Prevalence, presentation and prognosis of delirium in older people in the population, at home and in long term care: a review.

OBJECTIVE: The aim of this study is to provide an overview of prevalence, symptoms, risk factors and prognosis of delirium in primary care and institutionalized long-term care. DESIGN: The method used in this study is a systematic PubMed search and literature review. RESULTS: The prevalence of delirium in the population among the elderly aged 65+ years is 1-2%. Prevalence rises with age: 10% among a "general" population aged 85+ years. Prevalence rises up to 22% in populations with higher percentages of demented elder. In long-term care, prevalence ranges between 1.4% and 70%, depending on diagnostic criteria and on the prevalence of dementia. There is a significant increase of the risk of delirium with age and cognitive decline in all groups. Concerning prognosis, most studies agree that older people who previously experienced delirium have a higher risk of dementia and a higher mortality rate. Population and long-term care studies show the same tendency. CONCLUSIONS: Delirium in a non-selected population aged 65+ years is uncommon. However, prevalence rises very quickly in selected older groups. Primary care doctors should be aware of a relatively high risk of delirium among the elderly in long-term care, those older than 85 years and those with dementia.

Health care in patients 1 year post-stroke in general practice: research on the utilisation of the Dutch Transmural Protocol transient ischaemic attack/cerebrovascular accident.

This study evaluates the kind of aftercare that ischaemic stroke patients receive and the extent that aftercare fulfils the criteria of the 'Dutch Transmural Protocol transient ischaemic attack/cerebrovascular accident'. Fifty-seven patients were interviewed 1 year post-stroke about secondary prevention and aftercare. Forty general practitioners (GPs) completed a questionnaire about guidance and secondary prevention (concerning medication and lifestyle advice). Most patients would like to see their GP more regularly. More aftercare was required than was planned. The use of aspirin remained the same, fewer patients used statins and more used antihypertensives. Of the 40 GPs who participated, 12% did not apply prevention. Blood pressure, glucose and cholesterol were measured in 84%, 28% and 40% of patients. All of these measures were often elevated, but treatment was not given. Lifestyle advice was offered to one-quarter of patients. Considering all of the advice given in the Dutch Protocol, several aspects can be improved in relation to secondary prevention. Too little attention is paid to giving lifestyle advice, stricter medical checkups by GPs are necessary and there is a decrease in use of preventive medication, partly because GPs monitors use of medication inadequately. The use of the Dutch Protocol in aftercare can be improved by a more detailed description of advice.

Time for considering other blood pressure target values in elderly patients with type 2 diabetes?

Although blood pressure control has undoubtedly proven its benefits in reducing the high cardiovascular risk in patients with type 2 diabetes mellitus (T2DM), it still remains unclear whether intensive antihypertensive treatment in old age (> 75 years) is beneficial. Many of the current guidelines recommend a systolic blood pressure (SBP) < 140 mmHg or lower, unless patients are at high risk for possible adverse events such as postural hypotension (1,2). This perspective aims to get a discussion started on the appropriate target SBP value for patients with T2DM aged older than 75 years.We would like to propose the less stringent value of< 160 mmHg in this specific population.

Family doctor-driven follow-up for adult childhood cancer survivors supported by a web-based survivor care plan.

PURPOSE: To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors. METHODS: The SCP was accessible for survivors and their family doctors on a secure website and as a printed booklet. It included data on diagnosis, treatment and potential risks as well as recommendations for follow-up. Childhood cancer survivors who were off-treatment ≥5 years, aged ≥18 years and not involved in a long-term follow-up program were eligible. They were advised to visit their family doctor. The endpoints were numbers of participants, adherence of family doctors to the guidelines and satisfaction ratings. RESULTS: The eligibility criteria were fulfilled by 108 survivors. Three family doctors and 15 survivors refused, 10 survivors were non-responders. Of the remaining 80 survivors, 73 survivors visited 72 family doctors. Sixty-nine (96%) family doctors returned data of whom 60 (83%) fully adhered to the recommended tests. The majority of survivors and family doctors were satisfied about the SCP. CONCLUSIONS: A (web-based) SCP for survivors and family doctors can serve as an effective communication vehicle to provide adequate shared care by the long-term follow-up clinic and family doctors.

Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck.

