Computer-controlled flow resistance

A computer-controlled flow resistance (CCR), to be used in a computer-controlled lung model, is presented. Flow is forced through a slit between a cylinder and a sleeve around the cylinder. The resulting flow resistance depends on the width, circumferences and the variable length of the slit. The variation in the length is computer-controlled by the position of the sleeve with respect to the cylinder. The total flow resistance also depends on inlet and outlet resistance at both sides of the slit and on flow. The dependence on flow is primarily due to the shape of the inlet of the slit. The resistance of the slit itself is almost independent of flow. The resistance is calculated during a calibration phase at different positions of the sleeve, for flow values from 0.05 to 1.0 litre.s⁻¹ (inflow) and from −0.05 to −1.0 litre.s⁻¹ (outflow). To simulate a required resistance pattern, as, for instance, will occur during breathing, at each moment the set position of the sleeve is calculated by means of an interpolation from the relationship between flow resistance and position of the sleeve. The internal diameter of the sleeve is fixed. To tune the resistance range for a specific simulation, the cylinder is changed for one with different diameter, changing the width of the slit.     

Anti-HLA antibodies interfere in the detection of soluble HLA class I molecules.

Heart transplant rejection is routinely defined by histological evaluation of endomyocardial biopsies (EMB). As elevated levels of donor derived sHLA (dsHLA) can be detected in the serum of transplanted patients just before or during rejection, quantification of donor specific soluble counterparts of HLA Class I (sHLA-I) in the serum of the recipient may be a new way for non-invasive monitoring of graft rejection. However, not all patients show an increase of dsHLA at time of rejection. A reason for this might be that anti-donor-HLA antibodies, which are formed by the patient, form complexes with donor sHLA-I molecules. This masking or blocking of sHLA-I binding sites might cause false-negative results of tests detecting donor specific sHLA. Using HLA-antigen specific ELISA tests we could demonstrate that most anti-HLA antibodies block the detection of sHLA antigens in plasma, even in high dilutions of the antibody when the antibodies were not detectable in a CDC test. In general, HLA-antigen specific antibodies block the detection of sHLA molecules, while broadly-reactive antibodies, recognizing another epitope on the molecule, do not. The implication of these findings is that more than one dsHLA allotype within one patient should be tested to monitor graft rejection. In addition, sHLA monitoring must be combined with an HLA-antibody screening.     

Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists

AIMS: To determine interobserver variation in grading of dysplasia in Barrett's oesophagus (BO) between non-expert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand. METHODS AND RESULTS: In this prospective multicentre study, non-expert and expert pathologists graded biopsy specimens of 920 patients with endoscopic BO, which were blindly reviewed by one member of a panel of expert pathologists (panel experts) and by a second panel expert in case of disagreement on dysplasia grade. Agreement between two of three pathologists was established as the final diagnosis. Analysis was performed by kappa statistics. Due to absence of intestinal metaplasia, 127/920 (14%) patients were excluded. The interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for dysplasia/low-grade dysplasia (IND/LGD) versus high-grade dysplasia (HGD)/adenocarcinoma (AC)] between non-experts and first panel experts and between initial experts and first panel experts was fair (kappa = 0.24 and kappa = 0.27, respectively), and substantial for differentiation of HGD/AC from ND/IND/LGD (kappa = 0.62 and kappa = 0.58, respectively). CONCLUSIONS: There was considerable interobserver variability in the interpretation of ND or IND/LGD in BO between non-experts and experts, but also between expert pathologists. This suggests that less subjective markers are needed to determine the risk of developing AC in BO.     

Psychological and cognitive functioning in children and adolescents with congenital heart disease: a meta-analysis

OBJECTIVE: Findings in the literature are inconsistent on the impact of congenital heart disease (CHD) on the psychological and cognitive functioning of children and adolescents. The aim of the present study was to systematically review this empirical body of literature. METHODS: We conducted a meta-analysis to review studies on behavior problems and cognitive functioning in CHD. RESULTS: Only older children and adolescents with CHD displayed an increased risk of overall, internalizing, and to a lesser extent externalizing behavior problems. In addition, patients with severe CHD exhibited lower cognitive functioning than patients with less severe CHD, specifically with respect to performance intelligence. Moreover, decreased cognitive functioning remained relatively stable across different age groups. CONCLUSIONS: Children with severe heart disease may benefit from interventions specifically targeting perceptual organizational abilities, such as visual-spatial abilities. Moreover, older children and adolescents with CHD may benefit from psychological interventions reducing anxiety symptoms and depression.     

