Expression of acute-phase cytokines,surfactant proteins,and epithelial apoptosis in small airways of human acute respiratory distress syndrome

Purpose

Recent studies suggest a role for distal airway injury in acute respiratory distress syndrome (ARDS). The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small airway secretory functions are altered in ARDS.

Materials and Methods

We studied the lungs of 31 patients with ARDS (Pao₂/fraction of inspired oxygen ≤ 200, 45 ± 14 years, 16 men) and 11 controls (52 ± 16 years, 7 men) submitted to autopsy and quantified the expression of interleukin (IL) 6, IL-8, surfactant proteins (SP) A and SP-B in the epithelium of small airways using immunohistochemistry and image analysis. In addition, an index of airway epithelial apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphatase nick-end labeling assay, caspase 3, and Fas/Fas ligand expression. The density of inflammatory cells expressing IL-6 and IL-8 within the small airway walls was also quantified.

Results

Acute respiratory distress syndrome airways showed an increase in the epithelial expression of IL-8 (P = .006) and an increased density of inflammatory cells expressing IL-6 (P = .004) and IL-8 (P < .001) compared with controls. There were no differences in SP-A and SP-B epithelium expression or in epithelial apoptosis index between ARDS and controls.

Conclusion

Distal airways are involved in ARDS lung inflammation and show a high expression of proinflammatory interleukins in both airway epithelial and inflammatory cells. Apoptosis may not be a major mechanism of airway epithelial cell death in ARDS.     

The development of an observational screening tool to assess safe,effective and appropriate walking aid use in people with multiple sclerosis

Purpose: The purpose of this study was to identify potential items for an observational screening tool to assess safe, effective and appropriate walking aid use among people with multiple sclerosis (MS). Such a tool is needed because of the association between fall risk and mobility aid use in this population.

Methods: Four individuals with MS were videotaped using a one or two straight canes, crutches or a rollator in different settings. Seventeen health care professionals from Canada, Ireland and the United States were recruited, and viewed the videos, and were then interviewed about the use of the devices by the individuals in the videos. Interview questions addressed safety, effectiveness and appropriateness of the device in the setting. Data were analyzed qualitatively. Coding consistency across raters was evaluated and confirmed.

Results: Nineteen codes were identified as possible items for the screening tool. The most frequent issues raised regardless of setting and device were “device used for duration/abandoned”, “appropriate device”, “balance and stability”, “device technique”, “environmental modification” and “hands free.”

Conclusion: With the identification of a number of potential tool items, researchers can now move forward with the development of the tool. This will involve consultation with both healthcare professionals and people with MS.

• Implications for rehabilitation

• Falls among people with multiple sclerosis are associated with mobility device use and use of multiple devices is associated with greater falls risk.

• The ability to assess for safe, effective and efficient use of walking aids is therefore important, no tools currently exist for this purpose.

• The codes arising from this study will be used to develop a screening tool for safe, effective and efficient walking aid use with the aim of reducing falls risk.

     

Attention-Deficit/Hyperactivity Disorder: A Neurodevelopmental Approach

TOPIC. Attention-deficitlhyperactivity disorder is frequently overdiagnosed when a complete evaluation by a knowledgeable clinician is not undertaken. Because of the recent negative media campaign regarding psychos t im ulan t medication, it becomes more imperative that a thorough and accurate evaluation be completed before starting children and adolescents on psychostimulant medications.
PURPOSE. To describe the neurodevelopmental perspective in the assessment and treatment of ADHD.
SOURCES. Published literature and clinical experience.
CONCLUSION. It is useful in practice to conceptualize the dmelopmental path of children with ADHD not as disordered but as delayed, and to build on each child's strengths. The neurodmeloprnental approach provides the child psychiatric nurse a child-focused framework for assessment and development of individualized interventions.     

A systematic review of East African-Indian family of Mycobacterium tuberculosis in Brazil

Introduction

The Mycobacterium tuberculosis East African-Indian (EAI) spoligotyping family (belonging to lineage 1, Indo-Oceanic, defined by the region of deletion RD239) is distributed worldwide, but is more prevalent in Southeast Asia, India, and East Africa. Studies in Latin America have rarely identified EAI. In this study, we describe the occurrence of the EAI family in Brazil.

Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia

Background

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.

