Evaluating the Trabecular Micro-Bypass Stent Combined with Phacoemulsification Compared to Phacoemulsification Alone.

Aim: The aim of this study was to assess the effect of iStent (trabecular micro-bypass stent) implantation in combination with phacoemulsification on IOP and glaucoma medications and to compare this to the outcome of phacoemulsification alone. Patients and Methods: A retrospective consecutive comparative review was undertaken. 131 eyes with ocular hypertension and medically controlled glaucoma underwent phacoemulsification alone (n = 78 group I) or combined with gonioscopic-guided implantation of one iStent (n = 31, group II) or two iStents (n = 22, group III). Patients were assessed at postoperative weeks 1, 3 and 6, and months 3 and 6. Pre- and post-operative measures included visual acuity, IOP and glaucoma medications. Results: Post-operatively at 6 months, mean IOP decreased from 16.3 mmHg to 14.2 mmHg in group I (p < 0.01), from 16.7 mmHg to 15.1 mmHg in group II (p < 0.16) and from 17.0 to 13.8 in group III (p = 0.05). Mean glaucoma medication decreased from 1.9 to 1.6 in group I (8 %, p = 0.12), from 2.5 to 0.8 in group II (27 %, p = 0.04), and from 2.1 to 1.0 in group III (45 %, p < 0.01). Conclusions: iStent implantation resulted in similar IOP reduction to phacoemulsification alone but achieved a significantly greater reduction in glaucoma medications. This may improve compliance and quality of life, and reduce health care costs in patients with early to moderate glaucoma.

Validity of the FACIT-Sp to assess spiritual well-being in elderly patients

Among instruments measuring spiritual well-being, the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp-12) is the most widely used instrument in research. It has been validated in patients suffering from cancer or HIV/AIDS, but has rarely been used in elderly patients. The objectives of this study were to determine the psychometric properties and suitability of the FACIT-Spto assess spiritual well-being in hospitalized elderly patients. This cross-sectional study uses a mixed method approach. Subjects were patients (N = 208), aged 65 years and older, consecutively admitted in post-acute rehabilitation. Psychometric properties of the FACITSp were investigated. The internal structure of the FACIT-Sp (factor structure and internal consistency) was assessed. Convergent validity of the FACIT-Sp was assessed using the Spiritual Distress Assessment Tool (SDAT), the question "Are you at peace?" and the Geriatric Depression Scale (GDS). Predictive validity was assessed using length of stay (LOS) and discharge destination. Understanding and interpretation of FACIT-Sp items were consecutively assessed in a sub-sample of 135 patients. Results show that FACIT-Sp scores ranged from 7 to 46 (mean 29.6 ± 7.8); 23.1% of the patients had high spiritual well-being. Cronbach's α was g ood ( 0.85). Item-to-total correlations were all significant (0.34 to 0.73). Principal component analyses performed with 2 or 3 factors were only moderately consistent with previous work. FACIT-Sp correlated with SDAT, "Are you at peace?" and GDS (Rho = ͨ2;0.45, P < 0.001; 0.51, P < 0.001 and ͨ2;0.38, P < 0.001). No association was found with LOS or discharge destination. Spontaneous comments about one or more FACIT-Sp items were made by 97/135 (71.9%). Specifically, items that address purpose and meaning in life were frequently found difficult to answer. Analyses suggest that the FACIT-Sp may underestimate spiritual well-being in older patients. In conclusion, despite having acceptable psychometric properties, the FACIT-Sp presents limitations for measurement of spiritual well-being in hospitalized elderly patients.

Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [<1.0 mmol/L] for at least 2 h) were identified among 26 patients. During GD, we found a significant increase of CMD lactate (from 4±2.3 to 5.4±2.9 mmol/L), pyruvate (126.9±65.1 to 172.3±74.1 μmol/L), and lactate/pyruvate ratio (LPR; 27±6 to 35±9; all, p<0.005), while brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r=0.56; p<0.0001), while an inverse correlation (r=-0.11; p=0.04) was observed at elevated LPR >25. The correlation between blood and brain glucose also decreased from r=0.62 to r=0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

How to describe species richness patterns for bryophyte conservation?

