Trough to peak ratio as a guide to BP control: measurement and calculation.
Explore the source record for details and available documents.
Antihypertensive Agents↗
Biomedical subjects
T Morgan
Publications and source records attributed to T Morgan.
Circadian variations of renal sodium handling in patients with orthostatic hypotension.
BACKGROUND: Sodium wasting during the night has been postulated as a potential pathophysiological mechanism in patients suffering from orthostatic hypotension due to severe autonomic deficiency. METHODS: In this study, the diurnal variations in creatinine clearance, sodium excretion and segmental renal tubular handling of sodium were evaluated in 18 healthy subjects and 20 young patients with orthostatic hypotension (OH). In addition, 24-hour ambulatory blood pressure and the neuro-hormonal response to changes in posture were determined. The patients and their controls were studied on a free sodium intake. In a second protocol, 10 controls and 10 patients were similarly investigated after one week of a high salt diet (regular diet + 6 g NaCl/day). RESULTS: Our results demonstrate that, in contrast to normal subjects in whom no significant changes in glomerular filtration, sodium excretion and segmental sodium reabsorption were observed throughout the day, patients with OH were characterized by a significant increase in glomerular filtration rate during the nighttime (P = 0.03) and significant increases in urinary lithium excretion (P < 0.05) and lithium clearance (P = 0.05) during the night, suggesting a decreased proximal reabsorption of sodium. On a high sodium diet, the symptoms of orthostatic hypotension and the circadian variations in sodium reabsorption were significantly blunted. CONCLUSIONS: These results suggest that, while the patient is in a supine position the effective blood volume of those with OH becomes excessive due to the increased venous return. Hence, the kidney responds with an increase in glomerular filtration and a relative escape of sodium from the proximal tubular segments. These circadian variations in renal sodium handling may contribute to the maintenance of the orthostatic syndrome.
Adolescent↗
Human spiral artery renin-angiotensin system.
Pregnancy induces uterine spiral arteries to remodel into dilated uteroplacental vessels by an unknown mechanism called "physiological change." In women who develop preeclampsia, however, many spiral arteries remain unchanged or develop medial hyperplasia and atherosis. We recently demonstrated that angiotensinogen is expressed by remodeling spiral arteries in first-trimester decidua. We hypothesize that a local spiral artery renin-angiotensin system mediates pregnancy-induced remodeling of these vessels. In this study we tested for expression of renin, angiotensin-converting enzyme, and angiotensin II type 1 receptor genes in the first-trimester uterus using reverse-transcription polymerase chain reaction. Expression was localized by in situ hybridization and immunohistochemistry. Renin, angiotensin-converting enzyme, and the angiotensin II type 1 receptor are all expressed in and around remodeling spiral arteries. These observations suggest that a local spiral artery renin-angiotensin system may play a role in pregnancy-induced remodeling of these vessels. Elevated angiotensinogen expression in women homozygous for the A(-6) variant in the angiotensinogen promoter may promote abnormal remodeling, whereas relatively lower levels in women homozygous for G(-6) may permit enough normal remodeling to protect these women from preeclampsia.
Arteries↗
Profiting from restorative dentistry.
Explore the source record for details and available documents.
Dentist-Patient Relations↗
Case acceptance is cornerstone of dental wall.
Explore the source record for details and available documents.
Communication↗
Angiotensinogen T235 expression is elevated in decidual spiral arteries.
Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.
Alleles↗
A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST).
