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Biomedical subjects

K O'Malley

Publications and source records attributed to K O'Malley.

At least 37 records · Page 2Linked to original sources
PubMed1995

An HSV-1 vector expressing tyrosine hydroxylase causes production and release of L-dopa from cultured rat striatal cells.

In this report we demonstrate that a defective herpes simplex virus type one (HSV-1) vector can express enzymatically active tyrosine hydroxylase in cultured striatal cells that are thereby converted into L-DOPA-producing cells. A human tyrosine hydroxylase cDNA (form II) was inserted into an HSV-1 vector (pHSVth) and packaged into virus particles using an HSV-1 strain 17 mutant in the immediate early 3 gene (either ts K or D30EBA) as helper virus. Cultured fibroblasts were infected with pHSVth and 1 day later tyrosine hydroxylase immunoreactivity and tyrosine hydroxylase enzyme activity were observed. The tyrosine hydroxylase enzyme activity directed the production of L-DOPA. pHSVth infection of striatal cells in dissociated cell culture resulted in expression of tyrosine hydroxylase RNA and tyrosine hydroxylase immunoreactivity. Release of L-DOPA and low levels of dopamine were observed from cells in pHSVth-infected striatal cultures. Expression of tyrosine hydroxylase and release of catecholamines were maintained for at least 1 week after infection.

Animals↗
PubMed1995

Characterization of a chimeric human dopamine D3/D2 receptor functionally coupled to adenylyl cyclase in Chinese hamster ovary cells.

Dopamine D3 receptor pharmacology differs from that of the dopamine D2 receptor despite a high degree of receptor sequence similarity. The greatest divergence of the primary sequences of D3 and D2 receptors occurs in the predicted third intracellular loops of the receptors, a region implicated in G protein binding and function. To determine whether this domain specifies the distinct ligand binding and signal transduction characteristics of the D3 receptor, we developed a chimeric receptor, replacing the third intracellular loop of the human D3 receptor with the third intracellular loop of the human D2 receptor. The pharmacology of the chimeric receptor expressed in Chinese hamster ovary cells was examined and compared with that of human dopamine D2 and D3 receptors expressed in the same cell line. The chimeric receptor retained characteristic human D3 receptor binding; the D2 third intracellular loop present in the chimeric receptor did not reduce high affinity agonist binding, characteristic of the D3 receptor, or make high affinity sites sensitive to GTP analogs. Unlike the native human D3 receptor, the chimeric receptor was negatively coupled to adenylyl cyclase through a pertussis toxin-sensitive pathway, apparently mediated by the D2 third intracellular loop. The ability of D3 ligand binding domains to produce a D2 functional response implies that the third intracellular loop of the D3 receptor is unable to mediate this D2 response in Chinese hamster ovary cells. The inhibition of adenylyl cyclase seen with the chimeric receptor is less than the inhibition produced by D2 receptor coupling, suggesting that additional sequences in the D2 receptor contribute to normal G protein coupling.

Adenylyl Cyclases↗
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

Individual quality of life in the healthy elderly.

Quality of life research with the elderly has usually focused on the impact of decline in function, and used a pre-determined model of quality of life in old age. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL) allows individuals to nominate, weigh and assess those domains of greatest relevance to their quality of life. The SEIQoL was administered to 56 healthy elderly community residents at baseline and 12 months later. Quality of life levels were significantly higher at baseline (t = -2.04; p = 0.04) than that of a previously studied sample of healthy adults below 65 years of age, and did not change significantly over the study period. The domains nominated by both samples as relevant to their quality of life differed notably. Health status was not correlated with the perceived importance of health at baseline, and showed only a low correlation (r = 0.27) at 12 months. The weight placed on health did not increase over the study period despite a significant decline in health status. The value of allowing the individual to define personal quality of life values in a research context is explored.

Adult↗
PubMed1994

The need to retrieve the dropped stone during laparoscopic cholecystectomy.

