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Biomedical subjects

N A Scott

Publications and source records attributed to N A Scott.

At least 55 records · Page 3Linked to original sources

Surgical treatment of acute manifestations of Crohn's disease during pregnancy.

When requiring surgery, acute exacerbations of Crohn's disease in pregnancy have been reported to carry high maternal and fetal mortality. We report six cases. The women presented at 30, 28, 12, 11, 31 and 25 weeks' gestation and all proved to have intraperitoneal sepsis. In three, the acute symptoms were the first indication of Crohn's disease. All the women recovered and five had healthy babies; the other had a miscarriage when a colonic anastomosis dehisced. In pregnant women with Crohn's disease, the indications for surgery are the same as in non-pregnant patients. For acute manifestations we recommend removal of the source of the sepsis and exteriorization of the bowel ends.

Acute Disease↗

The role of the adventitia in the arterial response to angioplasty: the effect of intravascular radiation.

PURPOSE: In the current series of experiments we have characterized cell proliferation leading to vascular lesion formation in a porcine model for post-angioplasty restenosis and examined the mechanism of action of intravascular beta irradiation in the prevention of lesion formation in this model. METHODS AND MATERIALS: Juvenile male pigs were subjected to balloon overstretch injury of the left anterior descending and circumflex coronary arteries using clinical angioplasty catheters. Proliferating cells were labelled by injections of 50 mg/kg of bromo-deoxyuridine (BrDU) 24, 16 and 8 hrs prior to sacrifice and were detected by immunohistochemistry using a specific antibody to BrDU. In some cases, BrDU was given as a pulse 3 days after angioplasty and the animals sacrificed on day 14 to follow the migration of the cells which had proliferated earlier. Characterization of the proliferating cells was performed by immunohistochemistry using antibodies to specific cytoskeletal proteins specific for smooth muscle cells and myofibroblasts. Some vessels were treated at the time of angioplasty with 14 or 28 Gy (to a depth of 2 mm) intravascular irradiation using a flexible catheter with a pure beta emitter 90 SR/Y and the effect on cell proliferation and terminal transferase-mediated UTP nick-end labelling (TUNEL) examined 3 or 7 days later. RESULTS: The first major site of cell proliferation between 2-3 days after angioplasty is the adventitia and not the medial wall. Seven days after angioplasty cell proliferation is predominant in the neointima and is reduced in the media and adventitia. Differential staining with antibodies directed against smooth muscle alpha actin and other cytoskeletal proteins indicates that the proliferating adventitial cells are myofibroblasts. Pulse label studies with BrDU indicates that the proliferating adventitial myofibroblasts migrate into the neointima and contribute to the mass of the restenosis lesion. Fourteen days after angioplasty the myofibroblasts in the neointima and the adventitia express alpha smooth muscle actin and form a fibrotic scar in the adventitia surrounding the injury site. Endovascular irradiation appears to inhibit development of the restenosis lesion by significantly reducing cell proliferation in the media and adventitia at early time points after injury. There were no significant differences in the percent of TUNEL labelled cells in the irradiated vessels compared to controls. Alpha actin staining of myofibroblasts in the adventitia was reduced in the irradiated vessels suggesting a positive effect of intravascular irradiation on vascular remodeling. CONCLUSIONS: These studies have shown that adventitial myofibroblasts contribute to the problem of post-angioplasty restenosis by proliferating, forming a fibrotic scar surrounding the injury site, and migrating into the neointima. We hypothesize that the adventitial fibrosis which develops at the injury site contributes to negative vascular remodeling associated with clinical restenosis. Experiments in which vessels were exposed to intravascular irradiation at the time of angioplasty indicate that this treatment reduces post-angioplasty restenosis by inhibiting early cell proliferation in the media and adventitia and by preventing the fibrotic changes in the adventitia without a corresponding increase in cellular death or apoptosis in these tissues.

Angioplasty, Balloon, Coronary↗

Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries.

