past 5 years, the Accreditation Council for Graduate Medical Education (ACGME) has implemented the Outcomes and General Competencies projects to better ensure that physicians are appropriately trained in the knowledge and skills of their specialties. Concurrently, the American Board of Medical Specialties, including the American Board of Emergency Medicine (ABEM), has embraced the competency concept. The core competencies have been integral in ABEM's development of Emergency Medicine Continuous Certification and the development of the Model of Clinical Practice of Emergency Medicine (Model).¹ ABEM has used the Model as a significant part of its blueprint for the written and oral certification examinations in emergency medicine and is fully supportive of the effort to more fully define and integrate the ACGME core competencies into training emergency medicine specialists.To incorporate these competencies into our specialty, an Emergency Medicine Competency Taskforce (Taskforce) was formed by the Residency Review Committee–Emergency Medicine to determine how these general competencies fit in the Model.¹ This article represents a consensus of the Taskforce with the input of multiple organizations in emergency medicine. It provides a framework for organizations such as the Council of Emergency Medicine Residency Directors (CORD) and the Society for Academic Emergency Medicine to develop a curriculum in emergency medicine and program requirement revisions by the Residency Review Committee–Emergency Medicine. In this report, we describe the approach taken by the Taskforce to integrate the ACGME core competencies into the Model. Ultimately, as competency-based assessment is implemented in emergency medicine training, program directors, governing bodies such as the ACGME, and individual patients can be assured that physicians are competent in emergency medicine.