Design and Methods

Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.

Results

Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6–65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.

Conclusions

Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.     

The new European Society of Cardiology guidelines on myocardial revascularisation: an appraisal

The latest European Society of Cardiology (ESC) guidelines on myocardial revascularisation are reviewed. The nearly 300 recommendations make it difficult to apply them in their totality. The authors would propose 20-30 recommendations per guideline based on sound clinical evidence. Also, the scope of the current guidelines is very wide as it includes topics already incorporated in other guidelines, such as strategies for pre-intervention diagnosis and imaging as well as on secondary prevention. Some recommendations in the new guidelines are sensible and will not be disputed. In particular, the encouragement of a balanced multidisciplinary decision process (the 'heart team') is welcome. Although coronary revascularisation in unstable high risk patients is well accepted, this is less the case for the low risk patient with chest pain. This issue is controversial and a balanced discussion of the pros and cons of percutaneous coronary intervention is missing. Despite convincing evidence indicating lack of benefit of percutaneous coronary intervention for chronic total occlusion, this procedure is not discouraged. Lastly, most committee members were interventional cardiologists or cardiac surgeons. Guideline committees should be representative of the whole group of professionals as the interpretation of the evidence by specialists may be biased. There may be a role for procedure oriented guidelines but, in that case, the items at issue should remain confined to matters directly related to technical aspects of the procedure.     

Metabolic regulation is important for spermatogenesis

Male factor infertility is increasing in developed countries, and several factors linked to lifestyle have been shown to negatively affect spermatogenesis. Sertoli cells are pivotal to spermatogenesis, providing nutritional support to germ cells throughout their development. Sertoli cells display atypical features in their cellular metabolism; they can metabolize various substrates, preferentially glucose, the majority of which is converted to lactate and not oxidized via the tricarboxylic acid cycle. Why Sertoli cells preferentially export lactate for germ cells is not entirely understood. However, lactate is utilized as the main energy substrate by developing germ cells and has an antiapoptotic effect on these cells. Several biochemical mechanisms contribute to the modulation of lactate secretion by Sertoli cells. These include the transport of glucose through the plasma membrane, mediated by glucose transporters; the interconversion of pyruvate to lactate by lactate dehydrogenase; and the release of lactate mediated by monocarboxylate transporters. Several factors that modulate Sertoli cell metabolism have been identified, including sex steroid hormones, which are crucial for maintenance of energy homeostasis, influencing the metabolic balance of the whole body. In fact, energy status is essential for normal reproductive function, since the reproductive axis has the capacity to respond to metabolic cues.     

Atrial fibrillation and hyperthyroidism: relation between transoesophageal markers of a thrombogenic milieu and clinical risk factors for thromboembolism

Hyperthyroidism is a questionable risk factor for thromboembolism among patients with atrial fibrillation. Objective To correlate clinical risk factors for thromboembolism from a group of patients with atrial fibrillation related to hyperthyroidism with transoesophageal echocardiography (TOE) markers of a thrombogenic milieu. Design Clinical risk factors for thromboembolism, thyroid hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a thrombogenic milieu were assessed in consecutive patients with atrial fibrillation related to hyperthyroidism. The following TOE parameters were assessed to define the presence of thrombogenic milieu: dense spontaneous echo contrast, thrombi or left atrial appendage blood flow velocities <0·20 m/s. Clinical risk factors for thromboembolism were based on CHADS₂ (Cardiac failure, Hypertension, Age, Diabetes and Stroke) classification. Patients This study included 31 consecutive patients aged between 18 and 65 years with atrial fibrillation related to hyperthyroidism scheduled for TOE. Results Thrombogenic milieu was present in 14 of 31 (45·2%) patients. The thyroid status could not predict the presence of a thrombogenic milieu. Despite low CHADS₂ score of 0/1, 6 of 13 (46·1%) patients had a thrombogenic milieu, whereas 10 of 18 (55·6%) patients with score ≥2 had none. The probability of having a thrombogenic milieu did not correlate with the number of clinical risk factors. Conclusion Among patients younger than 65 years of age with atrial fibrillation related to hyperthyroidism, there is no association between clinical risk factors with TOE markers of a thrombogenic milieu. TOE adds useful information that may affect antithrombotic therapy guided by clinical risk classification.