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Biomedical subjects

B Lemmer

Publications and source records attributed to B Lemmer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of melatoninergic agonists on light-suppressed circadian rhythms in rats.

This study addressed the question whether light-suppressed circadian rhythms in cardiovascular parameters in rats could be restored by melatonin and a synthetic analogue. Blood pressure, heart rate, and locomotor activity were monitored by radiotelemetry in six Sprague-Dawley rats. After synchronization to a 12:12 light/dark (LD) schedule (lights on at 0700 hours, 100 lux), rats were kept in constant light (LL) of low intensity (5-10 lux) for 11 weeks. After 3 weeks of LL, rats received daily intraperitoneal (i.p.) injections at 1900 hours of vehicle, the melatonin agonist S-21767 (5 mg/kg) and melatonin (1 mg/kg). Spectral power, 24-h amplitudes and the differences between day and night means were calculated as measures of circadian rhythmicity. During LL a lengthening of the endogenous period to 26 h was observed, which was accompanied by a continuous decrease in circadian amplitude in all parameters monitored until, in the third week of LL, circadian rhythmicity was almost abolished. Neither vehicle, S-21767 nor melatonin were able to restore circadian rhythms in blood pressure and locomotor activity. In contrast, both agonists induced circadian rhythmicity in heart rate in two out of six rats. The day/night difference in heart rate of all animals was significantly increased by S-21767 and, to a smaller extent, by melatonin, whereas the circadian amplitude was not affected. In conclusion, melatonin and the synthetic agonist were able to partially synchronize circadian rhythmicity in heart rate during constant light, but could not restore circadian rhythms in blood pressure.

Animals↗
PubMed1998

Signal transduction in cardiac and vascular tissue from normotensive and transgenic hypertensive TGR(mREN2)27 rats.

Adenylyl cyclase and soluble guanylyl cyclase activities were measured in cardiac and aortic tissue from transgenic hypertensive TGR(mREN2)27 and normotensive Sprague-Dawley rats. Cardiac basal and stimulated adenylyl cyclase activity was significantly lower in TGR(mREN2)27 than in Sprague-Dawley rats except after uncoupling of G-proteins by Mn2+-ions. Aortic cAMP formation did not differ between both strains, indicating that the disturbance of cardiac adenylyl cyclase activity was due to local rather than systemic factors. Vascular cGMP formation was significantly reduced in TGR(mREN2)27 aortae under basal conditions and after stimulation with sodium nitroprusside, indicating that there is a subsensitive vasodilating second messenger pathway in the transgenic strain.

Adenylyl Cyclases↗
PubMed1998

Effects of chronic application of propranolol on beta-adrenergic signal transduction in heart ventricles from myopathic BIO TO2 and control hamsters.

1. In human congestive heart failure beta-adrenoceptor antagonists improve exercise tolerance and cardiac contractility. These beneficial effects are thought to reflect an up-regulation of cardiac beta-adrenoceptors, involving mainly the beta1-subtype. In the present study we evaluated the functional contribution of beta-adrenoceptor subtypes to stimulation of adenylyl cyclase in an animal model of dilated cardiomyopathy, and compared the effects of treatment with propranolol on cardiac beta-adrenergic signal transduction in myopathic and control hamsters. 2. Cardiomyopathic BIO TO2 hamsters and BIO F1B controls aged 270 days were used. In the treatment study, hamsters received drinking water with or without propranolol 40 mg kg(-1) d(-1) for 4 weeks prior to sacrifice. Density and subtype distribution of beta-adrenoceptors were determined in radioligand binding studies. Functional contributions of beta-adrenoceptors were evaluated by subtype-selective stimulation of adenylyl cyclase. Cardiac G-protein content was determined by immunoblotting. 3. Compared to BIO F1B controls, myopathic hamsters showed increases in cardiac total beta- and beta2-adrenoceptor density, G(s alpha) and G(i alpha) content. In BIO TO2 ventricles, beta1-adrenoceptors were almost completely uncoupled from adenylyl cyclase stimulation despite an unchanged density. Treatment of hamsters with propranolol resulted in increased density of beta1-adrenoceptors in both strains, but had no effect on their functional efficacy. Moreover, beta2-adrenergic stimulation of adenylyl cyclase was even reduced in propranolol-treated animals, which could not be explained by changes in cardiac G-protein content. 4. Cardiomyopathic BIO TO2 hamsters showed functional uncoupling of cardiac beta1-adrenoceptors, which could not be normalized by propranolol and, therefore, is unlikely to be solely due to agonist-dependent desensitization. The paradoxical reduction in beta2-adrenergic efficiency in propranolol-treated myopathic and control hamsters deserves further investigation.