OBJECTIVE: To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis. SETTING AND DESIGN: A randomized, single-blind clinical trial lasting 18 months conducted at 2 academic medical centers. PARTICIPANTS: A total of 439 community-dwelling adults, aged 60 years or older, with radiographically evident knee osteoarthritis, pain, and self-reported physical disability. INTERVENTIONS: An aerobic exercise program, a resistance exercise program, and a health education program. MAIN OUTCOME MEASURES: The primary outcome was self-reported disability score (range, 1-5). The secondary outcomes were knee pain score (range, 1-6), performance measures of physical function, x-ray score, aerobic capacity, and knee muscle strength. RESULTS: A total of 365 (83%) participants completed the trial. Overall compliance with the exercise prescription was 68% in the aerobic training group and 70% in the resistance training group. Postrandomization, participants in the aerobic exercise group had a 10% lower adjusted mean (+/- SE) score on the physical disability questionnaire (1.71 +/- 0.03 vs 1.90 +/- 0.04 units; P<.001), a 12% lower score on the knee pain questionnaire (2.1 +/- 0.05 vs 2.4 +/- 0.05 units; P=.001), and performed better (mean [+/- SE]) on the 6-minute walk test (1507 +/- 16 vs 1349 +/- 16 ft; P<.001), mean (+/-SE) time to climb and descend stairs (12.7 +/- 0.4 vs 13.9 +/- 0.4 seconds; P=.05), time to lift and carry 10 pounds (9.1 +/- 0.2 vs 10.0 +/- 0.1 seconds; P<.001), and mean (+/-SE) time to get in and out of a car (8.7 +/- 0.3 vs 10.6 +/- 0.3 seconds; P<.001) than the health education group. The resistance exercise group had an 8% lower score on the physical disability questionnaire (1.74 +/- 0.04 vs 1.90 +/- 0.03 units; P=.003), 8% lower pain score (2.2 +/- 0.06 vs 2.4 +/- 0.05 units; P=.02), greater distance on the 6-minute walk (1406 +/- 17 vs 1349 +/- 16 ft; P=.02), faster times on the lifting and carrying task (9.3 +/- 0.1 vs 10.0 +/- 0.16 seconds; P=.001), and the car task (9.0 +/- 0.3 vs 10.6 +/- 0.3 seconds; P=.003) than the health education group. There were no differences in x-ray scores between either exercise group and the health education group. CONCLUSIONS: Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability, physical performance, and pain from participating in either an aerobic or a resistance exercise program. These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis.
Activities of Daily Living↗
Adequate blood pressure control: perception and reality.
Blood pressure should be controlled over 24 h to reduce or prevent cardiac hypertrophy and reduce the prevalence of sudden death, myocardial infarction and myocardial ischaemia at the time of the morning rise in blood pressure. Anti-hypertensive medication is usually given once-daily in the morning and the dose is titrated on the basis of post-dose (peak) blood pressure. This frequently leads to inadequate control prior to the next drug dose unless drugs with appropriate pharmacokinetics or pharmacodynamics are used. ACE inhibitors exhibit an E(max) plasma concentration: blood pressure response relationship, and thus short-acting ACE inhibitors can exert an effect over 24 h if titrated based on pre-dose (trough) blood pressure. However, when titrated in clinical practice on post-dose (peak) blood pressure response, doses are used that are inadequate to control blood pressure for 24 h. ACE inhibitors with appropriate pharmacokinetics such as perindopril can control blood pressure when titrated at peak provided a dose is used (4 or 8 mg) that is known to have a T:P close to 1.0. Shorter-acting ACE inhibitors frequently give inadequate control when titrated at peak. An understanding of the pharmacokinetics and pharmacodynamics of a drug, coupled with knowledge of the time the drug was taken, together with the time of blood pressure measurements, enables control to be achieved with once-daily therapy even if the drug is titrated at peak response.
Angiotensin-Converting Enzyme Inhibitors↗
A study of caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): a potential model for aging research.
Caloric restriction has been demonstrated to retard aging processes and extend maximal life span in rodents, and is currently being evaluated in several nonhuman primate trials. We initiated a study in 32 adult cynomolgus monkeys to evaluate the effect of caloric restriction on parameters contributing to atherosclerosis extent. Following pretrial determinations, at which time a baseline measure of ad libitum (ad lib) dietary intake was assessed, animals were randomized to an ad lib fed group (control) or a caloric restriction group (30% reduction from baseline intake). The animals are being evaluated for glycated proteins, insulin, glucose, insulin sensitivity measures, and specific measures of body fat composition by CT scans (e.g., intra-abdominal fat) over specified intervals. The results from the first year of observation demonstrate a significant diet effect on body weight, and specifically intra-abdominal fat. Further, insulin sensitivity has been significantly increased after 1 year of caloric restriction compared to the ad lib fed group. These studies indicate that caloric restriction has a marked effect on a pathologic fat depot, and this change is associated significantly with an improvement in peripheral tissue insulin sensitivity.
