Telehealth mitigates COPD disease progression compared to standard of care: a randomized controlled crossover trial.

BACKGROUND: We showed excellent adherence and satisfaction with our telehealth care (TC) approach for COPD. Here, the results of a consecutive randomized controlled trial are presented. METHODS: Patients were randomly assigned to TC or standard care (SC). During TC, patients answered six daily questions online, and focused on the early recognition of exacerbations, in addition to SC. RESULTS: The mean increase in COPD assessment test (CAT) was 1.8 vs. 3.6 points/year in the TC and SC groups, respectively (P = 0.0015). Satisfaction with care (VAS) at baseline was 8.2; at the end of SC, 8.5 (P = 0.062); and after TC, 8.8 (P < 0.001). We detected significantly more moderate exacerbations during TC. CONCLUSION: Whilst receiving TC, the slope of the CAT increase - an indicator of the naturally progressive course of COPD - was reduced by 50%. Satisfaction with care increased with TC. The higher number of detected moderate exacerbations probably indicates a higher diagnostic sensitivity than without TC.

The association between discrimination and drinking among sexual minorities: A daily diary study.

Background: Among sexual minorities (SMs), experiencing discrimination has been associated with greater substance use at the day-level. However, variations in sample characteristics and measures of day-level discrimination limit the generalizability of findings. Furthermore, it is unknown how positive experiences due to minority identity ("Minority Strengths") may impact the association between experiencing discrimination and same day drinking. Methods: The present study extends prior research on discrimination and drinking using detailed discrimination measures, Minority Strengths measures, and a gender diverse sample. Participants (N = 61) were majority White (n = 45, 73.8 %) adult (mean age 26.8 years) self-identified SMs (e.g., 44.3 % identified as "gay") who engaged in alcohol use within the past month. Participants completed up to 31 days of daily diary surveys about their experiences and drinking. Recruitment took place in the northeastern U.S. from May to December 2021. Results: Multilevel model analysis indicated that experiencing discrimination was associated with increased same day drinking among Black, Indigenous, people of color (BIPOC) participants but not among White participants. A significant gender by discrimination interaction indicated that cisgender men drank more the same day they experienced discrimination compared to cisgender women and transgender/non-binary participants. Minority Strengths had no impact on these relationships. Conclusions: Results highlight that the experience of discrimination and its association with drinking may be influenced by a host of contextual factors that are attached to racial and gender identities. Future research should examine how discrimination in different contexts (e.g., regions) and based on specific identities may be associated with alcohol use.

A three-arm randomised controlled trial to evaluate the efficacy of a positive psychology and social networking intervention in promoting mental health among HIV-infected men who have sex with men in China.

AIMS: There is a lack of mental health promotion and treatment services targeting HIV-positive men who have sex with men (HIVMSM) in China. The aim of this study was to evaluate the mental health promotion efficacy of an online intervention that combined Three Good Things (TGT) with electronic social networking (TGT-SN) and an intervention that used TGT only (TGT-only), compared with a control group. METHODS: We conducted a randomised controlled trial among HIVMSM in Chengdu, China. The participants were randomly assigned to the TGT-SN, TGT-only, and control groups. The participants in the TGT-SN group were divided into five social network groups and asked to post brief messages to the group about three good things that they had experienced and for which they felt grateful. The participants in the TGT-only group were only required to write down their three good things daily without sharing them with others. The control group received information about mental health promotion once a week for a month. The primary outcome was probable depression. Secondary outcomes were anxiety, positive and negative affect, gratitude, happiness and social support. These outcomes were assessed at baseline, 1, 3, 6 and 12 months after the intervention. Repeated-measures analyses were conducted using generalised estimation equations. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13003252). RESULTS: Between June 2013 and May 2015, 404 participants were enrolled and randomly assigned to either the TGT-SN (n = 129), TGT-only (n = 139) or control group (n = 136). The main effects of TGT-SN (adjusted odds ratio (aOR) = 0.75, 95% CI 0.52-1.09; p = 0.131) and TGT-only (aOR = 0.83, 95% CI 0.57-1.21; p = 0.332) in reducing depression were statistically non-significant. The participants of the TGT-SN group showed significantly lower anxiety symptoms (aOR = 0.62, 95% CI 0.43-0.89; p = 0.009) and negative affect (ß = -1.62, 95% CI 2.98 to -0.26; p = 0.019) over time compared with those of the control group. No significant main effect was found for any secondary outcomes for the TGT-only group. CONCLUSIONS: The novel intervention combining the TGT exercise with electronic social networking was found effective in reducing anxiety and negative affect among HIVMSM.