Adenylyl Cyclases↗
PubMed1998

Successive surveys of an expert panel: research in decision-making with health visitors.

A United Kingdom expert panel was consulted to develop a self-completion instrument for research on decision making in health visiting practice. The use of a Delphi-type technique demonstrated how a stand-alone postal survey was an insufficient measure for health visitors, requiring a supplementary follow-up method to study types of casework. A review of literature raised questions about the significance of intuitive thinking and reasoning in health visitor practice, in relation to measuring professional service and individual performance.

Decision Making↗
PubMed1998

Effects of amlodipine once or twice daily on circadian blood pressure profile, myocardial hypertrophy, and beta-adrenergic signaling in transgenic hypertensive TGR(mREN2)27 rats.

The effects of amlodipine on blood pressure profiles, cardiac hypertrophy, and beta-adrenergic signal transduction were studied in transgenic hypertensive TGR(mREN2)27 rats (TGRs), which are characterized by an inverse circadian blood pressure rhythm. Cardiovascular parameters were monitored by radiotelemetry; beta-adrenoceptor density and function were measured by radioligand binding and by determination of beta-adrenergic stimulation of adenylyl cyclase. Ventricular weight and the activity of cardiac sarcolemmal 5-nucleotidase were used as measures of hypertrophy. Acute i.p. injection of amlodipine (1, 3, 10 mg/kg body weight) either at 8:00 or at 20:00 h dose-dependently reduced blood pressure irrespective of the dosing time. For long-term treatment, TGRs were divided into three groups: untreated; amlodipine, once-daily, 5 mg/kg; and amlodipine, twice daily, 2.5 mg/kg. Both treatment schedules resulted in decreased 24 h means in systolic and diastolic blood pressure and a reduction in ventricular hypertrophy but had no effects on cardiac beta-adrenergic signaling. Once-daily dose of amlodipine at 8:00 h decreased blood pressure predominantly during the daily resting period of the rats, whereas twice-daily dosing induced a bimodal blood pressure pattern. However, even after 5 weeks of treatment, typical circadian profiles could not be observed with either treatment, indicating a short duration of action of amlodipine in rats. Thus it remains an open question whether pharmacologic normalization of the circadian blood pressure pattern in TGRs will more effectively reduce myocardial hypertrophy and restore beta-adrenergic signaling than a reduction in 24-h blood pressure per se.

Adenylyl Cyclases↗
PubMed1998

Effects of SCN lesions on circadian blood pressure rhythm in normotensive and transgenic hypertensive rats.

Transgenic hypertensive TGR(mREN2)27 (TGR) rats, carrying an additional mouse renin gene, have been found to show inverse circadian blood pressure profiles compared to normotensive Sprague-Dawley rats. In order to evaluate the contributions of the suprachiasmatic nucleus (SCN) and the neurohormone melatonin to cardiovascular circadian regulation in TGR(mREN2)27 rats and Sprague-Dawley (SPRD) controls, we investigated the effects of melatonin agonist and antagonist treatment in SCN-lesioned and nonlesioned rats, which were kept under conditions of alternating light and darkness (LD). After destruction of the SCN, circadian rhythmicity in blood pressure, heart rate (HR), and motor activity (MA) was almost abolished in rats of both strains. One week of treatment with a synthetic melatonin agonist S-21634 was not able to restore circadian variation in the parameters monitored. In nonlesioned TGR(mREN2)27 rats and Sprague-Dawley control rats, the melatonin antagonist S-22365 had no suppressive effect on LD-synchronized circadian rhythmicity, indicating that LD itself may have a stronger influence on the SCN than endogenous melatonin.

Animals↗
PubMed1998

Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients.