Aging↗
The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night.
OBJECTIVE: To determine the clinic and ambulatory blood pressure when the same dose of perindopril (4 mg) is administered in the morning (0900 h), or at night (2100 h), in particular, to determine whether the early morning blood pressure rise, the duration of effect and the pattern of response differed. METHODS: Twenty male patients with diastolic blood pressure 95-110 mmHg when seated and 24 h mean ambulatory diastolic blood pressure > 85 mmHg after 4 weeks' placebo were allocated randomly to be administered 4 mg perindopril at 0900 h or at 2100 h. Clinic blood pressure (with the patient seated and erect) was measured 2 and 4 weeks after the therapy had been started and ambulatory blood pressure monitoring with a SpaceLabs device was performed for 26 h during week 4. The patients then crossed over to the other time of dosage and the measurements were repeated. The study was conducted from a hospital clinic. RESULTS: The clinic analysis concerned all 20 patients but the ambulatory analysis concerned 18 patients because the ambulatory blood pressure monitor data sets were inadequate for two patients. Compliance was high (97 +/- 3%), with a suggestion that it was better with the 0900 h dose. Clinic blood pressure (with the patient seated and erect) was lower under both regimes and the blood pressure with night-time administration of perindopril tended to be lower than that with daytime administration (P = 0.05-0.10). Twenty-four-hour mean, daytime and night-time means were lower with both doses than they were with placebo and did not differ. Both regimes reduced the early morning peak blood pressure rise and the effect tended to be greater with the 2100 h dose (P = 0.05-0.10). The 0900 h dose had an effect that persisted for > 24 h but the effect of the 2100 h dose had dissipated 18 h after the dose. There was no excessive night-time fall in blood pressure with the 2100 h dose. The trough : peak ratio with the 0900 h dose was 0.86 for systolic and 0.70 for diastolic blood pressure. CONCLUSION: The early morning blood pressure rise is reduced more when 4 mg perindopril is administered at 2100 h. However, the 2100 h dose regime does not reduce blood pressure over 24 h whereas 24 h control is achieved with the 0900 h dose. In clinical practice the 2100 h dose would have been titrated to the next dose range in more patients. This study indicates that the response profile obtained with an angiotensin converting enzyme inhibitor cannot be transformed from one dose time to another automatically and that chronobiology has important effects on a drug's action.
Adult↗
Compliance to exercise therapy in older participants with knee osteoarthritis: implications for treating disability.
This investigation examined predictors of compliance with exercise therapy in a clinical trial involving older adults with knee osteoarthritis (OA). The study sample was partitioned into tertiles by level of compliance to determine its effect on several clinical outcome measures in the trial (i.e., knee pain, difficulty with activities of daily living, and performance-related disability). The participants (N = 439) first completed all baseline assessments and were then randomly assigned to one of three treatment conditions: health education control, aerobic exercise, or resistance exercise. The two exercise treatments involved a 3-month center-based phase and a 15-month home-based phase. Variables in five categories (i.e., demographic, fitness, health-related quality of life, performance-related disability, and prior exercise behavior) were entered as predictors of attendance and time spent exercising during each session for three different periods of time across the course of the study. Results of these analyses revealed that it was possible to explain more variance for time spent exercising (approximately 40%) during the first 3 months than for attendance (approximately 10%). Furthermore, once participants completed the first 3 months of their training, prior behavior was the strongest predictor of exercise compliance. In most cases, the regression models accounted anywhere from 26 to 46% of the variance in attendance or time spent exercising (7 of the 8 P values < 0.01). In general, demographic, fitness, psychosocial, and disability-related measures did not predict compliance with any consistency across the various phases of the trial. Analysis of the dose-response data suggest that, in the use of aerobic exercise to deter disability in older people with knee OA, consideration should be given to prescribing frequent bouts of activity (at least 3 times each week) of moderate duration (approximately 35 min).
Activities of Daily Living↗
Hypertrophic osteoarthropathy in a blesbok (Damaliscus dorcas phillipsi).