BACKGROUND: The vascular disrupting agent combretastatin-A4-phosphate (CA4P) demonstrated antitumour activity in preclinical studies when combined with radiation. METHODS: Patients with non-small-cell lung cancer (NSCLC), prostate adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN) received 27 Gy in 6 fractions treating twice weekly over 3 weeks, 55 Gy in 20 fractions over 4 weeks, and 66 Gy in 33 fractions over 6 weeks respectively. CA4P was escalated from 50 mg/m2 to 63 mg/m2. CA4P exposure was further increased from one to three to six doses. Patients with SCCHN received cetuximab in addition. RESULTS: Thirty-nine patients received 121 doses of CA4P. Dose-limiting toxic effects (DLTs) of reversible ataxia and oculomotor nerve palsy occurred in two patients with prostate cancer receiving weekly CA4P at 63 mg/m2. DLT of cardiac ischaemia occurred in two patients with SCCHN at a weekly dose of 50 mg/m2 in combination with cetuximab. Three patients developed grade 3 hypertension. Responses were seen in 7 of 18 patients with NSCLC. At 3 years, 3 of 18 patients with prostate cancer had prostate-specific antigen relapse. CONCLUSIONS: Radiotherapy with CA4P appears well tolerated in most patients. The combination of CA4P, cetuximab, and radiotherapy needs further scrutiny before it can be recommended for clinical studies.

Incidence, prevalence, and consultation rates of shoulder complaints in general practice.

OBJECTIVE: To study the incidence, prevalence, and consultation rates of patients with shoulder complaints in general practice in the Netherlands during 10 years following initial presentation. METHODS: A primary care database with an average population of 30,000 patients per year aged 18 years or older was used to select patients who consulted their general practitioner (GP) with shoulder complaints in the northern part of the Netherlands in the year 1998. Information about consultations for shoulder complaints was extracted. Incidence and prevalence for men, women, and different age groups were calculated for 9 and 10 years. RESULTS: A total of 526 patients consulted their GP with a new shoulder complaint. During an average follow-up of 7.6 years, these patients consulted their GP 1331 times because of their shoulder complaints (average of 0.33 consultations per year). Almost half of the patients consulted their GP only once. Patients in the 45-64 age category had the highest probability of repeated GP consultations during follow-up. Average incidence was 29.3 per 1000 person-years. Women and patients in the 45-64 age category have the highest incidence. The annual prevalence of shoulder complaints ranged from 41.2 to 48.4 per 1000 person-years, calculated for the period 1998 to 2007, and was higher among women than among men. CONCLUSION: Although the incidence of shoulder complaints in general practice is as high as 29.3 per 1000 person-years, GPs' workload is generally low, as nearly half of these patients consult their GP only once for their complaint.

Coping with adverse drug events in patients with heart failure: Exploring the role of medication beliefs and perceptions.

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE perceptions in explaining these coping strategies was assessed using the Self-Regulation Model. We performed a cross-sectional study including 250 HF patients who experienced an ADE. Patients completed validated questionnaires assessing their coping strategies, ADE perceptions and medication beliefs. Social support (60%) and information seeking (32%) were the most commonly used strategies to cope with ADEs. Non-adherence was reported by 7% of the patients. Multivariate linear regression analysis showed that demographics, clinical factors and medication beliefs explained only a small amount of the variance in coping strategies, whereas ADE perceptions explained a substantial amount of variance. Path analysis showed that patients' perceptions about the timeline, consequences and controllability of ADEs by the health care provider were directly related to their coping behaviour. The effect of patients' medication beliefs on their coping strategies was consistent with mediation through their ADE perceptions. Our results support the value of the Self-Regulation Model in understanding patients' coping behaviour with regard to ADEs.

Transfer of information on palliative home care during the out-of-hours period.

BACKGROUND: Continuity of end-of-life care for patients receiving palliative care is an important challenge for out-of-hours services in general practice. AIM: To investigate how frequent information is transferred on patients receiving palliative care from GPs to the out-of-hours services, to explore the perceptions of GP's on this information transfer and to study the relation between information transfer and the used GP information systems. METHODS: This is a mixed-method design study. The frequency of information transfer to the out-of-hours services was investigated by analyzing a regional out-of-hours database. Barriers and promoting factors for this transfer of information were investigated by using semi-structured interviews among a purposive sample of GPs from the same region. The relation between information transfer and the GP information system was investigated by a postal questionnaire in a national random selection of GPs. RESULTS: When a palliative patient contacted the out-of-hours service, for 20% of these patients, a transfer of information was available and only half of these transfers included an anticipating end-of-life plan. All interviewed GPs considered continuity of care for these patients as important. However, some doubted whether a transfer of information is relevant for the quality of care. There was no relation between the information transfer and the used GP information systems. CONCLUSION: For only a minority of patients receiving palliative care, a transfer of information including an anticipating management plan was present. There is a large variation in the opinions of GPs on how to organize continuity of end-of-life care.

