Plasma markers in pulmonary hypertension subgroups correlate with patient survival.

BACKGROUND: Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival. METHODS: 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses. RESULTS: At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-ß (TGFß), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFß levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with < 3 years and > 3 years survival, in particular when inflammatory mediators were combined with clinical parameters. DISCUSSION: Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival. CONCLUSION: In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.

Simplified sperm testing devices: a possible tool to overcome lack of accessibility and inconsistency in male factor infertility diagnosis. An opportunity for low- and middle- income countries.

BACKGROUND: Manual semen assessment (MSA) is a key component in a male's fertility assessment. Clinicians rely on it to make diagnostic and treatment decisions. When performed manually, this routine laboratory test is prone to variability due to human intervention which can lead to misdiagnosis and consequently over- or under- treatment. For standardisation, continuous training, quality control (QC) programs and pricy Computer-Assisted Sperm Analysis (CASA) systems have been proposed, yet, without resolving intra- and inter-laboratory variability. In response, promising simplified sperm testing devices, able to provide cost-effective point-of-care male infertility diagnosis are prospected as a plausible solution to resolve variability and increase access to sperm testing. MATERIALS AND METHODS: A throughout literature research for semen testing, sperm analysis, smart-phone assisted semen analysis, 'at-home' semen testing, male infertility, infertility in developing countries, infertility in low- and middle-income countries (LMIC) and quantitative sperm analysis was performed. A total of 14 articles, specific to 'at-home' simplified sperm assessment, were included to treat the core subject. RESULTS: Continuous training and consistent QC, are sine qua none conditions to achieve accurate and comparable MSA. Compliance does not rule-out variability, nevertheless. Emerging simplified sperm assessment devices are an actual alternative to resolve the lack of standardisation and accessibility to sperm analysis. YO ® , SEEM ® , and ExSeed ® are commercially available, user-friendly smartphone-based devices which can accurately measure volume, sperm concentration (millions/ml) and total motile sperm count. More broadly, by cost-effectiveness, availability, accuracy and convenient application, these devices could effectively select patients for first-line artificial reproduction treatments such as intrauterine insemination. CONCLUSIONS: Accuracy and cost-effectiveness make smart-phone based sperm testing devices a practical and realistic solution to overcome variability in MSA. Importantly, these tools represent an actual opportunity to standardise and improve male subfertility diagnosis and treatment, especially in LMIC. However, before clinical application is possible, guidelines, further testing with special attention on accuracy in washed sperm, availability, cost-benefit and reliability are required.

Conventional dental radiology: what the general radiologist needs to know.

This article aims to provide an overview of intraoral and orthopantomographic radiographs, including technique, indications, artefacts, relevant anatomy, current notation and common dental pathology. The normal anatomy is emphasised, because it is required for effective radiographic interpretation. Dental pathology, i.e. caries, periodontal disease, periapical inflammatory lesions and dental anomalies are illustrated.

Microspectrophotometric detection of heparin in mast cells and basophilic granulocytes stained metachromatically with Toluidine Blue O.

A qualitative microspectrophotometric detection method for heparin in situ has been developed, using data obtained previously with a model system of polyacrylamide films containing pure glycosaminoglycans (Tas, 1975). This technique, based on the unique metachromatic properties of heparin with Toluidine Blue O in glycerol, has been worked out with rat peritoneal and mesenteric mast cells. After the smears containing the stained cells had been mounted in glycerol, a change with time of the recorded metachromatic peaks to lower wavelengths was found, leading to an equilibrium phase after some days. The metachromatic peaks recorded in this phase appeared to resemble closely the peak obtained for the heparin-Toluidine Blue O complex under similar conditions in the model experiments. With rat mast cells it was found that nucleic acids, basic proteins, histamine and lipids had no appreciable influence on the position of the final recorded peaks, nor did they influence the slope of the time course very much. This observed decrease with time in the wavelengths of the metachromatic peaks can be explained by the time necessary for equilibration of the cells in glycerol and by the possible influence of lower sulphated glycosaminoglycans on the peak of the heparin-Toluidine Blue O complex. It was found that the method can be used to detect unequivocally the presence of heparin in cells, even if they also contain up to 75% (mole/mole) of other, lower sulphated glycosaminoglycan. Only a limited number of cells is necessary with this method - in contrast to biochemical determinations. For the first time the presence of heparin in normal human basophilic granulocytes and mast cells has been proved directly. The experiments indicate the occurrence of virtually similar sulphated heparins in human mast cells and basophilic granulocytes, as well as in pig mast cells. A higher sulphated heparin, however, might be present in rat mast cells.