Design and baseline characteristics of the Biomarkers Of Risk In Colorectal Cancer (BORICC) Follow-Up study: A 12+ years follow-up.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Age is the strongest non-modifiable risk factor but it is estimated that over half of CRC cases are linked with lifestyle factors such as diet. The Biomarkers Of RIsk of Colorectal Cancer (BORICC) Study recruited 363 participants in 2005 to investigate the effects of lifestyle factors on biomarkers of CRC risk. AIM: In the present BORICC Follow-Up (BFU) Study, we are using a longitudinal study design to investigate the effects of ageing (12+ years) and lifestyle factors on biomarkers of CRC risk and on healthy ageing. METHODS: BFU Study participants attended a study visit at North Tyneside General Hospital (UK) for collection of biological samples, including blood and rectal biopsies, and information collected included anthropometric measurements, a Health & Medications Questionnaire, physical activity and sedentary behaviour, and habitual diet. Furthermore, musculoskeletal function was assessed by heel bone densitometry, timed up and go and hand grip strength as markers of healthy ageing. The BFU Study outcomes will be similar to those measured at baseline in the BORICC Study, such as DNA methylation and mitochondrial function, with additional measurements including the gut microbiome, faecal short-chain fatty acid concentrations and expression of genes associated with CRC. RESULTS: Participants' recruitment to BFU Study and all sample and data collection have been completed. Forty-seven of the original BORICC participants were re-recruited to the BFU Study (mean age 67 years, 51% female). The recruits included 37 initially healthy participants and 10 participants who had adenomatous polyps at baseline. Approximately 70% of participants were over-weight or obese. CONCLUSION: Ultimately, identifying lifestyle factors that can reduce CRC risk, and understanding the underlying mechanisms for the effects of lifestyle and ageing on CRC risk, could lead to early prevention strategies.

Design, Development and Implementation of a Decision Support Info-Portal for Integrated Coastal Management, KwaZulu-Natal, South Africa.

Coastal environments face mounting pressures from development and resource use, and appropriate coastal management supports long-term ecosystem functionality, viability and delivery of goods and services. Integrated coastal management (ICM) is advocated as a best practice approach to achieving this, but comes with its own challenges. Given the diverse nature of the coastal environment and the goods and services it offers, its management is complex. In South Africa, this is exacerbated by the legislative framework which delegates numerous responsibilities to local government without providing financial or human capacity to meet these requirements. These challenges have resulted in the development of a number of guidelines in support of achieving ICM objectives. This paper focuses on one coastal region in South Africa, KwaZulu-Natal, which is grappling with coastal management issues, including the implementation thereof for a 580 km coast with 76 estuaries. It considers the progressive, iterative development of an innovative Decision Support info-portal to assist local coastal managers in the absence of human capacity support and tools. Stakeholders were asked to complete a survey to provide feedback on their impression of the tool, its functions and usability. This facilitated stakeholder input into the info-portal development, which was essential in ensuring that the end product is useable, relevant and supportive of coastal management and decision making. Since its public release, the Decision Support info-portal has been implemented and utilised by government officials for both ongoing management and emergency response within the KZN province.

Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study.

SUMMARY: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown. INTRODUCTION: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N). METHODS: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models. RESULTS: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) µg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort. CONCLUSION: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.

Vitamin D status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart's Project.

UNLABELLED: In girls, a plateau in parathyroid hormone (PTH) was observed at a 25-hydroxyvitamin D (25(OH)D) concentration of approximately 60 nmol/l. In boys, there was no plateau in PTH concentrations as 25(OH)D concentration increased. A 25(OH)D threshold of 60 nmol/l appears to have implications for bone health outcomes in both girls and boys. INTRODUCTION: Our objective was to investigate if there is a threshold 25(OH)D concentration where a plateau in PTH concentration is evident and to examine the impact of this relationship on bone mineral density (BMD) and bone turnover in a representative sample of adolescents. METHODS: We conducted a cross-sectional analysis among 1,015 Northern Irish adolescents aged 12 and 15 years. Serum 25(OH)D, PTH, osteocalcin, type 1 collagen cross-linked C-telopeptide (CTx), and BMD of the nondominant forearm and heel were measured. Nonlinear regression analysis was used to model the association between 25(OH)D and PTH. RESULTS: In girls, a plateau in PTH was observed at a 25(OH)D concentration of approximately 60 nmol/l (PTH = 47.146 + 370.314 x exp((-0.092 x 25(OH)D))) while no plateau in PTH was observed in boys (PTH = 42.144 + 56.366 x exp((-0.022 x 25(OH)D))). Subjects with 25(OH)D levels <60 nmol/l had significantly higher osteocalcin concentrations (P < 0.05) compared with those who had >or=60 nmol/l, while no significant (P > 0.05) differences were noted for CTx concentrations. In girls only, nondominant forearm BMD but not heel BMD was significantly higher (P = 0.046) in those with 25(OH)D concentrations >or= 60 nmol/l. CONCLUSIONS: Serum 25(OH)D levels above 60 nmol/l in Northern Irish adolescent girls prevent an increase in serum PTH levels and maintaining 25(OH)D >60 nmol/l in both girls and boys may lead to improved bone health outcomes.

