Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Optimization of soft X-ray phase-contrast tomography using a laser wakefield accelerator.

X-ray phase-contrast imaging allows for non-invasive analysis in low-absorbing materials, such as soft tissue. Its application in medical or materials science has yet to be realized on a wider scale due to the requirements on the X-ray source, demanding high flux and small source size. Laser wakefield accelerators generate betatron X-rays fulfilling these criteria and can be suitable sources for phase-contrast imaging. In this work, we present the first phase-contrast images obtained by using ionization injection-based laser wakefield acceleration, which results in a higher photon yield and smoother X-ray beam profile compared to self-injection. A peak photon yield of 1.9 × 1011 ph/sr and a source size of 3 µm were estimated. Furthermore, the current laser parameters produce an X-ray spectrum mainly in the soft X-ray range, in which laser-plasma based phase-contrast imaging had yet to be studied. The phase-contrast images of a Chrysopa lacewing resolve features on the order of 4 µm. These images are further used for a tomographic reconstruction and a volume rendering, showing details on the order of tens of µm.

Incidence of neuromyelitis optica spectrum disorder in the Central Denmark Region.

OBJECTIVES: Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure AQP4-IgG in patients who fulfilled the clinical and radiological criteria of NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD in the region, according to both the 2006 Wingerchuk criteria and the 2015 International Panel for NMO Diagnosis criteria. MATERIALS AND METHODS: Medical records of all patients diagnosed with a demyelinating disorder in the region from 1 January 2012 to 31 December 2013 were reviewed. Patients were classified as having (i) "NMO" if the 2006 criteria were met, (ii) "NMOSD with AQP4-IgG" or (iii) "NMOSD without/unknown AQP-IgG" if the new 2015 NMOSD criteria were met. Patients with core symptoms were invited to provide a blood sample for AQP4-IgG analysis with an enzyme-linked immunosorbent assay and a cell-based indirect immunofluorescence assay. RESULTS: In 191 patients with core symptoms, one met the 2015 NMOSD with AQP4-IgG criteria. Two patients met the 2006 NMO and 2015 NMOSD without/unknown AQP4-IgG criteria. Among 108 patients providing a blood sample, all were seronegative. The estimated incidence of NMO (2006 criteria) and NMOSD (2015 criteria) was 0.08 and 0.12 per 100 000 person-years, respectively. CONCLUSION: NMO/NMOSD is a rare disease in the Central Denmark Region, with a considerably lower incidence rate than previously estimated in a neighbouring region.

Differences in hospital attendance for anaphylaxis between immigrants and non-immigrants: a cohort study.

BACKGROUND: The impact of migration on the risk of anaphylaxis remains unknown. We hypothesized that non-Western immigrants have a lower incidence of anaphylaxis compared to Danish-born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish-born including time- and age- trends. METHODS: A register-based, historical prospective cohort design. Refugees or family reunified immigrants (n = 127 250) who, between January 1, 1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1 : 6 ratio on age and sex with Danish-born individuals (n = 740 600). Personal identification numbers were cross-linked to the Danish National Patient Registry identifying all first-time hospital attendances for anaphylaxis from January 1, 1994 and December 31, 2010. Incidence rate ratios were estimated, stratified for sex and region of birth, adjusting for age using a Cox regression model including the influence of duration of residence and age when residence was obtained. RESULTS: In total 1053 hospital attendances for anaphylaxis were identified: 89 among non-Western immigrants, 9 among Western immigrants and 955 among Danish-born patients. Both male (RR = 0.65; 95%CI: 0.46;0.90) and female (RR = 0.64; 95%CI: 0.48;0.85) non-Western immigrants had a significantly lower risk ratio of hospital attendance for anaphylaxis compared to Danish-born. Compared to Danish-born, non-Western immigrants living in Denmark during the entire follow-up period also showed a decreased risk (RR = 0.65; 95%CI: 0.34;1.25). Compared to Danish-born, non-Western immigrants who obtained residence permission as children had a decreased risk of hospital attendance for anaphylaxis (RR = 0.48; 95%CI: 0.25;0.91). CONCLUSION: This Danish register-based study using nationwide data revealed fewer hospital attendances for anaphylaxis among non-Western immigrants compared to Danish-born; however this protection was lost over time.

