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Biomedical subjects

R A Perry

Publications and source records attributed to R A Perry.

At least 37 records · Page 2Linked to original sources

Disorders of the avian integument.

The avian integument consists of highly specialized structures that show extreme variations between species. Feathers are the most obvious part of the integument, and their color and beauty forms an important basis for the attraction of birds to humans. Any disorder in the feathers can be distressing for a client and frustrating for the avian practitioner. The cause of some disorders may be apparent, but others have a complex pathogenesis involving management, human-bird interaction, malnutrition, psychologic factors, disease, or hormone imbalances.

Animal Nutritional Physiological Phenomena↗

Changes in Doppler indices of cardiac function during and after percutaneous transluminal coronary angioplasty.

OBJECTIVE: To assess the sensitivities of Doppler indices to changes in global cardiac function during and after controlled myocardial ischaemia induced by coronary angioplasty. DESIGN: Continuous wave Doppler signals of aortic flow were recorded during coronary angioplasty. The following Doppler indices of cardiac function were measured before, during, and after balloon inflation: V (peak velocity), MA (mean acceleration), V2/T (T = time from onset to peak ejection), and MD (minute distance corrected for baseline heart rate). SETTING: A tertiary care cardiological unit in a university hospital. PATIENTS: Sixteen patients undergoing coronary angioplasty of the left anterior descending coronary artery. Eight patients had multivessel disease. MAIN OUTCOME MEASURES: The primary outcome measures were planned before data collection began. RESULTS: 12 patients showed a significant fall of three or more Doppler indices from their baseline values during balloon inflation. This occurred in all patients with multivessel disease. The Doppler indices V2 T, MD, V, and MA fell by 43.7%, 37.7%, 27.4%, and 23% respectively from their baseline values (p less than 0.0001). The relative sensitivities of the Doppler indices to ischaemia were V2/T greater than MD (p less than 0.02), MD greater than (p less than 0.001), and V greater than MA (p less than 0.01). The impairment of global left ventricular function resulting from brief balloon inflation during single vessel angioplasty was reversible in all the patients. CONCLUSIONS: The Doppler indices V2/T, MD, V, and MA are all sensitive, in order of magnitude, to falls in global cardiac function resulting from ischaemia. They may prove useful for assessing cardiac function during ischaemia in the clinical setting.

Adult↗

Analysis of the appearance of fenestrations in the blood vessels of the fetal sheep pituitary.

Using electron microscopy, the appearance of fenestrations within blood vessels of the fetal sheep pituitary gland was studied at 40, 80 and 122 days of gestation (term = 150 days). While fenestrations were extremely rare at 40 days of gestation, blood vessels contained characteristic regions of narrow endothelium, termed attenuations. There was an increase in the frequency of fenestrations with increasing gestational age, while there was a decrease in the number of attenuations, to the extent that the latter were not observed at 122 days of gestation. In order to examine the 'leakiness' of vessels with relatively few fenestrations, the fate of intracardially injected horseradish peroxidase (HRP) was studied in 50- and 51-day fetuses. Flocculant HRP reaction product was observed in the lumen of pituitary blood vessels, within endothelial cells, as well as within perivascular spaces and intercellular spaces between pituitary glandular cells. HRP was also observed in internalised vesicles within pituitary cells. These results indicate that even though fenestrations are scarce at early gestational ages, blood-borne substances can leave the portal network to interact with pituitary cells. The previously reported patency of the portal vascular system in the immature fetus is supported by our observations.

Animals↗

The effect of hypothalamo-pituitary disconnection on the functional and morphologic development of the pituitary-adrenal axis in the fetal sheep in the last third of gestation.