A reassessment of the vitamin D requirements of modern broiler genotypes.

We hypothesized that performance and bone mineralization of 2 broiler lines will benefit from increasing vitamin D (vitD) supplementation above current commercial levels and by partial substitution of D3 by 25-OH-D3. Male Ross 308 and 708 chicks (n = 576), were offered diets with low (LD; 1,000), medium (MD; 4,000) or high levels of D3 (HD; 7,000 IU/kg), and medium levels of vitD where the majority of D3 was substituted by 25-OH-D3 (25MD; 1,000 D3+3,000 25-OH-D3 IU/kg). Performance was measured at the end of starter (day 10), grower (day 24), and finisher periods (day 38). Three birds per pen were dissected at the end of each period to assess tibia and femur ash percentage (%), ash weight, bone breaking strength (BBS), and serum levels of 25-OH-D3. Remaining birds were gait scored (GS) at day 37 of age. Genotype and diet did not interact for any trait, whilst performance was not affected by diet. Ross 708 had lower body weight (P < 0.005), higher feed conversion ratio over the grower period (P < 0.05), similar levels of 25-OH-D3, but higher GS (P < 0.05) than Ross 308. Serum 25-OH-D3 levels were affected by diet at the end of the starter and grower periods (P < 0.05), being lowest for LD and highest for 25MD. Diet affected GS (P < 0.01), being higher in LD than 25MD. Femur ash % was higher at the end of the starter and grower periods for 25MD than LD and for both HD and 25MD than LD (P < 0.05). Femur and tibia ash weight were higher for 25MD in comparison to LD birds (P < 0.05) at the end of the grower period. Femur and tibia BBS were higher (P < 0.05) for 25MD in comparison to LD at the end of the grower and finisher periods, respectively. Overall, effects of vitD supply were more pronounced for femur than for tibia mineralization. Results do not suggest supplementation of vitD above current maximum levels and support partial substitution by 25-OH-D3.

No effect of monthly supplementation with 12000 IU, 24000 IU or 48000 IU vitamin D3 for one year on muscle function: The vitamin D in older people study.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

Higher bone resorption excretion in South Asian women vs. White Caucasians and increased bone loss with higher seasonal cycling of vitamin D: Results from the D-FINES cohort study.

Few data exist on bone turnover in South Asian women and it is not well elucidated as to whether Western dwelling South Asian women have different bone resorption levels to that of women from European ethnic backgrounds. This study assessed bone resorption levels in UK dwelling South Asian and Caucasian women as well as evaluating whether seasonal variation in 25-hydroxyvitamin D [25(OH)D] is associated with bone resorption in either ethnic group. Data for seasonal measures of urinary N-telopeptide of collagen (uNTX) and serum 25(OH)D were analysed from n=373 women (four groups; South Asian postmenopausal n=44, South Asian premenopausal n=50, Caucasian postmenopausal n=144, Caucasian premenopausal n=135) (mean (±SD) age 48 (14) years; age range 18-79years) who participated in the longitudinal D-FINES (Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England) cohort study (2006-2007). A mixed between-within subjects ANOVA (n=192) showed a between subjects effect of the four groups (P<0.001) on uNTX concentration, but no significant main effect of season (P=0.163). Bonferroni adjusted Post hoc tests (P≤0.008) suggested that there was no significant difference between the postmenopausal Asian and premenopausal Asian groups. Season specific age-matched-pairs analyses showed that in winter (P=0.04) and spring (P=0.007), premenopausal Asian women had a 16 to 20nmolBCE/mmol Cr higher uNTX than premenopausal Caucasian women. The (amplitude/mesor) ratio (i.e. seasonal change) for 25(OH)D was predictive of uNTX, with estimate (SD)=0.213 (0.015) and 95% CI (0.182, 0.245; P<0.001) in a non-linear mixed model (n=154). This showed that individuals with a higher seasonal change in 25(OH)D, adjusted for overall 25(OH)D concentration, showed increased levels of uNTX. Although the effect size was smaller than for the amplitude/mesor ratio, the mesor for 25(OH)D concentration was also predictive of uNTX, with estimate (SD)=-0.035 (0.004), and 95% CI (-0.043, -0.028; P<0.001). This study demonstrates higher levels of uNTX in premenopausal South Asian women than would be expected for their age, being greater than same-age Caucasian women, and similar to postmenopausal Asian women. This highlights potentially higher than expected bone resorption levels in premenopausal South Asian women which, if not offset by concurrent increased bone formation, may have future clinical and public health implications which warrant further investigation. Individuals with a larger seasonal change in 25(OH)D concentration showed an increased bone resorption, an association which was larger than that of the 25(OH)D yearly average, suggesting it may be as important clinically to ensure a stable and steady 25(OH)D concentration, as well as one that is high enough to be optimal for bone health.

