Effect of apolipoprotein E genotype on vitamin K status in healthy older adults from China and the UK

The vitamin K concentration in the circulation and the availability of vitamin K to bone may be affected by factors influencing lipoprotein metabolism, such as apoE genotype. The relationships between markers of vitamin K status, bone mineral content and apoE genotype were studied in healthy older men and women aged 60-83 years, 177 from Shenyang, China, and 132 from Cambridge, UK. Fasting plasma was analysed for vitamin K1, triacylglycerol, total osteocalcin, undercarboxylated osteocalcin (ucOC) and apoE genotype. Hip bone mineral content was measured using dual-energy X-ray absorptiometry. Subjects were grouped according to apoE genotype as E2/3, E3/3 and [E3/4+E4/4]. The mean plasma vitamin K1 concentration of the three genotype groups was significantly higher and the percentage ucOC was lower in the Chinese than in the British subjects (P<0.01). A higher vitamin K1 concentration was found in subjects with [E3/4+E4/4] than those with either E2/3 or E3/3 in Cambridge (32.2 (SE 14.6 ) %, P=0.03; 24.6 (SE 10.7 ) %, P=0.02). Similar trends were observed although were not statistically significant in Shenyang (26.5 (18.9) %, P=0.16; 23.1 (13.0) %, P=0.08). Subjects with [E3/4+E4/4] had a lower percentage ucOC (total osteocalcin adjusted) than did those with either E2/3 or E3/3 in Shenyang (65.1 (27.2) %, P=0.02; 49.6 (19.9) %, P=0.01 respectively) but not in Cambridge. This study demonstrates that a superior vitamin K status is associated with the apoE4 genotype in healthy older individuals from China and the UK.     

Effect of sulphinpyrazone and aspirin on latelet adhesion to activated charcoal and dialysis membranes in vitro.

Charcoal haemoperfusion is used in the treatment of severe drug overdosage, and is potentially useful in fulminant hepatic failure and chronic uraemia. Haemo-compatibility of early devices has improved, but platelet loss and occasional associated haemorrhage still occur. During a double blind cross-over study, in 8 healthy male volunteers, aspirin 600 mg/day, sulphinpyrazone 800 mg/day, or a combination of both or placebo were administered for 2 days at 14 day or longer intervals. The effects of these agents were measured with reference to 1) forearm bleeding times using a spring loaded device, 2) platelet adsorption during 2 hrs haemoperfusion of heparinized blood through 2% acrylic hydrogel coated or uncoated activated charcoal in vitro, and 3) platelet retention from citrated blood on PT₁₅₀ and PT₂₅₀ cuprophan dialysis membranes in vitro. Aspirin and aspirin in combination with sulphinpyrazone prolonged bleeding time, but sulphinpyrazone alone had no significant effect on bleeding time. Aspirin alone, sulphinpyrazone alone, and their combination reduced platelet adsorption on coated activated charcoal, and platelet retention on cuprophan membranes. Aspirin, and aspirin in combination with sulphinpyrazone, reduce platelet adsorption on uncoated charcoal, while sulphinpyrazone alone had no significant effect. The results indicate that 2 days treatment with sulphinpyrazone or aspirin produce significant antiplatelet action and that the effects of sulphinpyrazone on platelet function should be explored in relation to clinical haemoperfusion and haemodialysis.     

A microbiological study of neonatal conjunctivae and conjunctivitis.

To investigate the importance of chlamydiae, ureaplasmas, Mycoplasma hominis, and anaerobic bacteria in the pathogenesis of neonatal conjunctivitis in the Harrow population conjunctival specimens from 104 infants with conjunctivitis and 104 similar healthy neonates were examined. The incidence of neonatal conjunctivitis was 8-2%, and no case of neomycin-resistant disease occurred during the study. Staphylococcus aureus, viridans Streptococci, and Escherichia coli were the only micro-organisms isolated significantly more frequently from affected than from control eyes, which suggests that these bacteria may be a cause of the conjunctivitis. All cultures for chlamydiae, M. hominis, Neisseria gonorrhoeae, and anaerobic bacteria were negative. The mother's race, social status, illness, and obstetric events were found to have no effect on the incidence, time of onset of conjunctivitis, or micro-organisms isolated. The clinical characteristics of conjunctivitis were also not related to the micro-organisms isolated. No potential pathogens were isolated from 63-5% of the eyes showing conjunctivitis. The results suggest that some of these cases may be caused by chemical irritation, and the possibility of an infectious aetiology is also discussed.     

Early programming of adult diseases in resource poor countries.

Considerable evidence now exists to suggest that early exposure to nutritional deprivation can have long term consequences to health, with low birth weight now considered a risk factor for later health outcomes such as coronary heart disease, stroke, type 2 diabetes, and the metabolic syndrome. Of importance, such effects are most exaggerated when faced with over-nutrition in later life, forming the basis for the "thrifty phenotype" hypothesis. The evidence in support of these associations comes largely from retrospective cohort studies in which adult outcomes were correlated with birth weight records. Relatively little data is available from developing countries, where long term record keeping of birth weight data has not been a high priority. Arguably however, such countries are at the greatest risk from the mismatch of early nutritional deprivation and later nutritional affluence. This paper explores the importance of the "developmental origins of health and disease" hypothesis in resource poor countries.     

