Stromal cells can be cultured and characterized from diagnostic bronchoalveolar fluid samples obtained from patients with various types of interstitial lung diseases

Increased proliferation of stromal cells is a typical feature encountered in several lung diseases. The objective of this study was to evaluate the success of standardized process for culturing stromal cells from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples collected from various patients and to characterize the cultured cells. Small volumes (average 15 mL) of BAL fluid samples were collected from 98 patients who underwent bronchoscopy and BAL for diagnostic purposes. The cells were cultured in vitro and characterized by immunohistochemistry, electron microscopy, flow cytometry and differentiation tests. Cells could be cultured from 62% of samples with the success rate varying with the disease (p = 0.003). Cultures from samples of the patients with idiopathic pulmonary fibrosis, non‐specific interstitial pneumonia, connective tissue disorder associated interstitial lung disease and allergic alveolitis had a higher success rate than samples derived from control lung (p < 0.001, 0.03, 0.03 and 0.044, respectively). Smokers had a higher success rate compared with non‐smokers (p = 0.035). The cultured cells were fibroblasts or myofibroblasts, but shared also similarities with progenitor‐type cells. The study shows that mesenchymal cells can be cultured and studied from small volumes of diagnostic BAL fluid samples from patients with several different types of lung diseases.     

The association of active cancer with venous thromboembolism location: a population-based study

OBJECTIVE: To test active cancer for an association with venous thromboembolism (VTE) location.PATIENTS AND METHODS: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN, residents with incident VTE during the 35-year period 1966-2000 (N=3385). We restricted analyses to residents with objectively diagnosed VTE during the 17-year period from January 1, 1984, to December 31, 2000 (N=1599). For each patient, we reviewed the complete medical records in the community for patient age, gender, and most recent body mass index at VTE onset; VTE event type and location; and previously identified independent VTE risk factors (ie, surgery, hospitalization for acute medical illness, active cancer, leg paresis, superficial venous thrombosis, and varicose veins). Using logistic regression we tested active cancer for an association with each of 4 symptomatic VTE locations (arm or intra-abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism, and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE risk factors.RESULTS: In multivariate analyses, active cancer was independently associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P=.01), intra-abdominal DVT (OR, 2.22; P=.004), and bilateral leg DVT (OR, 2.09; P=.02), but not pulmonary embolism (OR, 0.93).CONCLUSION: Active cancer is associated with VTE location. Location of VTE may be useful in decision making regarding cancer screening.BMI = body mass index; CI = confidence interval; CTEPH = chronic thromboembolic pulmonary hypertension; DVT = deep venous thrombosis; OR = odds ratio; PE = pulmonary embolism; VTE = venous thromboembolismThe association between cancer and venous thromboembolism (VTE) is well-established and strong.^1-4 Active cancer with and without chemotherapy increases VTE risk by 5- to 6-fold.⁵ Furthermore, active cancer accounts for about 20% of the entire VTE burden occurring in a community.⁶ Indeed, VTE is the second most common cause of death among patients with cancer.⁷ Cancer patients with VTE have a 2-fold or greater increase in mortality compared with cancer patients without VTE, even after adjusting for stage.^8,9 Nearly half of the patients with cancer-associated VTE have distant metastases at the time of VTE diagnosis.⁸ The incidence of cancer in patients with recurrent idiopathic VTE is higher than that in patients with secondary VTE.³Opinions differ regarding screening for an underlying occult cancer after an idiopathic VTE event.^10,11 Although a small randomized clinical trial found that more occult cancers were detected at an early stage with extensive screening, which theoretically could improve cancer treatment potential, no difference in survival was noted between this strategy and usual care.¹⁰ Because anticoagulant therapy improves the outcomes of patients with VTE and cancer, it is still important to recognize which patients with VTE have an underlying active cancer.¹² The diagnosis of VTE may help to uncover previously occult cancer by prompting a complete physical examination and testing consistent with standard health care maintenance. However, indiscriminate cancer screening is not cost-effective.^13,14 To provide a more organized and cost-effective approach to cancer detection among patients with VTE, the VTE characteristics associated with cancer must be recognized. Although evidence shows that idiopathic VTE and bilateral deep venous thrombosis (DVT) correlate with subsequent cancer diagnosis,^3,15 there is a paucity of data regarding the association between active cancer and VTE location. The current study aims to determine whether underlying cancer is associated with particular VTE locations.     

