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Biomedical subjects

D O'Regan

Publications and source records attributed to D O'Regan.

13 recordsLinked to original sources

Quantitative assessment of iron-oxide-enhanced magnetic resonance imaging of the liver: Vessel isointensity is a potential characteristic of liver hemangiomas on late T1-weighted images.

PURPOSE: To test whether a new quantitative measure, the tumor-to-vessel ratio, obtained from late post-iron-oxide-enhanced T1-weighted images allows for differentiating hemangiomas from liver metastases or all malignant liver lesions. MATERIAL AND METHODS: Twenty-six patients (mean 57, range 33-79 years) were prospectively studied at 1.5T magnetic resonance imaging (MRI) with a T1-weighted 2D fast low-angle shot (FLASH) sequence (repetition time/echo time/flip angle; 200 ms/4.8 ms/90 degrees ) and a T2-weighted turbo spin-echo sequence (4072 ms/99 ms/180 degrees ). Imaging was carried out before and at intervals up to 18 min after IV injection of Ferucarbotran (Resovist, Schering, Germany). In 19 patients, one representative malignant lesion was analysed. Eleven hemangiomas were evaluated in 7 patients. Two readers performed a consensus reading with a signal intensity measurement in a lesion, normal liver and hepatic veins, from which ratios were computed. RESULTS: On T1-weighted iron-oxide-enhanced MRI of 30 lesions, tumor-to-vessel signal intensity ratios were distinct in hemangiomas (median 1.04, range 0.99-1.10) as opposed to either metastases (0.64, 0.33-0.77; P < 0.05) or all malignant lesions taken together (0.64, 0.33-0.98; P < 0.05), while the tumor-to-liver ratio was not. CONCLUSION: The tumor-to-vessel ratio may help to differentiate between hemangiomas and metastases. A ratio greater than 0.98 allowed differentiating hemangiomas from metastases with a wide safety margin.

Adult↗

Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology.

Glucocorticoid overexposure in utero may underlie the association between low birth weight and subsequent development of common cardiovascular and metabolic pathologies. Previously, we have shown that prenatal dexamethasone (DEX) exposure in rat reduces birth weight and programs the hypothalamic-pituitary axis and fasting and postprandial hyperglycemia in adult males and hypertension in adult males and females. This study aimed to determine 1) whether there were gender differences in prenatal DEX-programmed offspring, and 2) whether the renin-angiotensin system (RAS) plays a role in the programming of hypertension. Rats exposed to DEX in utero (100 microg.kg(-1).day(-1) from embryonic days 14-21) were of lower birth weight (by 12%, P < 0.01) and displayed full catch-up growth within the first month of postnatal life. DEX-treated male offspring in adulthood selectively displayed elevated plasma adrenocorticotropic hormone (by 221%) and corticosterone (by 188%, P < 0.05), postprandial insulin-glucose ratios (by 100%, P < 0.05), and hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (by 38%, P < 0.05). Conversely, DEX-programmed females were hypertensive (by 11%, P < 0.05), with elevated hepatic angiotensinogen mRNA expression (by 9%, P < 0.05), plasma angiotensinogen (by 61%, P < 0.05), and renin activity (by 88%, P < 0.05). These findings demonstrate that prenatal glucocorticoids program adulthood cardiovascular and metabolic physiology in a gender-specific pattern, and that an activated RAS may in part underlie the hypertension associated with prenatal DEX programming.

Adrenocorticotropic Hormone↗

Characteristics of arterial wall shear stress which cause endothelium-dependent vasodilatation in the anaesthetized dog.