We have investigated the effect of hypothalamo-pituitary disconnection (HPD) on the maturation of basal ir-ACTH and cortisol concentrations in fetal sheep plasma, and on the development of the anterior pituitary corticotroph population in the last third of gestation. After HPD, fetal plasma ir-ACTH concentrations were significantly elevated, and continued to rise with increasing gestational age. However, despite elevated ir-ACTH concentrations, there was no increase in fetal plasma cortisol concentrations, and parturition was delayed for at least 8 days beyond normal term. Furthermore, HPD resulted in a significant disruption of the maturation of the pars distalis corticotrophs. We also examined the change in fetal plasma concentrations of ir-ACTH and cortisol to exogenous CRF after HPD. There was a significant increase in plasma ir-ACTH in response to CRF administration in the HPD fetuses, which was qualitatively similar to that observed in sham-operated fetuses. In contrast, the plasma cortisol response was less in HPD fetuses when compared to that in sham-operated fetuses. The results of this study demonstrate that ir-ACTH secretion is not maintained by the fetal hypothalamus in the last third of gestation, and that ir-ACTH secretion is tonically inhibited by the hypothalamus during this time. The disconnection of the pituitary from the hypothalamus disrupts the maturation of the pituitary-adrenal axis, thus demonstrating the fundamental importance of the hypothalamo-pituitary axis in the normal maturational cascade which culminates in birth in this species.

Adrenal Glands↗

Effect of adrenalectomy or long term cortisol or adrenocorticotropin (ACTH)-releasing factor infusion on the concentration and molecular weight distribution of ACTH in fetal sheep plasma.

It is unclear whether the maturation of corticotrophs from the fetal to the adult type in the fetal sheep pituitary in late gestation is associated with changes in the sensitivity of the fetal pituitary to corticotrophic secretagogues and in the form of ACTH-containing peptides (IR-ACTH) secreted into the circulation. The maturation of the pituitary corticotroph population is known to be accelerated by intrafetal cortisol infusion and delayed by bilateral fetal adrenalectomy. We have therefore investigated the mol wt profile of IR-ACTH present in fetal sheep plasma from 110 days gestation until term (147 +/- 3 days) and determined whether intrafetal cortisol infusion between 105-117 days (2.5 mg cortisol/day), or bilateral fetal adrenalectomy can alter the mol wt profile of IR-ACTH in fetal sheep plasma. We have also investigated whether prior exposure to cortisol alters the subsequent responsiveness of the fetal pituitary to a long term infusion of ovine (o) CRF (10 micrograms oCRF/day). In the control group, the proportion of IR-ACTH which eluted in the low-mol wt (LMW) range (i.e. less than 12K) was significantly higher between 121-125 days (43.9 +/- 4.2%) than between 126-139 days (26.8 +/- 9.3%) but not different to that after 140 days gestation (29.9 +/- 5.5%). Between 110-117 days, cortisol infusion had no effect on the proportion of IR-ACTH in the LMW range (43.9 +/- 5.7%, saline infused; 44.1 +/- 2.4%, cortisol infused). Between 121-125 days, the proportion of IR-ACTH in the LMW range in the CRF-infused groups (with or without prior exposure to cortisol) was significantly lower (27.4 +/- 2.1%) than in the saline-infused control group. In contrast, after fetal adrenalectomy, the proportion of IR-ACTH in the LMW range between 126-139 days was significantly higher (48.0 +/- 6.7%) than in intact control animals (23.8 +/- 3.5%). We conclude that the change in the mol wt profile of IR-ACTH in fetal plasma after 125 days may be a consequence of changes in the morphological and/or functional characteristics of the corticotrophic cells in the fetal pituitary. Infusion of oCRF appears to accelerate the normal maturation of the fetal pituitary-adrenal relationship, and oCRF acting either directly or via secretion of cortisol may play a role in the posttranslational processing of POMC in the fetal sheep pituitary after 125 days gestation.

Adrenalectomy↗

An objective computer system for the quantification of artery stenoses.

