Inhibition of staphylococcal enterotoxin A-induced superantigenic and lethal activities by a monoclonal antibody to toxic shock syndrome toxin-1

Staphylococcal toxic shock syndrome is caused by a family of related superantigens that includes toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins (SEs) A, B, and C. The cross-inhibitory activity against SEA by a novel anti-TSST-1 monoclonal antibody (MAb), MAb5, which also cross-inhibits SEB-induced superantigenic activities, was investigated. MAb5 blocked SEA binding to human monocytes, cross-neutralized SEA-induced T cell mitogenesis and TNF-alpha secretion in human peripheral blood mononuclear cells, and prevented lethality in mice. Epitope mapping revealed that MAb5 binds to residues SEA(154-161) within the central alpha helix that is structurally highly conserved among TSST-1, SEA, and SEB. The cross-inhibitory activity of MAb5 is likely due to steric hindrance of this conserved motif, although the precise function of this motif shared among related staphylococcal superantigens remains to be further elucidated.     

Tissue Doppler echocardiographic evidence of atrial mechanical dysfunction in coronary artery disease

BACKGROUND: Atrial function is an integral part of cardiac function which is often neglected. The presence of coronary artery disease (CAD) may impair atrial function. This study investigated if atrial mechanical dysfunction was present in patients with CAD by tissue Doppler echocardiography (TDI). METHODS: Echocardiography with TDI was performed in 118 patients with CAD, and compared with 100 normal controls with comparable age and heart rate. Regional atrial function was assessed at the left (LA) and right (RA) atrial free wall and inter-atrial septum (IAS). The peak regional atrial contraction velocity of (V(A)) and the timing of mechanical events were compared. RESULTS: The V(A) in the LA (5.0+/-2.6 Vs 7.7+/-2.6 cm/s), IAS (4.8+/-1.7 Vs 5.7+/-1.5 cm/s) and RA (6.8+/-3.1 Vs 9.2+/-2.9 cm/s) were significantly decreased in patients with CAD when compared with controls (all p<0.001). Patients with impaired systolic function (ejection fraction50% (both p<0.001); and were lower in those with restrictive filling pattern (RFP) than non-RFP of diastolic dysfunction (both p<0.05). The V(A) in all the subgroups was lower than controls. In contrast, transmitral atrial velocity was unable to reveal any abnormality except in the subgroup with a RFP. The LA dimension, area and volume were increased in the disease groups, but were largely unchanged in the RA despite abnormal V(A). The physiological inter-atrial delay for the onset and peak atrial contraction between the RA and LA were unaffected by CAD. CONCLUSIONS: The atrial contractile function in both atria was impaired in the presence of CAD, especially in the LA. This was detected even in patients with preserved systolic function or mild diastolic dysfunction such as non-RFP. Direct assessment of atrial velocity by TDI may better reflect atrial mechanical function than transmitral atrial velocity.     

Exposure to solvents in female patients with scleroderma

The role of exposure to solvents was investigated in female patients with connective tissue disease and Raynaud's phenomenon using a questionnaire. Sixteen out of the 63 patients with systemic sclerosis had been exposed to solvents. A borderline significance was demonstrated compared to matched female controls (P < 0.05). Fourteen out of the 66 patients with undifferentiated connective tissue disease, 18/86 of patients with Raynaud's phenomenon, 6/45 with systemic lupus erythematosus, 1/16 with dermatopolymyositis, 1/15 with rheumatoid arthritis and 0/13 with primary Sj?gren's syndrome had been exposed to solvents. None of these groups of patients showed a statistical significance compared to matched controls. Our present findings indicate that, at least in certain areas of the world, exposure to solvents may be a provoking factor in female scleroderma, but it must be emphasised that only a borderline significance was found between the scleroderma patients and controls. A large multicenter study seems to be required to clarify the importance of solvents as provoking factors of scleroderma. Furthermore, exposure to solvents does not seem to be a provoking factor among females for the other connective tissue diseases.     