Prevalence of suboptimal vitamin D status in young, adult and elderly Irish subjects.

With the exception of the elderly, there is a dearth of information about the vitamin D status of Irish subjects. Therefore, we assessed the prevalence of suboptimal vitamin D status in a number of age-groups within the Irish population (including females aged, 11-13 years, 23-50 years, 51-69 years, and 70-75 years; and males, aged 20-64 years) during late-winter and late-summer. In females, depending on the age-group studied, between 4 and 19% and between 34 and 85% had an inadequate serum 25 (OH) D level (<50 nmol/l) during late-summer and late-winter, respectively. During late-summer, there was a marked absence of severe and moderate vitamin D deficiency in all subjects, while, 7% of men and, depending on the age-group studied, between 4 and 19% of females had mild vitamin D deficiency. During late-winter, none of the subjects had severe vitamin D deficiency. While none of the men had moderate vitamin D deficiency, 33% of men had mild vitamin D deficiency. In females, depending on the age-group studied, between 32 to 55% of females had mild vitamin D deficiency, and between 2 to 30% of females had moderate vitamin D deficiency, during late-winter. These findings show that inadequate vitamin D status is quite common in healthy Irish subjects, especially and notably so in young girls and more elderly women.

Vitamin D, Muscle Function, and Cardiorespiratory Fitness in Adolescents From the Young Hearts Study.

CONTEXT: Vitamin D insufficiency is common among the adolescent population and may have implications for health outcomes in later life. Few studies have investigated the role of vitamin D status in muscle function and cardiorespiratory fitness (CRF) during adolescence. OBJECTIVE: The aim of this study was to investigate the association between vitamin D status and fat-free mass (FFM), muscle strength, muscle power, and CRF in a representative sample of adolescents from Northern Ireland. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study involving 1015 adolescents (age 12 and 15 y), who had 25-hydroxyvitamin D [25(OH)D] data available as part of the Young Hearts Study 2000. MAIN OUTCOME MEASURES: The main outcome measures of this study were FFM (kg) and FFM corrected for height [fat-free mass index; FFM (kg)/height (m(2))], muscle strength (kg), peak muscle power (kW) and VO2 max (CRF; mL/kg/min). RESULTS: Multinomial regression analyses, controlling for environmental and lifestyle factors, demonstrated that boys age 15 years in the highest tertile of standardized serum 25(OH)D concentration (> 51 nmol/L) had significantly higher muscle strength (ß = 3.90; P ≤ .001) compared with those in the lowest tertile (< 32 nmol/L). These results were not evident in any other age-sex group and vitamin D status was not significantly associated with muscle power or CRF in any of the four age-sex groups. CONCLUSION: These results support a role for vitamin D in muscle function in adolescent males and suggest the need for more research in this vulnerable age group.

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.

Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence assembled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100012 Da (PDE5A1). Extracts prepared from yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was inhibited by the selective PDE5 inhibitors zaprinast and DMPPO. PDE5A mRNA is expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protein with eight unique amino acids at the amino terminus. PDE5A maps to chromosome 4q 25-27.

Alterations in cerebral blood flow, oxygen metabolism, and electrical activity produced by high dose sodium thiopental.