OBJECTIVE: To determine the antihypertensive efficacy and the potential impact on circadian blood pressure pattern of morning versus evening administration of amlodipine to essential hypertensive patients. METHODS: Twelve mild-to-moderate essential hypertensives were investigated in this open, randomized cross-over study. Blood pressure and heart rate were measured by use of ambulatory blood pressure monitoring after a wash-out period of 1 week and after treatment schedules with 5 mg amlodipine once a day either at 0800 h or at 2000 h for 3 weeks. Effects were evaluated by linear and rhythm analysis using the ABPM-FIT program. RESULTS: Both morning and evening administrations of amlodipine significantly (P < 0.01) reduced the elevated systolic and diastolic blood pressures during daytime. However, due to baseline values being lower during night-time, a significant (P < 0.05) reduction was observed only in systolic, not in diastolic, blood pressure. Maximal blood pressure values were significantly (P </= 0.01) decreased by both treatment regimens, whereas nightly minimum values remained unchanged. The early morning rise in blood pressure was decreaseed after morning and slightly more pronounced aftger evening dosing of amlodipine. Though both amlodipine treatments more effectively reduced daytime blood pressure levels, the circadian profile was not greatly affected. Amlodipine treatment had no effect on heart rate. CONCLUSION: The results demonstrate that, independently from the dosing time, the long-acting calcium antagonist amlodipine sufficiently reduced blood pressure in essential hypertensive patients without increasing the nightly drop. The drug-induced decrase in the early morning rise in blood pressure may be advantageous in reducing the early morning cardiovascular risk.

Journal Article↗
PubMed1998

Chronopharmacological aspects for the prevention of acute coronary syndromes.

This review discusses the circadian phase dependency in the anti-anginal effects and in the pharmacokinetics of drugs used in the treatment of coronary heart diseased patients. beta-receptor blocking agents seem mainly to reduce ischaemic events during daytime hours and are of therapeutic value in the morning hours which are the hours of high cardiovascular risk. Calcium channel blockers seem to be less effective in reducing ischaemic event during the night and early morning. However, the galenic formulation and the type of calcium channel blocker may play an important role. Whereas the effects of the anti-ischaemic properties of oral nitrates are well established, their influence of the circadian organization of cardiovascular events needs to be clarified. Only limited data are available concerning the circadian phase dependency in the dose-response relationship of anti-anginal drugs. Such data would be valuable for a better understanding of the need of a time-specified drug treatment which is based on the circadian phase dependency of cardiovascular events such as coronary infarction and angina pectoris attacks.

Acute Disease↗
PubMed1997

Effects of beta-adrenoceptor blockade on beta-adrenergic signal transduction in cardiomyopathic hamster (BIO 8262) hearts.

In myopathic BIO 8262-hamsters beta1-adrenergic stimulation of cardiac adenylyl cyclase has been found to be markedly reduced compared to that of healthy controls. In order to test the hypothesis that the functional uncoupling of beta1-adrenoceptors in diseased hamster hearts is due to agonist-dependent desensitization, we investigated the effects of prolonged treatment with beta-adrenoceptor antagonists on cardiac beta-adrenergic signaling. Groups of hamsters aged 240 days received either drinking water, or drinking water containing metoprolol (10 or 100 mg/kg/day) or propranolol (4 or 40 mg/kg/day). After 4 weeks' treatment animals were killed and heart ventricles were prepared for determination of beta1- and beta2-adrenoceptor densities and their functional contribution to stimulation of adenylyl cyclase. Markers of myocardial hypertrophy, i.e. absolute and relative ventricular weight and 5-nucleotidase activity, were not affected by the different treatment regimens. Neither absolute densities nor relative proportions of beta-adrenoceptor subtypes differed between untreated and treated hamster groups. Metoprolol had no effects on the functional efficacy of beta1- and beta2-adrenoceptors. Hamsters treated with high dose propranolol showed unchanged beta1-adrenoceptor function but reduced beta2-adrenergic stimulation of adenylyl cyclase. The findings of the present study demonstrate that the disturbed coupling of cardiac beta1-adrenoceptors to adenylyl cyclase cannot be reversed by in vivo treatment with beta-adrenoceptor antagonists and, therefore, is unlikely to be due to agonist-dependent desensitization.

5'-Nucleotidase↗
PubMed1997

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation.

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3-24.3 (median 15.0) years who had been transplanted 1.5-8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m2. Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants.

Adolescent↗
PubMed1997

Using research to find the effects of process-oriented educational assessment in critical care nursing practice.