Potential use of P-32 ophthalmic applicator: Monte Carlo simulations for design and dosimetry

Postoperative beta-irradiation after pterygium excision has been considered a valuable therapeutic procedure to reduce the recurrence rate. Recently, it was reported that beta-irradiation also substantially reduced the risk of surgical failure after glaucoma surgery. Pure beta-irradiation using a 90Sr/Y applicator has been almost exclusively used for this purpose. As an alternative to 90Sr/Y beta-irradiation, we propose treatment with betas of a 32P source. While 32P has a lower maximum energy (1.71 MeV) than 90Sr/Y (2.27 MeV), it has an average energy comparable to that of 90Sr/Y. Furthermore, it can be produced easily in a nuclear reactor by neutron activation and is considered a less hazardous material. Monte Carlo simulations for the dosimetry of proposed 32P applicators were performed using the MCNP5 code. The structure and dimension of the 32P applicators were based on those of the 90Sr/Y applicators currently available, while medical plastic encapsulation and liquid source were chosen to enhance beta-dose to the surface of the conjunctiva. The 32P applicator showed that the surface dose distribution (up to 0.75 mm depth) is very similar to that of 90Sr/Y. However, beyond 0.75 mm depth, the 32P doses decrease with depths more rapidly than 90Sr/Y doses. In order to achieve the same surface dose rate, the required 32P activity is about three times that for a 90Sr/Y applicator. We conclude that the proposed 32P applicator can deliver therapeutic doses to the target lesion while sparing the lens better than the 90Sr/Y applicator. The 32P activity required to deliver therapeutic doses can be produced in a 30 MW reactor available at the Korea Atomic Energy Research Institute.     

Sonographic median nerve change after steroid injection for carpal tunnel syndrome

Introduction: The sonographic changes of the median nerve after steroid injection for carpal tunnel syndrome (CTS) still require investigation. Methods: Sixty‐two patients with CTS were included. The Boston Carpal Tunnel Questionnaire was administered, and ultrasonographic examinations were performed before and at 2, 6, and 12 weeks after steroid injection. At 12 weeks, general improvement was scored on a 6‐point Likert scale. Results: After treatment, the cross‐sectional area (CSA) of the median nerve was significantly reduced at 2‐, 6‐, and 12‐week follow‐ups (for each, P < 0.001, analysis of variance). The “significant improvement” group (n = 39) had a significantly greater reduction in the CSA at the carpal tunnel inlet (P = 0.014) and CSA in the proximal carpal tunnel (P = 0.003) compared with the “little/no improvement” group (n = 23). Discussion: Sonographic measurement of CSA may be considered complementary to the standard clinical evaluation in monitoring of treatment response in patients with CTS. Muscle Nerve 58 : 402–406, 2018     

Canadian Health Care Professionals’ Familiarity with Chronic Cough Guidelines and Experiences with Diagnosis and Management: A Cross-Sectional Survey

Introduction

Educational programs on chronic cough may improve patient care, but little is known about how Canadian physicians manage this common debilitating condition. We aimed to investigate Canadian physicians’ perceptions, attitudes, and knowledge of chronic cough.

Methods

We administered a 10-min anonymous, online, cross-sectional survey to 3321 Canadian physicians in the Leger Opinion Panel who managed adult patients with chronic cough and had been in practice for?>?2 years.

Results

Between July 30 and September 22, 2021, 179 physicians (101 general practitioners [GPs] and 78 specialists [25 allergists, 28 respirologists, and 25 ear/nose/throat specialists]) completed the survey (response rate: 5.4%). In a month, GPs saw a mean of 27 patients with chronic cough, whereas specialists saw 46. About one-third of physicians appropriately identified a duration of?>?8 weeks as the definition for chronic cough. Many physicians reported not using international chronic cough management guidelines. Patient referrals and care pathways varied considerably, and patients frequently experienced lost to follow-up. While physicians endorsed nasal and inhaled corticosteroids as common treatments for chronic cough, they rarely used other guideline-recommended treatments. Both GPs and specialists expressed high interest in education on chronic cough.

Conclusion

This survey of Canadian physicians demonstrates low uptake of recent advances in chronic cough diagnosis, disease categorization, and pharmacologic management. Canadian physicians also report unfamiliarity with guideline-recommended therapies, including centrally acting neuromodulators for refractory or unexplained chronic cough. This data highlights the need for educational programs and collaborative care models on chronic cough in primary and specialist care.