Maternal preconceptional weight and gestational length

Recent animal studies suggest that preconceptional undernutrition shortens gestation. We retested this idea among rural Gambian women who experience annual fluctuations in energy balance caused by the rains (with lowest weights in September to November) using records from 1918 infants. Pregnancies conceived in September to November were significantly shorter than those from better-fed months (38.6 vs 39.0 weeks; log-rank chi 2 = 17.4, P < .0001).     

Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's disease

BACKGROUND: Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. METHODS: A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). RESULTS: 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4, 139) = 5.60, p < 0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p < 0.05 in each case). This effect could not be explained by age or by smoking status. CONCLUSION: Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome.     

Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's disease

OBJECTIVE: To investigate the possibility that response to cholinesterase inhibitor therapy could be predicted by easily measurable variables that are known to change as a result of treatment (such as the Mini Mental State Examination), measures of function (such as the instrumental activities of daily living and the social behaviour subscales of the Nurse's Observation Scale for Geriatric Patients), and measures of attention (such as the Digit Symbol Substitution Test; DSST), or that might influence response through structural (for example, age, cerebrovascular disease, medial temporal lobe (MTL) atrophy, hypertension) or chemical (for example, smoking) mechanisms. METHOD: This was a cohort study of 160 consecutive outpatients with probable Alzheimer's disease who commenced cholinesterase inhibitor treatment over a 3 year period in a semi-rural area of Scotland. RESULTS: The overall response rate was 42.1%. Stratification of response between good and poor responders was possible using baseline DSST and a measure of MTL thickness using CT. Among the patients, 60.4% of those above the cut off point for both DSST and MTL thickness (29/48 subjects) were classified as good responders, compared with 6.3% of subjects below the cut off point for both (1/16 subjects). Subjects above the cut off point for both measures were more likely to be classified as good responders than subjects with only one or no values above the respective cut off points (chi(2) = 10.61, df = 1, p = 0.001) CONCLUSIONS: The DSST and a measure of MTL thickness derived from CT scanning may be useful in improving the prediction of response to cholinesterase inhibitors in subjects with AD. Subjects with low DSST scores and more severe MTL atrophy are unlikely to respond to treatment. These preliminary data justify a prospective trial of the usefulness of our suggested predictive measures.     

Locomotor adaptations for changes in the slope of the walking surface

The goal of this study was to examine the transition of walking from a level surface onto different inclined surfaces. Kinematic data of limb and trunk segments were recorded from individuals as they approached and stepped onto four different ramped surfaces (slopes=3°, 6°, 9°, 12°). This transition introduced significant adaptations to the swing limb trajectory that were evident in even the lowest ramp condition and appear to be scaled to the ramp inclination although the nature of this scaling seemed to change between the 6° and 9° conditions. An increased forward pitch of the trunk orientation during all ramp conditions was initiated early on during the preceding stance phase on level ground. The swing limb modification essentially consisted of a two-stage response. The initial response of the limb trajectory changes was not specific to the degree of inclination but later changes were dependent on the ramp condition. The initial response is to ensure a safe toe clearance as the foot approaches the edge of the ramp and then later modifications provide the appropriate positioning of the limb to prepare for an elevated foot contact. Early changes were actively produced through an increased pull-off by the hip flexors and an elevation of the swing limb by the active muscle control of the stance limb. Ankle dorsiflexion also appears to have a supporting role increasing toe clearance. Absorption at the hip and knee during later swing contribute to control and position the limb in preparation for foot contact. These strategies were similar to those adopted for step changes in the level of the walking surface where there are similar demands of the quickly moving the limb forward and upward, however, the positioning of the limb for new angled landing surface requires further adaptations.     

Dietary acid-base balance and intake of bone-related nutrients in Cambridge teenagers

OBJECTIVES: To evaluate the diet of 16-18-y-old boys and girls with particular reference to intakes of nutrients believed to affect bone health and dietary acid-base balance. DESIGN: A 7-day food diary was completed between the months of October and December. SETTING: Cambridge, UK. SUBJECTS: A total of 111 boys and 101 girls aged 16-18 y who were recruited into the Cambridge Bone Studies. MAIN OUTCOME MEASURES: Mean daily intakes of foods and selected nutrients (protein, calcium, phosphorus, magnesium, potassium, vitamins C and K) were calculated. Two estimates of acid-base balance were calculated from the diet using the formulae of Remer (net acid excretion, estimated indirectly; NAE(ind)) and Frassetto (protein/potassium ratio). RESULTS: Mean calcium and phosphorus intakes were above the UK Reference Nutrient intake (RNI). In all, 39% of the boys and 36% of the girls had vitamin K intakes lower than 1 microg/kg body weight/day. Calcium intake was positively correlated with all other nutrients except vitamins C and K. Boys had a significantly higher estimated net acid excretion (NAE(ind)) than girls (P<0.001). Although a strong correlation (r=0.76, P<0.001) was found between the two methods, at higher acid levels a divergence was observed. A significant positive correlation was found between NAE(ind) and the weight consumed per day of milk, cheese, meat and cereal foods and a negative correlation was found with the weight of potatoes and fruit. Diet composition is such that a lower NAE(ind) is accompanied by a lower calcium intake. CONCLUSIONS: The interpretation of the effects of calcium and other nutrients on bone cannot be considered in isolation from the other components of the diet. These results challenge some of the accepted perceptions about what constitutes an optimal diet for the promotion of bone health in adolescents.