Releasability of human hypereosinophilic eosinophils is related to the density of the cells

The activity of eosinophils and neutrophils with respect to the release of granule proteins was studied in 11 patients with the hypereosinophilic syndrome (HES). Granulocytes or purified eosinophils were stimulated with serum-opsonized Sephadex particles (C3b-induced release), and the released amounts of eosinophil cationic protein (ECP), eosinophils protein-X (EPX) and myeloperoxidase (MPO) were measured by means of specific radioimmunoassays (RIA). Eosinophils obtained from patients with HES released significantly more ECP ( P <0·002) and EPX ( P <0·01) after 20 min of incubation than cells from the control group. The cellular content of ECP and EPX in eosinophils obtained from the patients with HES was significantly reduced to 50% and 62%, respectively, of the content of these granule proteins of eosinophils from the control group. In separated eosinophils light-density eosinophils released more of both ECP and EPX than normal density eosinophils. There was no difference in MPO release between the patients and the control group. We conclude that the eosinophils from patients with HES have an increased propensity to release their granule proteins and the releasability seems to be related to the density of the cells.     

Treatment of cardiogenic shock in myocardial infarction by intraaortic balloon counterpulsation surgery.

Thirty-seven patients in cardiogenic shock due to acute myocardial infarction were treated with intraaortic balloon counterpulsation and/or surgery. Eighteen of these patients were treated with counterpulsation alone; eight survived and five were in functional class I or II at the time of follow-up; two were in functional class III, and one was in functional class IV. Nineteen patients were treated surgically, eight survived and seven were in functional class I or II at the time of follow-up; one was in functional class III. Good functional recovery with counterpulsation alone is most common with inferior infarction. With surgery, functional recovery depends not only on the extent of the infarction and the coronary anatomy, but also on the ability to perform surgery within 12 hours of infarction or to support the patient with mechanical means for 10 to 14 days after the infarction and then perform surgery.     

Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

Granzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.     

Microarchitecture of medication-related osteonecrosis of the jaw (MRONJ); a retrospective micro-CT and morphometric analysis

Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (AR) drugs such as bisphosphonates (BP) and denosumab (Dmab). Although several risk factors are described, the etiology of MRONJ is still not fully elucidated. Bone-strengthening is the primary aim of antiresorptive therapy; however, overly increased bone mass and microcrack accumulation are also discussed in MRONJ etiologies. The aim of this study is to evaluate the microarchitecture of jaw bones with micro?computed tomography (micro-CT) in AR-treated patients with or without MRONJ.Human jaw bone samples of AR-treated patients were separated into 11 groups by AR treatment bisphosphonate (BP), denosumab (Dmab), both (M) and control groups. Subgroups were divided according to the clinical localization as AR-exposed vital jaw bone (BP_exp, Dmab_exp, M_exp), osteonecrosis–margin of a sequestrum (BPO_mar, DmabO_mar, MO_mar) and osteonecrosis–sequestrum (BPO_seq, DmabO_seq, MO_seq). Healthy jaw bone (C_HB) and osteoporotic jaw bone (C_OP) represent control groups. Samples underwent retrospective micro-CT and morphometric analysis in representative units by bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tr.Th.), trabecular number (Tr.N.), trabecular space (Tr.Sp.), Euler characteristic for bone connectivity, bone mineral density (BMD) and tissue mineral density (TMD).A total of 141 samples from 78 patients were analyzed. BV/TV of M_exp group (mean: 0.46 ± 0.27) was significantly higher than in the C_OP group (mean: 0.14 ± 0.05; p = 0.0053). Tr.Th. differed significantly between the BP_exp group (mean: 0.32 ± 0.15) and the M_exp group (mean: 0.57 ± 0.20; p = 0.0452) as well as between the BPO_seq group (mean: 0.25 ± 0.10) and the MO_seq group (mean: 0.39 ± 0.18; p = 0.0417). Signs of trabecular thickening and unorganized trabecular microarchitecture from AR-exposed- to sequestrum groups, were analyzed in 3D reconstructions. However, BS/BV, Tr.N., and Tr.Sp. showed no significant differences. Euler characteristic of the BPO_seq group (median: 7.46) doubled compared to that of the BP_exp group (median: 14.97; p = 0.0064). Mineralization parameters BMD and TMD were similar in all groups.Findings show evidence of enhanced bone mass and suspect microarchitecture in some AR-treated jaw bone compared to osteoporotic jaw bone. Despite increased bone mass, some MRONJ samples showed decreased trabecular connectivity by Euler characteristic compared to AR-treated jaw bone. These samples may indicate extensive ossification and ineffective bone mass with superficially higher bone mass without existing or even reduced mechanical stability, indicated by connectivity loss. This result might also suggest a high risk to microcrack accumulation. At some point, possibly some kind of over-ossification could lead to under-nourishment and microarchitectural weakness, creating instability, subsequently increasing vulnerability to MRONJ.     

