The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation

Tissue-resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis, and tumor formation. Here, we define a population of resident lung MSCs (luMSCs) that function to regulate the severity of bleomycin injury via modulation of the T-cell response. Bleomycin-induced loss of these endogenous luMSCs and elicited fibrosis (pulmonary fibrosis), inflammation, and pulmonary arterial hypertension (PAH). Replacement of resident stem cells by administration of isolated luMSCs attenuated the bleomycin-associated pathology and mitigated the development of PAH. In addition, luMSC modulated a decrease in numbers of lymphocytes and granulocytes in bronchoalveolar fluid and demonstrated an inhibition of effector T-cell proliferation in vitro. Global gene expression analysis indicated that the luMSCs are a unique stromal population differing from lung fibroblasts in terms of proinflammatory mediators and profibrotic pathways. Our results demonstrate that luMSCs function to protect lung integrity after injury; however, when endogenous MSCs are lost, this function is compromised illustrating the importance of this novel population during lung injury. The definition of this population in vivo in both murine and human pulmonary tissue facilitates the development of a therapeutic strategy directed at the rescue of endogenous cells to facilitate lung repair during injury.     

A randomized clinical trial of the effectiveness of mechanical traction for sub-groups of patients with low back pain: study methods and rationale

Background  

Patients with signs of nerve root irritation represent a sub-group of those with low back pain who are at increased risk of persistent symptoms and progression to costly and invasive management strategies including surgery. A period of non-surgical management is recommended for most patients, but there is little evidence to guide non-surgical decision-making. We conducted a preliminary study examining the effectiveness of a treatment protocol of mechanical traction with extension-oriented activities for patients with low back pain and signs of nerve root irritation. The results suggested this approach may be effective, particularly in a more specific sub-group of patients. The aim of this study will be to examine the effectiveness of treatment that includes traction for patients with low back pain and signs of nerve root irritation, and within the pre-defined sub-group.     

Pediatric HIV adherence: an ever-evolving challenge

Providers working with children living with HIV strive to achieve "good adherence," often viewed only as consistent pill taking by the infected child. This goal, while important, needs to be expanded with a thorough examination of the many biopsychosocial factors impacting the HIV affected family. The complexity of the issues affecting adherence to a pediatric HIV medical regimen can overwhelm both the practitioner and the patient. By utilizing a developmental framework and emphasizing the critical importance of the relationship between provider, patient and family, the authors (both of whom are social workers who have worked over a period of many years with children and families living with terminal and serious chronic illnesses) describe a developmental approach that includes comprehensive assessment to address the multiple challenges faced by individuals and families they have worked with.     

Decreased lung function associated with perinatal exposure to Dutch background levels of dioxins

Perinatal exposure to Dutch background dioxin levels is rather high. Studies of calamities have shown that dioxins negatively influence the respiratory system. It was hypothesized that perinatal exposure to background dioxin levels leads to lung suboptimality, probably through developmental interference. This study aimed to assess lung function in relation to perinatal dioxin exposure. Spirometry was performed in 41 healthy children (aged 7-12 y, mean 8.2 y) with known perinatal dioxin exposure. The ratio of forced expiratory volume in 1 s to forced vital capacity (FEV 1 /FVC ratio) was determined. A complete medical history was taken. The prenatal exposure ranged from 8.74 to 88.8 (mean 34.6) ng TEQ dioxin kg fat -1 , measured in breast milk. The postnatal exposure ranged from 4.34 to 384.51 (mean 75.4) ng TEQ dioxin. Twelve children had to be excluded. significant decrease in lung function in relation to both prenatal ( p = 0.045) and postnatal ( p = 0.0002) dioxin exposure was seen in the 29 non-excluded children. A clinical association between chest congestion and perinatal dioxin exposure was seen.

Conclusion: Perinatal background dioxin exposure may be inversely associated with the FEV 1 /FVC ratio.     

An investigation into the possibility of transmission of tick-borne pathogens via blood transfusion

BACKGROUND: Tick-borne illnesses were diagnosed in a group of National Guard members, including some who had donated blood a few days before the onset of symptoms. A voluntary recall of those blood components was issued and a multistate investigation was conducted to determine if transfusion-transmitted illness had occurred. STUDY DESIGN AND METHODS: Donors and recipients were asked to complete questionnaires regarding symptoms and risk factors for infection and to provide blood samples for laboratory analysis. RESULTS: Among National Guard personnel who donated blood, 12 individuals were found to have a confirmed or probable case of Rocky Mountain spotted fever or ehrlichiosis. A total of 320 units (platelets or packed red cells) from 377 donors were transfused into 129 recipients. Although 10 recipients received units from National Guard personnel with confirmed or probable infection, none became ill. CONCLUSION: Transfusion-transmitted illness did not occur. Despite the awareness of the risk for tick-borne diseases and the use of tick-preventive measures, many National Guard personnel reported exposure to ticks. In addition to augmenting current tick-preventive measures, scheduling blood drives before rather than after field exercises could further reduce the potential for transmission of tick-borne pathogens.     

The management of metastases to eye and orbit from carcinoma of the breast

This report describes 11 patients who developed visual symptoms due to choroidal or orbital metastases from carcinoma of the breast. All patients were treated using palliative radiotherapy with regression of metastases in five of six patients (83%) having choroidal involvement and three of five patients (60%) having orbital metastases. There were no complications due to radiotherapy. All these patients had advanced metastatic breast cancer with poor survival following development of orbital or choroidal metastases.