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Biomedical subjects

C M Brophy

Publications and source records attributed to C M Brophy.

50 records · Page 3Linked to original sources

Angioscopy of arm vein infrainguinal bypass grafts.

Between January 1988 and December 1990, 56 patients underwent 66 arm vein infrainguinal bypass grafts for limb salvage. Thirty-nine grafts were intraoperatively monitored by the standard methods of continuous wave Doppler alone (30) and arteriography (9). Twenty-seven grafts were prepared and monitored by intraoperative angioscopy. No significant findings requiring intraoperative revision or correction were noted in the grafts monitored by the standard methods. However, in those grafts prepared and monitored by angioscopy, intraluminal abnormalities of the arm veins were detected and corrected in 20/27 (74%). None of the grafts prepared or monitored by angioscopy occluded within 30 days, whereas, in those grafts monitored by continuous wave Doppler and arteriography, 7/39 failed within 30 days, a primary patency rate of 32/39 (82%) (x2 with yates correction, p = 0.055). This study shows that angioscopic preparation and monitoring of arm vein bypass grafts allows the detection and correction of unsuspected intraluminal abnormalities, which appears to improve the early primary patency of arm vein infrainguinal bypass grafts.

Aged↗

The role of inflammation in nonspecific abdominal aortic aneurysm disease.

The predominant pathologic feature of abdominal aortic aneurysm is elastin destruction, and elastin destruction may be mediated by inflammation. In this investigation serial sections of abdominal aortic aneurysm specimens were selectively stained to study the relationship between inflammation and elastin degradation. In addition, soluble aortic extracts were examined for the presence of immunoglobulins. An inflammatory infiltrate was present in 8 of 10 of the abdominal aortic aneurysm specimens examined. The infiltrate was mononuclear, commonly located at the junction of the media and adventitia; it did not codistribute with loss of elastin. The presence of an inflammatory component in abdominal aortic aneurysm was associated with a large amount of immunoglobulin in soluble extracts from aneurysmal tissue compared to atherosclerotic and normal control extracts. This study further characterizes the microscopic pathology of abdominal aortic aneurysm and describes the presence of immunoglobulin in soluble tissue extracts. In addition, the possible role of inflammation in abdominal aortic aneurysm as it relates to protease expression is detailed.

Aorta, Abdominal↗

Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report.

Important concepts underlying the pathophysiology of abdominal aortic aneurysm (AAA) disease include a genetic predisposition, male predominance, and increased proteolysis. Proteolytic activity is carefully controlled by an abundance of protease inhibitors and the increased proteolysis may reflect a decrease in inhibitory activity. The recent assignment for the major tissue inhibitor of metalloproteinases (TIMP) to the X chromosome provides a potential link between the male predominance and increased proteolysis noted in AAA. The purpose of this investigation was to measure the amount of TIMP in normal and diseased aorta. A polyclonal antibody to recombinant human TIMP was produced in rabbit and used to establish an immunoassay. Immunoreactive TIMP in normal and diseased aorta was then measured. There was more TIMP in the matrix-associated fraction than in the soluble fraction. There was significantly less immunoreactive TIMP in aortic extracts from AAA than from control as measured both by Western blot and radioimmunoassay. These results suggest that a diminished amount of TIMP in the aortic matrix in AAA patients may contribute to the increased proteolysis observed in AAA.

Aorta, Abdominal↗

Persistent platelet activation by passivated grafts.