A large amount of data for inconspicuous taxa is stored in natural history collections; however, this information is often neglected for biodiversity patterns studies. Here, we evaluate the performance of direct interpolation of museum collections data, equivalent to the traditional approach used in bryophyte conservation planning, and stacked species distribution models (S-SDMs) to produce reliable reconstructions of species richness patterns, given that differences between these methods have been insufficiently evaluated for inconspicuous taxa. Our objective was to contrast if species distribution models produce better inferences of diversity richness than simply selecting areas with the higher species numbers. As model species, we selected Iberian species of the genus Grimmia (Bryophyta), and we used four well-collected areas to compare and validate the following models: 1) four Maxent richness models, each generated without the data from one of the four areas, and a reference model created using all of the data and 2) four richness models obtained through direct spatial interpolation, each generated without the data from one area, and a reference model created with all of the data. The correlations between the partial and reference Maxent models were higher in all cases (0.45 to 0.99), whereas the correlations between the spatial interpolation models were negative and weak (-0.3 to -0.06). Our results demonstrate for the first time that S-SDMs offer a useful tool for identifying detailed richness patterns for inconspicuous taxa such as bryophytes and improving incomplete distributions by assessing the potential richness of under-surveyed areas, filling major gaps in the available data. In addition, the proposed strategy would enhance the value of the vast number of specimens housed in biological collections.

Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers.

Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1 genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once daily (arm B), separated by ?3 days, in a crossover design. After 1 week on each regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations were measured by liquid chromatography-tandem mass spectrometry in multiple samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by noncompartmental methods. UGT1A1 promoter variants were detected with a commercially available kit and published primers. The primary outcome was the ratio of plasma raltegravir C(tau), or concentration at the end of the dosing interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean ratios (95% confidence interval, P value) for plasma raltegravir C(tau), area under the concentration-time curve from 0 to 12 h (AUC(0-12)), and raltegravir-glucuronide/raltegravir AUC(0-12) were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to 2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele, but these were not associated with metabolite formation. Although atazanavir significantly reduced the formation of the glucuronide metabolite, its steady-state boosting of plasma raltegravir did not render the C(tau) with a once-daily raltegravir dose of 400 mg similar to the C(tau) with the standard twice-daily dose. UGT1A1 promoter variants did not significantly influence this interaction.

Creation of an Age-Adjusted, Dual-Energy X-ray Absorptiometry-Derived Trabecular Bone Score Curve for the Lumbar Spine in Non-Hispanic US White Women.

The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone microarchitecture texture extracted from anteroposterior dual-energy X-ray absorptiometry images of the spine. Previous studies have documented the ability of TBS of the spine to differentiate between women with and without fractures among age- and areal bone mineral density (aBMD)-matched controls, as well as to predict future fractures. In this cross-sectional analysis of data collected from 3 geographically dispersed facilities in the United States, we investigated age-related changes in the microarchitecture of lumbar vertebrae as assessed by TBS in a cohort of non-Hispanic US white American women. All subjects were 30 yr of age and older and had an L1-L4aBMDZ-score within ±2 SD of the population mean. Individuals were excluded if they had fractures, were on any osteoporosis treatment, or had any illness that would be expected to impact bone metabolism. All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE-Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1-L4 but also for all other possible vertebral combinations. To validate the cohort, a comparison between the aBMD normative data of our cohort and US non-Hispanic white Lunar data provided by the manufacturer was performed. A database of 619 non-Hispanic US white women, ages 30-90 yr, was created. aBMD normative data obtained from this cohort were not statistically different from the non-Hispanic US white Lunar normative data provided by the manufacturer (p = 0.30). This outcome thereby indirectly validates our cohort. TBS values at L1-L4 were weakly inversely correlated with body mass index (r = -0.17) and weight (r = -0.16) and not correlated with height. TBS values for all lumbar vertebral combinations decreased significantly with age. There was a linear decrease of 16.0% (-2.47 T-score) in TBS at L1-L4 between 45 and 90 yr of age (vs. -2.34 for aBMD). Microarchitectural loss rate increased after age 65 by 50% (-0.004 to -0.006). Similar results were obtained for other combinations of lumbar vertebra. TBS, an index of bone microarchitectural texture, decreases with advancing age in non-Hispanic US white women. Little change in TBS is observed between ages 30 and 45. Thereafter, a progressive decrease is observed with advancing age. The changes we observed in these American women are similar to that previously reported for a French population of white women (r(2) > 0.99). This reference database will facilitate the use of TBS to assess bone microarchitectural deterioration in clinical practice.