Hibernoma-like brown fat in the bone marrow: report of a unique case.

We report on a bone-marrow biopsy of a 61-year-old female patient that was performed because of the clinical suspicion of a myeloproliferative disease. The trephine biopsy showed morphological features that were consistent with an essential thrombocythaemia (ET). The diagnosis of a myeloproliferative disease could be corroborated by demonstration of the V617F mutation of JAK2. Besides the histological features of ET, the marrow showed a peculiar infiltrate that consisted of multivacuolated cells that were immunohistochemically identified as brown adipose tissue with a hibernoma-like picture. To the best of our knowledge, this is the first report on brown adipose tissue in the bone marrow.

[Risk stratification and follow-up assessment of patients with pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Risikostratifizierung und Verlaufskontrollen bei PAH-Patienten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to risk stratification and follow-up assessment of patients with PAH. This manuscript summarizes the results and recommendations of this working group.

[Targeted therapy of pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Gezielte Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensuskonferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the targeted therapy of PAH. This article summarizes the results and recommendations of the working group on targeted treatment of PAH.

The acute-phase protein alpha 1-antitrypsin inhibits transferrin-receptor binding and proliferation of human skin fibroblasts.

Transferrin (Tf) is required for proliferation of most cells, because cellular iron uptake is mainly mediated by binding of Tf to its specific cell surface receptors (TfR). The acute-phase protein alpha 1-antitrypsin (alpha 1-AT) completely inhibits binding of diferric Tf to TfRs on human skin fibroblasts in a dose-dependent fashion. The inhibition is competitive as proved in equilibrium saturation binding and kinetic studies. In saturation binding experiments alpha 1-AT apparently increased the dissociation constant (KD), but did not change the maximal density of binding sites (Bmax). As shown in kinetic studies, this reduction of the affinity of Tf to its receptor caused by alpha 1-AT was due to a decrease of the association rate constant (k + 1), whereas the dissociation rate constant (k - 1) remained unchanged. Furthermore, alpha 1-AT almost completely prevented internalization of the Tf-TfR complex. These interactions demonstrated biological implication, as alpha 1-AT reduced the proliferation of human fibroblasts up to maximal 30% of control. The inhibitory potency of alpha 1-AT was already seen in physiologic concentrations; the maximal effect, however, was achieved at concentrations above the normal range, which are attained in the course of inflammation and infection. Therefore, we suppose that alpha 1-AT as an endogenous factor modulates the complex mechanism of fibrogenesis not only by its known antiproteolytic function but also by inhibiting the proliferation of fibroblasts.

Different patterns of deactivation of chemotaxis and haptotaxis of human peripheral blood mononuclear leukocytes by soluble and surface-bound attractants.

Soluble mediators and inducible cell-surface and matrix-bound molecules coordinate the cascade of events giving rise to leukocyte emigration. Knowledge of the specific mechanisms underlying the attraction of cells into a local site, however, remains sketchy. In particular, it is unclear how chemoattractants cause rapidly moving immune cells to adhere to the blood vessel wall and to enter tissues. Here we show that the neuroendocrine human growth hormone, a chemoattractant for monocytes and lymphocytes in vitro, promotes haptotaxis, the migration of the cells induced by surface-bound gradients. Combination of soluble growth hormone with soluble attractants, RANTES or formyl peptide, deactivates the migratory responses, as do combinations of surface-bound growth hormone with surface-bound RANTES or formyl peptide. In contrast, exposure of mononuclear leukocytes to combinations of soluble chemotactic with surface-bound haptotactic gradients of attractants does not deactivate migration. The findings suggest that growth hormone may act as haptotactic agent, on the one hand, and that soluble attractants do not appear to affect haptotaxis when acting in concert with a surface-bound attractant, on the other. This observation may have implications for the differential regulation of leukocyte accumulation in the vessel wall at systemic and local sites.

Effect of Boophone disticha on human neutrophils.