This 1-year study was undertaken in the southeast of England to investigate whether a process-oriented educational assessment procedure was sustainable, following research in a sample of five critical care environments. Data were derived from clinical practice supervisors and students in each of two consecutive post-registration cohorts, selected from the following areas: intensive and coronary care units; neonatal nursing; medical-surgical units; operating theatres; and accident and emergency departments. The existing measure and then a modified assessment measure for resuscitation ability, were used to evaluate the effect of educational assessment in clinical settings. Data were collected using questionnaires with cohort 1 before and cohort 2 after introduction of an assessment grid developed by the course team based on data from focus group discussions during the clinical supervisors' workshops. The findings indicated that the descriptors of levels of attainment generated by the students and supervisors were in accord with Benner's descriptors (this had increased by phase 2 of the research). Students and supervisors considered that the assessment process increased their critical thinking abilities, but that finding time for supervision and assessment was difficult. Future work will focus on the development of a generic grid with criteria that can be used to guide assessment of any practice experience.

Clinical Competence↗
PubMed1997

Circadian blood pressure changes in untreated children with kidney disease and conserved renal function.

Ambulatory blood pressure monitoring over 24 h was applied in 31 children with kidney disease, aged 3-19 (median 11) years, in the absence of renal insufficiency and without antihypertensive therapy. Median creatinine clearance was 112 ml/min/1.73m2. Ambulatory blood pressure monitoring revealed that eight patients (26%) were hypertensive during the daytime, compared to 62% through casual recordings obtained in the office and 38% when blood pressure was taken at home. Nocturnal hypertension was detected by ambulatory monitoring in six patients, two of whom had normal blood pressure in the daytime. Median nocturnal dipping was 13% for systolic and 21% for diastolic blood pressure, i.e. similar to healthy children. Rhythm analysis recognized a distorted circadian pattern for systolic and/or diastolic blood pressure in eight patients. In conclusion, ambulatory blood pressure monitoring allows the evaluation of hypertension more reliably than casual recordings in the office. Nocturnal hypertension, as a major risk factor for renal deterioration, is detected in a similar proportion as daytime hypertension in almost 20% of untreated children with kidney disease and normal renal function.

Adolescent↗
PubMed1997

Analysis of telemetric time series data for periodic components using DQ-FIT.

DQ-FIT and CV-SORT have been developed to facilitate the automatic analysis of data sampled by radiotelemetry, but they can also be used with other data sampled in chronobiological settings. After import of data, DQ-FIT performs conventional linear, as well as rhythm analysis according to user-defined specifications. Linear analysis includes calculation of mean values, load values (percentage of values above a defined limit), highest and lowest readings, and areas under the (parameter-time) curve (AUC). All of these parameters are calculated for the total sampling interval and for user-defined day and night periods. Rhythm analysis is performed by fitting of partial Fourier series with up to six harmonics. The contribution of each harmonic to the overall variation of data is tested statistically; only those components are included in the best-fit function that contribute significantly. Parameters calculated in DQ-FIT's rhythm analysis include mesor, amplitudes, and acrophases of all rhythmic components; significance and percentage rhythm of the combined best fit; maximum and minimum of the fitted curve and times of their occurrence. In addition, DQ-FIT uses the first derivative of the fitted curve (i.e., its slope) to determine the time and extent of maximal increases and decreases within the total sampling interval or user-defined intervals of interest, such as the times of lights on or off. CV-SORT can be used to create tables or graphs from groups of data sets analyzed by DQ-FIT. Graphs are created in CV-SORT by calculation of group mean profiles from individual best-fit curves rather than their curve parameters. This approach allows the user to combine data sets that differ in the number and/or period length of harmonics included. In conclusion, DQ-FIT and CV-SORT can be helpful in the analysis of time-dependent data sampled by telemetry or other monitoring systems. The software can be obtained on request by every interested researcher.

Animals↗
PubMed1997

Chronopharmacological aspects of PK/PD modelling.

Nearly all physiological functions as well as pathophysiological events display reproducible rhythmic changes within 24 hours of a day, including the cardiovascular system. Clinical chronopharmacological studies with antihypertensive drugs gave evidence that effects on the rhythms in blood pressure and heart rate are also dependent on the time of day. Chronopharmacokinetic studies with propranolol, oxprenolol, nifedipine, verapamil, etc. also revealed daily variations in the drugs' kinetics. In general, Cmax was higher and/or tmax shorter after morning than evening dosing of these rather lipophilic drugs. However, independently of whether or not daily variations in the kinetics were found the dose-response relationship was always dependent on the time of day. These data demonstrate that PK/PD modelling has to take into account reproducible rhythmic variations both in the kinetics and/or effects of cardiovascular active drugs.