Short-term effects of enhanced treatment for depression in primary care: results from a randomized controlled trial.

BACKGROUND: Depression is a highly prevalent, often recurring or persistent disorder. The majority of patients are initially seen and treated in primary care. Effective treatments are available, but possibilities for providing adequate follow-up care are often limited in this setting. This study assesses the effectiveness of primary-care-based enhanced treatment modalities on short-term patient outcomes. METHOD: In a randomized controlled trial we evaluated a psycho-educational self-management intervention. We included 267 adult patients meeting criteria for a DSM-IV diagnosis of major depressive disorder, assessed by a structured psychiatric interview. Patients were randomly assigned to: the Depression Recurrence Prevention (DRP) program (n=112); a combination of the DRP program with psychiatric consultation (PC+DRP, n=39); a combination with brief cognitive behavior therapy (CBT+DRP, n=44); and care as usual (CAU, n=72). Follow-up assessments were made at 3 months (response 90%) and 6 months (85%). RESULTS: Patient acceptance of enhanced care was good. The mean duration of the index episode was 11 weeks (S.D.=9.78) and similar in CAU and enhanced care. Recovery rate after 6 months was 67% overall; 17% of all participants remained depressed for the entire 6-month period. CONCLUSION: Enhanced care did not result in better short-term outcomes. We found no evidence that the DRP program was more effective than CAU and no indications for added beneficial effects of either the psychiatric evaluation or the CBT treatment to the basic format of the DRP program. Observed depression treatment rates in CAU were high.

Research goals for folate and related B vitamin in Europe.

In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements, for example, among women of child-bearing age who could lower the risk of having a baby with a neural tube defect, food-based strategies aimed at increasing the intake of folate and other B-group vitamins should be a priority for future research. These should include the development of a combined strategy of supplemental folate (possibly with vitamin B(12)), biofortification using engineered plant-derived foods and micro-organisms and food fortification for increasing folate intakes in the general population. Currently, the most effective population-based strategy to reduce NTDs remains folic acid fortification. However, the possible adverse effect of high intakes of folic acid on neurologic functioning among elderly persons with vitamin B(12) deficiency needs urgent investigation. The results of ongoing randomized controlled studies aimed at reducing the prevalence of hyperhomocysteinemia and related morbidity must be available before food-based total population approaches for treatment of hyperhomocysteinemia can be recommended. Further research is required on quantitative assessment of folate intake and bioavailability, along with a more thorough understanding of physiological, biochemical and genetic processes involved in folate absorption and metabolism.

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults.

OBJECTIVES: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. DESIGN: A randomized, double-blind intervention study. SUBJECTS: A total of 12 young (<30 y) and 12 middle-aged (> or =50 y) healthy volunteers were recruited. METHODS: Volunteers were randomized to receive daily supplementation with 400 mug folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [(2)H(2)]folic acid test doses using isotope kinetics in plasma. RESULTS: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P = 0.03) and after (P = 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P = 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young (+50%; P = 0.05) but not in the middle-aged (+18%; P = 0.5) adults. CONCLUSIONS: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults. SPONSORSHIP: Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).

Increasing fat in the diet does not improve muscle performance in patients with mitochondrial myopathy due to complex I deficiency.

Four myopathic patients with complex I deficiency followed diets containing 55 energy per cent (En%) as fat or 25 En% as fat, both for three weeks. Maximal workload and muscle force were not different on either diet. Exercise endurance time, oxygen consumption and lactate levels were also not different, but one patient had diminished endurance time on 25 En% as fat. Our observations do not support the use of increasing the fat in the diet of patients with mitochondrial complex I deficiency.

Oral estradiol decreases plasma homocysteine, vitamin B6, and albumin in postmenopausal women but does not change the whole-body homocysteine remethylation and transmethylation flux.