Boophone disticha (Amaryllidaceae) are mainly used in Southern Africa for inflammatory conditions. It is also known for its toxic effects. Because of the putative effects on components of the immune system and inflammatory response the effects of extracts of the bulb of Boophane disticha were investigated on ATP production in isolated human neutrophils. Furthermore, one possible mechanism of Boophone disticha's therapeutic properties might be its inhibition of superoxide release from neutrophils. The effect of the extracts on superoxide production of human neutrophils was also investigated. Aqueous and ethanol extracts of the outer and inner scales of the bulb of Boophone disticha was investigated for their effect on human neutrophils. It was decided to test the dry other scales separately from the fleshy inner scales as the parts are also used separately by traditional healers for different applications. ATP production was significantly decreased by ethanol extracts of the inner scales of the bulb. Superoxide production was significantly inhibited by aqueous extracts of the inner and outer scales of the bulb.

Release of chemoattractants for human monocytes from endothelial cells by interaction with neutrophils.

OBJECTIVE: The release of monocyte chemoattractant protein-1 (MCP-1) in the vessel wall may lead to accumulation of monocytes in the subendothelial space. The role of neutrophils (PMNL) in the initiation of this process is unknown. We tested whether PMNL are able to induce the production and release of MCP-1 in endothelial cells. METHODS: PMNL were allowed to interact with human umbilical vein endothelial cell (HUVEC) monolayers in culture. Culture media were collected and assessed for chemotactic activity on mononuclear leukocytes (MNC) or purified monocytes in a modified Boyden chamber assay. Additionally, MCP-1 levels in supernatants were quantified by ELISA. RESULTS: Media from unstimulated HUVEC culture supernatants induced a slight increase (1.2-fold) of MNC and purified monocyte chemotaxis, which was significantly augmented by addition of PMNL for 1 h (1.4-fold; P < 0.05). The increase in chemotaxis was time- and dose-dependent and could be blocked by an anti-MCP-1 monoclonal antibody. Media obtained after coculture of PMNL and HUVEC for 1-5 h contained increased amounts of MCP-1 as measured by ELISA; addition of cycloheximide abolished this response. CONCLUSIONS: Interaction of PMNL with endothelium induces the release of functionally active MCP-1 suggesting that in the vascular wall, PMNL may play a role in the recruitment of MNC.

Attraction of human monocytes by the neuropeptide secretoneurin.

Secretoneurin is a newly discovered 33-amino-acid peptide derived from secretogranin II (chromogranin C) that is found in sensory afferent C-fibers. We show here that secretoneurin triggers the selective migration of human monocytes in vitro and in vivo. Combinations of secretoneurin with the sensory neuropeptides, substance P or somatostatin, synergistically stimulate such migration. The attraction of monocytes represents the first established function of secretoneurin as a sensory neuropeptide.

Specific binding of a 125I-secretoneurin analogue to a human monocytic cell line.

Secretoneurin (SN) is a novel neuropeptide expressed in the central and peripheral nervous system as well as in various endocrine tissues. SN inhibits growth of aortic pulmonary and endothelial cells and is a potent chemoattractant for endothelial cells, skin fibroblasts and monocytes. We investigated here the presence of specific high affinity binding sites for SN on a target tissue. SN was iodinated with the Bolton-Hunter (BH) reagent and purified by isocratic reversed phase chromatography. Specific binding sites for 125I-BHSN were identified on human Mono Mac 6 cells, a monocytic cell line. Scatchard analysis revealed a single class of binding sites with a Kd value of 7.3 nM and a Bmax of 322 (fmol/mg protein). Competition studies demonstrated that the 15 C-terminal amino acids of SN could displace authentic SN, whereas shorter fragments were inactive. Other sensory neuropeptides like substance P, calcitonin gene-related peptide or galanin as well as the chemokine receptor ligand Rantes or the typical chemoattractant FMLP could not displace SN. Our studies demonstrate specific high affinity binding sites for SN on a monocytic cell line. Since SN exerts a potent chemotactic activity towards monocytes and increases cytosolic calcium in these cells, these binding sites might well represent a putative functional plasma membrane receptor for SN.

Similar involvement of VIP receptor type I and type II in lymphocyte chemotaxis.