The effect of bile and gallstones on the peritoneal cavity was evaluated in an experimental animal study. Ninety male Sprague-Dawley rats were randomly allocated to one of six groups (n = 15). Groups 1 to 3 received an intraperitoneal injection (2 mL) of saline, sterile bile, and infected bile, respectively. Groups 4 to 6 underwent a lower midline abdominal incision (3 to 5 mm). In groups 4 and 5, a single gallstone (< 3 mm diameter) was placed in the right upper quadrant and, after closure of the wound, the animals were injected with sterile bile and infected bile, respectively. Group 6 animals underwent laparotomy alone, followed by injection of sterile saline (2 mm). All animals were killed at 4 weeks and the peritoneal cavity was carefully examined. No intra-abdominal lesions were noted in groups 1 to 3. Adhesions were noted in 11 (73%) and 10 (67%) animals of groups 4 and 5, respectively. Two intra-abdominal abscesses were noted in group 4 animals. No intra-abdominal lesions were noted in any group 6 animals. This study suggests that bile in combination with gallstones in the peritoneal cavity is associated with an increased risk of intra-abdominal adhesion formation and possible abscess formation, and that every attempt should be made to retrieve stones lost during cholecystectomy.

Animals↗
PubMed1994

The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials.

The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.

Aged↗
PubMed1994

Using Hawksley random zero sphygmomanometer as a gold standard may result in misleading conclusions.

We combined a database of paired blood pressure measurements taken using the Hawksley random-zero sphygmonanometer and a standard mercury sphygmomanometer and a database of paired measurements made on a SpaceLabs 90202 ambulatory blood pressure recorder and standard sphygmomanometer to determine how the SpaceLabs 90202 would have fared if it had been assessed against the Hawksley random-zero sphygmomanometer instead of a standard sphygmomanometer. The pooled database contained 255 triplicate readings. Using the standard sphygmomanometer as gold standard, the Spacelabs had a median error of 2 mm/Hg for both systolic and diastolic. Against the Hawksley random-zero sphygmomanometer, median error was -3 mm systolic and -6 mm diastolic. The proportion of errors > 10 mm rose from 11% (systolic) and 9% (diastolic) with the standard sphygmomanometer to 16% and 29% with the Hawksley random-zero sphygmomanometer. Because it underestimates systolic and diastolic pressures, the use of the Hawksley random-zero sphygmomanometer as a gold standard may have resulted in misleading conclusions about performance of some automated BP recorders.

Adult↗
PubMed1993

Measurement error in the Hawksley random zero sphygmomanometer: what damage has been done and what can we learn?

The Hawksley random zero sphygmomanometer is used in all aspects of blood pressure research, from clinical trials to evaluation of new blood pressure recorders. It is designed to reduce observer bias in blood pressure measurement. The problem is that it also underestimates blood pressure. Furthermore, this was first reported more than two decades ago. In this paper Rónán Conroy and colleagues explore the consequences of using an inaccurate instrument for important research and why prestigious organisations like the World Health Organisation continue to use it.

Blood Pressure Determination↗
PubMed1993

The association of age with plasma arginine vasopressin and plasma osmolality.

We investigated the association of age with supine and ambulant plasma osmolality (pOSM) and arginine vasopressin (AVP). Twenty-eight healthy-status-defined subjects were studied. Following an overnight fast, blood samples were withdrawn after one hour supine rest and two hours' ambulation. Neither supine nor ambulant pOSM nor AVP varied significantly with age. The results suggest that in healthy subjects age does not influence plasma osmolality or AVP.

Adult↗
PubMed1993

Aging and human hormonal and pressor responsiveness to angiotensin II infusion with simultaneous measurement of exogenous and endogenous angiotensin II.

A decline in the function of the renin angiotensin aldosterone system may induce adaptive changes in response to angiotensin II (ANG II) with age. We have examined platelet ANG II receptor density, blood pressure and aldosterone responses to ANG II [Asn1, Val5-ANG II] (Hypertensin, Ciba Geigy, Horsham, Sussex, England) infusion in 8 young, 24 to 30 years, and 8 older, 54 to 65 years, healthy volunteers. To measure circulating ANG II, we established a new method for specific and simultaneous measurement of exogenous [Asn1, Val5] (Hypertensin) and endogenous [Asp1,Ile5] ANG II in plasma by using isocratic HPLC and radioimmunoassays with cross-reacting antibodies and compared results with immunoreactive ANG II which was measured conventionally using monoclonal antibodies. Baseline endogenous ANG II (Asp1,Ile5-ANG II) levels in venous plasma were marginally, but not significantly, lower in the old [mean (95% confidence limits): 3.4 (< 0.1 to 7.7) v 3.7 (1.2 to 6.2), fmol/mL] and during suppression by the Hypertensin infusion appeared consistently, but not significantly, lower in the old [0.9 (0 to 3.1) v 2.1 (0.6 to 3.7), after 3 ng/kg/min], while the same infusion rate in young and old resulted in similar plasma Hypertensin levels. Baseline systolic blood pressure (SBP) was similar in both groups but the percentage increases in SBP at infusion rates of 1, 3.0, and 10 ng/kg/min were greater in the old than in the young (9.1 v 2.8, P < .05; 16.3 v 8.0, P < .01; 30.4 v 14.0%, P < .001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Relationship between blood pressure measured in the clinic and by ambulatory monitoring and left ventricular size as measured by electrocardiogram in elderly patients with isolated systolic hypertension.