Effect of shared care on blood pressure in patients with chronic kidney disease: a cluster randomised controlled trial

Background

Chronic kidney disease (CKD) is highly prevalent in patients with diabetes or hypertension in primary care. A shared care model could improve quality of care in these patients

Aim

To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension.

Design and setting

A cluster randomised controlled trial in nine general practices in The Netherlands.

Method

Five practices were allocated to the shared care model and four practices to usual care for 1 year. Primary outcome was the achievement of blood pressure targets (130/80 mmHg) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60ml/min/1.73m².

Results

Data of 90 intervention and 74 control patients could be analysed. Blood pressure in the intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = −1.0 to 3.2) compared to −0.2 (95% CI = −3.8 to 3.3)/−0.5 (95% CI = −2.9 to 1.8) in the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group (73% versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P = 0.01, and P = 0.002]).

Conclusion

A shared care model between GP, nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care.     

Comparative Study of IS6110 Restriction Fragment Length Polymorphism and Variable-Number Tandem-Repeat Typing of Mycobacterium tuberculosis Isolates in the Netherlands,Based on a 5-Year Nationwide Survey

In order to switch from IS6110 and polymorphic GC-rich repetitive sequence (PGRS) restriction fragment length polymorphism (RFLP) to 24-locus variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates in the national tuberculosis control program in The Netherlands, a detailed evaluation on discriminatory power and agreement with findings in a cluster investigation was performed on 3,975 tuberculosis cases during the period of 2004 to 2008. The level of discrimination of the two typing methods did not differ substantially: RFLP typing yielded 2,733 distinct patterns compared to 2,607 in VNTR typing. The global concordance, defined as isolates labeled unique or identically distributed in clusters by both methods, amounted to 78.5% (n = 3,123). Of the remaining 855 cases, 12% (n = 479) of the cases were clustered only by VNTR, 7.7% (n = 305) only by RFLP typing, and 1.8% (n = 71) revealed different cluster compositions in the two approaches. A cluster investigation was performed for 87% (n = 1,462) of the cases clustered by RFLP. For the 740 cases with confirmed or presumed epidemiological links, 92% were concordant with VNTR typing. In contrast, only 64% of the 722 cases without an epidemiological link but clustered by RFLP typing were also clustered by VNTR typing. We conclude that VNTR typing has a discriminatory power equal to IS6110 RFLP typing but is in better agreement with findings in a cluster investigation performed on an RFLP-clustering-based cluster investigation. Both aspects make VNTR typing a suitable method for tuberculosis surveillance systems.     

Effects of transmembrane region variability on cell surface expression and allorecognition of HLA-DP3

The functional relevance of polymorphisms outside the peptide binding groove of HLA molecules is poorly understood. Here we have addressed this issue by studying HLA-DP3, a common antigen relevant for functional matching algorithms of unrelated hematopoietic stem cell transplantation (HSCT) encoded by two transmembrane (TM) region variants, DPB1^*03:01 and DPB1^*104:01. The two HLA-DP3 variants were found at a overall allelic frequency of 10.4% in 201 volunteer stem cell donors, at a ratio of 4.2:1. No significant differences were observed in cell surface expression levels of the two variants on B lymphoblastoid cell lines (BLCL), primary B cells or monocytes. Three different alloreactive T cell lines or clones showed similar levels of activation marker CD107a and/or CD137 upregulation in response to HLA-DP3 encoded by DPB1^*03:01 and DPB1^*104:01, either endogenously on BLCL or after lentiveral-vector mediated transfer into the same cellular background. These data provide, for the first time, direct evidence for a limited functional role of a TM region polymorphism on expression and allorecognition of HLA-DP3 and are compatible with the notion that the two variants can be considered as a single functional entity for unrelated stem cell donor selection.