Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry

BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS: Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION: These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.     

Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann's thrombasthenia

Glanzmann's thrombasthenia is a bleeding disorder, inherited in an autosomal recessive way and characterized by an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa complex. Recently, we and others demonstrated that cultured human umbilical vein endothelial cells synthesized a membrane protein complex similar to the platelet GP IIb/IIIa complex. In this article, we demonstrate that endothelial cells isolated from the umbilical vein of a newborn with Glanzmann's thrombasthenia, as compared with normal endothelial cells, show no difference in their ability to synthesize and express this GP IIb/IIIa complex. Our results indicate that Glanzmann's thrombasthenia is not accompanied by an "endotheliopathy."     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Single oral high-dose vitamin D3 prophylaxis in the elderly

A poor vitamin D status is common in the elderly during the winter months. Because it is possible that hypovitaminosis D may be a cause of senile osteopenia, a simple method of prophylaxis would be useful. The single, oral, high-dose method was tested in two old-age homes, and the efficacy of vitamin D3 was compared with that of 25-hydroxyvitamin D3 (25-OHD3). The trials showed that 25-OHD3 caused a higher peak value in the serum 25-OHD levels in the second week than did vitamin D3. However, follow-up after four to five months showed that in those patients who received a single, oral dose of 25-OHD3, the serum 25-OHD levels had returned to the baseline low values, whereas in those patients who had had oral vitamin D3, the serum 25-OHD levels still remained significantly raised compared with the baseline values and were within normal limits. It is concluded that the single, oral, high-dose method using vitamin D3 is a safe and simple method of prophylaxis and could be used easily in large populations of elderly persons.     

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

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.     

Keggin‐Type Polyoxometalate ([PMo12O40]3−) in Radical Initiating Systems: Application to Radical and Cationic Photopolymerization Reactions

New photoinitiating systems based on a polyoxometalate (POM) are proposed: phosphomolybdic acid in combination with silane, germane, or iodonium salt can be used to generate silyl, germyl, or phenyl radicals as well as silylium cations. The photochemical mechanisms are studied by steady‐state photolysis and electron spin resonance. The phosphomolybdic acid/silane/iodonium salt system can initiate either the radical photopolymerization of acrylates or the cationic photopolymerization of epoxides. The synthesis of interpenetrated polymer networks can also be carried out. The mechanical properties of the synthesized polymers are affected by the presence of POM in the matrix, as shown by their dynamic mechanical analysis (DMA).

     

Novel Highly Efficient Organophotocatalysts: Truxene–Acridine‐1,8‐diones as Photoinitiators of Polymerization

Truxene–acridine‐1,8‐dione derivatives ( Tr_AD ) are proposed as new photoinitiators of polymerization under very soft irradiation (by a household halogen lamp), as well as laser‐diode exposure at 405 nm. They exhibit a strong absorption around 380 nm. The Tr_AD /diphenyl iodonium salt/9‐vinylcarbazole combination is able to promote the ring‐opening polymerization of an epoxide, whereas the Tr_AD /alkyl halide/amine system is very efficient in initiating the radical photopolymerization of an acrylate. Excellent polymerization profiles are obtained. Acrylate/epoxide blends are also easily polymerized. These Tr_ADs in the three‐component systems behave as photocatalysts according to oxidative cycles. The mechanisms are discussed for the different multicomponent initiating systems.