A 4.5-yr-old female blesbok (Damaliscus dorcas phillipsi) was radiographed following the appearance of lameness and swelling of the right front fetlock. Radiographic interpretation at that time was osteoarthritis caused by periosteal proliferation of the right metacarpus with periarticular osteophytes surrounding the fetlock. No treatment was initiated. Gradual abdominal enlargement over several months was interpreted as evidence of pregnancy. Six months after the initial lameness complaint, the blesbok suddenly collapsed and was unable to stand. Physical examination revealed a large firm mass occupying most of the abdomen that was found to be inoperable. Following exploratory laporotomy, the blesbok was euthanized. At necropsy, the mass weighed 17 kg. It had probably caused the animal's collapse. Histologically, the bony lesions of the right metacarpus, seen radiographically at the previous examination, were consistent with hypertrophic osteoarthropathy and may have been a sequela of the intra-abdominal mass.
Abdominal Neoplasms↗
Evaluation and comparison of two new prostate carcinoma markers. Free-prostate specific antigen and prostate specific membrane antigen.
BACKGROUND: Two new prostate cancer markers, free-prostate specific antigen (f-PSA) and prostate specific membrane antigen (PSMA) were recently introduced. This report summarizes a prospective two-year multicenter test of their diagnostic or prognostic capabilities. Total PSA was also measured. METHODS: There were four clinical groups studied: (1) 226 individuals from a screening project undergoing ultrasound and biopsy evaluation had markers obtained: (2) 68 patients suspected of having prostate cancer and undergoing 2 or more biopsies had the markers obtained on multiple occasions: (3) 100 patients undergoing radical prostatectomy had markers obtained pre- and post-operatively: and (4) 31 patients with metastatic prostate cancer each had multiple samples for marker assay obtained over a 2-year period. In all, 465 patients had one or more samples obtained and studied. RESULTS: Free-PSA affords little additional diagnostic advantage compared with total PSA in the screening population. The receiver operating characteristic curves for diagnostic accuracy were ranked: (1) PSA density; (2) total PSA; (3) f-PSA; and (4) PSMA, PSMA showed the best correlation with stage of the primary tumor in the screened group. In the multiple negative biopsy group, f-PSA varied from 12 to 21%. PSMA values were evaluated in all histologic categories. PSA density was > or = 0.15 in all categories. In the prostatectomy cases PSA values postoperatively were quite low in Stage II; f-PSA was of no value. Later, f-PSA was increased in association with elevated total PSA values. Mean PSMA values were above normal in all postoperative time periods except in Stage III patients at 6 months to 1 year postoperatively. PSA densities were all > or = 0.15. In patients with metastatic carcinoma, elevated PSMA values correlated best with a poor prognosis (clinical progression), as has been described. CONCLUSIONS: These data suggest that f-PSA values do not provide additional diagnostic benefit compared with total PSA in screening populations, in the presence of suspected cancer, postprostatectomy, or in metastatic disease. PSMA is of prognostic significance, especially in the presence of metastatic disease, and correlates well with the stage of disease in cancers detected in a screened population.
Antigens, Neoplasm↗
The renin-angiotensin system and the heart: beyond 2000.
Renin-angiotensin is both a circulatory and a local tissue system. However, in most circumstances, renin present in the heart and blood vessels is taken up from the plasma, and the kidney is the prime source of this renin. Tissues can then modulate and control the production of angiotensin II. In various organs, angiotensin II has local actions. In the heart, working through the AT1 receptor, it increases contractility and may cause cardiocyte hypertrophy. Indirectly, the heart is also very much affected by the vascular actions of angiotensin II. However, the net result on the heart is the product of an important interaction between a large number of factors. There is little doubt that an inappropriately high plasma (and tissue) level of renin, related to sodium balance, is associated with increased left ventricular hypertrophy and cardiovascular complications. The genetic approach will lead to an understanding of genomic risk factors in hypertension and may identify control systems--at present unknown--which will lead to a new approach to the prevention of cardiovascular death. It is, however, unlikely that such a factor will clearly predict an individual's prognosis, but it will, rather, identify groups at risk. Constellations of genomic interactions with multiple environment factors reduce this power. Modification of the response to angiotensin II using present treatment, or interrupting the response at more distal sites, may enable us to achieve the beneficial effects on cardiac hypertrophy without the detrimental effects.