We have developed a low cost, clinically usable system for the objective assessment of the severity of coronary artery stenoses from single view angiograms. The system is based on a desktop computer with incorporated frame grabber. Images are captured by means of a video camera. The user selects a region of interest which encompasses the stenosis. Facilities are provided for automatic or manual definition of the artery centre line and edges. The computer then calculates the artery diameter and cross-sectional area by videodensitometry along profile lines which are orthogonal to the long axis of the artery. These results can be expressed numerically as a percentage stenosis when compared to a normal region of the artery. The image is corrected for geometric distortion using a grid test object. The image grey scale is corrected by means of a ramp test object such that a pixel value is proportional to the attenuator thickness. The ramp is placed on the patient during the X-ray examination and an iterative technique has been developed for subtracting the underlying structures from the superimposed ramp image. The system has been assessed using test objects constructed in Perspex which simulate arteries of known cross-sectional area and stenoses of known severity.

Algorithms↗

Sustained improvement in left ventricular function after successful coronary angioplasty.

The short and long term effects of successful percutaneous transluminal coronary angioplasty on left ventricular function, at rest and on exercise were investigated in 49 patients. Thirty-four had had no previous infarction (group 1) and 15 had (group 2). Technetium-99m gated blood pool images were obtained at rest and during exercise before, six weeks after, and a mean of fifteen months after successful angioplasty. Before angioplasty the mean (SD) ejection fraction fell significantly on exercise in both groups from 58 (10)% to 53 (13)% in group 1 and from 48 (10)% to 40 (16)% in group 2. This change was paralleled by a worsening wall motion score (from 0.6 (0.4) to 1.6 (1.2) in group 1 and from 2.3 (1.9) to 3.3 (2.4) in group 2). Six weeks after the procedure there was little change in resting ejection fraction but it increased significantly on exercise (to 62 (11)% in group 1 and to 53 (13)% in group 2). There was a concomitant significant improvement in the exercise wall motion score (to 0.4 (0.6) in group 1 and to 1.8 (1.1) in group 2). This improvement in exercise ejection fraction and wall motion was maintained at later follow up with no significant deterioration in either variable and a clearly sustained improvement in ejection fraction (60 (10)% in group 1 and 51 (10)% in group 2) and wall motion score (0.2 (0.2) in group 1 and 1.3 (0.8) in group 2) compared with values before angioplasty. The initial improvement in left ventricular function on exercise after successful angioplasty was maintained for at least 9-24 months both in patients with previous myocardial infarction and in those without.

Angioplasty, Balloon, Coronary↗

Hypothalamo-pituitary disconnection in the fetal sheep.

In this study we have applied the technique of hypothalamo-pituitary disconnection (HPD) to the fetal sheep at 108-112 days of gestation. The pituitary is surgically disconnected from the hypothalamus by the removal of the neural component of the median eminence above the level of the portal circulation. This procedure results in the complete disconnection of the pituitary from the hypothalamus. After HPD, the lactotroph response to the dopamine antagonist chlorpromazine was significantly reduced (p less than 0.005) indicating the functional isolation of the pituitary gland from the hypothalamus. The increase in plasma prolactin in response to exogenous thyrotrophin-releasing factor was maintained following HPD. HPD resulted in the complete atrophy of the pars nervosa. At 132-135 days of gestation after HPD there was no change in the volume or appearance of the pars distalis; small infarcts were observed in the pars distalis of some HPD fetuses, but these occupied less than 1% of the volume of the anterior lobe of the pituitary. There was a significant increase (p less than 0.05) in the volume of the pars intermedia after HPD. Gestation was prolonged for at least 8 days beyond normal term following HPD, indicating that the processes integral to the initiation of parturition at term had been disrupted. We conclude that HPD provides a good in vivo model for the investigation of the activity of the isolated pituitary gland, and for the examination of the role of neuroendocrine mechanisms in fetal sheep development in the latter third of gestation.

Animals↗

Proopiomelanocortin messenger RNA levels are increased in the anterior pituitary of the sheep fetus after adrenalectomy in late gestation.