Switch to Sirolimus-based immunosuppresion in stable renal transplant recipients

Purpose: Sirolimus (SRL) has been used to replace calcineurin inhibitors (CNI) for various indications including CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of switching from CNI to SRL in stable renal transplant recipients (RTR) with low grade proteinuria (<1 g/24 h). Methods and materials: Between 2001 and 2007, 41 patients (20 females, 21 males; mean age 47 ± 13) were switched after a median time post-transplantation of 73.5 months (range 0.2-273.2 months). Indications for switch were CNI nephrotoxicity (39%), thrombotic micro-angiopathy (14.6%), post-transplantation cancer (24.4%), CNI neurotoxicity (7.4%), or others (14.6%). Mean follow-up after SRL switch was 23.8±16.3 months. Mean SRL dosage and through levels were 2.4 ± 1.1 mg/day and 8 ± 2.2 ug/l respectively. Immunosuppressive regiments were SRL + mycophenolate mofetil (MMF) (31.7%), SRL + MMF + prednisone (36.58%), SRL + prednisone (19.51%), SRL + Azathioprine (9.75%), or SRL alone (2.43%). Results: Mean creatinine decreased from 164 to 143 μmol/l (p <0.03), mean estimated glomerular filtration rate (eGFR) increased significantly from 50.13 to 55.01 ml/minute (p <0.00001), mean systolic and diastolic blood pressure decreased from 138 to 132 mm Hg (p <0.03) and from 83 to78 mm Hg (p <0.01), but mean proteinuria increased from 0.21 to 0.63 g/24 h (p <0.001). While mean total cholesterolemia didn't increased significantly from 5.09 to 5.56 mmol/l (p = 0.06). The main complications after SRL switch were dermatitis (19.5%), urinary tract infections (24.4%), ankle edema (13.3%), and transient oral ulcers (20%). Acute rejection after the switch occurred in 7.3% of patients (n = 3), and 2 acute rejections were successfully treated with corticosteroids and 1 did not respond to treatment (not related to switch). SRL had to be discontinued in 17% of patients (2 nephrotic syndromes, 2 severe edema, 1 acute rejection, 1 thrombotic micro-angiopathy, and 1 fever). Conclusion: In conclusion, we found that switching from CNI to SRL in stable RTR was safe and associated with a significant improvement of renal function and blood pressure. Known side-effects of SRL led to drug discontinuation in less than 20% of patients and the acute rejection rate was 7.3%. This experience underlines the importance of patient selection before switching to SRL, in particular regarding preswitch proteinuria.

Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011.

BACKGROUND AND PURPOSE: Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. METHODS: A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990-April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I(2), and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. RESULTS: 60 studies with 9845 patients harbouring 10 845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I(2)=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I(2)=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. CONCLUSIONS: In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours.

BACKGROUND: EMD 521873 (Selectikine), an immunocytokine comprising a DNA-targeting antibody, aimed at tumour necrosis, fused with a genetically modified interleukin-2 (IL-2) moiety, was investigated in this first-in-human phase I study. METHODS: Patients had metastatic or locally advanced solid tumours failing previous standard therapy. Selectikine was administered as a 1-hour intravenous infusion on 3 consecutive days, every 3weeks. A subgroup of patients also received 300mg/m(2) cyclophosphamide on day 1 of each cycle. Escalating doses of Selectikine were investigated with the primary objective of determining the maximum tolerated dose (MTD). RESULTS: Thirty-nine patients were treated with Selectikine alone at dose levels from 0.075 to 0.9mg/kg, and nine were treated at doses of 0.45 and 0.6mg/kg in combination with cyclophosphamide. A dose-dependent linear increase of peak serum concentrations and area under curve was found. The dose-limiting toxicity was grade 3 skin rash at the 0.9mg/kg dose-level; the MTD was 0.6mg/kg. Rash and flu-like symptoms were the most frequent side-effects. No severe cardiovascular side-effects (hypotension or vascular leak) were observed. At all dose-levels, transient increases in total lymphocyte, eosinophil and monocyte counts were recorded. No objective tumour responses, but long periods of disease stabilisation were observed. Transient and non-neutralising Selectikine antibodies were detected in 69% of patients. CONCLUSIONS: The MTD of Selectikine with or without cyclophosphamide administered under this schedule was 0.6mg/kg. The recommended phase II dose was 0.45-0.6mg/kg. Selectikine had a favourable safety profile and induced biological effects typical for IL-2.

