Conformational variability of a picornavirus capsid: pH-dependent structural changes of Mengo virus related to its host receptor attachment site and disassembly

The structure of Mengo virus had been determined from crystals grown in the presence of 100 mM phosphate buffer at pH 7.4. It is shown that Mengo virus is poorly infectious at the phosphate concentration similar to that in which it was crystallized. Maximal infectivity is achieved at 10 mM phosphate or less in physiological saline. The phosphate effect is ameliorated when the pH is lowered to 4.6. Although it has not been possible to study the crystal structure of the virus at low phosphate concentrations, it is shown that increasing the Cl- concentration at pH 6.2 or decreasing the pH to 4.6 causes substantial conformational changes confined to the "pit," a deep surface depression. These structural changes involve a movement of the "FMDV loop" (GH loop) in VP1, an ordering of the "VP3 loop" (GH loop in VP3) between 3176 and 3182, the displacement of a bound phosphate near the "FMDV loop" (GH loop in VP1), and movement of the carboxy terminus of VP2. The changes in conformation are correlated with the dissociation of the virion into pentamers at pH 6.2 and 150 mM Cl-. The localization of the conformational changes and the correlated role of the phosphate in controlling infectivity support the hypothesis that the "pit" is the receptor attachment site.     

Conjunctival impression cytology in trachoma

Trachoma is one of the leading causes of blindness and clinical examination remains the mainstay of diagnosis. However there is need to evaluate simple, inexpensive techniques which can be used for screening of trachoma in endemic regions. We report two cases where conjunctival impression cytology played a part in confirming the diagnosis of trachoma. We used a modified technique of obtaining conjunctival impressions, which not only met with better patient compliance and minimal ocular distress, but also provided better cellularity and morphology of cells for evaluation. The impression smears showed squamous metaplasia and loss of goblet cells. The cytoplasm of these cells had a hazy, moth eaten appearance and showed presence of intracytoplasmic inclusions. These basophilic inclusions were present singly and in clusters and were around 5 μm in diameter. A large number of these inclusions were present extracellularly as well. Conjunctival impression cytology is a simple procedure which needs to be evaluated for its potential to be used for screening trachoma in endemic areas. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Water calorimeter dosimetry for 160 MeV protons.

The absorbed dose to water from a 160 MeV proton beam as determined by a flexible, temperature regulated, sealed glass core, water calorimeter was compared to that determined from ionization chambers used in accordance with AAPM Report 16. The ratios of these doses as obtained from two experiments done over four months apart, are 0.992 +/- 0.004 and 0.990 +/- 0.004. As there are no radiation dependent parameters required for the water calorimeter, these data add to the growing body of evidence which supports the use of the calorimeter as a reliable absorbed dose standard. They also support the use of 60Co-calibrated ionization chambers used in accordance with AAPM Report 16 for the dosimetry of proton beams.     

Role of intraoperative transesophageal echocardiography in patients having coronary artery bypass graft surgery

Background

Previous studies have shown that intraoperative transesophageal echocardiography provides important preoperative and postoperative information in various cardiac and noncardiac surgeries that may alter patient management and outcome. The role of intraoperative transesophageal echocardiography in patients in whom isolated coronary artery bypass graft surgery is anticipated has been reported only in small selected groups. This study was designed to prospectively evaluate the role of intraoperative transesophageal echocardiography in a large, nonselected group of patients undergoing primarily coronary artery bypass graft surgery.

Methods

From January 2001 to December 2003, 474 consecutive patients (76% men, 24% women) aged 30 to 89 years (mean age of 70 ± 10 years) who were undergoing coronary artery bypass graft surgery had prebypass and postbypass intraoperative transesophageal echocardiography. New findings and alterations in the surgical plan were documented prospectively.

Results

New prebypass findings were found in 10% of patients, and the surgical plan was altered in 3.4% of patients. New postbypass findings were found in 3.2% of patients, altering the surgical plan in 2% of patients.

Conclusions

This large consecutive, nonselected, prospective study reveals the significant impact of intraoperative transesophageal echocardiography in patients having coronary artery bypass graft surgery as a primary procedure. New findings (prebypass and postbypass) were found in 13% of patients overall, and the surgical plan was altered in 5.5% of patients. This study supports the use of intraoperative transesophageal echocardiography in patients undergoing primarily coronary artery bypass graft surgery.     

Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.     

Critical appraisal of transesophageal echocardiography in cardioversion of atrial fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia and an important health concern in the United States because of the increasing aging population. Cardioversion of atrial fibrillation to sinus rhythm to relieve symptoms and to reduce the incidence of thromboembolism is now common practice. Recently, transesophageal echocardiography (TEE)-facilitated cardioversion emerged as an acceptable therapeutic alternative owing to the assumption that early cardioversion can obviate many of the concerns and disadvantages associated with the conventional approach. We review the current standing of TEE-facilitated early cardioversion vis-à-vis the salient cardioversion issues and its potential future role amid evolving cardioversion paradigms.