We have investigated the effect of bilateral adrenalectomy at 116-119 days' gestation on the levels of the messenger (m) RNA for proopiomelanocortin (POMC) in the anterior pituitary of the fetal sheep and in the ovine placentome during late gestation (134-136 days' gestation). After fetal adrenalectomy there was a significant (p less than 0.001) and sustained increase in circulating ACTH concentrations in the adrenalectomised group (1,838 +/- 155 ng/l at 130-136 days) when compared with the intact control group (131 +/- 25 ng/l at 130-136 days). The mean levels of POMCmRNA relative to 18S RNA were also significantly higher (p less than 0.001) in the adrenalectomised fetal sheep pituitaries (2.8 +/- 0.12; n = 4) than in the intact/control fetal sheep pituitaries (1.31 +/- 0.13; n = 4). In contrast to the findings in the anterior pituitary, POMCmRNA was not detected in RNA extracted from the placentomes of either the adrenalectomised or intact fetal sheep. There was also a significant arteriovenous difference in ACTH concentrations in the umbilical circulation in both adrenalectomised and intact fetal sheep at 134-136 days' gestation. This study demonstrates therefore that the fetal adrenals act to suppress POMCmRNA levels in late gestation and also that the increase in circulating ACTH after adrenalectomy originates from the pituitary and not the placentome.

Adrenalectomy↗

Total coronary arterial occlusion: real or apparent?

We describe a case in which the angiographic appearance of total occlusion of the left anterior descending coronary artery was not due to a complete anatomical obstruction, but due to competitive and retrograde flow in the distal segment of the artery from collaterals via the contralateral vessel. This case has implications on our current practice and results of coronary angioplasty in total coronary arterial occlusion.

Angina Pectoris↗

Balloon occlusion during coronary angioplasty as a model of myocardial ischaemia: reproducibility of sequential inflations.

In order to evaluate the potential of balloon occlusion during coronary angioplasty as a model of myocardial ischaemia in man we have measured coronary sinus blood flow (CSBF), myocardial oxygen consumption (MVO2), lactate extraction (LER) and electrocardiographic changes in 11 patients undergoing left anterior descending artery (LAD) angioplasty. Baseline measurements were made before balloon crossing and between inflations. Four consecutive inflations each of 60 s duration were made; 5 min return to baseline was allowed between inflations. There was a significant reduction in CSBF and MVO2 (ml min-1) during inflations 2, 3 and 4 (CSBF: 121 +/- 66----94 +/- 53, 113 +/- 49----99 +/- 42, 124 +/- 66----102 +/- 41, P less than 0.02; MVO2: 11.3 +/- 6.6-9.1 +/- 3.9, 10.4 +/- 3.7-8.7 +/- 2.4, 12.2 +/- 4.4----9.4 +/- 2.8, P less than 0.05). However during the first period of balloon occlusion there were inconsistent changes in coronary flow with an overall rise in mean flow (97 +/- 35----128 +/- 80 ml min-1, P = NS) and an overall rise in mean myocardial oxygen consumption (9.6 +/- 3.8----12.5 +/- 7.5 ml min-1, P = NS). There was lactate production during all four inflations but the changes during the first one did not achieve statistical significance. These inconsistent changes during the first inflation were thought to be due to partial obstruction of the stenosis by the deflated balloon before primary dilatation. The changes due to crossing and during the first two inflations were further investigated in another group of 12 patients undergoing LAD angioplasty. Great cardiac vein flow (GCVF), CSBF, MVO2 and LER were recorded at baseline, during crossing and during the first two inflations. With the deflated balloon across the stenosis there were no changes in CSBF or MVO2 but there was a fall in GCVF (103 +/- 28----77 +/- 50, P = NS) and a significant fall in LER (77 +/- 57----16 +/- 37, P less than 0.01). Although there was a fall during the first inflation in CSBF, GCVF, MVO2 and lactate extraction none of these changes were significant. During the second inflation these changes were of greater magnitude and achieved statistical significance. While balloon occlusion during coronary angioplasty has the potential of providing a model of ischaemia in man we have found the first inflation period unreliable, due to the variable degree of occlusion by the deflated balloon. We suggest that only subsequent inflations after the primary dilatation are used for observations.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗

The development of corticotrophs in the fetal sheep pars distalis: the effect of adrenalectomy or cortisol infusion.