Development of knowledge tests for multi-disciplinary emergency training: a review and an example.

BACKGROUND: The literature is sparse on written test development in a post-graduate multi-disciplinary setting. Developing and evaluating knowledge tests for use in multi-disciplinary post-graduate training is challenging. The objective of this study was to describe the process of developing and evaluating a multiple-choice question (MCQ) test for use in a multi-disciplinary training program in obstetric-anesthesia emergencies. METHODS: A multi-disciplinary working committee with 12 members representing six professional healthcare groups and another 28 participants were involved. Recurrent revisions of the MCQ items were undertaken followed by a statistical analysis. The MCQ items were developed stepwise, including decisions on aims and content, followed by testing for face and content validity, construct validity, item-total correlation, and reliability. RESULTS: To obtain acceptable content validity, 40 out of originally 50 items were included in the final MCQ test. The MCQ test was able to distinguish between levels of competence, and good construct validity was indicated by a significant difference in the mean score between consultants and first-year trainees, as well as between first-year trainees and medical and midwifery students. Evaluation of the item-total correlation analysis in the 40 items set revealed that 11 items needed re-evaluation, four of which addressed content issues in local clinical guidelines. A Cronbach's alpha of 0.83 for reliability was found, which is acceptable. CONCLUSION: Content and construct validity and reliability were acceptable. The presented template for the development of this MCQ test could be useful to others when developing knowledge tests and may enhance the overall quality of test development.

Concomitant medication among persistent opioid users with chronic non-malignant pain.

BACKGROUND: Recent guidelines for opioid treatment of chronic non-malignant pain discourage co-medication with benzodiazepines and benzodiazepine-related hypnotics, whereas co-medication with non-opioid analgesics and co-analgesics may offer a beneficial opioid sparing effect, and is recommended. The aim of this study was to describe 1-year periodic prevalence of co-medication with benzodiazepines, benzodiazepine-related hypnotics, non-opioid analgesics, co-analgesics and antidepressants in persistent opioid users with chronic non-malignant pain. METHODS: The study is based on data from the Norwegian Prescription Database, covering all drugs dispensed to outpatients in 2008. Concomitant medication levels were compared between users in two definitions of persistent opioid use, all Norwegian adults dispensed opioids in 2008 and the Norwegian background population. RESULTS: Of the Norwegian adult population studied, 1.2% met the criteria of persistent opioid use based on prescription pattern and prescription level. Sixty percent of persistent opioid users were dispensed a benzodiazepine or benzodiazepine-related hypnotic in amounts indicating regular use, with 15% dispensed a high amount of both classes. Sixty-two percent of persistent opioid users were dispensed one or more non-opioid analgesics, 47% an antidepressant and 33% were dispensed an antiepileptic drug. CONCLUSION: Approximately 60% of persistent opioid users also receive benzodiazepines or benzodiazepine-related hypnotics in amounts indicating regular use. This is in conflict with recent guidelines for the treatment of chronic non-malignant pain and may indicate that these users are at an increased risk of developing problematic opioid use.

Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses.