Adrenergic beta-Antagonists↗
PubMed1996

Signal transduction in animal models of normotension and hypertension.

Experiments in inbred strains of normotensive and hypertensive rats have clearly demonstrated circadian rhythms in blood pressure and heart rate. Pre- and postsynaptic signal transduction processes in vitro can, but need not, vary with circadian time, greatly depending on the strain of rats investigated. These data highlight the notion of a strain-dependent, and thus genetic, regulation of the cardiovascular system. Obviously, circadian rhythms in blood pressure cannot be explained by single biochemical parameters, but results from both in vitro and in vivo studies give first evidence that the vascular nitric oxide-cGMP system may be involved in the circadian regulation of blood pressure in WKY and SHR rats. In secondary hypertensive TGR and in their normotensive controls, SPRD, the guanylyl cyclase system does not seem to play a role in circadian blood pressure regulation. In neither of the four strains studied did aortic adenylyl cyclase show any time-dependent variation. Because vascular tissue was taken from the thoracic aorta of the rats, a contribution of adenylyl cyclase to circadian blood pressure regulation in small resistance arteries cannot be ruled out. Further studies in different parts of the vascular tree are needed to definitely answer that question. No data are available on time-dependent variation in the activity of phospholipase C, the second messenger pathway of vascular alpha-adrenoceptors and angiotensin II AT1-receptors, both of which mediate vasoconstriction. Future research into this system will be helpful in identifying mechanisms involved in blood pressure regulation in SPRD and TGR.

Animals↗
PubMed1996

The clinical relevance of chronopharmacology in therapeutics.

Circadian rhythms in the functions of the body are well established, e.g. in cardiovascular (blood pressure, heart rate, blood flow, etc.), pulmonary, hepatic and renal functions. Also the symptoms and the onset of diseases are not randomly distributed within 24 hours of a day (e.g. coronary infarction, angina pectoris attacks, silent ischaemia, asthmatic attacks). Accordingly, the effects and/or pharmacokinetics of drugs can display significant daily variations. Recent data on the chronopharmacodynamics and chronopharmacokinetics of H2-blockers, antiasthmatics (theophylline, beta-agonists, glucocorticoids), cardiovascular active drugs (beta-blockers, organic nitrates, calcium channel blockers, ACE-inhibitors) are described as representative examples. The data demonstrate that biological rhythms can have an impact on drug therapy.

Animals↗
PubMed1996

Blood pressure rhythm and endocrine functions in normotensive women on oral contraceptives.

DESIGN AND METHODS: Twenty-four hour blood pressure profiles were determined by non-invasive ambulatory blood pressure measurements in young normotensive women during the follicular and luteal phases of the menstrual cycle. Forty women participated, 20 of whom were on oral contraceptives (ethinyl-ethylestradiol 0.03 mg + levonorgestrel 0.15 mg) and 20 of whom were age- and weight-matched control individuals not on oral contraceptives. Data on systolic and diastolic blood pressure and heart rate were analyzed in each case by linear and rhythm analysis. Urine was collected day and night on each occasion on which ambulatory blood pressure measurements were recorded. RESULTS AND CONCLUSION: Daytime, night-time, and 24 h mean systolic and diastolic blood pressure and heart rate did not depend on the cycle phase. The nocturnal fall in blood pressure was preserved in both groups and during both phases. Rhythm analysis by partial Fourier series showed that, of 240 individual 24 h blood pressure profiles, only 12 (5%) did not exhibit a significant circadian rhythm. Linear and rhythm analyses revealed that during both phases of the menstrual cycle systolic and diastolic blood pressure were significantly higher throughout the 24 h, especially during the night, in women taking oral contraceptives. During both phases of the menstrual cycle urinary aldosterone excretion was significantly higher in women taking oral contraceptives. This increase could contribute to the night-time blood pressure elevations caused by oral contraceptives. The results suggest a modulating influence of sex steroids on the circadian blood pressure profile even in normotensive healthy volunteers.

Adult↗