Diagnostic procedure in osteodystrophia deformans Paget

Simultaneous scintigraphic and X-ray examination has been evaluated in 30 patients with Paget's disease for estimation of extension and activity of the disease. Scintigraphy produces a comprehensive picture of the pathophysiologic condition. When compared with X-rays the procedure is more economic with regards to cost, time and radiation dosage. Therefore, the use of radioisotopes for evaluation of the skeleton is strongly recommended for follow-up examination in Paget's disease.     

Pathophysiological characterization of drug hypersensitivity to tribenoside

Background

Tribenoside is a semisynthetic sugar derivative that is mainly indicated for treatment of chronic venous insufficiency. Up to 10% of patients treated by tribenoside can suffer from skin side effects. The adverse effects usually present as angioedema, urticaria, or maculopapular exanthema. The pathophysiology of the reaction has not as yet been elucidated.

Methods

In this study, we examined 22 patients with drug eruptions caused by tribenoside. Patch tests were performed to investigate in vivo cellular reactions. Laboratory investigations were carried out by lymphocyte transformation tests and basophil activation tests.

Results

We found a positive patch test reaction to tribenoside in one patient. The lymphocyte transformation test elicited a borderline positive reaction in one patient, and the basophil activation test gave a clearly positive reaction in another patient.

Conclusion

The diagnosis of drug hypersensitivity reactions is a challenge. Both delayed and immediate immunologic response may play a role in the etiology of tribenoside-induced exanthemas. Our investigation and results indicate that benzoic acid could be the antigenic determinant in drug hypersensitivity to tribenoside.     

Partial‐volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial‐volume‐based over probabilistic‐based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex‐matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel‐wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub‐region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect.     

Cognitive mapping style relates to posterior–anterior hippocampal volume ratio

As London taxi drivers acquire “the knowledge” and develop a detailed cognitive map of London, their posterior hippocampi (pHPC) gradually increase in volume, reflecting an increasing pHPC/aHPC volume ratio. In the mnemonic domain, greater pHPC/aHPC volume ratios in young adults have been found to relate to better recollection ability, indicating that the balance between pHPC and aHPC volumes might be reflective of cross‐domain individual differences. Here, we examined participants' self‐reported use of cognitive map‐based navigational strategies in relation to their pHPC/aHPC hippocampal volume ratio. We find that greater reported cognitive map use was related to significantly greater posterior, relative to anterior, hippocampal volume in two separate samples of young adults. Further, greater reported cognitive map usage correlated with better performance on a self‐initiated navigation task. Together, these data help to advance our understanding of differences between aHPC and pHPC and the greater role of pHPC in spatial mapping.     

A Community Study of SARS-CoV-2 Detection by RT-PCR in Saliva: A Reliable and Effective Method

Efficient, wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) or oropharyngeal swabs. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here, we used a novel saliva collection device designed to favour the safe and correct acquisition of the sample, as well as the processivity of the downstream molecular analysis. We tested 1003 nasopharyngeal swabs and paired saliva samples self-collected by individuals recruited at a public drive-through testing facility. An overall moderate concordance (68%) between the two tests was found, with evidence that neither system can diagnose the infection in 100% of the cases. While the two methods performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent subjects. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study describes a testing strategy of self-collected saliva samples, which is reliable for wide-scale COVID-19 screening in the community and is particularly effective for contact tracing.     

A comparative study of hemorheological parameters in transient ischemic attack and acute ischemic stroke patients: possible predictive value

A complete neurological and laboratory assessment was made of 31 transient ischemic attack (TIA) and 33 acute ischemic stroke patients. Laboratory parameters were compared with 33 age- and sex-matched controls. Erythrocyte deformability was characterised by determining the relative cell transit time (RCTT) with a St. George filtrometer. Plasma viscosity was measured with a Haake microviscosimeter. In comparison with controls, fibrinogen content, erythrocyte sedimentation rate (ESR), platelet and leukocyte count, erythrocyte RCTT and plasma viscosity were found to be significantly higher in stroke patients. In TIA patients the elevation of these values was not significant with the exception of platelet count. Our results suggest that the hemorheological alterations observed in TIA and stroke are largely non-specific findings and associated with the atherosclerotic disease of patients. The significant elevation of leukocytes, fibrinogen and plasma viscosity in acute stroke versus TIA probably reflects the systemic acute phase response of organism to cerebral infarction.     

Calcium distribution in the vessel wall and intima-media thickness of the human carotid arteries

Increased common carotid artery (CCA) intima-media thickness (IMT) measured by B-mode ultrasound is an early marker of the atherosclerotic process. Arterial calcification is not clearly understood. Using the particle-induced X-ray emission (PIXE) method, we have looked for the location in the artery wall where calcium accumulated in the early phase of atherosclerosis. Twelve segments of CCAs of deceased stroke patients were investigated. In-vivo, carotid duplex ultrasound was performed with bilateral CCA IMT measurement at plaque-free sections. During autopsy, segments of carotid arteries were collected and filled under pressure with a stained histologic embedding material. The frozen arteries were cut into 60-microm-thick slices. Calcium distribution maps from the segments of arteries were determined by PIXE method. IMT measured by ultrasound and calcium distribution maps measured by PIXE were compared. In our cross-sectional study, using the PIXE analysis and ultrasound images, we could demonstrate early calcium accumulation in the media layer. Our results have also shown a significant relationship between calcium content of distributional maps measured by PIXE analysis and corresponding IMT on B-mode ultrasound images of human CCAs.     

MKK4 and metastasis suppression: a marriage of signal transduction and metastasis research

MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed.     

Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjögren’s syndrome to facilitate their concerted migration

CCR9 + T helper (Th) cells can induce Sjögren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjögren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjögren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.