Vascular grafts in canines exhibit similar healing patterns to humans in that the graft surface forms a pseudointima over time but endothelializes only near the anastomotic sites. Thus the pseudointima at the midportion of the graft may represent a nidus for persistent platelet activation. The purpose of this investigation was to examine the effect of the maturing graft surface on platelet activation. Long Dacron subcutaneous carotid to aorta grafts (50 cm x 8 mm) were placed in nine dogs. Blood samples were obtained by direct graft puncture, at the proximal and distal ends of the graft, at 1, 24, 48, 72 hours, 1, 2, 3, 4 weeks, and monthly thereafter for 8 months. Seven sham dogs had subcutaneous grafts implanted without arterial anastomoses, and blood samples were drawn from the femoral artery. Platelet counts were determined with a platelet counter. Platelet aggregation and release of adenosine triphosphate was determined with a whole blood aggregometer by use of arachidonic acid, collagen, and adenosine diphosphate as agonists. No difference was found in platelet aggregation to collagen or adenosine diphosphate stimulation across the graft, but platelets released significantly less adenosine triphosphate to collagen and adenosine diphosphate stimulation distally versus proximally. In the graft dogs a decrease in systemic platelet counts of 50% occurred from the preoperative level which persisted over 8 months (p less than 0.01). Also less response occurred to collagen and ADP stimulated platelet aggregation in the graft animals than the sham animals during the first month of study. These data suggest that significant platelet-graft interactions occur even after the graft has formed a mature pseudointima.

Adenosine Triphosphate↗

Angioscopically directed valvulotomy: a new valvulotome and technique.

Despite a large experience with "blind" retrograde valvulotomy in in situ vein bypass grafting, the incidence of residual competent valves remains high, and valvulotome-induced injury is common. In this study we describe a new valvulotome and technique of angioscopically directed valvulotomy and review the video tape recordings of 85 completion angioscopies of in situ femorodistal bypasses. Fifty-three vein grafts were prepared with the blind retrograde valvulotomy technique and 32 vein grafts with the new valvulotome and angioscopy. The use of the new valvulotome and technique is compared with that of the standard blind retrograde valvulotomy technique, and the normal endoluminal anatomy and incidence of primary disease in saphenous vein grafts was noted. The incidence of valvulotome-induced injury was 5/32 (15.6%) and 45/53 (85%) in vein grafts prepared with angioscopically directed valvulotomy and blind retrograde valvulotomy, respectively. Residual competent valves were found in 10/53 (18.9%) in blind retrograde valvulotomy and 0/25 of angioscopically directed valvulotomy vein grafts (p = 0.0114). In 22/53 vein grafts unsuspected primary disease was detected. Angioscopically directed valvulotomy with the new valvulotome and technique is feasible, reliable, and safe. It avoids residual competent valves, minimizes valvulotome-induced injury, and allows the detection and correction of unappreciated primary vein graft abnormalities. The new valvulotome and technique is a first step in the complete endoluminal preparation of the in situ vein graft.

Aged↗

Tissue inhibitor of metalloproteases (TIMP) is matrix associated in aortic tissue: report of a radioimmunoassay.

Tissue inhibitor of metalloproteinases (TIMP) is the major inhibitor of collagenase, gelatinase, proteoglycanase, stromelysin, and metalloelastases. An imbalance between proteases and inhibitors has been implicated in numerous disease processes including tumor invasion, rheumatoid arthritis, emphysema, and aortic aneurysm disease. The purpose of this investigation was to develop a polyclonal antibody to recombinant TIMP and establish an immunoassay to measure immunoreactive protein in normal and diseased tissues. A polyclonal antibody was produced in rabbit against recombinant human TIMP which was characterized and used to establish a radioimmunoassay. The assay was used to measure immunoreactive protein in fibroblast conditioned medium, human serum, and aortic extracts. There was more immunoreactive TIMP in matrix associated urea extracts than soluble salt extracts from human aorta, suggesting that TIMP is matrix associated. The sensitivity of the assay enables the specific measurement of this inhibitor in serum, fibroblast culture medium, and tissue extracts.

Aorta, Abdominal↗

Hydrocortisone rapidly induces aortic rupture in a genetically susceptible mouse.

The Blotchy mouse has an X-linked trait that leads to aortic aneurysms and subsequent fatal rupture in nearly all affected male mice. Heterozygous female mice occasionally develop aneurysms, but they rarely rupture. Ten heterozygous female mice received 0.45 mg/mL of hydrocortisone acetate in drinking water. Within 2 weeks, 9 of 10 mice were dead (6 with proved aortic rupture, 3 with presumed rupture). The 10th mouse was documented to have an aortic aneurysm. A dose-response curve was generated. Hydrocortisone's effect was shown to be dose-dependent. In another experiment, normal female mice received 0.10 mg/mL of hydrocortisone acetate for 14 days. Two mice developed aneurysms, and the others developed aortic ectasia. These experiments establish the role of hydrocortisone in the induction of aortic rupture in a mouse with genetic susceptibility and the induction of aneurysms and ectasia in normal mice.

