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Biomedical subjects

E T O'Brien

Publications and source records attributed to E T O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dexamethasone inhibits trabecular cell retraction.

Glucocorticosteroids such as dexamethasone (Dex) are known to cause an increased resistance to aqueous outflow in the intact and cultured eye. We investigated whether Dex treatment of cultured endothelial or trabecular meshwork (TM) cells might interfere with the cell separations and retraction induced by the facility-enhancing agents ethacrynic acid (ECA), cytochalasin B and the calcium chelator EGTA. Our hypothesis was that Dex-induced changes in the response of our model cells in vitro might serve as a paradigm for those produced in the cells of the outflow pathway, perhaps through influencing the changing dimensions of the pathway for aqueous humor through the juxtacanalicular tissue and/or inner wall of Schlemm's canal. We treated calf pulmonary artery endothelial (CPAE) and human and porcine TM cells with Dex (1-100 microns, 1-9 days), and then assessed monolayer and cytoskeletal integrity by immunofluorescence microscopy for tubulin and direct fluorescence staining for F-actin after exposure to the agents named above. We found that Dex-pretreated CPAE and TM cells gradually (over 5-7 days) became refractory to the effects of both ECA and EGTA, but not to cytochalasin B. Despite the preservation of general cell shape and attachment after ECA in Dex-treated cells, microtubule disruption still took place as in controls. Dex-treated cells also demonstrated a reorganization of filamentous actin staining after ECA and EGTA. Combination experiments of ECA and EGTA in Dex-treated cells suggested that the Dex effects were due to a greater strength of cell-to-cell and cell-to-substrate attachment, possibly due to interference with the normal cellular signaling required for coordinated cellular retraction and junctional disruption.

Actins↗
PubMed1996

Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.

Aged↗
PubMed1996

Ethacrynic acid disrupts steady state microtubules in vitro.

PURPOSE: Ethacrynic acid (ECA) has been shown to increase facility of aqueous outflow in whole eyes and perfused anterior segments, to open up spaces between cells in the trabecular meshwork and inner wall of Schlemm's canal, and to cause separation and retraction of trabecular meshwork and endothelial cells in culture. One mechanism by which ECA has been proposed to act in cells is via disruption of microtubules, leading to cell retraction. Although it is known that ECA can inhibit de novo assembly of microtubules from tubulin subunits in vitro, we wanted to determine, as a better correlate to the proposed effect of ECA in cells, whether ECA could disrupt microtubule polymers that had reached steady state. We also wanted to determine whether calcium ion could enhance this process. METHODS: We therefore assembled purified and crude porcine brain tubulin to steady state at 37 degrees C and then added ECA and/or calcium. Reaction kinetics were followed spectrophotometrically. RESULTS: We found that ECA effectively disrupted assembled microtubules in vitro. Although 0.8-1.0 mM ECA was required to produce a half-maximal effect in pure tubulin microtubules and 0.2-0.3 mM ECA was necessary with crude microtubule protein, significant disassembly also occurred in the 0.01-0.2 mM range. Calcium had a greater maximal effect than ECA, and was more potent on a molar basis, showing half maximal effect between 2 and 12 microM free calcium ion. Combination experiments showed that ECA did not act synergistically with calcium to increase microtubule disassembly. CONCLUSIONS: Our results are consistent with the proposed disruptive action of ECA on the assembled microtubules of outflow pathway cells, but do not support a rise in intracellular calcium as being an added factor.

Animals↗
PubMed1996

Surgical principles and planning for the rheumatoid hand and wrist.

Each surgical procedure available for the rheumatoid hand has a score card. The most indicated and necessary procedures include: extensor tenosynovectomy and Darrach for the impending or already ruptured extensor tendons; flexor tenosynovectomy and carpal tunnel release for the patient with impaired median nerve function; stabilization of the deformed unstable thumb with MP or IP arthrodesis; and flexor tenosynovectomy in the palm and finger of a motivated patient with significant disparity between active and passive motion. Relative indications for surgery include arthrodesis for the unstable wrist; MP arthroplasty for the fixed MP volar and ulnar subluxation with inability to open the hand; synovectomy for the occasional patient with painful boggy synovitis of the MP or PIP joint; and reconstruction of the fixed swan neck deformity with relatively good PIP joints. Both MP and PIP joints can and should be operated on at the same time. Extensive wrist surgery, that is, tenosynovectomy and Darrach or arthrodesis, should not be performed at the same time as MP arthroplasty. Try to do the "winner operations" first.