Estrogens, both endogenous and exogenous, lower the fasting levels of the independent risk factor for cardiovascular disease homocysteine. The mechanism behind this observation remains unclear. In a randomized, placebo-controlled, double-blind study, 25 postmenopausal women with a screening homocysteine concentration above 10 micromol/liter were included. We investigated the influence on homocysteine levels of a 3-month treatment with a daily oral dose of 4 mg 17beta-estradiol (ET) or 4 mg ET combined with 10 mg dydrogesterone (EPT); the comparison group received placebo treatment. We performed primed continuous infusions of L-[2H3-methyl-13C]methionine to assess steady-state flux rates of transmethylation, remethylation, and transsulfuration. Homocysteine concentration relationships with S-adenosylmethionine, S-adenosylhomocysteine, creatinine, albumin, vitamins B6 and B12, and folate status were determined as well. The mean change from baseline in homocysteine concentration by both treatments compared with placebo (ET, -13%; EPT, -10%) was accompanied by a decrease in the concentration of vitamin B6 (ET, -25%; EPT, -38%) and albumin (ET, -7%; EPT, -11%). No significant changes in flux rates were observed. In a .multiltivariate analysis, changes in homocysteine concentration were related to changes in albumin concentration. No relation to other variables was observed. We conclude that the ET- and EPT-induced homocysteine changes in this study were not accompanied by a significant change in methionine-homocysteine flux rates and hypothesize that an estrogen-induced lowering of homocysteine levels is primarily part of a change in albumin metabolism.

Hormone replacement influences homocysteine levels in the methionine-loading test: a randomized placebo controlled trial in postmenopausal women.

OBJECTIVE: To investigate the mechanism by which exogenous oestrogen influences the homocysteine metabolism in postmenopausal women. STUDY DESIGN: A randomized placebo controlled trial in which a methionine-loading test was performed, in 25 healthy postmenopausal women, before and after a 12-week oral treatment with placebo or daily 4 mg 17beta-estradiol with (HRT) or without (ERT) 10 mg dydrogesterone. Fasting and post-load homocysteine as well as Vitamins B(6), B(12) and folate were determined. RESULTS: In both treatment groups a significant 12% decrease in fasting homocysteine was observed. This decrease was accompanied by a post-load homocysteine increase of more than 20%. Vitamin B(6) values were decreased by more than 25%. CONCLUSION: The hormone therapy induced lowering of fasting homocysteine and Vitamin B(6) levels and an increase in post-load homocysteine, supporting the hypothesis that homocysteine-methionine metabolism is modulated by hormone therapy in postmenopausal women.

Nutritional support in 111 pediatric intensive care units: a European survey.

OBJECTIVE: To study current strategies in nutritional management of pediatric intensive care units (PICUs) in Europe, focusing on energy requirements. DESIGN AND SETTING: Survey by a 35-item questionnaire sent to representatives of 242 PICUs in 28 countries. Addresses were obtained from national PICU associations and the members' list of the European Society of Pediatric and Neonatal Intensive Care. PARTICIPANTS: Staff members of 111 European PICUs (46%) from 24 countries. MEASUREMENTS AND RESULTS: Predominantly physicians were reported to be responsible for nutritional support. In 73% of PICUs a multidisciplinary nutritional team was available. In most PICUs daily energy requirements were estimated using weight, age, predictive equations and correction factors. In 17% of PICUs energy expenditure was regularly measured by indirect calorimetry. Nutritional status was mostly assessed by weight, physical examination, and a wide range of biochemical blood parameters. Approximately 70% of PICUs used dedicated software for nutritional support. A similar percentage of PICUs regarded "nutrition" as a research topic and part of the residents' training program. CONCLUSIONS: Most European PICUs regard nutritional support as an important aspect of patient care, as shown by the presence of nutritional teams, software, research, and education. However, energy requirements of pediatric intensive care patient were based predominantly on estimations rather than on measurements.

5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism.

