Cost-effectiveness analysis of guidelines for antihypertensive care in Finland

Background  

Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).     

Training effects of cross-country skiing and running on maximal aerobic cycle performance and on blood lipids

Summary Two experiments were carried out to compare the cardiorespiratory and metabolic effects of cross-country skiing and running training during two successive winters. Forty-year-old men were randomly assigned into skiing (n = 15 in study 1,n = 16 in study 2), running (n = 16 in study 1 andn = 16 in study 2) and control (n = 17 in study 1 andn = 16 in study 2) groups. Three subjects dropped out of the programme. The training lasted 9–10 weeks with 40-min exercise sessions three times each week. The training intensity was controlled at 75%–85% of the maximal oxygen consumption (VO_2max) using portable heart rate metres and the mean heart rate was 156–157 beats·min^–1 in the training groups. In the pooled data of the two studies the mean increase in theVO_2max (in ml·min^–1·kg^–1) on a cycle ergometer was 17% for the skiing group, 13% for the running group and 2% for the control group. The increase inVO_2max was highly significant in the combined exercise group compared to the control group but did not differ significantly between the skiing and running groups. The fasting serum concentrations of lipoproteins and insulin did not change significantly in any of the groups. These results suggested that training by cross-country skiing and running of the same duration and intensity at each session for 9–10 weeks improved equally the cardiorespiratory fitness of untrained middle-aged men.     

Angiogenic potential of human mesenchymal stromal cell and circulating mononuclear cell cocultures is reflected in the expression profiles of proangiogenic factors leading to endothelial cell and pericyte differentiation

Endothelial progenitors found among the peripheral blood (PB) mononuclear cells (MNCs) are interesting cells for their angiogenic properties. Mesenchymal stromal cells (MSCs) in turn can produce proangiogenic factors as well as differentiate into mural pericytes, making MSCs and MNCs an attractive coculture setup for regenerative medicine. In this study, human bone marrow‐derived MSCs and PB‐derived MNCs were cocultured in basal or osteoblastic medium without exogenously supplied growth factors to demonstrate endothelial cell, pericyte and osteoblastic differentiation. The expression levels of various proangiogenic factors, as well as endothelial cell, pericyte and osteoblast markers in cocultures were determined by quantitative polymerase chain reaction. Immunocytochemistry for vascular endothelial growth factor receptor‐1 and α‐smooth muscle actin as well as staining for alkaline phosphatase were performed after 10 and 14 days. Messenger ribonucleic acid expression of endothelial cell markers was highly upregulated in both basal and osteoblastic conditions after 5 days of coculture, indicating an endothelial cell differentiation, which was supported by immunocytochemistry for vascular endothelial growth factor receptor‐1. Stromal derived factor‐1 and vascular endothelial growth factor were highly expressed in MSC‐MNC coculture in basal medium but not in osteoblastic medium. On the contrary, the expression levels of bone morphogenetic protein‐2 and angiopoietin‐1 were significantly higher in osteoblastic medium. Pericyte markers were highly expressed in both cocultures after 5 days. In conclusion, it was demonstrated endothelial cell and pericyte differentiation in MSC‐MNC cocultures both in basal and osteoblastic medium indicating a potential for neovascularization for tissue engineering applications.     

Effect of carboxylesterase 1 c.428G?>?A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

Aim

The aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers.

Methods

In a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h.

Results

The area under the plasma concentration–time curve from 0 h to infinity (AUC_0–∞) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC_0–∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril.

Conclusions

The CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril.     