Effects of vasoactive intestinal peptide (VIP) on T cell migration are mediated by structurally distinct types I (VIPR1) and II (VIPR2) G protein-associated receptors. The two receptor types were proposed to transduce opposite effects on human T cells, since cytokine-induced chemotaxis of VIPR1-bearing HuT 78 human T cells, in contrast to T cells that express VIPR2, was inhibited by VIP. We studied chemotactic effects of VIP and related agonists with different affinities for VIP- and peptide histidine-isoleucine (PHI)-related receptors. All, VIP, secretin (SEC), a specific ligand for VIPR1, helodermin (HEL), an activator of helodermin-preferring VIPR2, as well as PHI, stimulated chemotaxis into micropore filters of both normal human peripheral blood T and B cells. Involvement of VIPRs was supported by inhibition of VIP-related agonist-induced migration of T and B cells with a VIPR antagonist. Peripheral blood lymphocyte (PBL) chemotaxis to VIP, SEC, HEL and PHI was reduced by inhibition of tyrosine kinase and pertussis or cholera toxin, whereas inhibition of protein kinase C only affected SEC-induced chemotaxis of PBL significantly. VIP-related agonists induced deactivation of migration at high concentrations. Findings in PBL suggest that VIPR1 activation can stimulate normal T and B cell chemotaxis. Different signaling mechanisms may be involved in mediating chemotactic activation of VIPRs and PHIRs, which may allow further exploration of receptor-dependent mechanisms and signaling pathways of VIP as mediator of PBL functions.

Interleukin-8-induced human peripheral blood B-lymphocyte chemotaxis in vitro.

We studied chemotactic effects of interleukin-8 (IL-8) on human peripheral blood lymphocytes (PBL) using micropore filter assays. As identification of chemotactic responses depends on the status of activation of cells, magnetic cell sorting (MACS) was performed providing freshly isolated B-lymphocytes of highest purity. B-lymphocytes responded chemotactically to IL-8 in a dose-dependent manner. We conclude that IL-8 may play a role in both T- and B-lymphocyte trafficking by acting directly on the cells.

Augmentation of tumor necrosis factor-alpha-induced priming of fMet-Leu-Phe-stimulated neutrophils by pentoxifylline.

Tumor necrosis factor-alpha (TNF) is reported to cause tissue damage via enhanced neutrophil (PMNL) degranulation, superoxide production and altered PMNL migration. We investigated the effect of pentoxifylline (PTX) on TNF-induced respiratory burst activity of the PMNL. Since PTX has been reported to influence TNF-induced PMNL functions, our studies focused on the effects of timing and duration of the presence of PTX on superoxide anion production by PMNL exposed to TNF. When PMNL are exposed to PTX prior to priming with TNF and triggering with fMLP, respiratory burst activity was significantly enhanced by PTX, whereas the stimulatory effect of TNF was completely blunted by the continuous presence of PTX. Since free radical-scavenging properties of PTX have only recently been identified and may explain inhibitory effects on TNF-induced respiratory burst reported in the literature, our data for the first time suggests additive priming actions of PTX and TNF on PMNL respiratory burst activity.

The dose-related hyper-and-hypokalaemic effects of salbutamol and its arrhythmogenic potential.

1. The hypokalaemic effect of salbutamol after more than 30 min of administration has been well described. A hyper-and-hypokalaemic effect for adrenaline has been reported, but no such hyperkalaemic effect for salbutamol. 2. The possible hyper-and-hypokalaemic effects of salbutamol with the concomitant potential for pro-arrhythmia were assessed in the baboon (Papio ursinus). 3. Male and female baboons were anaesthetized with ketamine (15 mg kg-1) and maintained with 6% pentobarbitone as spontaneously breathing animals. Six baboons in each group received either 10, 100 or 500 micrograms kg-1 salbutamol i.v. Lead II of the ECG and femoral i.a. blood pressure were recorded continuously for 10 min. Arterial blood samples were collected at 0 min and then after 3 and 10 min of salbutamol administration. 4. All the animals developed sinus tachycardia (above 200 beats min-1) within 30 s of each dose of salbutamol administration and the high heart rate persisted throughout the experiment. All the animals were hyperkalaemic after 3 min and hypokalaemic after 10 min for each dose of salbutamol. Left ventricular conduction defects were seen in 3 animals during the hyperkalaemic phase. No arrhythmia was seen during the hypokalaemic phase. 5. Salbutamol has a transient hyperkalaemic and a more prolonged hypokalaemic effect in the baboon. The hypokalaemia could not be associated with arrhythmia although conduction defects were associated with the hyperkalaemia. 6. Since salbutamol is used as a bronchodilator in asthmatic patients and to treat acute hyperkalaemia, it is suggested that caution should be exercised when using salbutamol in high doses to treat acute asthma especially during the first few minutes of administration. The finding of hyperkalaemia with salbutamol questions its use in the treatment of hyperkalaemia.