BACKGROUND: In the present series of experiments, we examined the onset of cell proliferation and growth factor expression after balloon overstretch injury to porcine coronary arteries. METHODS AND RESULTS: Domestic juvenile swine underwent balloon overstretch injury to the left anterior descending and circumflex coronary arteries with standard percutaneous transluminal coronary angioplasty balloon catheters. To identify proliferating cells, 5-bromo-2-deoxyuridine (BrDU) was administered over a period of 24 hours before the animals were killed at either 1, 3, 7, or 14 days after injury. Immunohistochemistry was performed with monoclonal antibodies to BrDU and smooth muscle cell markers. Three days after injury, a large number of proliferating cells were located in the adventitia, with significantly fewer positive cells found in the media and lumen. Seven days after injury, proliferating cells were found primarily in the neointima, extending along the luminal surface. In situ hybridization for PDGF A-chain and beta-receptor mRNAs revealed that the expression of these two genes was closely correlated with the sites of proliferation at each time point. Studies in which BrDU was injected between days 2 and 3 and the animals were killed on day 14 suggested that the proliferating adventitial cells may migrate into the neointima. CONCLUSIONS: These data suggest that adventitial myofibroblasts contribute to the process of vascular lesion formation by proliferating, synthesizing growth factors, and possibly migrating into the neointima. Increased synthesis of alpha-smooth muscle actin observed in the adventitial cells after arterial injury may constrict the injured vessel and contribute to the process of arterial remodeling and late lumen loss after angioplasty.

Animals↗

"Bailout" coronary stenting in patients with a recent myocardial infarction.

Patients who underwent bailout intracoronary stenting within 7 days of a myocardial infarction had lower clinical and angiographic success rates and a higher incidence of emergent coronary artery bypass graft surgery than patients who underwent bailout stenting without a history of a recent myocardial infarction. In addition, there was a trend toward more cardiac events after discharge in patients who received stents after a recent myocardial infarction.

Aged↗

The influence of acoustic impedance mismatch on post-stenotic pulsed-Doppler ultrasound measurements in a coronary artery model.

Acoustic impedance mismatch at the fluid-wall interface was shown to affect the spectra from an intravascular Doppler device in an in vitro model with a diameter typical of human coronary arteries. Measurements were obtained first under Poiseuille flow conditions with impedance mismatches of 0%, 7% and 12%, and then under stenosed conditions for the 0% and 7% mismatch cases. For the zero mismatch case, the Doppler spectra could be readily interpreted in terms of fluid mechanical phenomena. When mismatch was present, the spectra from Poiseuille flow exhibited multiple peaks which could not be directly related to the velocity profile. Also, the spectra from stenosed flow with a mismatch of 7% were similar to those from the zero mismatch case but did not exhibit the specific flow-related features as clearly. These results indicate that the impedance mismatch alters the acoustic environment inside the model and that this causes artifact in the Doppler spectra.

Blood Flow Velocity↗

Local intracoronary heparin delivery with a microporous balloon catheter.

Arterial thrombosis plays a major role in the pathogenesis of acute coronary syndromes such as unstable angina and acute myocardial infarction. Heparin is efficacious in treating both disorders; however, systemically administered heparin is associated with bleeding complications. Local intracoronary delivery of heparin may be a safer, more effective method of administration. This study was performed to determine the fate of heparin infused with a specially designed catheter for local intracoronary delivery. To quantitate heparin delivery, tritiated-labeled heparin was dissolved in a solution of unlabeled heparin (1,000 U/ml). A microporous balloon catheter was placed in the left anterior descending (LAD) and left circumflex arteries of anesthetized pigs (n = 15), and 1 ml of the heparin solution was infused. The animals were euthanized within 1 hour, and the treated arteries and controls were harvested, processed, and the tritiated activity was measured. To assess the distribution of the heparin in the arterial wall, 1 ml of fluorescein-isothiocyanate (FITC)-labeled heparin was locally delivered into the walls of the LAD and left circumflex arteries with the microporous balloon catheter. To visualize the dynamic fluid transfer of the device, a microporous balloon catheter was inflated in the LAD, and 1 ml of diluted contrast medium was infused under cinefluoroscopy. The arteries treated with tritiated-labeled heparin contained 0.6% +/- 0.2% of the infused heparin dose. Control arteries contained 0.01% of the administered heparin. Animals that were infused with FITC-labeled heparin displayed fluorescence throughout all layers of the artery, especially in the adventitia. In animals that were injected with 1 ml of diluted contrast medium through the microporous balloon, a relatively large amount of the infusate appeared in the arterial lumen proximal to the balloon. In conclusion, these results suggest that heparin can be delivered to coronary arteries with a microporous balloon catheter. However, <1% of the infused dose can be found in the artery 1 hour after delivery. Infused heparin is distributed throughout the arterial wall, but most of the infused solution appears in the arterial lumen proximal to the inflated balloon and is probably washed downstream after balloon deflation.

Animals↗

Randomized comparison of flexible versus nonflexible femoral sheaths on patient comfort after angioplasty.

