Monocyte-derived dendritic cells express and secrete matrix-degrading metalloproteinases and their inhibitors and are imbalanced in multiple sclerosis

Dendritic cells (DC) are antigen-presenting cells (APC) that most efficiently initiate and control immune responses. Migration processes of blood DC are crucial to exert their professional antigen-presenting functions. Matrix-degrading metalloproteinases (MMP) are proteolytic enzymes, which are considered to be key enzymes in extracellular matrix (ECM) turnover and mediators of cell migration. Tissue inhibitors of metalloproteinases (TIMP) are important regulators of MMP activity. Here we investigate whether blood monocyte-derived immature DC (iDC) and mature DC (mDC) express, produce and secrete functionally active MMP-1, -2, -3 and -9 and their inhibitors TIMP-1 and -2, and examine their involvement in multiple sclerosis (MS). On mRNA level, we observed high numbers of MMP-2 and TIMP-2 mRNA expressing iDC in MS. On protein level, high percentages of MMP-1, -2 and -9 expressing iDC by flow cytometry, and high MMP-1 secretion by Western blot together with high MMP-2 and -9 activities in iDC supernatants as studied with zymography were observed. Similarly, MS is associated with high percentages of MMP-2 and -3 and of TIMP-1 expressing mDC by flow cytometry together with high MMP-3 secretion and high MMP-9 activity in culture supernatants. Spontaneous migratory capacity of both iDC and mDC over ECM-coated filters was higher in MS compared to healthy controls (HC).In conclusion, blood monocyte-derived iDC and mDC express, produce and secrete several MMP and TIMP. Alterations in these molecules as observed in MS may be functionally important for DC functioning.     

Die suprakondyläre Oberarmfraktur im Kindesalter – eine Effizienzstudie Ergebnisse der multizentrischen Studie der Sektion Kindertraumatologie der Deutschen Gesellschaft für Unfallchirurgie – Teil II: Aufwand und Nutzen der Behandlung

The following are the results and conclusions of a retrospective research study done on 886 patients with supracondylar fractures of the humerus. The study evaluates how effective the treatment procedures of the fractures are. The patients' fractures were categorized into four groups. It made it easier to differentiate between dislocated and undislocated fractures (see part I Weinberg A et al.). The following parameters were established to evaluate the treatment procedures and to create relevancy to the final outcome depending on the degree of difficulty of the fractures: Length of hospitalization, amount of repositioning procedures (including if an open or closed procedure was needed), amount of post repositioning procedures and the recommended change of therapy, method of retention and fixation, necessary metal removal, amount of check ups needed. The amount of x-ray exams could not be established due to insufficient documentation. The study showed a rather random pattern regarding length of hospitalization and the amount of check ups especially among type I and II patients. Open versus closed repositioning procedures did not seem to be advantageous. The implanted wires did not prevent infections. It just increased the treatment procedure by another hospitalization and anesthesia to remove the implanted wires. Physical therapy was not necessary and was only prescribed in cases of prolonged immobilization. The results of this study generated consequences regarding treatment procedures and developed a more efficient treatment protocol: Type I and II (dislocated and undislocated fractures in one plane) will be treated conservatively on an out-patient basis. Type I in a cast. Type II in a blount or plaster cast with flexed angle between 100 degrees and 130 degrees. Type III an IV (dislocated and undislocated fractures in two or three planes) will be treated if possible with a closed repositioning procedure. Otherwise a close repositioning procedure will be necessary and followed with some kind of KD-osteosynthese to capture the fracture. The patient will be hospitalized for a short period. The blount procedure will not be sufficient for this type of fracture. Therapy and procedure will be translated put in a perspective research study.     

Activated protein C resistance in patients with central retinal vein occlusion in comparison to patients with a history of deep-vein thrombosis and a healthy control group Vergleich mit Patienten mit tiefer Becken- und Beinvenenthrombose und gesunder Kontrollgruppe

Background: The recently described “APC resistance” caused by a mutant form of factor V (factor V Leiden) is the most frequent cause of hereditary thrombosis. This study was carried out to investigate the association between activated protein C resistance and central retinal vein occlusion (CRVO). We evaluated the prevalence of APC resistance in patients with CRVO, patients with a history of deep-vein thrombosis, and a healthy control group.     

Difference in the Blood Monocyte Phenotype Between Uremic Patients and Healthy Controls: Its Relation to Monocyte Differentiation into Macrophages in the Peritoneal Cavity