Relationship between cigarette smoking and abdominal obesity

Background: Although smokers tend to have a lower body-mass index (BMI) than non-smokers, smoking may affect body fat (BF) distribution. Some studies have assessed the association between smoking, BMI and waist circumference (WC), but, to our knowledge, no population-based studies assessed the relation between smoking and BF composition. We assessed the association between amount of cigarette smoking, BMI, WC and BF composition. Method: Data was analysed from a cross-sectional population-based study including 6'187 Caucasians aged 32-76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance. Abdominal obesity was defined as a WC 0102 cm for men and 088 cm for women and normal WC as <94 cm for men and <80 cm for women. In men, excess BF was defined as %BF 028.1, 28.7, 30.6 and 32.6 for age groups 32-44, 45-54, 55-64 and 65-76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and 44.4. Cigarette smoking was assessed using a self-reported questionnaire. Results: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9% and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in women, respectively. Smokers had lower age-adjusted mean WC and percent of BF compared to non-smokers. However, among smokers, mean age-adjusted WC and BF increased with the number of cigarettes smoked per day: among light (1-10 cig/day), moderate (11-20) and heavy smokers (>20), mean ± SE %BF was 22.4 ± 0.3, 23.1 ± 0.3 and 23.5 ± 0.4 for men, and 31.9 ± 0.3, 32.6 ± 0.3 and 32.9 ± 0.4 for women, respectively. Mean WC was 92.9 ± 0.6, 94.0 ± 0.5 and 96.0 ± 0.6 cm for men, and 80.2 ± 0.5, 81.3 ± 0.5 and 83.3 ± 0.7 for women, respectively. Compared with light smokers, the age-adjusted odds ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to 1.85) for moderate smokers and 1.06 (0.57 to 1.99) for heavy smokers in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72), respectively, in women (p-trend = 0.04). Odds ratio for abdominal obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend <0.01), and 1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03). Conclusion: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women, whereas only WC was dose dependently and significantly associated with the amount of cigarettes smoked per day in men. This suggests that heavy smokers, especially women, are more likely to have an excess of BF and to accumulate BF in the abdomen compared to lighter smokers.

Purification and activity standardisation of a (166m)Ho solution.

As part of a project to use the long-lived (T(1/2)=1200a) (166m)Ho as reference source in its reference ionisation chamber, IRA standardised a commercially acquired solution of this nuclide using the 4pibeta-gamma coincidence and 4pigamma (NaI) methods. The (166m)Ho solution supplied by Isotope Product Laboratories was measured to have about 5% Europium impurities (3% (154)Eu, 0.94% (152)Eu and 0.9% (155)Eu). Holmium had therefore to be separated from europium, and this was carried out by means of ion-exchange chromatography. The holmium fractions were collected without europium contamination: 162h long HPGe gamma measurements indicated no europium impurity (detection limits of 0.01% for (152)Eu and (154)Eu, and 0.03% for (155)Eu). The primary measurement of the purified (166m)Ho solution with the 4pi (PC) beta-gamma coincidence technique was carried out at three gamma energy settings: a window around the 184.4keV peak and gamma thresholds at 121.8 and 637.3keV. The results show very good self-consistency, and the activity concentration of the solution was evaluated to be 45.640+/-0.098kBq/g (0.21% with k=1). The activity concentration of this solution was also measured by integral counting with a well-type 5''x5'' NaI(Tl) detector and efficiencies computed by Monte Carlo simulations using the GEANT code. These measurements were mutually consistent, while the resulting weighted average of the 4pi NaI(Tl) method was found to agree within 0.15% with the result of the 4pibeta-gamma coincidence technique. An ampoule of this solution and the measured value of the concentration were submitted to the BIPM as a contribution to the Système International de Référence.

A general model to predict individual exposure to solar UV by using ambient irradiance data

Excessive exposure to solar ultraviolet (UV) is the main cause of skin cancer. Specific prevention should be further developed to target overexposed or highly vulnerable populations. A better characterisation of anatomical UV exposure patterns is however needed for specific prevention. To develop a regression model for predicting the UV exposure ratio (ER, ratio between the anatomical dose and the corresponding ground level dose) for each body site without requiring individual measurements. A 3D numeric model (SimUVEx) was used to compute ER for various body sites and postures. A multiple fractional polynomial regression analysis was performed to identify predictors of ER. The regression model used simulation data and its performance was tested on an independent data set. Two input variables were sufficient to explain ER: the cosine of the maximal daily solar zenith angle and the fraction of the sky visible from the body site. The regression model was in good agreement with the simulated data ER (R(2)=0.988). Relative errors up to +20% and -10% were found in daily doses predictions, whereas an average relative error of only 2.4% (-0.03% to 5.4%) was found in yearly dose predictions. The regression model predicts accurately ER and UV doses on the basis of readily available data such as global UV erythemal irradiance measured at ground surface stations or inferred from satellite information. It renders the development of exposure data on a wide temporal and geographical scale possible and opens broad perspectives for epidemiological studies and skin cancer prevention.

Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche.

Both late menarcheal age and low calcium intake (Ca intake) during growth are risk factors for osteoporosis, probably by impairing peak bone mass. We investigated whether lasting gain in areal bone mineral density (aBMD) in response to increased Ca intake varies according to menarcheal age and, conversely, whether Ca intake could influence menarcheal age. In an initial study, 144 prepubertal girls were randomized in a double-blind controlled trial to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9-8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41 to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the mean aBMD gain from baseline remained significantly greater in girls below, but not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P = 0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl., 276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the timing of menarche, which, in turn, could influence long-term bone mass gain in response to Ca supplementation. Thus, both determinants of early menarcheal age and high Ca intake may positively interact on bone mineral mass accrual.

Alteration of brain glycogen turnover in the conscious rat after 5h of prolonged wakefulness.

Although glycogen (Glyc) is the main carbohydrate storage component, the role of Glyc in the brain during prolonged wakefulness is not clear. The aim of this study was to determine brain Glyc concentration ([]) and turnover time (tau) in euglycemic conscious and undisturbed rats, compared to rats maintained awake for 5h. To measure the metabolism of [1-(13)C]-labeled Glc into Glyc, 23 rats received a [1-(13)C]-labeled Glc solution as drink (10% weight per volume in tap water) ad libitum as their sole source of exogenous carbon for a "labeling period" of either 5h (n=13), 24h (n=5) or 48 h (n=5). Six of the rats labeled for 5h were continuously maintained awake by acoustic, tactile and olfactory stimuli during the labeling period, which resulted in slightly elevated corticosterone levels. Brain [Glyc] measured biochemically after focused microwave fixation in the rats maintained awake (3.9+/-0.2 micromol/g, n=6) was not significantly different from that of the control group (4.0+/-0.1 micromol/g, n=7; t-test, P>0.5). To account for potential variations in plasma Glc isotopic enrichment (IE), Glyc IE was normalized by N-acetyl-aspartate (NAA) IE. A simple mathematical model was developed to derive brain Glyc turnover time as 5.3h with a fit error of 3.2h and NAA turnover time as 15.6h with a fit error of 6.5h, in the control rats. A faster tau(Glyc) (2.9h with a fit error of 1.2h) was estimated in the rats maintained awake for 5h. In conclusion, 5h of prolonged wakefulness mainly activates glycogen metabolism, but has minimal effect on brain [Glyc].

Infusion of atrial natriuretic peptide to patients with congestive heart failure.

Atrial natriuretic peptides (ANP) exert vasodilating and natriuretic actions. The present study was undertaken to test the effect of low dose infusions of synthetic ANP on hemodynamic and humoral variables of patients with severe heart failure. Eight patients, aged 26 to 71 years, with severe congestive heart failure due to ischemic heart disease or idiopathic dilated cardiomyopathy were included in the study. Synthetic human (3-28) ANP was infused at doses ranging from 0.5 to 2 micrograms/min for up to 3 h. Pulmonary capillary wedge pressure fell from 24 +/- 1 to 16 +/- 2 mm Hg (mean +/- SEM) (p less than 0.01) and cardiac index tended to rise from 2 +/- 0.2 to 2.3 +/- 0.2 L/min/m2 (NS), while blood pressure and heart rate did not change. One patient experienced a marked drop in pulmonary capillary wedge and arterial blood pressure that necessitated the administration of saline. ANP infusion did not alter plasma renin activity or plasma aldosterone, norepinephrine, or vasopressin levels. It decreased plasma epinephrine levels from 0.472 +/- 0.077 to 0.267 +/- 0.024 nmol/L (p less than 0.05). Plasma ANP levels were markedly elevated in all patients before initiating the infusion. They had no predictive value for the hemodynamic response to exogenous ANP. No correlation was observed between the hemodynamic effects of ANP and those induced by the subsequently administered converting enzyme inhibitor captopril, which seemed to improve cardiac function more consistently.(ABSTRACT TRUNCATED AT 250 WORDS)