AIM: Defined daily dose (DDD) is the most common measurement unit used in drug consumption studies. The DDD for opioids may not reflect their relative clinical potencies. The aim of this study was to explore whether opioid consumption data may be interpreted differently when adding oral morphine equivalent (OMEQ) dose as a measurement unit compared with using DDD. METHODS: The equianalgesic ratio of each opioid relative to morphine was tabulated. Data on opioid consumption expressed in DDD were converted to OMEQs using the equianalgesic ratios. The opioid consumption was compared in three different study settings: clinical data from an opioid switching study, trends within one country and a comparison between countries. RESULTS: Using DDD, the opioid consumption in Norway between 2004-2008 increased of 6.7%, while the increase was 23.6% using OMEQ. While DDD/1000 inhabitants/day showed that Sweden had the highest consumption of opioids among the Nordic countries, OMEQ/1000 inhabitants/day showed that Denmark had the highest consumption. In the switching study DDD indicated a reduction in analgesic dosing and OMEQ an increase when switching from WHO step II to III. CONCLUSION: OMEQ reflects clinical dosing better than DDD, and can give additional insight into opioid consumption when combined with DDD. Using OMEQ can also lead to different conclusions in opioid consumption studies compared with using DDD alone.

Enhanced laser-driven proton acceleration using nanowire targets.

Laser-driven proton acceleration is a growing field of interest in the high-power laser community. One of the big challenges related to the most routinely used laser-driven ion acceleration mechanism, Target-Normal Sheath Acceleration (TNSA), is to enhance the laser-to-proton energy transfer such as to maximize the proton kinetic energy and number. A way to achieve this is using nanostructured target surfaces in the laser-matter interaction. In this paper, we show that nanowire structures can increase the maximum proton energy by a factor of two, triple the proton temperature and boost the proton numbers, in a campaign performed on the ultra-high contrast 10 TW laser at the Lund Laser Center (LLC). The optimal nanowire length, generating maximum proton energies around 6 MeV, is around 1-2 [Formula: see text]m. This nanowire length is sufficient to form well-defined highly-absorptive NW forests and short enough to minimize the energy loss of hot electrons going through the target bulk. Results are further supported by Particle-In-Cell simulations. Systematically analyzing nanowire length, diameter and gap size, we examine the underlying physical mechanisms that are provoking the enhancement of the longitudinal accelerating electric field. The parameter scan analysis shows that optimizing the spatial gap between the nanowires leads to larger enhancement than by the nanowire diameter and length, through increased electron heating.

Somatosensory function is impaired in patients with idiopathic REM sleep behaviour disorder.

BACKGROUND: Idiopathic REM sleep behaviour disorder (iRBD) has been recognised as a significant biomarker for developing a neurodegenerative alpha-synucleinopathy, which is why iRBD is considered to be a prodromal state for alpha-synucleinopathies including Parkinson's disease (PD). Many patients with PD suffer from complaints of pain and present impaired somatosensory function. We hypothesized that pain perception and somatosensory function could be altered already in a preclinical stage of PD including iRBD. Hence, the objective of this study was to investigate pain perception and somatosensory function in patients with iRBD. METHODS: Quantitative sensory testing (QST), laser evoked potentials (LEPs), and conditioned pain modulation (CPM) testing were performed in 13 iRBD patients without any clinical signs of PD or narcolepsy (11 males, 2 females, mean age 65.2 years) and 15 gender- and age-matched healthy control subjects (12 males, 3 females, mean age 65.8 years). RESULTS: Thermal detection thresholds were higher in the iRBD group compared with the control group (cold detection threshold (CDT) p = 0.020, thermal sensory limen (TSL) p = 0.001), indicating an impaired temperature sensation in iRBD patients. The N2/P2 LEPs amplitude was smaller in iRBD patients than controls, but not statistically significant (p = 0.053). CONCLUSIONS: This study found an impaired somatosensory function in iRBD patients, suggesting that somatosensory impairment might be an early feature in the neurodegenerative process of PD.

Population-derived comparisons of ambulatory and office blood pressures. Implications for the determination of usual blood pressure and the concept of white coat hypertension.

