39 research outputs found
Nine-Tenths of the Law: The English Copyright Debates and the Rhetoric of the Public Domain
Background: The role of vitamin D supplementation as adjuvant treatment of tuberculosis (TB) has lately attracted increasing interest. Our aim was to investigate the capacity of alveolar macrophages (AMs) from patients with or without exposure to TB to control intracellular growth of virulent Mycobacterium tuberculosis (Mtb). Methods: AMs were freshly harvested from the bronchoalveolar lavage fluid of 7 patients with a history of TB (4 patients with previous TB and 3 patients with current TB) and 4 non-TB subjects. The H37Rv strain, genetically modified to express Vibrio harveyi luciferase, was used to determine the growth of Mtb by luminometry in the AMs from study subjects. Cytokine levels in culture supernatants were determined using a flow cytometry-based bead array technique. Results: AMs from patients with a TB history were less efficient in restricting Mtb growth. Stimulation with 100 nM1, 25-dihydroxyvitamin D (1,25D3) did not significantly influence the capacity of AMs from any study subjects to control the infection. Out of the cytokines evaluated (TNF-α, IL-1β, IL-10 and IL-12p40) only TNF-α demonstrated detectable levels in culture supernatants, but did not respond to stimulation with 1,25D3. Conclusions: We conclude that AMs of TB-patients show reduced ability to control mycobacterial growth in vitro, and, that AMs in this pilot study do no respond to 1, 25D3-stimulation. The former observation supports the concept that innate immunity is crucial for the control of TB infection
Telemonitoring of COPD Patients to Evaluate the "Rome Proposal"
For the first time in a telemonitoring context, we apply the Rome Proposal (RP), recently adopted by GOLD 2023, to assess the severity of exacerbations (ECOPD). So far, we have analysed 387 study weeks, which include only 18 ECOPDs; 4 mild, 13 moderate and 1 severe according to the criteria from RP. There is a promising potential of telemonitoring based on the RP
The Health Diary Telemonitoring and Hospital-Based Home Care Improve Quality of Life Among Elderly Multimorbid COPD and Chronic Heart Failure Subjects
Background: Elderly, multimorbid patients with advanced chronic obstructive pulmonary disease (COPD) and/or chronic heart failure (CHF) exhibit poor health-related quality of life (HRQoL). Telemonitoring, based on digital pen technology, supported by hospital-based home care (HBHC) significantly reduces the number of hospitalizations. We hypothesized that the same intervention would prevent the deterioration of HRQoL that follows upon disease progression. Methods: Elderly computer-illiterate subjects with amp;gt;= 2 hospitalizations the previous year were included. HRQoL was assessed at inclusion (baseline) and at 1, 6 and 12 months employing EuroQol-5 Dimensions (EQ-5D) and RAND-36 for general HRQoL, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) and St. Georges Respiratory Questionnaire (SGRQ) for disease-specific HRQoL. Healthcare contacts, hospitalizations, as-needed medications, prescription changes and healthcare costs were registered. Results: Ninety-four patients were enrolled of which 53 subjects completed the 12-month study period. Compared to baseline, most domains of RAND-36 were improved significantly at 1 time-point or more. Only among COPD subjects, the disease-specific HRQoL was worsened at the 12 month evaluation. Measures of healthcare dependency were associated with poor HRQoL. Conclusion: The Health Diary system and HBHC together improve general HRQoL, and measures of healthcare dependency are associated with HRQoL variables.Funding Agencies|county council of Ostergotland (Region Ostergotland); E-care@home: a "SIDUS -Strong Distributed Research Environment" project - Swedish Knowledge Foundation; European Regional Development Fund through the NovaMedTech venture; RISE Research Institutes of Sweden AB</p
Oxidant status, iron homeostasis, and carotenoid levels of COPD patients with advanced disease and LTOT
Background: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with oxidative stress. Both iron (Fe) and oxygen are involved in the chemical reactions that lead to increased formation of reactive oxygen species. Oxidative reactions are prevented by antioxidants such as carotenoids. Objective: To study the differences in Fe status, carotenoid levels, healthy eating habits, and markers of inflammation and oxidative damage on proteins in subjects with severe COPD ± long-term oxygen therapy (LTOT) and lung-healthy control subjects. Methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included. Questionnaires about general health, lifestyle, and dietary habits were answered. Lung function tests and blood sampling were performed. Results: COPD subjects (±LTOT) did not demonstrate increased oxidative damage, assessed by protein carbonylation (PC), while levels of soluble transferrin receptors (sTfRs) were slightly elevated. Soluble TfRs, which is inversely related to Fe status, was negatively associated with PC. Levels of carotenoids, total and ß-cryptoxanthin, a- and ß-carotenes, were significantly lower in COPD subjects, and their diet contained significantly less fruits and vegetables. Lutein correlated inversely with IL-6, lycopene correlated inversely with SAT, while ß-carotene was positively associated with a Mediterranean-like diet. Conclusions: Fe could favor oxidative stress in COPD patients, suggesting a cautious use of Fe prescription to these patients. COPD subjects ate a less healthy diet than control subjects did and would, therefore, benefit by dietary counseling. COPD patients with hypoxemia are probably in particular need of a lycopene-enriched diet
Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study
Steroid injections are often employed as an alternative treatment for radicular pain in patients with degenerative spinal disorders. Prospective randomised studies of the lumbar spine reveal contradictory results and non-randomised and most often retrospective studies of the cervical spine indicate pain reduction from steroid injections. No prospective randomised study on transforaminal steroid injections for the treatment of radicular pain in the cervical spine focusing on short-term results has been performed. Forty consecutive patients were employed for the study. The inclusion criteria were one-sided cervical radiculopathy with radicular distribution of arm pain distal to the elbow and corresponding significant degenerative pathology of the cervical spine at one or two levels on the same side as the radicular pain and visualised by MRI. A transforaminal technique was used for all injections. A positive response to a diagnostic selective nerve root block at one or two nerve roots was mandatory for all patients. The patients were randomised for treatment with steroids/local anaesthetics or saline/local anaesthetic. Only the neuroradiologist performing the blocks was aware of the content of the injection; all other persons involved in the study were blinded. Follow up was made 3 weeks after the randomised treatment by a clinical investigation and with a questionnaire focusing on the subjective effects from the injections. At follow up, there were no differences in treatment results in the two patient groups. Statistical analysis of the results confirmed the lack of difference in treatment effect. Further studies have to be performed before excluding steroids in such treatment and for evaluating the influence of local anaesthetics on radiculopathy in transforaminal injections
A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that usually results in respiratory failure and death. Pirfenidone was approved as the first licensed therapy for IPF in Europe based on phase III trials where patients with a forced vital capacity (FVC) >50% of predicted were included. The aim of this study was to characterise patients treated with pirfenidone in Swedish clinical practice and to describe the adherence to the reimbursement restriction since reimbursement was only applied for patients with FVC below 80% of predicted. Methods: This was a retrospective, observational chart review of IPF patients treated with pirfenidone from three Swedish university clinics. Patients initiated on treatment during the period 28 June 2012 to 20 November 2014 were included. Data on patient characteristics, basis of diagnosis, treatment duration, quality of life, and adverse drug reactions (ADRs) were collected from medical charts. Results: Forty-four patients were screened and 33 were included in the study. The mean treatment duration from start of pirfenidone until discontinuation or end of study was 38 weeks. At the initiation of pirfenidone treatment, FVC was 62.7% (12.1) [mean (SD)], diffusion capacity (DLco) was 45.1% (13.8) of predicted, and the ratio of forced expiratory volume on 1 sec (FEV1) to FVC was 0.78 (0.1). The percentage of patients with an FVC between 50 and 80% was 87%. Ten of the patients had ADRs including gastrointestinal and skin-related events, cough and signs of impaired hepatic function, but this led to treatment discontinuation in only two patients. Conclusion: Data from this chart review showed that adherence to the Swedish reimbursement restriction was followed in the majority of patients during the study period. At the start of pirfenidone treatment, lung function, measured as FVC, was lower in the present cohort of Swedish IPF patients compared with other registry and real-life data. About a third of the patients had ADRs, but discontinuation of the treatment because of ADRs was relatively uncommon
Quantitative lung SPECT applied on simulated early COPD and humans with advanced COPD
BACKGROUND:Reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers. METHODS:In the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers. RESULTS:A significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the five healthy volunteers and five patients with advanced COPD (p < 0.05). CONCLUSIONS:While our results are promising, the potential of the AUC(CVT) method to detect less advanced COPD in patients needs further clinical studies
Oxidant-induced autophagy and ferritin degradation contribute to epithelial-mesenchymal transition through lysosomal iron
Transforming growth factor (TGF)-ß1 triggers epithelial-mesenchymal transition (EMT) through autophagy, which is partly driven by reactive oxygen species (ROS). The aim of this study was to determine whether leaking lysosomes and enhanced degradation of H-ferritin could be involved in EMT and whether it could be possible to prevent EMT by iron chelation targeting of the lysosome
Quantitative lung SPECT applied on simulated early COPD and humans with advanced COPD
BACKGROUND:Reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers. METHODS:In the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers. RESULTS:A significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the five healthy volunteers and five patients with advanced COPD (p < 0.05). CONCLUSIONS:While our results are promising, the potential of the AUC(CVT) method to detect less advanced COPD in patients needs further clinical studies