Functionalities and input methods for recording food intake: A systematic review

BackgroundIncreasing healthcare costs related to lifestyle-related chronic diseases require new solutions. Research on self-management tools is expanding and many new tools are emerging. Recording food intake is a key functionality in many of these tools. Nutrition monitoring is a relevant method to gain an overview of factors influencing health. However, keeping a food diary often constitutes a challenge for a patient, and developing a user-friendly and useful electronic food diary is not straightforward.PurposeTo gain insight into the existing approaches to recording food intake, and to analyze current functionalities and input methods.MethodsWe searched digital libraries, vendor markets and social networks focusing on nutrition. Selection criteria were publications written in English, and patient-oriented tools that offered recording of food intake or nutrition. The system properties that we searched for were types of data, types of terminal, target population, and types of reports and sharing functionalities. We summarized the properties based on their frequency in the reviewed sample.Results31 publications met the selection criteria. The majority of the identified food recording systems (67%) facilitated entry of food type and the consumed quantity of food; 16% of the systems were able to record more than one type of data. The three most frequent target populations were people with obesity, diabetes and overweight. Mobile phones were used as terminals in 35% of the cases, personal computers (PCs) in 29%, and personal digital assistants in 23%. Only 10% supported both PCs and mobile phones. Data sharing was provided by 71% and reports by 51% of the systems. We searched for apps in Google Play and the Apple Store and tested 45 mobile applications that stored food intake data, of which 62% supported recording of types of food, 24% recording of carbohydrate intake and 15% recording of calorie intake. The majority of the mobile applications offered some kind of reports and data sharing, mainly via All of the tested social-network-enabled applications supported access from a personal computer and a mobile phone, search in a food database, reports, graphical presentation, listing of favorite foods, overview of own meals, and entering of consumed food type and quantity.ConclusionThe analyzed apps reflected a variety of approaches to recording food intake and nutrition using different terminals – mostly mobile phones (35%), followed by PCs (29%) and PDAs (23%) for older studies, designed mainly for users with obesity (45%), diabetes mellitus (42%) and overweight (32%), or people who want to stay healthy (10%). The majority of the reviewed applications (67%) offered only input of food type and quantity. All approaches (n = 31), except for two, relied on manual input of data, either by typing or by selecting a food type from a database. The exceptions (n = 2) used a barcode scanning function. Users of mobile phone applications were not limited to data recording, but could view their data on the screen and send it via email. The tested web applications offered similar functionalities for recording food intake. The systems studied provided some degree of personalization: users can access some systems via PCs or mobile phones and they can choose among various types of data input content for recording food intake. Many functions, such as search in a food database, reports, graphical presentation, listing of favorite foods, and overview of the user's own meals, are optimized to simplify the recording process and save time. Data sharing and reports are common features of the reviewed systems. However, none use the user's recorded food history to make suggestions on new nutritional intake, during the food recording process. This may be an area for future research.