BACKGROUND: Ambulatory blood pressures (BPs) have generally been reported to be lower than office blood pressures, but population-based data are lacking. METHODS: To better characterize ambulatory and office BP relationships, we explored the interrelationships of BPs measured in the office by mercury sphygmomanometry, 24-hour ambulatory BP measured with a portable device, and echocardiographic left ventricular mass in a random sample of 50 men aged 51 to 72 years drawn from a much larger pool. Office BP was based on the mean of 10 measurements performed over five visits. RESULTS: Among all participants, mean 24-hour ambulatory and mean office BPs were highly correlated: r (systolic/diastolic) = .90/.79; and both mean 24-hour and mean awake ambulatory BPs were significantly higher than mean office BPs. For the subsample not receiving antihypertensive therapy, mean ambulatory and office BPs were similar in terms of their associations with Penn left ventricular mass index (LVMI). No association between BP and left ventricular mass was observed among the subjects receiving antihypertensive medication. CONCLUSIONS: We conclude that a single session of 24-hour ambulatory BP monitoring is unlikely to improve the determination of usual BP in older white men beyond that achievable with BP carefully measured over five separate office visits; and that white coat hypertension is rare in this population.

Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study.

OBJECTIVES: To compare 5 antihypertensive drugs and placebo for changes in quality of life (QL). To assess the relationship of lifestyle factors and change in lifestyle factors to QL in participants with stage I diastolic hypertension. METHODS: The Treatment of Mild Hypertension Study (TOMHS) was a randomized, double-blind, placebo-controlled clinical trial with minimum participant follow-up of 4 years. It was conducted at 4 hypertension screening and treatment academic centers in the United States. The cohort consisted of 902 men and women with hypertension, aged 45 to 69 years, with diastolic blood pressures less than 100 mm Hg. Informed consent was obtained from each participant after the nature of the procedures had been fully explained. Sustained nutritional-hygienic intervention was administered to all participants to reduce weight, to reduce dietary sodium and alcohol intake, and to increase physical activity. Participants were randomized to take (1) acebutolol (n = 132); (2) amlodipine maleate (n = 131); (3) chlorthalidone (n = 126); (4) doxazosin mesylate (n = 134); (5) enalapril maleate (n = 135); or placebo (n = 234). Changes in 7 QL indexes were assessed based on a 35-item questionnaire: (1) general health; (2) energy or fatigue; (3) mental health; (4) general functioning; (5) satisfaction with physical abilities; (6) social functioning; and (7) social contacts. RESULTS: At baseline, higher QL was associated with older age, more physical activity, lower obesity level, male gender, non-African American race, and higher educational level. Improvements in QL were observed in all randomized groups, including the placebo group during follow-up; greater improvements were observed in the acebutolol and chlorthalidone groups and were evident throughout follow-up. The amount of weight loss, increase in physical activity, and level of attained blood pressure control during follow-up were related to greater improvements in QL. CONCLUSIONS: In patients with stage I hypertension, antihypertensive treatment with any of 5 agents used in TOMHS does not impair QL. The diuretic chlorthali-done and the cardioselective beta-blocker acebutolol appear to improve QL the most. Success with lifestyle changes affecting weight loss and increase in physical activity relate to greater improvements in QL and show that these interventions, in addition to contributing to blood pressure control, have positive effects on the general well-being of the individual.

Sodium chloride raises blood pressure in normotensive subjects. The study of sodium and blood pressure.