Angiotensin II↗
Individual considerations in wound management.
Explore the source record for details and available documents.
Aged↗
How important is 24-hour control of blood pressure?
Control of blood pressure over the full 24-hour period is important to prevent, or allow resolution of, cardiac and vascular hypertrophy. In addition, the peak incidence of sudden death, myocardial infarction and stroke occurs at the time of the blood pressure increase associated with awakening and arising. There is at present no objective evidence that "good' 24-hour blood pressure control will improve prognosis. Once-daily therapy has created problems in hypertension management. The problem in assessing new drugs was that, in order to achieve blood pressure control before the next drug dose, excessive falls in blood pressure occurred at peak drug concentrations or excessive blood drug concentrations were produced. This led to the concept of a trough: peak ratio. This is not a unique property of a drug and if drugs have an Emax effect (i.e. the drug produces a plateau response) it is dose dependent. Interpreting a trough: peak ratio requires an understanding of the interaction between the pharmacokinetics and pharmacodynamics of a drug. The answer is to use drugs with an elimination half-life close to or greater than the dose interval (24 hours); to use drugs with an "effective' half-life close to or greater than the dose interval, which can be achieved either by modification of the pharmaceutical delivery system or by using drugs that produce a persistent effect because of physiological changes induced; or to give drugs more frequently than once a day. 24-hour blood pressure control is important and the trough: peak ratio of a drug gives a guide as to whether it can be achieved.
Antihypertensive Agents↗
Clinical pathway effects on treatment of the alcohol withdrawal syndrome.
We investigated whether initiating a clinical pathway, that incorporated the use of an alcohol withdrawal assessment scale, would decrease length of stay (LOS) for and/or amount of benzodiazepine prescribed during uncomplicated alcohol detoxification. We retrospectively reviewed alcohol detoxification admissions on an inpatient unit: 66 admissions before, 56 after, and 75 admissions 1-year after initiation of the pathway. Admissions were grouped into completers and non-completers. Comparison of group means before and after pathway implementation demonstrated a significant decrease in LOS for completers of the detoxification service from 7.35 to 4.77 days, and from 6.67 to 4.31 days for all admissions. Similarly, total benzodiazepine exposure decreased to a third of the mg amount given per admission prior to the pathway. There were no increases in the "irregular" discharge rate or complication rate. These findings suggest that a clinical pathway, with an incorporated withdrawal assessment scale, can decrease LOS and benzodiazepine prescribing on an alcohol detoxification unit.
Alcohol Withdrawal Delirium↗
A study of the efficacy of felodipine given once or twice daily in the management of elderly hypertensive patients.
The use of medication given once daily in clinical practice may lead to inadequate control of blood pressure (BP) over 24 h because medication is frequently titrated at the time of peak effect. Twenty-three patients aged 65-84 completed a study in which they received placebo, felodipine 2.5 mg once daily, felodipine 2.5 mg 12-hourly, and felodipine 5 mg once daily in a randomized, double-blind crossover design. BP response was assessed in the clinic 24 h after medication and by 24 h ambulatory monitoring. The trough/peak ratio was defined as the fall in BP in the 23rd and 24th hour post dose divided by the fall in BP in the 3rd and 4th hour post dose. BP fell with all three regimes and the clinic BPs did not differ from each other but were lower than placebo. Peak BP responses from the ambulatory BP monitor recording were similar with each dose but a greater percentage of the effect was maintained prior to the morning dose with 2.5 mg 12 hourly and 5 mg once daily. Felodipine 2.5 mg once daily reduces BP and in some people this effect persists for 24 h. However if this dose is used BP should be measured prior to the dose of the drug to ensure that 24 h control is maintained. Felodipine 5 mg once daily and felodipine 2.5 mg b.d. were equally effective at maintaining control and there was no significant advantage in using the twice daily regime. If felodipine 5 mg once daily or higher doses are used BP can be titrated post dose with the knowledge that more than 75% of the effect will still be present prior to the next dose of the drug. Thus once daily felodipine extended release (ER) 5 mg or more can be used effectively to maintain BP control over 24 h in clinical practice. In some elderly patients felodipine ER 2.5 mg once daily is an adequate regime.
Aged↗