Patients who undergo percutaneous transluminal coronary angioplasty (PTCA) by the femoral approach are usually required to lie flat in bed for 6 to 24 hours, which may result in significant discomfort. This study was performed to evaluate the safety and benefit of a flexible sheath that enables patients to sit at a 60-degree angle while the sheath is in place in the femoral artery. Sixty patients were randomly assigned to receive either flexible or nonflexible sheaths before PTCA. Patients with flexible sheaths were allowed to sit at an angle of 60 degrees after the procedure. Heparin management was the same in both groups. Frequency of calls to nurses for back pain was recorded for both groups. For analgesia, nalbuphine was administered in 2-mg increments. All sheaths were removed the day after the procedure. Femoral ultrasound was used to detect groin complications (hematoma, pseudoaneurysm, or arteriovenous fistula) and was performed in all patients. Baseline characteristics were similar in both groups. There were no differences in ease of sheath insertion or guide catheter movement through the sheaths. The arterial pressure waveform was not dampened in any of the flexible sheath patients while in the sitting position. Patients with flexible sheaths had fewer calls for back pain and required less nalbuphine than patients with nonflexible sheaths. Groin complications were similar in both groups. In conclusion, by allowing patients to sit up to an angle of 60 degrees, flexible sheaths have a beneficial effect in reducing back pain and the need for analgesics after PTCA.

Aged↗

Potential role of the adventitia in arteritis and atherosclerosis.

The role of the adventitia in vascular lesion formation has been largely ignored despite numerous studies which have suggested its potential importance. Adventitial reactions are common in atherosclerosis as well as arteritis. Experimental hypercholesterolemia in pigs and non-human primates stimulates the accumulation of inflammatory cells in the arterial adventitia. The extent of adventitial inflammation associated with human atherosclerotic plaques is correlated with the severity of intimal disease. Adventitial reactions also occur after balloon angioplasty. Our studies indicate that the major site of cell proliferation after angioplasty of porcine coronary arteries is the adventitia and not the medial wall. These cells have been identified as myofibroblasts on the basis of differential staining with smooth muscle specific antibodies and a role for these cells in arterial remodeling associated with angioplasty and late lumen loss is postulated. Evidence from pulse studies with bromodeoxyuridine suggests that adventitial myofibroblasts have the capacity to migrate into the forming intimal lesion after angioplasty and may be a major component of the neointima. Additional work will have to be directed at a more detailed examination of the response of adventitial cells to balloon injury and in the setting of atherosclerosis and arteritis to determine what role these cells might play vascular lesion development.

Angioplasty, Balloon, Coronary↗

Management of intra-abdominal abscesses in Crohn's disease.

Over a 5-year period, 54 intra-abdominal abscesses were observed in 40 (20.8%) of 192 patients with Crohn's disease. The median age was 39 years (range 17-76 years); median interval from diagnosis, 7.5 years (range 0-24 years) and the median number of surgical operations was 2 (range 0-7). Forty abscesses (74.1%) were spontaneous and 14 (25.9%) were postoperative. Thirty abscesses were initially managed by laparotomy, 14 by percutaneous drainage, nine by incision and drainage and in one case the abscess drained spontaneously. Intra-abdominal abscesses were managed successfully by laparotomy in 23 (76.7%) of 30 patients, with a 93% success rate (13 of 14) for spontaneous abscesses managed by resection and primary anastomosis. Three of 8 (37.5%) spontaneous abscesses were managed successfully by percutaneous drainage, a temporising effect being achieved in a further two cases. There was no significant difference in sepsis score or duration of hospital stay for patients managed initially by laparotomy and those managed by drainage. However, patients with stricturing or fistulating Crohn's disease were much more likely to have initial management by laparotomy and in these patients surgical intervention was found to be an effective initial strategy.

Abdominal Abscess↗

Inhibition of platelet-dependent thrombosis by local delivery of heparin with a hydrogel-coated balloon.