We describe a liquid chromatography (LC) tandem mass spectrometry (MS-MS) method for the determination of 5-methyltetrahydrofolic acid (5-methylTHF) and folic acid concentrations and enrichments in human plasma. It was used to study absorption and initial metabolism in five volunteers with two simultaneously administered oral test doses ([(13)C(6)]folic acid in capsules and [(2)H(2)]folic acid in a drink). [(13)C(5)]5-methylTHF and [(2)H(4)]folic acid were used as internal standards. Plasma samples (2 ml) were purified using folate binding protein affinity columns, followed by a concentration step. After LC separation, folates were detected using positive electrospray ionization MS-MS under multiple reaction monitoring conditions. Calibrations were linear for 5-methylTHF over the range 1.2 x 10(-11) (=limit of detection) to 3.2 x 10(-7)mol/L and for folic acid over the range 5 x 10(-10) (=limit of detection) to 4.5 x 10(-8)mol/L. For 5-methylTHF concentration in plasma, intraassay coefficient of variation was within 8.6% (and for unlabeled 5-methylTHF it was within 2.8%) and interassay coefficient of variation was within 9.0%. For folic acid concentrations these coefficient of variations were within 7.5% and within 6.5%, respectively. The [(13)C(6)] and [(2)H(2)] isotopomers of folic acid and 5-methylTHF were measured in the plasma of each volunteer for 8h. After accounting for the time delay due to capsule opening, the modeling results showed no significant differences in absorption time, first pass effect, and elimination rate in the folic acid test doses in capsule or drink. We conclude that LC-MS-MS offers increased sensitivity for quantification of plasma concentrations and enrichments of 5-methylTHF and folic acid and is applicable to stable-isotope studies in humans.

Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis.

OBJECTIVE: Glucocorticoid treatment of children often leads to growth retardation, and the precise target(s) in the growth plate responsible for this effect are unknown. Angiogenesis is an important part of the endochondral ossification process, and VEGF expressed in the growth plate is essential for proper angiogenesis to occur. Since glucocorticoid treatment down-regulates VEGF expression in cultured chondrocytes, we hypothesized that in vivo glucocorticoid treatment could result in VEGF down-regulation in the growth plate and disturbed angiogenesis, thus contributing to the growth retardation. DESIGN: We treated 6-week-old prepubertal piglets (10 kg) for 5 days with prednisolone (50 mg/day). Tibial growth plate sections were studied for apoptosis and the expression of VEGF protein and mRNA and MMP-9 protein. Capillaries in the metaphysis were visualized by CD31 immunostaining. Growth plate morphology (width of various zones) was determined by interactive measurements on hematoxylin/eosin stained sections and apoptotic cells were detected by TUNEL assay. RESULTS: In the prednisolone-treated animals, the total width of the growth plate decreased to 81% of controls (P<0.02), which was explained by a decrease of the width of the proliferative zone to 73% (P<0.05). The treatment had no effect on the orderly organization of the chondrocyte columns. In the growth plates of control animals, apoptosis was shown in 5.8% of the hypertrophic chondrocytes and was limited to the terminal hypertrophic chondrocytes. In prednisolone-treated animals, 40.5% of the hypertrophic chondrocytes was apoptotic (P<0.02), with apoptotic chondrocytes also appearing higher in the hypertrophic zone. We observed fewer capillaries and loss of their parallel organization in the metaphysis in the prednisolone-treated animals. The capillaries were shorter and chaotic in appearance. In contrast to controls, in prednisolone-treated animals VEGF mRNA and protein could not be detected in the hypertrophic zone of the growth plate. Trabecular bone length in the primary spongiosa was also diminished by the treatment. No changes were observed in the expression pattern of MMP-9, a matrix metalloproteinase, which is also important for angiogenesis and bone formation. CONCLUSIONS: These results indicate that short-term glucocorticoid treatment of growing piglets severely disturbs the width of the growth plate, apoptosis of chondrocytes, VEGF expression by hypertrophic chondrocytes, the normal invasion of blood vessels from the metaphysis to the growth plate and bone formation at the chondro-osseous junction. These effects could alter the dynamics of endochondral ossification and thus contribute to glucocorticoid-induced growth retardation.

Energy expenditure in infants with congenital heart disease, including a meta-analysis.