OBJECTIVE: To assess the additional diagnostic precision conferred by ambulatory blood pressure monitoring on clinic blood pressure measurement in evaluating the severity of isolated systolic hypertension. METHODS: The association between left ventricular size as determined by ECG voltages [R-wave voltages in lead V5 (RV5) and S-wave voltages in lead V1 (SV1)] and blood pressure as assessed by clinic measurements and ambulatory blood pressure monitoring was studied in 97 elderly patients included in the placebo run-in phase of the Syst-Eur trial. The additional diagnostic precision conferred by ambulatory monitoring on clinic blood pressure measurements was assessed by relating the residual ambulatory blood pressure level to the ECG-left ventricular size. The residual ambulatory blood pressure level was calculated by subtracting the predicted ambulatory blood pressure level for each patient (using the linear regression equation relating both techniques for the group) from the observed ambulatory blood pressure. RESULTS: Clinic systolic blood pressure was on average 20 mmHg higher (P < 0.001) than daytime ambulatory blood pressure while diastolic blood pressure was similar with both techniques. The sum of SV1 + RV5 was significantly related to clinic systolic pressure (r = 0.25), and 24-h (systolic, r = 0.37; diastolic, r = 0.29), daytime (systolic, r = 0.30; diastolic, r = 0.19) and night-time (systolic, r = 0.33; diastolic, r = 0.28) ambulatory blood pressure levels. These findings were not affected by adjustment for gender, age and the body mass index. The sum of SV1 + RV5 was significantly related to the residual 24-h (systolic, r = 0.30; diastolic, r = 0.31), daytime systolic (r = 0.20) and night-time (systolic, r = 0.31; diastolic, r = 0.29) ambulatory blood pressure monitoring levels. CONCLUSION: Ambulatory blood pressure monitoring adds to the diagnostic precision of clinic blood pressure measurement in assessing the severity of hypertension in this population. The ongoing side project on ambulatory blood pressure monitoring in the Syst-Eur study should establish whether these findings hold true for morbidity and mortality.

Aged↗
PubMed1993

Comparative accuracy of six ambulatory devices according to blood pressure levels.

OBJECTIVE: To assess the accuracy of six ambulatory blood pressure measuring systems at low, medium and high blood pressures. RESULTS: The CH-Druck, Profilomat, SpaceLabs 90207 and Novacor DIASYS 200R, having previously achieved A to C grading for systolic and diastolic blood pressures according to the British Hypertension Society (BHS) protocol and having fulfilled the criteria of the Association for the Advancement of Medical Instrumentation, have been recommended for measurement of ambulatory blood pressure in clinical practice; the Pressurometer IV and Takeda TM-2420, achieved only C and D grades and failed to satisfy the Association for the Advancement of Medical Instrumentation criteria. In this study the data from the original validations are re-analysed for three pressure ranges of systolic and diastolic blood pressures: low range < or = 130/80 mmHg, medium range 130-160/80-100 mmHg and high range > or = 160/100 mmHg. All six devices maintained their overall grading or improved them slightly in the low and medium blood pressure ranges, but in the high blood pressure range the CH-Druck slipped from an overall A/A grading to B/C, the Profilomat from B/A to C/D, the SpaceLabs from B/B to C/C and the Pressurometer IV from C/D to D/D. The Takeda remained unchanged with a D grading, but the results within this grading were worse in the higher blood pressure range, and the Novacor rose from C/C to C/B. CONCLUSIONS: This analysis suggests that the CH-Druck is the most accurate ambulatory system across the pressure range, although it does not perform as well in the high blood pressure range as in the medium and low blood pressure ranges. The SpaceLabs 90207 is accurate in the low and medium blood pressure ranges and reasonably accurate in the high blood pressure range. If blood pressures only in the low and medium ranges are to be measured, a wider selection of ambulatory systems becomes available because, in addition to the CH-Druck and SpaceLabs 90207, the Profiloat and Novacor DIASYS 200R are accurate.

Blood Pressure↗
PubMed1993

Twenty-four-hour ambulatory blood pressure measurement in a primigravid population.