BACKGROUND: Systemic administration of heparin can decrease mortality and morbidity of acute ischemic coronary syndromes such as unstable angina and myocardial infarction. Hemorrhage is the major limiting factor in the clinical use of systemic heparin. The objective of the present study was to determine whether local delivery of heparin could inhibit platelet-dependent thrombosis without altering systemic bleeding parameters. METHODS AND RESULTS: Hydrogel-coated angioplasty balloon catheters were dipped in a heparin solution, dried, and applied to a platelet-rich mural thrombus in a chronic ex vivo porcine arteriovenous shunt. 111In-labeled platelet deposition was quantified by gamma camera imaging. In a separate series of experiments, 3H-heparin was used to estimate the amount of heparin delivered to the thrombus with the coated balloon. Systemic heparin administration produced a dose-dependent decrease in platelet-dependent thrombus formation that was maximal at 200 units/kg. Bleeding times and activated partial thromboplastin times were prolonged at this dose. An equal inhibition of thrombus formation was achieved after the coated balloon was dipped in a heparin solution (10,000 units/mL) and deployed at the mural thrombus. In contrast to systemic heparin administration, there was no alteration in bleeding parameters associated with local heparin delivery. The estimated amount of heparin delivered with the coated balloon was 40 units. CONCLUSIONS: Local delivery of heparin in amounts sufficient to inhibit platelet-dependent thrombosis can be accomplished with a hydrogel-coated coronary angioplasty balloon catheter. Local heparin delivery can inhibit thrombus formation in amounts that are several orders of magnitude lower than the required systemic dose. Local delivery of heparin was not associated with prolongation of bleeding parameters.

Acrylic Resins↗

Management aspects of induced twinning in beef suckler cows using in vitro fertilised embryos.

Twin and single pregnancies were induced in two groups of oestrus-synchronised beef cows by using a combination of artificial insemination and the transfer of in vitro fertilised (IVF) embryos. Single IVF embryos transferred non-surgically to the uterine horn contralateral to the corpus luteum of 43 previously inseminated cows resulted in a calving rate of 72 per cent with a twinning rate of 38.7 per cent. In 45 cows, two IVF embryos were transferred non-surgically to one uterine horn resulting in a calving rate of 51.1 per cent with a twinning rate of 39.1 per cent. The median gestation length for cows bearing twins was 10 days shorter than that of cows bearing single calves (P < 0.001). The proportions of cows that received assistance at calving were similar for twin and single births (57 per cent vs 45 per cent, P > 0.05), but the incidence of retained fetal membranes was much higher after the birth of twins (62 per cent vs 3 per cent, P < 0.001). Nineteen per cent of twin calves were stillborn compared with 6 per cent of single calves (P > 0.05). The median birthweight of the twin calves was 32 kg (68 per cent of the median weight of single calves). The nutrition of twin-bearing cows in late pregnancy was adequate when assessed in terms of their plasma glucose, non-esterified fatty acid and beta-hydroxybutyrate concentrations. Serum immunoglobulin concentrations were similar in single and twin calves suggesting that the passive transfer of antibody was not compromised in the twin calves.

Animal Nutritional Physiological Phenomena↗

Risk factors in patients presenting as an emergency with colorectal cancer.

Of 905 patients with colorectal cancer admitted to a single district general hospital, 272 (30 per cent) were admitted as emergencies. Emergency patients had more advanced tumours (Dukes stage B and C 96 per cent versus 88 per cent of those admitted electively, P < 0.006), a shorter history (median 3 versus 11 weeks, P < 0.0001), were less likely to be fully ambulatory (44 versus 80 per cent, P < 0.0001) and more likely to have abdominal pain (74 versus 51 per cent, P < 0.001) and vomiting (40 versus 10 per cent, P < 0.0001). More emergency patients were given stomas (56 versus 35 per cent, P < 0.0001) and died in hospital (19 versus 8 per cent, P < 0.0001). Of those who survived to be discharged, patients admitted as an emergency spent longer in hospital (median stay 16 versus 13 days, P < 0.0001) and had a poorer overall 5-year survival rate (29 versus 39 per cent, P = 0.0001). Emergency patients were significantly older (median 74 versus 72 years, P = 0.04) and much more likely to be widowed (41 versus 27 per cent, P = 0.0002) than those admitted for elective surgery. If the personal and resource disaster of emergency colorectal cancer admission is to be reduced, screening strategies targeted by demographic characteristics require investigation.

Adult↗

Anastomotic configuration does not affect recurrence of Crohn's disease after ileocolonic resection.

The influence of anastomotic configuration on recurrence of symptomatic Crohn's disease has been assessed in a sequential study of patients undergoing resection of ileal Crohn's disease. Between 1972 and 1991 92 patients had 102 ileocolonic anastomoses constructed after resection of intestinal Crohn's disease. The configuration of the ileocolonic anastomosis was either end to side (ES, n = 68) or side to side (SS, n = 34). The majority of patients in both groups were female and both groups were similar for duration of Crohn's disease at resection, steroid therapy, previous number of intestinal resections, indication for surgery and length of ileum resected at operation. No anastomotic leak occurred in either group. A total of 39 patients developed symptomatic recurrent Crohn's disease including 31 (46%) in the ES group and 8 (24%) in the SS group. This difference was related to the length of follow-up, the annual rate of symptomatic recurrence was almost identical for both end to side (0.066) and side to side (0.052) anastomoses.