Arthritis, Rheumatoid↗
PubMed1995

The trough-to-peak ratio as an instrument to evaluate antihypertensive drugs. The APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension Trial.

The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A method of quantifying retinal microvascular alterations associated with blood pressure and age.

OBJECTIVE: To find an objective, sensitive method for quantifying microvascular alterations associated with level of blood pressure and age. DESIGN: A prospective cross-sectional study. SUBJECTS AND METHODS: Seventy-four previously untreated hypertensive patients, referred to a hospital outpatients department, and 26 normotensive volunteers participated. Twenty-four-hour ambulatory blood pressure monitoring and bilateral fundal photography were performed. The fundal photographs were projected on a screen such that the optic disc filled a circle of radius 5 cm. Microvessels crossing the border of a concentric circle of radius 20 cm were identified as arteriolar or venular, counted and their luminal diameters measured. MAIN OUTCOME MEASURES: Arteriolar and venular numbers, mean diameters and vascularities (arteriolar and venular vascularities defined as the sum of arteriolar and venular diameters, respectively). RESULTS: The technique was reproducible. As blood pressure increased, arteriolar vascularity declined and venular vascularity increased. These associations resulted in a strong inverse correlation between blood pressure level and the ratio arteriolar vascularity: venular vascularity (r = 0.48, P < 0.001). Arteriolar number declined with increasing diastolic blood pressure (r = 0.22, P < 0.05). Mean arteriolar diameter appeared to have a U-shaped relationship with diastolic blood pressure levels (r = 0.27, P < 0.05). Venular dilation was associated with increasing blood pressure levels (r = 0.22, P < 0.05). Mean arteriolar and venular diameters declined significantly with age (r = 0.33 and 0.26, respectively; P < 0.01) and there was no association between arteriolar vascularity:venular vascularity ratio and age. CONCLUSIONS: The method detected disparate retinal microvascular alterations with age and blood pressure. The arteriolar vascularity:venular vascularity ratio shows promise as a non-invasive, prognostic and therapeutic guide in hypertension.

Adolescent↗
PubMed1994

Clinical trials with ambulatory blood pressure monitoring: fewer patients needed? Syst-Eur Investigators.

We have tested the concept that fewer patients are needed in trials of antihypertensive treatment if blood pressure is measured by ambulatory monitoring rather than by conventional sphygmomanometry. 233 patients (> or = 60 years old) with isolated systolic hypertension were randomly allocated placebo (n = 119) or active treatment (n = 114). Blood pressure measurements were compared by Wilcoxon's test and blood pressure profiles by ANOVA. With either method of measurement, the same number of patients (40 in each treatment group) was required to show a reduction after 1 year in clinic (13/8 mm Hg) or average blood pressure over 24 h (9/5 mm Hg). To detect that the decrease in systolic pressure was not steadily maintained through the day, 40 patients in each treatment group were needed for blood pressure profiles made up of 4-hourly or 2-hourly means and 60 for profiles of 1-hourly means. For diastolic pressure, the corresponding numbers were 80, 100, and more than the number of available patients, respectively. We conclude that parallel-group trials focusing on the average blood pressure over 24 h, rather than on conventionally measured blood pressure, cannot economise on sample size. Moreover, trials studying the full course of blood pressure throughout the day, require more--not fewer--patients than studies of only the conventional or average 24 h blood pressure.

Aged↗
PubMed1994

Ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database.