OBJECTIVE: To establish the profiles of 24-h non-invasive ambulatory blood pressure measurement (ABPM) during the trimesters of pregnancy and the puerperium in normotensive healthy primigravidae. DESIGN: A prospective study in which 24-h ABPM was performed on five occasions in each subject: in the first trimester between 9 and 16 weeks' gestation; in the second trimester between 18 and 24 weeks; in the third trimester between 26 and 32 weeks and between 33 and 40 weeks; and finally at 6 weeks post partum. METHOD: One hundred and six Caucasian primigravid women who were normotensive at their first booking visit were recruited consecutively from the antenatal clinic and had 24-h ABPM performed with the SpaceLabs 90207 ambulatory system. RESULTS: Of the 106 women recruited, 98 completed 24-h ABPM on four of the five measurement occasions. Four women delivered prematurely before 33 weeks' gestation, thereby missing one ABPM measurement. Changes during pregnancy and the puerperium were assessed against the ABPM performed in the first trimester. There was no difference for daytime or night-time systolic blood pressure between 9 and 33 weeks, but it rose significantly from 33 to 40 weeks. At 6 weeks post partum, systolic blood pressure was not significantly different from the daytime pressure in the first-trimester ABPM but was raised significantly at night. Diastolic blood pressure decreased significantly between 18 and 24 weeks for both daytime and night-time. From 33 to 40 weeks it increased in parallel with systolic blood pressure, and at 6 weeks post partum it was raised significantly compared with first-trimester values for daytime and night-time. The nocturnal fall in blood pressure was preserved throughout pregnancy with a significant difference between daytime and night-time measurements present on all measurement occasions for systolic, diastolic and mean blood pressures and heart rate. There were significant differences between daytime ABPM and clinic blood pressure for both systolic and diastolic blood pressure up to 33 weeks. From 33 weeks until 6 weeks post partum there was no significant difference between daytime ambulatory and clinic blood pressures. CONCLUSION: This study provides reference values for ABPM in healthy primigravidae with generally uncomplicated pregnancies.

Adult↗
PubMed1993

Antihypertensive therapy and circadian blood pressure profiles: a retrospective analysis utilising cumulative sums.

The results of previous studies on the effects of antihypertensive agents on circadian blood pressure patterns are inconclusive, possibly due to the lack of a simple, objective, universally accepted method of quantifying circadian blood pressure profiles. In order to investigate for differences in the effects of antihypertensive drugs on circadian changes we utilised a recently described modified cumulative sums technique to quantify circadian alteration magnitude (CAM). CAM is simply calculated as the difference between crest and trough blood pressures, the mean blood pressures of the 6-h periods of highest and lowest sustained pressures respectively. The records from all 24-h ambulatory blood pressure monitoring performed over a 7 year period on subjects either on no medication (1208), or on treatment with a single first-line antihypertensive agent (578), were examined retrospectively. A sample (n = 40) stratified for trough diastolic blood pressure, age and sex was randomly selected from each of the following 5 groups: subjects on no medication, and subjects being treated with bendrofluazide, atenolol, class 2 calcium-channel blockers or captopril alone. Untreated subjects, those on bendrofluazide and those on a class 2 calcium channel blocker had similar circadian patterns. Subjects on atenolol therapy (25.9 +/- 1.7/18.3 +/- 1.3, systolic CAM +/- SE/diastolic CAM +/- SE) had attenuated circadian changes (p < 0.05) when compared to the untreated group (29.8 +/- 1.8/23.6 +/- 1.1), while those on captopril (34.9 +/- 2.4/25.7 +/- 1.8) exhibited markedly increased systolic and diastolic circadian blood pressure swings, which differed from those of the atenolol treated group (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Evaluation of blood pressure measuring devices.

Validation of blood pressure measuring devices is a relatively new field of research. There are two national protocols for validating blood pressure measuring devices: the protocol of the American Association for the Advancement of Medical Instrumentation (AAMI) and the protocol of the British Hypertension Society (BHS), each of which has recently been revised. 19 blood pressure measuring devices have been validated according to one or both of these protocols. These protocols have been beneficial in drawing attention to the potential inaccuracy of blood pressure measuring systems, they permit comparison between devices and they have brought manufacturers of blood pressure measuring devices into closer contact with the profession. There are some inherent weaknesses in both protocols which include the fallibility of the 'gold standard', the lack of provision for validation in special circumstances and in special groups, such as the elderly and pregnant women, and failure to allow for deteriorating accuracy with higher pressure levels. The revised BHS protocol attempts to redress these deficiencies.

Blood Pressure Monitors↗