The phenotypic alterations between blood monocytes from 11 patients with end-stage renal disease, who had been on peritoneal dialysis for less than one week, and blood monocytes from 10 healthy controls, were analyzed. In addition, peritoneal macrophages in the dialysate effluent were enclosed. Analysis of functional receptor density was performed using immunostaining and flow cytometry. The phenotypic characterization was selected to represent various biological functions such as adhesion, phagocytosis (CD11b/CD18, CD11c/CD18, CD16), antigen-presentation (HLA-DR, ICAM-1), differentiation (transferrin receptor, CD71), receptor for LPS (CD14) and initiation of the coagulation cascade (Tissue factor, CD142). The proportion of CD16-positive blood monocytes and the quantitative level of ICAM-1 were higher in the patient group, compared to healthy controls. A significant increase in the quantitative level of CD11b/CD18, CD11c/CD18, HLA-DR and ICAM-1, transferrin receptor, CD 14 and CD 16, was found on peritoneal macrophages, compared to monocytes, harvested both from the corresponding patients, as well as from healthy donors. In contrast, we did not find any significant differences in the expression of tissue factor between monocytes and peritoneal macrophages. In conclusion, phenotypic differences exist between monocyte populations in the blood circulation of CAPD patients, and healthy individuals. We also show that transmigration of monocytes into the peritoneal cavity implies a selective up-regulation of functional receptors, preferentially related to adhesion, and antigen-presentation in a steady-state situation in non-infected CAPD patients.     

Long-term parvovirus B19 viraemia associated with pure red cell aplasia after allogeneic bone marrow transplantation.

BACKGROUND: Parvovirus B19 infection is associated with a variety of symptoms like erythema infectiosum, anaemia and arthritis. In immunocompetent persons, viraemia is usually cleared a few weeks after infection. OBJECTIVE: An immunocompromised adult female patient was persistently infected with B19 after allogenic bone marrow transplantation (BMT) and developed chronic anaemia. STUDY DESIGN: B19-specific antibodies were determined by ELISA and viral load was assessed using a quantitative real time B19 PCR. The patient was evaluated clinically. RESULTS: Two years after successful BMT, the patient received intensified immunosuppressive treatment, erythropoetin and erythrocyte concentrates due to chronic graft-versus-host disease with renal failure. Despite of this treatment, the aplastic anaemia worsened. PCR revealed B19 viraemia with 10(12) geq/ml serum. After 7 months of repeated applications of immunoglobulins and reduction of immunosuppressive treatment, reticulocyte counts and haemoglobin levels normalized and the viral load finally dropped to 10(3) geq/ml serum. One of the back-up samples of the erythrocyte concentrates tested positive, the respective transfusion had been applied 2 months after the beginning of viraemia. CONCLUSIONS: The source of the primary infection remained unclear, but at least re-infection by blood transfusion is likely. Treatment did not result in virus elimination from peripheral blood but in resolvement of symptoms.     

“Same same or different?” A review of reviews of person-centered and patient-centered care

Objective

To provide a synthesis of already synthesized literature on person-centered care and patient-centered care in order to identify similarities and differences between the two concepts.

Annual screening detects celiac disease in children with type 1 diabetes

Objective:  To investigate the prevalence of celiac disease (CD) in a cohort of type 1 diabetes mellitus (T1DM) children and adolescents at the time of clinical diagnosis and to evaluate the screening procedure and possible role of human leukocyte antigen (HLA)-DQ during a 5-yr follow-up.
Research design and methods:  The study group was a cohort of 300 newly diagnosed T1DM children and youths younger than 20 yr followed for 5 yr at six clinical centers for pediatric diabetes in the region Skåne in Sweden. Immunoglobulin A endomysium antibodies were used to screen the patients annually to be considered for an intestinal biopsy. All patients were analyzed for HLA-DQA1-B1 genotypes.
Results:  While 0.7% (2/300) already had a diagnosed symptomatic CD, an additional 3% (10/300) had silent CD at the diagnosis of T1DM. During follow-up, another 6% (17/300) developed CD as follows: 10 after 1 yr, 5 after 2 yr, 1 after 3 yr, and 1 after 5 yr. Therefore, the cumulative frequency of CD confirmed by intestinal biopsies was 10% (29/300). HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.
Conclusions:  Our study confirmed the low prevalence (0.7%) of diagnosed symptomatic CD at the time of clinical diagnosis but document by screening an increasing prevalence of silent CD during a 5-yr follow-up to reach an overall prevalence of 10%. We suggest that children with T1DM should be screened for CD at the onset of T1DM and annually for a minimum of at least 2 yr. HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.     

Living with experiences following a myocardial infarction.

Coronary heart disease is a major cause of sudden death and morbidity in the developed world, as well as a cause of great suffering. Research within this area has primarily focused symptoms, risk factors and treatment. The aim of this paper was to explore women's experiences following a myocardial infarction (MI). Eight women were interviewed; the interviews were audiotaped and transcribed into text and analysed using a phenomenological approach. To explore the meaning that is experienced in the lived world of the patient a method of reflective lifeworld research, based upon phenomenological epistemology has been used. The results indicate that the body is vital for the women in their lifeworlds. After a MI the patient's natural and unreflective relationship with the body and the lived world is interrupted. Uncertainty about life and death as well as the body is experienced as a suffering in the women's lifeworlds. In relation to this, the women's existence is characterised by an uncertainty and a loss of context. It is through reconciliation with their bodies and their illnesses that the women can achieve a sense of well-being and harmony in life. In that process the women can re-establish a natural relationship with their bodies and lifeworlds.