OBJECTIVE: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP < or = 140/90 mmHg), 719 were borderline hypertensive (systolic CBP 141-159 mmHg or diastolic CBP 91-94 mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP > or = 160 mmHg) and 1310 had diastolic hypertension (diastolic CBP > or = 95 mmHg). Combined systolic and diastolic hypertension was present in 861 subjects. Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. RESULTS: The 95th centiles of the ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg for 24-h ABP, 140 and 88 mmHg for daytime ABP and 125 and 76 mmHg for night-time ABP, respectively. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP < 133 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP < 82 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. In comparison with 24-h ABP, the overlap in the daytime and night-time ABP between normotensive and hypertensive subjects was of similar magnitude and was influenced by the same factors. CONCLUSIONS: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Adolescent↗
PubMed1994

Ambulatory pressure decreases on long-term placebo treatment in older patients with isolated systolic hypertension. Syst-Eur Investigators.

OBJECTIVE: This long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo. METHODS: One hundred and twelve older (> or = 60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up. RESULTS: At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (+/- SD) averaged 176 +/- 12/86 +/- 7 mmHg and 24-h SBP/DBP 151 +/- 15/81 +/- 10 mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo. After the 112 patients had received placebo for 1 year (median), clinic SBP/DBP fell by 6.6 +/- 15.9 (P < 0.001)/1.4 +/- 7.4 (P = 0.06)mmHg and 24-h SBP by 2.4 +/- 10.7 mmHg (P < 0.05), whereas 24-h DBP did not change significantly. The 24-h SBP decreased more with higher baseline level and longer follow-up (5-21 months). CONCLUSIONS: These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo. Like those using conventional sphygmomanometry, long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design.

Aged↗
PubMed1994

A consistent reference frame for ambulatory blood pressure monitoring is found in different populations.

This study investigated the consistency of a reference frame for ambulatory pressure monitoring, which using various approaches was determined in two different populations. The two reference groups were 718 subjects randomly selected from the population and 895 bank employees. The reference values derived in these two groups were subsequently tested in 591 untreated hypertensive patients. The ambulatory pressures equivalent to a conventional pressure of 140 mmHg systolic and 90 mmHg diastolic were calculated by regression analysis in all subjects. In addition, in subjects who were normotensive by conventional sphygmomanometry, the mean +2 and +3 standard deviations and the 90th, 95th and 99th percentiles of the ambulatory measurements were determined. The distributions of the ambulatory measurements were similar in the two reference groups and the aforementioned parameters therefore agreed within 4 mmHg in the two populations. There was considerable overlap in the ambulatory pressures between the two reference groups and the hypertensive patients. Classification of the patients according to the means +3 standard deviations and the regression limits gave the same results because in both reference groups these boundaries approximated to each other within 1 mmHg. For the 24 h pressures in the population sample these boundaries were 140 mmHg systolic and 88 mmHg diastolic. Of the patients with systolic hypertension (> or = 160 mmHg on conventional measurement), 39% had a 24 h systolic pressure of < 140 mmHg and of those with diastolic hypertension (> or = 95 mmHg), 44% had a 24 h diastolic pressure of < 88 mmHg; if the corresponding boundaries derived in the bank employees (143/90 mmHg) were applied, these proportions were 47% and 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Short report: ambulatory blood pressure in normotensive compared with hypertensive subjects. The Ad-Hoc Working Group.

OBJECTIVE: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP < or = 140/90 mmHg), 719 were borderline hypertensive (systolic CBP 141-159 mmHg or diastolic CBP 91-94 mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP > or = 160 mmHg) and 1310 had diastolic hypertension (diastolic CBP > or = 95 mmHg). Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. RESULTS: The 95th centiles of the 24-h ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP < 133 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP < 82 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. CONCLUSIONS: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Adolescent↗
PubMed1992

Twenty-four hour blood pressure monitoring in the Syst-Eur trial.

This article describes the objectives and protocol of a study on ambulatory blood pressure in elderly patients with isolated systolic hypertension. This study constitutes an optional side-project to the Syst-Eur trial. The multicentre Syst-Eur trial investigates whether antihypertensive treatment of elderly patients with isolated systolic hypertension will influence the incidence of stroke. Secondary endpoints include cardiovascular events, such as myocardial infarction. The main objective of the side-project is to investigate whether ambulatory blood pressure monitoring will improve the prediction of cardiovascular complications based on blood pressure measurement in the clinic. The side-project also provides the opportunity to evaluate the diurnal profile of blood pressure in elderly patients with isolated systolic hypertension randomized to placebo or active antihypertensive treatment.

Aged↗