High dose barbiturate therapy is being used with increasing frequency in the management of a widening spectrum of neurological disorders. Accurate regulation of the barbiturate dose is essential to maximize cerebral vasoconstriction and reduce brain metabolism while avoiding the cardiovascular depressant side effects of the drug. The purpose of this study was to determine whether the electroencephalogram (EEG) could be used to regulate administration of the agent. In nine mongrel dogs cerebral blood flow (CBF) was determined using the radioactive microsphere technique. After the determination of control CBF, a slow infusion of sodium thiopental was begun. CBF determinations were repeated when the periods of burst suppression in the EEG over several minutes averaged 30, 60, 120, and 240 seconds. CBF and oxygen metabolism showed a nearly identical pattern of a precipituos drop from control levels reaching a plateau at burst suppression between 30 and 60 seconds. Changes in cerebrovascular resistance were of a similar but opposite nature. Significant increases in heart rate occurred with burst suppression of 30 seconds, whereas the arterial pressure and cardiac index decreased with burst suppression between 30 and 60 seconds. In this study cerebral metabolic depression and vasoconstriction from sodium thiopental reached a plateau when sufficient barbiturate was administered to produce EEG burst suppression of between 30 and 60 seconds. At this level there was no important cardiovascular depression. Administration of additional barbiturates significantly decreased systemic arterial pressure and cardiac output, but produced no further decrement in the cerebral metabolic rate of oxygen or the CBF. There was no predictable relationship between cerebral metabolism or cardiovascular function and blood levels of sodium thiopental.

Influence of a continuous high dose infusion of mannitol on cerebral blood flow in normal dogs.

In normal dogs, the continuous infusion of 2 g of mannitol per kg resulted in a transient increase in cerebral blood flow of approximately 30%, which was accompanied by a concomitant reduction in cerebrovascular resistance. These changes were maximal 30 minutes after the infusion was initiated and resolved by 180 minutes. The changes were not related to alterations in arterial blood gases, systemic arterial or central venous pressures, or heart rate.

Influence of changes in arterial pCO2 on cerebral blood flow and metabolism during high-dose barbiturate therapy in dogs.

In 13 dogs the response of the cerebral circulation to changes in PaCO2 ranging from 20 to 60 torr was studied before and after administration of high doses of sodium thiopental. Infusion of sufficient barbiturate to produce 30- to 60-second burst suppression in the electroencephalogram was associated with a profound degree of cerebral vasoconstriction, equivalent to that produced by hypocapnia with PaCO2 = 20 torr. Furthermore, once sodium thiopental was administered, no significant difference in cerebral blood flow (CBF) or vascular resistance (CVR) was noted between PaCO2 of 30 and 20 torr. However, changes of approximately 15% in CBF and 30% in CVR were noted between PaCO2 at 40 and 20 torr. These data suggest that hyperventilation of PaCO2 of less than 30 torr may not effectively increase the degree of cerebral vasoconstriction in these circumstances.

Vitamin D intakes in 18-64-y-old Irish adults.

OBJECTIVE: To estimate vitamin D intakes in a representative sample of Irish adults and to assess the contribution of foods to these intake estimates. DESIGN: Vitamin D intakes in 1379, 18-64-y-old adults from the North/South Ireland Food Consumption Survey were estimated using a combination of new analytical data for vitamin D in foods, determined by HPLC, and used to revise recipe calculations, together with existing data from McCance and Widdowson's The Composition of Foods, 5th Edition plus supplements. RESULTS: The total mean daily intake (MDI) of vitamin D (1 microg=40 IU) from all sources was 4.2 microg. The MDI was significantly higher (P<0.001) when the contribution from nutritional supplements was included (4.2 microg) compared with food sources only (3.2 microg). Men had significantly higher intakes (4.4 microg) than women (4.0 microg; P<0.001), which increased significantly (P<0.001) with age in both sexes. Meat/meat products (30.1%), fish/fish products (14.3%) and eggs/egg dishes (9.1%) were the main contributors to vitamin D intake. Supplements contributed 6.8 and 12% to MDI in men and women, respectively. In all, 74% of adults had an MDI of vitamin D that was less than the median (5 microg) of the recommended daily range of 0-10 microg. CONCLUSION: The findings of this study suggest that a large number of Irish adults have low vitamin D intakes. This, along with emerging evidence of low vitamin D status in at least some population subgroups, suggests that strategies to increase vitamin D intakes, including fortification of food, should be investigated.

The response of spinal cord blood flow to high-dose barbiturates.

The response of spinal cord blood flow (SCBF) to high-dose barbiturate therapy is documented. In nine mongrel dogs with an arterial pCO2 (PaCO2) of 40 mm Hg, sodium thiopental was administered to produce 30, 60, 120, and 240 seconds of electroencephalographic (EEG) burst suppression. At 30-second intervals of EEG suppression, cervical and thoracic cord segments demonstrated a decrease in SCBF of 47% and 39%, respectively, from control values. Isoelectric EEG intervals longer than 30 seconds were not associated with any further significant decrease in SCBF. In 13 other dogs and in the absence of barbiturates, hypocapnia to 20 mm Hg from PaCO2 of 60 mm Hg produced reductions in SCBF of 89% for the cervical and 82% for the thoracic segments. In the presence of thiopental-induced 30- to 60-second intervals of EEG silence, the decrement in SCBF in response to the same degree of hypocapnia was 83% and 75%, respectively, although the absolute value of this reduction was half that without barbiturates. These findings of a significant reduction in SCBF in response to high-dose barbiturate therapy are suggestive of a protective effect of barbiturates upon spinal cord injury as occurs in the brain. Further studies of the influence of barbiturates upon spinal cord compressive syndromes are indicated.