The effects of dietary sodium on blood pressure in normotensive adults is not well characterized. The Study of Sodium and Blood Pressure (SNaP) is a randomized, double-blind crossover trial using a placebo or 96 meq sodium in 4-week treatment periods separated by a 2-week washout period. Before capsule treatment periods, participants were instructed in a low sodium diet for 10 weeks to reduce urinary sodium excretion to less than 35 meq/8 hr. The low sodium diet was continued throughout the capsule treatment periods. Participants (n = 48; 47 white, 1 black) were 79% male and had an average age of 52 years, a body mass index of 27.6, and a baseline blood pressure of 131/84 mm Hg. Baseline overnight urinary sodium excretion was 51 meq/8 hr and 19 meq/8 hr after the low sodium diet run-in period, before the capsule treatment periods began. Resting, seated blood pressure was measured twice at each visit in a standard fashion. Differences between sodium and placebo treatment periods were as follows: systolic blood pressure, 123.9 versus 120.3 mm Hg, respectively (p less than 0.001); diastolic blood pressure, 78.7 versus 76.4 mm Hg, respectively (p = 0.005); and sodium excretion, 51.3 versus 30.9 meq/8 hr, respectively (p less than 0.001). Both systolic and diastolic blood pressures increased significant amounts in normotensive adults on a low sodium diet supplemented with 96 meq/day sodium. Long-term effects and dose-response relations need further study.

Racial and ethnic modifiers of the salt-blood pressure response.

The relation between sodium and blood pressure is a centuries-old question. A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension. Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect. Further, similar studies in biracial populations have also demonstrated a greater prevalence of "salt sensitivity" in blacks compared with whites. The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role. Salt sensitivity appears to be a widespread phenomenon. However, it is critically important to determine what factors account for racial differences in salt sensitivity. Moreover, the prevalence of salt sensitivity in the general population is unknown. Current definitions of salt sensitivity are varied and unidirectional. In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations. More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Higher education and income are related to a better Na:K ratio in blacks: baseline results of the Treatment of Mild Hypertension Study (TOMHS) data.

In the United States, blacks have higher rates of hypertension than whites. A possible contributing factor to this higher rate of hypertension could be dietary differences between blacks and whites relating to sodium and potassium intake, which in turn could be related to socioeconomic differences between blacks and whites. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess differences in the urinary excretion of sodium and potassium, and the Na:K ratio between black and white participants, and also to explore the relationship of socioeconomic status (SES) and urinary electrolyte excretion within each ethnic group. Participants were men and women ages 45 to 69 with stage I diastolic hypertension (DBP < or = 99 mm Hg). Level of education and annual household income were used as indicators of SES. Two overnight urine samples were collected and analyzed for Na and K at entry on 172 black and 710 white participants. Blacks had a significantly higher mean Na:K ratio than whites, 4.3 v 3.6 (P < .001). This was primarily due to higher urinary Na excretion in blacks than whites, 57.8 v 52.7 mmol/8 h (P = .05). Analysis by education and income level showed that higher levels of urinary Na and Na:K in blacks than whites was restricted to those with lower education and income levels. For higher education and income levels, blacks had slightly lower levels of urinary Na and Na:K than whites. Correspondingly, education and income levels were related to urinary Na and Na:K in blacks but not in whites. This suggests that lower SES blacks could benefit from interventions to reduce dietary Na and increase dietary K, which would decrease their urinary Na:K ratio and may make them less prone to developing hypertension.

Urinary sodium and potassium profile of blacks and whites in relation to education in two different geographic urban areas. TOMHS Research Group. Treatment of Mild Hypertension Study.

The high Na/low K environment of modern society is related to the genesis of hypertension and stroke. There is prior evidence of racial, geographical, and social class differences in Na and K intake and blood pressure. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess urinary Na and K excretion profiles by race, clinic geographic area, and education. Participants were adult black and white hypertensive patients from the Birmingham, Alabama, and Chicago, Illinois, area. Level of education was categorized as: less than college graduate and college graduate or more. Two overnight urine samples were collected and analyzed for Na and K at entry from 154 blacks and 281 whites. The urinary Na:K ratio was significantly higher in both blacks (5.1 v 3.8, P < .001) and whites (4.1 v 3.4, P < .005) in Birmingham compared with Chicago. This was primarily due to the lower excretion of urinary K in blacks (12.8 v 16.9 mmol/8 h, P < .01) and whites (14.0 v 16.5 mmol/8 h, P < .01). The highest urinary Na:K ratio was observed in blacks in Birmingham with lower education level; urinary Na excretion was high in blacks with a lower education level in both cities. No such differences were seen in whites. Although TOMHS was not population-based, these findings suggest the possibility that potassium intake among persons with stage 1 hypertension is related to geographic area in both blacks and whites, and sodium intake is inversely related to education level in blacks.

Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions in mild hypertension.

Renal effects of mild hypertension and therapy have not been established. Since urinary albumin and N-acetyl-beta-D-glucosaminidase excretions reflect renal effects of hypertension, they were related to blood pressure, other cardiovascular risk factors, cardiac target organ effects, and response to therapy in mild hypertension (diastolic blood pressure 85-99 mm Hg). Participants were from two clinics of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized, double-blind, controlled trial. Participants received nutritional-hygienic therapy and one of five active drugs or placebo. Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions were assessed prospectively using office "spot" collections from one clinic (n = 213) and retrospectively using overnight collections from the other clinic (n = 210). Relationships were determined between protein excretions and blood pressure, age, gender, race, blood glucose, cholesterol concentrations, and indices of body mass and left ventricular mass and function at baseline. Treatment effects were assessed after 3 to 12 months. Spot and overnight albumin excretions related positively to baseline systolic blood pressure by univariate analyses. Spot albumin excretion related positively to systolic blood pressure, age, creatinine clearance, and left ventricular function while overnight albumin excretion related positively to left ventricular mass and female gender by multiple regression analyses. Spot, but not overnight, albumin excretion declined significantly with active drug therapy. N-acetyl-beta-D-glucosaminidase excretion did not relate to blood pressure or decline with therapy. The combined results suggest albumin excretion correlates with blood pressure, decreases with antihypertensive drug therapy, and is associated with greater left ventricular function and mass, as well as glomerular filtration rate, even at mild levels of hypertension.

LTP in the lateral perforant path is beta-adrenergic receptor-dependent.

Norepinephrine induces an activity-independent long-lasting depression of synaptic transmission in the lateral perforant path input to dentate granule cells, whereas high frequency stimulation induces activity-dependent long-term potentiation (LTP). We investigated the role of endogenous activation of beta-adrenergic receptors in LTP of the lateral and medial perforant paths under conditions affording selective stimulation of these pathways in the rat hippo-campal slice. Propranolol (1 microM), a beta-receptor antagonist, blocked LTP induction of both lateral and medial perforant path-evoked field excitatory postsynaptic potentials. The results indicate a broad requirement for norepinephrine in different types of synaptic plasticity, including activity-independent depression and activity-dependent LTP in the lateral perforant path.

Proteinuria is a risk factor for mortality over 10 years of follow-up. MRFIT Research Group. Multiple Risk Factor Intervention Trial.

Proteinuria has been shown to be strongly associated with the prevalence and incidence of cardiovascular disease. It has been difficult to determine if the link is causal and independent. The mortality follow-up for the Multiple Risk Factor Intervention Trial (MRFIT) randomized cohort provides an opportunity to examine these relationships. Between 1973 and 1975, 361,662 men, ages 35 to 57, were screened for blood pressure, serum cholesterol, and cigarette smoking. Patients receiving medication for diabetes were excluded. Men in the upper 10 to 15% of coronary heart disease (CHD) risk (12,866) were randomized into the MRFIT trial. Standard casual urine dipstick determinations (Labstix) for protein were done at baseline and annually for six years. Post-trial cause-specific mortality was ascertained using the National Death Index. During the trial, 2326 (18.1%) of participants had + or higher proteinuria, and 593 (4.6%) had +2 or higher proteinuria. The presence of proteinuria during the six years of follow-up was consistently associated with higher all cause, cardiovascular disease (CVD) and CHD mortality, even after adjusting for other risk factors. The higher and more persistent the proteinuria, the greater the risk. In this data set, proteinuria is a strong and independent risk factor for CVD mortality.