1. The effects of changes in the mean and amplitude of arterial wall shear stress on endothelium-dependent arterial dilatation of the iliac artery of the anaesthetized dog were examined. 2. Changes in the mean and amplitude of blood flow and wall shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and the stimulation of the left ansa subclavia. Changes in the diameter of a segment of the iliac artery with the endothelium intact, relative to a segment with no endothelium, were used as an index of the release of nitric oxide. 3. The increase in mean blood flow was from 84 +/- 12 to 527 +/- 53 ml min-1 and in amplitude was from 365 +/- 18 to 695 +/- 38 ml min-1 (means +/- S.E.M.). The increase in mean wall shear stress was from 1.78 +/- 0.30 to 7.66 +/- 1.01 N m-2 and in amplitude was from 7.37 +/- 0.46 to 13.9 +/- 2.00 N m-2 (means +/- S.E.M.). 4. Increases in mean shear stress caused an increase in the diameter only of the section of artery with endothelium; the slope of the relationship was 0.064 +/- 0.006 mm N-1 m2 (mean +/- S.E.M., P < 0.001); changes in the amplitude of shear stress did not cause an increase in diameter. Changes in both the mean and amplitude of shear stress had no significant effect on the diameter of the section of artery with no endothelium. 5. These findings coupled with the known anti-atheroma effects of nitric oxide and the effect of shear stress on cell adhesion and platelet aggregation offer a possible explanation for the disposition of atheroma in those parts of the arterial system which have low mean and high amplitude of wall shear stress.

Acetylcholine↗

Glucocorticoid programming of pituitary-adrenal function: mechanisms and physiological consequences.

Increasing epidemiological evidence supports the notion that adverse events in fetal life permanently alter the structure and physiology of the adult offspring, a phenomenon dubbed 'fetal programming'. In particular, low weight or thinness at birth in humans is associated with an increased risk of cardiovascular and metabolic disorders as well as neuroendocrine dysfunction in adult life. Glucocorticoid administration during pregnancy is well-documented to both reduce offspring birth weight and alter the maturation of organs (hence their use to accelerate fetal lung maturation in premature labour). Here data are reviewed which show, in rodents and other models, that antenatal exposure to endogenous or exogenous glucocorticoids reduces offspring birth weight and produces permanent hypertension, hyperglycaemia, hyperinsulinaemia, altered behaviour and neuroendocrine responses throughout the lifespan. Processes underlying fetal programming include determination of the 'set point' of the hypothalamic-pituitary-adrenal (HPA) axis and of tissue glucocorticoid receptor (GR) expression. Similar HPA axis hyperreactivity occurs in lower birth weight humans and may be an early manifestation of the 'low birth weight' phenotype.

Adult↗

Progression to 100% off-pump coronary artery bypass with the Octopus 1 dual holder.

BACKGROUND: Can off-pump coronary artery bypass grafting become the routine standard in all elective primary coronary artery bypass grafting (CABG) operations? This paper shows how this aim has been achieved during one year in 130 off-pump cases performed through a sternotomy. This strategy allows for full revascularization (up to six grafts) without the disadvantage of cardiopulmonary bypass. The study introduces a variant of the Octopus stabilizer, a single Octopus 1 arm (Medtronic, Inc., Minneapolis, MN) with a dual holder. MATERIALS AND METHODS: From November 1998 through February 2000, 130 patients underwent coronary artery bypass grafting through a sternotomy off-pump utilizing a stabilizer and CO2 blower. The stabilizer most frequently used to achieve this was a single Octopus 1 arm equipped with a dual holder to accommodate two straight suction pods. The holder allowed increased flexibility and manipulation of the suction pods with an equivalent of seven degrees' freedom of motion at the dual holder junction. Techniques for carrying out total revascularization are discussed. The progress of proportion of elective primary CABG revascularization performed off-pump is shown and results are compared with published reviews of the literature for off-pump coronary revascularization. RESULTS: Patient demographics included: age range 32 to 87, mean 61.3; female sex: 17%; ejection fraction < 50%: 54%; presence of left main stem disease: 17%. Overall Parsonnet risk score ranged 0-31, with a mean of 8.8. Graft numbers carried out were: 34 x 2, 34 x 3, 32 x 4, 25 x 5 and 5 x 6 anastomoses respectively. The mean number of distal anastomoses was 3.6 +/- 1.0. There was extensive coverage of the lateral aspect of the heart (153 circumflex territory grafts, 33%). Radial artery, left internal mammary artery or saphenous vein sequential (jump) grafts were used in 26 cases (20%). Apart from general experience, the use of the dual holder and wide opening of the right pleura were the two important factors allowing freedom for multi-vessel lateral and posterior wall grafting. Thirteen Genzyme (Genzyme Surgical Products, Inc., Cambridge, MA) and ten Octopus 2 (or 2+) stabilizers were used, mostly for two or three grafts. The remainder were carried out using the Octopus 1 (dual holder: 83). In the first three-month period, 31% of cases were off-pump compared to the last three-month period, when 96% were off-pump. In the last two months we performed 100% of all 27 cases referred off-pump. There were no deaths, strokes or myocardial infarctions. Ventricular arrhythmia occurred in two cases. Conversions to bypass were undertaken twice. Two unexpected renal failures occurred, neither of which were from the 13 patients with preoperative incipient renal failure, of whom none suffered a rise in postoperative creatinine of greater than 30%. The results compare favorably with published results despite having a large mean number of grafts of 3.6. CONCLUSION: Off-pump surgery with full revascularization has now become feasible for all primary elective coronary artery graft operations.