Bedside analysis of arterial blood gases and electrolytes during and after cardiac surgery.

Intraoperative changes in arterial blood gas tensions and serum electrolyte concentrations may contribute to the development of arrhythmias and cardiovascular insufficiency. Rapid intraoperative assessment of these parameters may improve patient care by permitting earlier treatment of abnormalities. We evaluated a portable blood gas and electrolyte analyzer in six patients undergoing coronary artery bypass surgery. Evaluation by anesthesia personnel took place in the operating room. The analyzer produced rapid, accurate, and reliable data that were comparable to clinical laboratory data. Correlation coefficients between the analyzer and laboratory determinations for PaO2, PaCO2, pH, K+, Ca++, and hematocrit were all greater than 0.92. Large changes in circulating ionized calcium (18%) and potassium (38%) concentrations were noted during cardiac surgery. Bedside blood gas and electrolyte analyzers represent a new technology worthy of further evaluation.

Vitamin D status and measures of cognitive function in healthy older European adults.

BACKGROUND/OBJECTIVES: Data from human studies that have investigated the association between vitamin D status and cognitive function in elderly adults are conflicting. The objective of this study was to assess vitamin D status (reflected by serum 25-hydroxyvitamin D (25(OH)D)) in older European subjects (n=387; aged 55-87 years) and examine its association with measures of cognitive function. SUBJECTS/METHODS: Serum 25(OH)D was assessed using enzyme-linked immunosorbent assay, whereas measures of cognitive function were assessed using a comprehensive Cambridge Neuropsychological Testing Automated Battery (CANTAB). RESULTS: In all, 12, 36 and 64% of subjects had serum 25(OH)D concentrations <30, <50 and <80 nmol/l, respectively, throughout the year. Serum 25(OH)D was significantly and inversely correlated with four assessments within the spatial working memory (SWM) test parameter (SWM between errors (r=-0.166; P=0.003); SWM between errors 8 boxes (r=-0.134; P=0.038); SWM strategy (r=-0.246; P<0.0001); and SWM total errors (r=-0.174; P<0.003)). When subjects were stratified on the basis of tertiles (T) of serum 25(OH)D (<47.6 (T(1)); 47.6-85.8 (T(2)); and >85.8 (T(3)) nmol/l), fewer errors in SWM test scores occurred in subjects in the third T when compared with the first T (P<0.05-0.084). Stratification by sex showed that these differences between tertiles strengthened (P<0.001-0.043) in the females, but the differences were not significant (P>0.6) in males. CONCLUSIONS: Vitamin D insufficiency, but not deficiency, is widespread in the older population of several European countries. Low vitamin D status was associated with a reduced capacity for SWM, particularly in women.

Central core disease: clinical and pathological evidence of progression within a family.

A family is described whose members showed different clinical presentations of central core disease. In 4 members the myopathy was congenital and nonprogressive, but in 2, muscle weakness first developed in adult life. Two further members had raised CPK levels without muscle weakness. Muscle weakness in one of the late-onset cases increased over eighteen months. This was associated with evidence of loss of type 2 fibres and the appearance of type 3 fibres on muscle biopsy. It is suggested that central core disease involves reinnervation of type 2 fibres by type 1 axons, and that the clinical manifestation of the disease depends on the age of onset and rate of progression of this process.

Influence of superficial temporal artery to middle cerebral artery bypass on cerebral blood flow in dogs with middle cerebral artery occlusion.

Eight dogs had a superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis, followed immediately by ligation of the ipsilateral middle cerebral artery. Subsequently, utilizing the radioactive microsphere technique, regional cerebral blood flow determinations were made both before and after ligation of the superficial temporal artery. A significant reduction in blood flow of 20-35% was noted in both cerebral hemispheres, caudate and thalamic nuclei, brain stem and cerebellum following occlusion of the bypass. It is our impression that this generalized reduction in flow is due to a redistribution of blood from normal areas previously supplied by the bypass. This implies that the newly created extracranial to intracranial arterial anastomosis reduces the shunting of blood from zones of higher to zones of lower flow through the circle of Willis and leptomeningeal collaterals. It also suggests a mechanism for the development in neurological function referable to areas of the brain remote from the bypass which is detected in some patients after STA-MCA anastomosis.