Acute leukocyte,cytokine and adipocytokine responses to maximal and hypertrophic resistance exercise bouts

The purpose of this study was to examine the acute immune response (circulating levels of leukocytes, cytokines and adipocytokines) to maximal resistance (MAX, 15 × 1RM) and hypertrophic resistance (HYP, 5 × 10RM) exercise bouts. Twelve healthy men (age = 28.2 ± 3.5 years, weight = 78.6 ± 10.4 kg, height 178.8 ± 5.0 cm, fat percentage = 16.5 ± 3.5 %) participated in the study. Blood was sampled before, immediately after and 15 and 30 min after exercise. Leukocytes (WBC) significantly increased immediately after HYP (p < 0.01), whereas in MAX, increases in WBC became significant after 30 min (p < 0.05). Lymphocytes increased only after HYP (p < 0.001), while MAX induced lymphopenia during recovery (p < 0.01). Monocyte chemoattractant protein-1 (MCP-1) decreased (p < 0.05) and interleukin-1 receptor antagonist (IL-1ra) increased after HYP, which were not observed after MAX. Adipsin and resistin decreased after both exercise bouts (p < 0.05), which suggest that heavy resistance exercise is at least transiently beneficial for adipocytokine profile. Immediate mechanical stress seemed similar as no differences in myoglobin response were observed. The higher magnitude of metabolic demand reflected in higher lactate response in HYP could be the reason for the significantly high responses in WBC, IL-1ra and decrease in MCP-1.     

Preoperative Systemic Bone Quality Does Not Affect Tibial Component Migration in Knee Arthroplasty: A 2-Year Radiostereometric Analysis of a Hundred Consecutive Patients

BackgroundBone quality and other preoperative predictive factors may affect implant migration and the survival of knee arthroplasty.MethodsIn a prospective cohort of 100 consecutive patients (65 women) at a mean age of 67.7 years (range 39-87 years), we investigated preoperative predictors of postoperative tibial component migration in cemented and cementless total knee arthroplasties or cemented unicompartmental knee arthroplasty. Predictors consisted of Knee Injury and Osteoarthritis Outcome Score (KOOS) and Oxford Knee Score, questionnaires, bone turnover markers of CTX and P1NP, systemic bone mineral density (BMD), and knee osteoarthritis (OA) grade. Tibial component migration was measured with radiostereometry postoperative, at 1 and 2 years of follow-up.ResultsBetween 1 and 2 years, 19 tibial components migrated continuously (maximum total point motion [MTPM] > 0.2 mm). In general, there was no difference in age, body mass index, BMD, KOOSs, or OA grade between patients with continuous tibial migration compared to patients without continuous migration (P > .11). However, cementless tibial components with continuous migration had a lower KOOS pain score (more pain), lower vitamin D, and a higher bone turnover (CTX) value than patients without continuous migration. There was no association between the BMD and MTPM at 1-year follow-up regardless of prothesis type (P > .17). Patients with osteoporosis and normal BMD had similar mean tibial component MTPM at 2 years (3 prostheses combined; P = .34).ConclusionMigration of tibial components inserted with or without bone cement was not affected by the preoperative bone quality in terms of systemic BMD, bone turnover markers, and OA grade in the knee.     

Liposomal Targeting of Bcl-2 Antisense Oligonucleotides with Enhanced Stability into Human Myeloma Cell Lines

Cationic liposomes improve the delivery of antisense oligonucleotides (ODNs) into cells. However, there is marked variability in the cellular uptake of ODNs into different cell lines. We used liposomes containing dimethyloctadecylammonium bromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE) to increase the delivery of phosphodiester ODNs into four different myeloma cell lines. The delivery by cationic liposomes increased the delivery of bcl-2 antisense ODNs by a factor of 9 to 45 as compared to plain ODNs. The stability of ODNs was increased with liposomes both in the culture medium and within the cells. Intact liposomal ODNs were detected inside the cells up to 24 hours with gel electrophoresis and phosphor imager analysis. Antisense ODNs had no effect on bcl-2 mRNA levels. Also the proliferation of myeloma cells remained unchanged during the 3-day incubation period. Our study shows that liposomal antisense ODNs targeting bcl-2 of human myeloma cells result in increased stability of ODNs with minimal toxicity. However, further modifications are needed to gain biological effects of antisense ODNs on human myeloma cells.