Tissue-specific stilbene accumulation is an early response to wounding/grafting as revealed by using spatial and temporal metabolomics.

Grafting is widely used in horticulture. Shortly after grafting, callus tissues appear at the graft interface and the vascular tissues of the scion and rootstock connect. The graft interface contains a complex mix of tissues, we hypothesised that each tissue has its own metabolic response to wounding/grafting and accumulates different metabolites at different rates. We made intact and wounded cuttings and grafts of grapevine, and then measured changes in bulk flavonoid, phenolic acid and stilbenoid concentration and used metabolite imaging to study tissue-specific responses. We show that some metabolites rapidly accumulate in specific tissues after grafting, for example, stilbene monomers accumulate in necrotic tissues surrounding mature xylem vessels. Whereas other metabolites, such as complex stilbenes, accumulate in the same tissues at later stages. We also observe that other metabolites accumulate in the newly formed callus tissue and identify genotype-specific responses. In addition, exogenous resveratrol application did not modify grafting success rate, potentially suggesting that the accumulation of resveratrol at the graft interface is not linked to graft union formation. The increasing concentration of complex stilbenes often occurs in response to plant stresses (via unknown mechanisms), and potentially increases antioxidant activity and antifungal capacities.

Effect of pravastatin-to-simvastatin conversion on low-density-lipoprotein cholesterol.

The effects of a pravastatin-to-simvastatin conversion program on low-density-lipoprotein (LDL) cholesterol levels were studied. Patients receiving pravastatin at a Veterans Affairs medical center were switched to simvastatin beginning in 1997. The dosage of simvastatin was based on the additional percent reduction in LDL cholesterol needed to achieve the goal specified by the National Cholesterol Education Program. The primary endpoint was the change in the percentage of patients meeting their LDL cholesterol goal at baseline and follow-up. Changes in lipid indices, the relative risk (RR) of coronary heart disease (CHD), and program costs were also evaluated. A total of 1032 patients completed the program. The mean +/- S.D. daily doses of pravastatin and simvastatin were 25.2 +/- 11.3 and 22.7 +/- 13.3 mg, respectively. Median baseline and follow-up LDL cholesterol concentrations were 116 and 99 mg/dL, respectively (p < 0.001). Overall, 44% of the patients met their LDL cholesterol goal while taking pravastatin, compared with 69% after conversion to simvastatin (p < 0.001). The predicted mean RR of a future CHD event (based on changes in serum lipids) was 0.87 (95% confidence interval, 0.83-0.91) four years after conversion. The total cost of the program was $40,644 in the first year, and there was a net saving thereafter. Therapeutic interchange between pravastatin and simvastatin increased the number of patients meeting their LDL cholesterol goal.

Rationale, design, and baseline results of the Pravastatin-to-Simvastatin Conversion Lipid Optimization Program (PSCOP).

A program designed to increase the percentage of patients at a Department of Veterans Affairs health system who meet their cholesterol goals as recommended by the National Cholesterol Education Program (NCEP) is described, and baseline results are reported. Patients with an active prescription for pravastatin between February 4 and June 4, 1997, were identified for conversion to simvastatin by means of the Pravastatin-to-Simvastatin Conversion Lipid-Optimization Program; 1361 patients were eligible for conversion. Each patient was mailed a survey for determining risk factors for coronary heart disease (CHD) and NCEP-recommended low-density lipoprotein (LDL) cholesterol goal and was asked to provide a fasting blood sample for determination of lipid profile, liver function, and serum creatine phosphokinase concentration. The patients were asked to make a follow-up laboratory visit six to seven weeks after they had started taking simvastatin. The percentage change from baseline and the percentage of patients who meet their LDL cholesterol goal before and after the conversion will be determined. A total of 1115 patients were converted to simvastatin. Only 35.4% of patients taking pravastatin to prevent a second CHD-related event met or exceeded their LDL cholesterol goal. Only 36.2% of patients with two or more CHD risk factors who were taking pravastatin for primary prevention met or exceeded their LDL cholesterol goal. In a veterans population, less than half of patients receiving a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor had LDL cholesterol concentrations that met goals recommended by the NCEP.

The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin.

Forty-six adult patients maintained on warfarin therapy were converted from pravastatin to simvastatin. Mean international normalized ratio (INR) significantly increased from 2.42 to 2.74, p = 0.002. Although warfarin doses were reduced in 7 patients and increased in 4 patients following the post-conversion INR measurements, the pre- and postconversion median weekly warfarin dose of all 46 patients did not differ significantly. The number of patients with an INR > 3.0 increased significantly from 6 to 16 following the conversion. There was no report of unusual episodes of bleeding. The results indicate that antihyperlipidemic therapy can be changed safely from pravastatin to simvastatin in patients who are taking warfarin concomitantly. Additional anticoagulation monitoring is not necessary in institutions where patients are followed in formal anticoagulation clinics.

"What will happen to my child when I'm gone?" A support and education group for aging parents as caregivers.

This article describes the rationale, design and implementation of a support and education group for parents caring for disabled children in later life. In a supportive and informative environment, parents found peers facing similar challenges relating to the provision of care in light of their own aging, a lifetime of caregiving, and their concerns about their children's futures. The experience of this group intervention strategy provides insight into the needs and strengths of this neglected segment of the caregiving population and suggests implications for future research and practice.