AIM: To assess energy requirements and body composition in preoperative children with congenital heart disease (CHD). METHODS: In 11 infants with CHD (2-8 mo), total daily energy expenditure (TDEE) and total body water (TBW) were measured with doubly labelled water and compared with historic data from healthy controls. Within the patient group, energy expenditure of infants with versus those without congestive heart failure was compared. Subsequently, the data were pooled with literature data in meta-analyses. RESULTS: CHD patients showed increased TBW (mean +/- SD 66 +/- 3 vs 58 +/- 5% of body weight, p < 0.05) and energy expenditure (381 +/- 42 vs 298 +/- 36 kJ kg(-1) d(-1), p < 0.001). Meta-analyses showed that CHD infants have 35% increased TDEE (376 vs 278 kJ kg(-1) d(-1) , p < 0.00001) and 7% higher TBW (p < 0.0001). Coexistent congestive heart failure (treated with diuretics) had no influence on TDEE (mean difference 14 kJ kg(-1) d(-1) , not significant). In patients with heart failure and growth retardation, an energy balance study showed an average 12% loss of initially ingested energy due to vomiting, increased TDEE and low faecal energy loss, resulting in low energy available for growth, compared with controls (42 +/- 30 vs 96 +/- 61 kJ kg(-1) d(-1) , p < 0.05). CONCLUSION: Many infants with CHD require substantially higher energy intake (at least 100 kJ kg(-1) d(-1) extra) owing to increased TDEE, which is not explained by a higher percentage of body water. Coexistent heart failure does not appear to have an additional influence on TDEE. In infants with CHD and growth failure factors other than elevated TDEE, including vomiting, may explain the disturbed energy balance.

Determination of 13C and 15N enrichments of urea in plasma by gas chromatography-combustion isotope ratio mass spectrometry and gas chromatography-mass spectrometry using the 2-methoxypyrimidine derivative.

We describe a GC-MS and GC-c-IRMS method for the determination of labeled urea tracer enrichments in plasma as a result of combined 13C- and 15N(2)-urea infusion experiments in piglets. Urea was converted into 2-methoxypyrimidine, a stable derivative, suited for analyses by both GC-MS and GC-c-IRMS. Using calibration curves for the respective working ranges (13C-urea: 0-1% APE; 15N(2)-urea: 0-7% MPE) enrichments were established in single point measurements; for 15N(2)-urea as values+/-0.15% MPE (95% confidence interval); for 13C-urea as values+/-0.02% APE (95% confidence interval). 15N(1)-urea enrichments were determined by measurement of the same sample with GC-c-IRMS and GC-MS. Subtraction of the 13C specific GC-c-IRMS data from the nondiscriminating GC-MS data for the sum of 13C- and 15N(1)-urea resulted in 15N(1)-urea enrichments+/-0.15% MPE (95% confidence interval). Application of the method in a combined 13C-urea bolus and 15N(2)-urea primed constant infusion experiment in piglet was demonstrated.

S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations.

BACKGROUND: It is unclear whether homocysteine itself is causal in the pathogenesis of cardiovascular disease. Alternatively or additionally, the association between homocysteine and cardiovascular disease may be because of its metabolic precursor, S-adenosylhomocysteine, or of the ratio of S-adenosylmethionine to S-adenosylhomocysteine. Therefore, it is relevant to know how these moieties are interrelated, and whether, as is the case for homocysteine, they are influenced by blood levels of folate, cobalamin or vitamin B6. DESIGN: We cross-sectionally studied a population-based cohort of 97 Caucasian subjects aged 60-85 years. Concentrations of homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, folate, cobalamin and vitamin B6 were measured in fasting blood samples. RESULTS: In multiple regression analysis, homocysteine was associated with vitamin B12 (per 50 pmol L-1 increase of cobalamin, change in homocysteine, -0.70 mmol L-1; 95% CI, -1.30 to -0.10 mmol L-1) and folate (per 100 nmol L-1 increase in erythrocyte folate, change in homocysteine, -0.68 mmol L-1; 95% CI -1.28 to -0.08 mmol L-1). S-adenosylhomocysteine, S-adenosylmethionine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with serum folate, cobalamin or vitamin B6, nor with erythrocyte folate. Furthermore, plasma homocysteine showed a negative correlation with the ratio of S-adenosylmethionine to S-adenosylhomocysteine in plasma (r = -0.27; P < 0.01) but not in erythrocytes. CONCLUSIONS: In contrast to homocysteine, the plasma concentrations of S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with the folate, cobalamin and vitamin B6 concentrations in the present study. If these precursors in part explain why homocysteine is associated with cardiovascular disease, homocysteine-lowering treatment with B vitamins may be less effective than currently expected, at least in an elderly population.