At 90 days gestation a uniquely fetal-type and an adult-type corticotroph have been observed in the fetal sheep pars distalis (term approximately 147 days). Between 90 and 130 days gestation the fetal type is predominant, and its numbers decline toward term. In this study the effect of the endogenous cortisol surge on the change in the population of corticotrophs in the pars distalis was investigated in sheep fetuses after bilateral adrenalectomy at 120 days gestation or after an infusion of 2 mg cortisol/day between 109 and 115 days gestation. The total proportion of corticotrophs, expressed as a percentage, decreased significantly (P less than 0.01) from 115 days in saline-infused controls (21.09 +/- 1.10%) and 135 days in intact controls (14.59 +/- 1.12%). The percentage of adult-type corticotrophs increased significantly (P less than 0.01) from 5.65 +/- 0.77 at 115 days, to 11.93 +/- 1.41 at 135 days. The percentage of fetal-type corticotrophs decreased significantly (P less than 0.001) from 14.91 +/- 0.35 at 115 days to 2.33 +/- 0.48 at 135 days. A small proportion of ACTH-immunoreactive cells could not be defined as either adult- or fetal-type corticotrophs. These changes in the corticotroph population had not occurred at 135 days in fetuses that had been adrenalectomized at 120 days; the percentage of corticotrophs relative to unstained cells (21.70 +/- 0.46%), the percentage of adult-type corticotrophs (6.42 +/- 0.29%), and the percentage of fetal-type corticotrophs (14.65 +/- 0.49%) were similar to those in 115-day-old fetuses, indicating that the normal change in the corticotroph population between 115 and 135 days gestation was dependent upon the presence of the fetal adrenal. In fetuses exposed to exogenous cortisol between 109 and 115 days gestation, the percentage of corticotrophs relative to unstained cells (16.53 +/- 1.68%), the percentage of adult-type corticotrophs (12.40 +/- 1.34%), and the percentage of fetal-type corticotrophs (3.78 +/- 0.58%) were similar to those at 135 days. This indicates that a short period of increased fetal plasma cortisol can bring about premature maturation of the corticotrophs in the fetal sheep pars distalis. We have also described an ACTH-immunoreactive cell which has characteristics of both an adult- and a fetal-type corticotroph. Its morphological appearance suggests that it may be a transitional stage from the fetal- to the adult-type corticotroph.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

Coronary angioplasty in unstable angina and stable angina: a comparison of success and complications.

One hundred and five patients with unstable angina and 175 with chronic stable angina were treated by primary percutaneous transluminal coronary angioplasty. Patients with unstable angina had had symptoms for a shorter time and were more likely to have angiographically complex lesions and lesions less than 10 mm in length than patients with chronic stable angina. Other baseline variables were not significantly different in the two groups. The overall primary success rate was similar in both groups (87% v 86%). Nine of the 14 unsuccessful procedures in those with unstable angina and nine of the 24 unsuccessful procedures in those with stable angina were the result of acute occlusion. These results led to a 9% frequency of procedure related myocardial infarction in patients with unstable angina and a 5% rate in those with stable angina (NS). The procedure related infarct rate tended to be higher in patients with unstable angina who had coronary angioplasty soon after an episode of unstable angina (mean 10 days) than in those in whom it was delayed (mean 35 days) (12% v 3%) (NS). In patients with unstable angina who had had a previous myocardial infarction procedure related infarction was significantly more common (18%) than in patients with no previous myocardial infarction (3%). The difference between those with and without previous infarction was also significant in patients with stable angina (10% v 3%).

Angina Pectoris↗

Management of unstable angina soon after myocardial infarction.

The recurrence of angina soon after myocardial infarction is not uncommon and represents areas of viable myocardium at risk from infarct extension and thus a worse prognosis. A better understanding of the pathogenesis of acute ischaemic syndromes and developments in interventional cardiology in the past decade have helped us rationalize our approach to this high-risk subset and achieve maximal myocardial salvage with its short- and long-term benefits.