Surfactant-free redispersible nanoparticles in fast-dissolving composite microcarriers for dry-powder inhalation

Spray-drying was investigated for the stabilization of surfactant-free nanoparticles as carriers for dry-powder inhalers. The microparticles rapidly dissolve after inhalation yielding dispersed nanoparticles.Nanoparticles were prepared by a solvent displacement technique avoiding any surfactants. Microcarriers were prepared by spray-drying nanoparticle suspensions with lactose, mannitol or α-cyclodextrin as stabilizers. Nanoparticle size and ζ-potential before and after spray-drying were analyzed with photon correlation spectroscopy and laser Doppler anemometry, respectively. Cell uptake into macrophages was studied using U 937 cells by confocal microscopy.Stabilization of nanoparticle suspensions by spray-drying with α-cyclodextrin yielded redispersible particles smaller than 200 nm. α-Cyclodextrin was a more efficient stabilizer than commonly used excipients. Microparticles with a mass median aerodynamic diameter of 4.3 μm showed properties suitable for dry-powder inhalation. The cell culture experiments with redispersed nanoparticles seem to suggest less interaction and uptake with macrophages compared to polymeric microparticles.In conclusion, nanoparticles can easily be transferred to dry-powders suitable for inhalation by spray-drying. This allows the pulmonary application of nanoparticles in high concentrations.     

Delivery of an LGA infant and the maternal risk of diabetes: A prospective cohort study

Aims

Was to determine whether the birth weight of the infant predicts prediabetes (impaired fasting glucose, impaired glucose tolerance, or both) and type 2 diabetes (T2DM) during long-term follow-up of women with or without gestational diabetes mellitus (GDM).

Assessment of Relationship of Serum Neurokinin-B Level in the Pathophysiology of Pre-eclampsia: A Case–Control Study

Introduction

Pre-eclampsia is a pregnancy-induced disorder that complicates approximately 5–7% of pregnancies. It is the leading cause of maternal and foetal morbidity and mortality worldwide.

Aim

To determine the role of serum neurokinin-B level in the pathophysiology of pre-eclampsia.

Methods

This was a case–control study. A total of 80 pregnant women in their third trimester of pregnancy were included in the study. They were divided into two groups (40 pre-eclamptic and 40 normotensive) according to the presence or absence of clinical parameters of pre-eclampsia. Serum level of neurokinin-B was measured with ELISA.

Results

Maternal age, weight, BMI, pulse, systolic BP and diastolic BP were statistically higher in the pre-eclampsia group compared to the normotensive group (P?<?0.0001). Moreover, statistically higher levels were observed for neurokinin-B in the normotensive group as compared to the pre-eclamptic group. The mean value of neurokinin-B was 83.50 ng/L in the pre-eclamptic group compared to 111.5 ng/L in the normotensive group (P?=?0.006).

Conclusion

Higher levels of serum neurokinin-B were observed in the normotensive pregnant females as compared to the pre-eclamptic females. Thus, apparently, it seems that serum neurokinin-B plays no role in the pathophysiology of pre-eclampsia, and further large multicentre prospective studies may be required to ascertain its role.

     

Unacylated ghrelin is associated with changes in insulin sensitivity and lipid profile during an exercise intervention

Objective Ghrelin has been implicated in energy homeostasis, body weight regulation and glucose metabolism. Level of unacylated ghrelin (UAG), but not acylated ghrelin (AG), has been suggested to increase during long‐term exercise. However, the association of the level of UAG with exercise‐induced changes of insulin sensitivity and lipid metabolism has not been previously investigated. We hypothesized that an increase in UAG level in response to a long‐term exercise programme improves insulin sensitivity and associated lipid profile, independently of weight loss. Design, patients and measurements A prospective study of 552 young men (mean age 19·3 and range 19–28 years) undergoing military service with structured 6‐month exercise training programme. Exercise performance, clinical and biochemical measurements were obtained at baseline and follow‐up. Association between UAG level and fasting glucose, insulin, insulin sensitivity and lipid levels were evaluated. Results An overall increase in the level of UAG was observed during the 6‐month follow‐up (P < 0·001), which was largest among those with weight loss ≥ 2·5% or among those whose reduction in waist circumference was largest (P = 0·007 and P < 0·001, respectively). A change in UAG level correlated inversely with a change in fasting glucose and insulin levels, HOMA‐IR, total cholesterol and total triglyceride levels (P < 0·001 for all). The association between change in the UAG level and the change in insulin sensitivity was independent of weight loss or reduction in waist circumference. Conclusions Increase in UAG level was associated with improved insulin sensitivity via mechanisms independent of weight loss during an intensive, long‐term exercise intervention in young healthy men.