Effect of inhibitors of Na+/H+-exchange and gastric H+/K+ ATPase on cell volume, intracellular pH and migration of human polymorphonuclear leucocytes.

1. Stimulation of chemotaxis of human polymorphonuclear leucocytes (PMNs) with the chemoattractive peptide fMLP (N-formyl-Met-Leu-Phe) is paralleled by profound morphological and metabolic alterations like changes of intracellular pH (pHi) and cell shape. The present study was performed to investigate the interrelation of cell volume (CV) regulatory ion transport, pHi and migration of fMLP stimulated PMNs. 2. Addition of fMLP to PMNs stimulated directed migration in Boyden chamber assays and was accompanied by rapid initial intracellular acidification and cell swelling. 3. Inhibition of the Na+/H+ exchanger suppressed fMLP stimulated cell migration, accelerated the intracellular acidification and inhibited the fMLP-induced cell swelling. 4. Step omission of extracellular Na+ caused intracellular acidification, which was accelerated by subsequent addition of gastric H+/K+ ATPase inhibitor SCH 28080, or by omission of extracellular K+ ions. In addition Na+ removal caused cell swelling, which was further enhanced by fMLP. 5. H+/K+ATPase inhibitors omeprazole and SCH 28080 inhibited stimulated migration and blunted the fMLP-induced increase in CV. 6. Increasing extracellular osmolarity by addition of mannitol to the extracellular solution caused cell shrinkage followed by regulatory volume increase, partially due to activation of the Na+/H+ exchanger. In fMLP-stimulated cells the CV increase was counteracted by simultaneous addition of mannitol. Under these conditions the fMLP stimulated migration was inhibited. 7. The antibacterial activity of PMNs was not modified by Hoe 694 or omeprazole. 8. Western analysis with a monoclonal anti gastric H+/K+ ATPase beta-subunit antibody detected a glycosylated 35 kD core protein in lysates of mouse and human gastric mucosa as well as in human PMNs. 9. The results indicate that fMLP leads to cell swelling of PMNs due to activation of the Na+/H+ exchanger and a K+-dependent H+-extruding mechanism, presumably an H+/K+ ATPase. Inhibition of these ion transporters suppresses the increase in CV and precludes PMNs from stimulated migration.

Human chorionic gonadotrophin: a chemoattractant for human blood monocytes, neutrophils and lymphocytes.

Treatment of rats with human chorionic gonadotrophin (hCG) induced in the testes an inflammation-like reaction characterized by migration of leukocytes into the interstitial space. In order to find out whether hCG acts in a direct manner in this process, we tested peripheral human blood leukocyte attraction by hCG in vitro. Chemotaxis through cellulose nitrate to gradients of test substances was measured using a 48-well microchemotaxis chamber. Human CG was found to be a potent attractor of neutrophils, monocytes and lymphocytes in vitro in the picomolar concentration range. Checkerboard analyses revealed that the type of migration depends on positive concentration gradients of hCG. The chemoattractant nature of hCG is consistent with its having a role to play in regulation of tissue accumulation of these cells within the reproductive tract.

CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer.

AIMS: Recent results generated in a mouse model suggest that tumour angiogenesis/vasculogenesis can be initiated and maintained by bone marrow derived endothelial progenitor cells. This present study investigated the distribution and frequency of CD133 positive endothelial progenitor cells in patients with non-small cell lung cancer (NSCLC) (tumour tissue and tumour free lung regions) and healthy controls using fresh frozen specimens. The novel marker CD133 identifies human haemopoetic precursor cells, in addition to human endothelial progenitor cells. METHODS: Seventy nine lung cancer specimens and 66 adjacent histologically tumour free tissues of the same patient cohort were analysed; 11 postmortem specimens from control patients who did not suffer from malignant disease served as controls. Cryostat sections were stained for CD133, CD31, vascular endothelial growth factor receptor 2 (VEGFR-2; KDR), p53, and the proliferation marker Ki-67, and the correlations were analysed. RESULTS: Forty three of 63 evaluable tumour specimens had increased numbers of CD133 positive cells and in some cases capillary forming CD133 positive structures were detectable. In addition, 30 of 63 specimens had raised expression of KDR and 29 of 63 had increased MVD. Increased CD133 expression marginally correlated with raised KDR expression but not with p53 and Ki-67. CONCLUSION: A significant increase in CD133 positive cells was documented in patients with NSCLC, suggesting an involvement of endothelial progenitor cells in tumour vasculogenesis and tumour growth in these patients.