Adrenergic beta-Antagonists↗

Success and complication rates of coronary angioplasty in patients with and without previous myocardial infarction.

The primary success rate and incidence of major complications have been retrospectively assessed in a consecutive series of 224 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) in one centre. The patients have been divided into three groups; those with angina and no previous myocardial infarction (Group 1; N = 130), those with angina and a previous transmural myocardial infarction (TMI) (Group 2; N = 59), and those with angina and a previous non-transmural myocardial infarction (NTMI) (Group 3; N = 26). The three groups were well matched for age, gender and angiographic severity of stenosis. The primary success rate in Group 1 was 90% compared to 64% in Group 2. The success rate in Group 3 lay in between at 77%. The lower success rates in Groups 2 and 3 were mainly due to an increase in the frequency of major complications. Acute coronary occlusion occurred in seven patients in Group 1, nine patients in Group 2 and four patients in Group 3. In all these patients in Groups 2 and 3 the outcome of acute occlusion was a procedure-related clinical myocardial infarction despite immediate re-angioplasty and/or emergency coronary artery bypass grafting whereas only four patients in Group 1 sustained an acute infarct. In this series of patients undergoing coronary angioplasty for symptom limiting angina, previous myocardial infarction appears to be a risk factor for a lower success rate mainly due to an increase in the frequency and severity of major complications.

Adult↗

Studies on the maturation of the small intestine of the fetal sheep. I. The effects of bilateral adrenalectomy.

The effect of bilateral adrenalectomy at 120 d gestation on subsequent maturation of proximal and distal small intestine was investigated in chronically catheterized fetal sheep. Ten adrenalectomized and fourteen controls were examined at 136 d; some following infusion of [3H]thymidine at 3-6 d or 4 h before termination of pregnancy. Mean plasma cortisol levels were 5.3 +/- 0.7 ng/ml in the adrenalectomized group; control values ranged from 14 to 39 ng/ml level during the 2-week experimental period. Fetal body growth was significantly increased following adrenalectomy. In the small intestine, growth of mucosal structures was reduced, especially in distal regions. Villus height was significantly reduced in both regions. External muscle thickness was significantly increased in both regions. Despite these changes there was no alteration in villus enterocyte morphology, nor were there any significant changes in villus or crypt densities. The proportion of crypt cells labelled with [3H]thymidine was unaffected by adrenalectomy. In proximal regions, migration rate of labelled enterocytes declined from 12.0 to 5.83% villus height/d (P less than 0.025) after adrenalectomy; there was no change in migration rate in distal regions. The estimated renewal time was greater in both proximal and distal regions in adrenalectomized compared with control fetuses.

Adrenalectomy↗

Studies on the maturation of the small intestine in the fetal sheep. II. The effects of exogenous cortisol.

The effect of cortisol on small intestinal maturation was investigated in catheterized fetal sheep by infusing 2 mg cortisol/d between 105 and 115 d gestation (term ca. 147 d). This treatment resulted in a fivefold increase in plasma cortisol compared with catheterized control fetuses of the same age. There were no detectable changes in enterocyte morphology after the cortisol infusion; the size and density of most intestinal components were largely unaffected by the treatment. By contrast, the kinetics of the enterocyte population were significantly altered by the raised cortisol levels. The proportion of crypt cells labelled was significantly increased from 0.20 +/- 0.04 to 0.33 +/- 0.03 in the proximal region (P less than 0.01) and from 0.22 +/- 0.03 to 0.31 +/- 0.02 in the distal region (P less than 0.01). The migration of enterocytes in both regions was significantly increased to nearly twice the control values (P less than 0.05). Correspondingly, renewal time was almost halved in both regions, while cell density was unchanged in distal and decreased in proximal regions. Hence cell loss appeared to have increased as a result of the cortisol infusion. The kinetic parameters for the villus enterocyte population of the fetuses receiving cortisol before 115 d were of similar magnitude to those previously seen in the normal near-term fetus. To this extent exogenous cortisol treatment given before a pre-partum surge mimicked the action of the endogenous hormone in late gestation.

Animals↗