Adult↗

Use of a pulsatile beating heart model for training surgeons in beating heart surgery.

BACKGROUND: Coronary artery bypass on the beating heart has undergone resurgence with the introduction of minimally invasive techniques and new stabilizing devices. It is important to develop a method for training surgeons to perform accurate anastomoses despite cardiac motion and to develop the skills needed for consistent results in this demanding field. METHODS: A prosthetic model of the beating heart was created by Limbs and Things, Ltd. (Bristol, UK) and used in our center to simulate clinical situations of beating heart surgery. Anastomotic quality was evaluated using a pre-established set of criteria on patency and suturing with each anastomosis graded on a 12-point scale. RESULTS: The average scores for trainees using the Pulsatile Beating Heart Model were 8.5 while that of the expert surgeon with MIDCAB experience was 11. Defects seen included cross-wall suturing and significant narrowing of the toe of the anastomosis. Scores improved with increasing practice during each session. Operators with more clinical experience scored higher. All surgeons felt the model duplicated the exposure and feel of the tissue characteristic of clinical cases. CONCLUSIONS: The beating heart simulator provides excellent training for new as well as experienced surgeons, provides visual feedback of anastomotic errors, and instills increasing confidence in the participants in their ability to construct accurate anastomoses on the beating heart.

Cardiopulmonary Bypass↗

Aprotinin and bleeding in profoundly hypothermic perfusion.

Clinical observation led us to believe that aprotinin fails to preserve haemostatic function in patients undergoing deep hypothermic perfusion with or without circulatory arrest. A retrospective study was made of blood loss in 80 consecutive acute Type A dissection patients before and during the aprotinin era (1987-1992). After 1988 all patients were cooled below 20 degrees C pending circulatory arrest. Fourteen patients underwent aortic root replacement and 66 replacements of the ascending aorta. Age distribution (range 22-79 years) and type of operation were similar in the aprotinin and control groups. The impervious Hemashield (Meadox) graft was used for all but five patients. These underwent aortic root replacement with preclotted, valved conduits. Overall the mean blood loss for 27 patients operated without aprotinin was 837 ml per 24 h (standard error +/- 90) and for 53 patients with aprotinin 1,929 ml per 24 h (standard error +/- 90). There was a significant difference between the two groups when profoundly hypothermic perfusion was used, with greater bleeding in aprotinin-treated patients. There were six re-entries in the aprotinin group and none in the control patients. There were ten hospital deaths (11.1%). A greater incidence of bleeding and thrombosis-related deaths was recorded for the aprotinin-treated patients. In addition, four surviving aprotinin patients suffered severe coagulation defect with blood loss greater than 4,500 ml and platelets less than 50 x 10(6). We suggest that aprotinin inhibits the protease enzymes which maintain the fluid state of blood during hypothermic low flow and arrest states. Disseminated intravascular coagulation may consume platelets thereby predisposing to abnormal bleeding and potentially fatal thrombotic events. The use of aprotinin in profoundly hypothermic perfusion should be adopted cautiously.

Adult↗

Does modern cardiac surgery require conventional intensive care?