Adolescent↗

Effect of lateral sphincterotomy on internal anal sphincter function. A computerized vector manometry study.

PURPOSE: This study was designed to investigate the effect of lateral sphincterotomy on internal anal sphincter function in patients with chronic anal fissure. METHODS: Using an eight-channel perfusion catheter and computerized data analysis, a prospective manometric study was performed on patients with chronic anal fissure undergoing lateral sphincterotomy (LS). RESULTS: Mean resting pressure (MRP) in patients with anal fissure (85.1 mmHg) was significantly higher (P = 0.012) than control subjects (63.3 mmHg). One week following LS there was a significant reduction in MRP (50.0 mmHg; P = 0.0014), and this was maintained when reassessed five weeks later (MRP = 56.4 mmHg; P = 0.0019). There was no significant difference in coefficient of variation (a measure of the degree of manometric asymmetry of the anal canal) in the control group (mean, 8.9 percent) and in patients with anal fissure (mean, 7.7 percent; P = 0.43). LS created a significant increase in anal canal resting manometric asymmetry when assessed at one (mean, 17.3 percent; P = 0.0013) and six weeks (mean, 11.7 percent; P = 0.027) after the procedure. CONCLUSION: LS produces a global and symmetric decrease in anal canal resting pressure. In addition, it produces a significant increase in manometric asymmetry of the resting anal canal by creating a detectable segmental defect.

Adult↗

Seeding of intracoronary stents with immortalized human microvascular endothelial cells.

Intracoronary stents are effective in decreasing the complications associated with acute closure during coronary angioplasty. A major complication associated with the use of coronary stents is acute thrombotic occlusion. It has been postulated that the stent loses its thrombogenic potential after it becomes covered with a layer of endothelial cells. Human dermal microvascular endothelial cells were transfected with a plasmid containing the simian virus 40 large T-antigen gene. Stents were placed in culture media with cells for 2 weeks. Seeding efficiency of the stent with the endothelial cells was assessed by scanning electron microscopy. Balloon-expandable coronary stents placed in cell culture with immortalized human microvascular endothelial cells showed near-complete coverage after 2 weeks. After balloon inflation, persistence of cells on the stent was noted only on the lateral aspect of the balloon-expanded stents. If these stents were placed in culture, complete recovery of the monolayer was noted after 3 days. Stents were then covered with endothelial cells and frozen for 4 days. After thawing, the cells adhered to the devices and divided to form a monolayer in tissue culture. Seeded balloon-expandable stents were frozen for 4 months, thawed, and then implanted in a pig coronary artery. Human endothelial cells were identified on the stent 4 hours after deployment. These studies demonstrate the feasibility of using a human microvascular endothelial cell line to seed an uncoated metal stent. The cells remain adherent to the stent, are functional after freezing, and remain on the stent at least 3 hours after intracoronary implantation.

Angioplasty, Balloon, Coronary↗

Comparison of the thrombogenicity of stainless steel and tantalum coronary stents.

This study was designed to compare the thrombogenicity of stainless steel and tantalum coronary stents of the same design. Stainless steel and tantalum coronary stents are being evaluated for their utility in treating acute closure and restenosis. A major disadvantage of stainless steel stents is radiolucency. To determine whether radioopaque tantalum stents may be safely substituted for stainless steel stents, we compared the relative thrombogenicity of these materials in stents of identical design. Total platelet and fibrin deposition on the stents were determined from measurements of indium 111-labeled platelet and iodine 125-labeled fibrinogen accumulation after deployment into exteriorized chronic arteriovenous shunts in seven untreated baboons. In another series of experiments, 111In-platelet deposition was compared 2 hours after stent implantation in coronary arteries of pigs. In baboons, platelet thrombus formation on stainless steel and tantalum stents was equivalent and plateaued at approximately 2.5 x 10(9) platelets after 1 hour (p > 0.05). Fibrin deposition averaged approximately 1 mg/stent and did not differ between the stainless steel and tantalum stents (p > 0.05). In the porcine coronary model there was no significant difference in 111In-labeled platelet deposition between the stainless steel and tantalum stents (p > 0.05). This result was confirmed by scanning electron microscopic analysis of the coronary stents. Based on these two models, we conclude that there is no significant difference in the thrombogenicity of stainless steel and tantalum wire coil stents.

Animals↗