We considered that, with modern perfusion equipment and mildly hypothermic cardiopulmonary bypass, protracted post-operative ventilation in an intensive care unit (ITU) is no longer required after most cardiac operations. We used a three-bedded cardiac recovery area (CRA) within the operating suite for 1,000 patients between January 1990 and June 1991. Forty-five patients with special needs were managed in the ITU. The time to extubation (T50%; range) for coronary bypass, aortic valve, mitral valve, and double-valve patients was 2.0 (0-42), 2.5 (0-12), 3.0 (0-15), and 3.0 (1-36) hours, respectively. Recovery beds were re-used allowing 5-6 operations daily. The difference in nursing staff complement for a CRA versus ITU bed was 4.5/7.8. Patient management was by nurse specialists supported by cardiac surgeons. Intervention by cardiac anaesthetists or intensivists was limited to specific ventilatory problems or renal failure. The early extubation policy failed in ten patients (five coronary, three aortic, one mitral and one double-valve patient) through poor pre-operative respiratory function, left ventricular failure or intra-operative events. The overall mortality in CRA was 1.4%. The mean duration of post-operative stay was 7 days (range 5-12). We conclude that a CRA staffed by nurse practitioners provides a safe and effective alternative to the anaesthetist-managed ITU. A rapid turnover of CRA beds removes the constraints of ITU bed availability.

Adolescent↗

A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition.

The effects of clorgyline were compared with the effects of (-)-deprenyl using measures of rewarding hypothalamic self-stimulation, regional monoamine metabolism and monoamine oxidase activity. Male Wistar rats trained to self-stimulate at half-maximal rates with unilateral bipolar lateral hypothalamic electrodes on a continuous reinforcement schedule were implanted subcutaneously with osmotic minipumps which delivered 1 mg X kg-1 drug per day or vehicle for 13 days. A response rate/stimulation frequency (reward summation) function was determined the day before minipump implantation and on days 5 and 13 of drug administration. Only clorgyline induced a shift to the left in the reward summation function at 5 and 13 days, indicating enhancement of reinforcement. Clonidine (50 micrograms X kg-1 IP) probe tests were run on days 2 and 10 to determine the sensitivity of alpha 2-noradrenaline receptors. Clorgyline induced an attenuation of the clonidine response on day 10 relative to day 2. The other groups exhibited no change in response to clonidine. Clorgyline also induced a progressive increase in self-stimulation rates; this effect was not observed with the other groups. The clorgyline effects were accompanied by an increase in regional brain levels of dopamine, noradrenaline and 5-hydroxytryptamine and a reduction of their acid metabolites. Clorgyline selectively inhibited type A monoamine oxidase, whereas (-)-deprenyl selectively inhibited type B monoamine oxidase.

Animals↗

An assessment of occult blood testing to determine which patients with large bowel symptoms require urgent investigation.

One hundred and fifty-two consecutive patients with symptoms suggestive of colorectal disease were offered occult blood testing before undergoing barium enema examination or colonoscopy; one hundred and thirty-nine successfully completed the test. Thirty-four had positive results of whom thirteen had a cancer and eight an adenomatous polyp (diagnostic yield for neoplasia of 59 per cent). No false negative results occurred, a sensitivity of 100 per cent, and only 21 false positives occurred, a specificity for malignancy of 84 per cent. Subjects attending outpatients should be offered occult blood testing; those with a positive test should undergo colonoscopy. The cost-benefit of such a scheme is emphasized.

Aged↗

HLA antigen frequencies in an Irish population.

Two-hundred-and-fifty-three unrelated Irish adults were typed for 24 alleles at the HLA--A and B loci. A high frequency of HLA--B8 (34.8%) was observed compared with results published for other populations. Results of other gene frequencies, haplotype frequencies and linkage disequilibrium values were similar to those of Caucasian population studies. Close similarity of HLA polymorphism distribution was seen in relation to another relatively homogeneous Celtic population from the islands of the Outer Hebrides, off the coast of Scotland.

Alleles↗

HlA antigens and steroid responsive nephrotic syndrome of childhood.

Fifty-four unrelated children with steroid responsive nephrotic syndrome of childhood were studied for 24 alleles at the HLA--A and B loci. A significantly increased incidence of HLA--B8 (Pc less than 0.01) was observed compared to controls. No association between response to cyclophosphamide therapy and HLA antigens was seen.

Adrenal Cortex Hormones↗