Animals↗

Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse.

Propranolol prevents or delays the formation of aortic aneurysms in both the lathyritic turkey and the Blotchy mouse models. This finding in the turkey is reported to be a direct effect on crosslinking of aortic collagen and elastin, independent of effects on pulse and blood pressure. The present work was performed to evaluate this hypothesis in the mouse model by studying the effect of propranolol on the insolubility of matrix proteins of skin, which would isolate the phenomenon from direct hemodynamic effects. Eight 6- to 8-week-old Blotchy mice were fed a diet containing 0.10% (w/w) propranolol for 12 weeks, and six Blotchy controls ate regular chow. At sacrifice the skins were extracted with 8 M urea, and the soluble and insoluble fractions were analyzed for hydroxyproline to determine the collagen contents. The elastin was estimated by subtracting the collagen from the insoluble fraction. There was a 147% increase in insoluble elastin with propranolol and a lesser increase of 54% in insoluble collagen. These results suggest that propranolol has a direct effect on crosslinking of matrix components.

Animals↗

"Pseudoascites" secondary to an amylase-producing serous ovarian cystadenoma. A case study.

Large intraabdominal cystic tumors may mimic ascites. In particular, large ovarian cystadenomas may be mistaken for ascites, and when tapped, may contain an elevated cyst fluid amylase. The amylase from ovarian neoplasms, however, is distinguishable from pancreatic or salivary amylase in that it is more acidic in its isoelectric focusing. Additionally, epithelial cells from the tumor do not contain zymogen granules when examined with electron microscopy. We describe what we think is the third reported case of a patient with "pseudoascites" secondary to an amylase-producing serous cystadenoma.

Adult↗

Liver cell adenoma: diagnosis and treatment of a rare hepatic neoplastic process.

Liver adenomatosis is a rare entity in which multiple liver cell adenomas (more than 10) occur in patients with no prior history of steroid use or glycogen storage disease. This report describes a case of liver adenomatosis, distinguishes liver adenomatosis from other benign liver lesions, and discusses the diagnosis and treatment of this disorder.

Adenoma↗

Focal segmental ischemia of the terminal ileum mimicking Crohn's disease.

The clinical, radiographic, and pathologic features of focal segmental ischemia are similar to Crohn's disease. We report a patient with focal segmental ischemia mimicking Crohn's disease and discuss the histologic distinction between the two entities. Ischemia must be considered when "Crohn's-like" lesions are encountered in elderly patients.

Aged↗

Age of onset, pattern of distribution, and histology of aneurysm development in a genetically predisposed mouse model.

The blotchy mouse has an X chromosome mutation affecting crosslinking of collagen and elastin, which results in aneurysmal dilatation of the aorta. The age of onset, patterns of distribution, and histologic features of these lesions have not been characterized in detail in previous studies. Male normal and blotchy mice 1 to 8 months of age were killed and latex was injected into the left ventricles to facilitate exposure, examination, histologic sampling, and photography of the aorta. Aneurysms were not detected in any normal animals but the affected animals had a progressive increase in the incidence of aneurysms with age, reaching 100% by 6 months. Most aneurysms occurred in the ascending aorta, with some also present in the descending thoracic and abdominal segments. Some animals had multiple aneurysms. Histologically the blotchy mice aortas exhibited disrupted elastic lamellae and thickening of the interlamellar spaces. These spaces contained conspicuously pleomorphic smooth muscle cells, confirmed by electron microscopy. These changes occurred as early as 21 days, when there was no gross evidence of aneurysmal development. Aortic aneurysms develop in blotchy mice in a consistent fashion, with characteristic gross and histologic changes. These animals provide a practical model for further studies of aneurysmal disease, including possible therapeutic interventions to prevent aneurysm development.

Age Factors↗

Variability of gastric emptying measurements in man employing standardized radiolabeled meals.

Radiolabeled liquid and solid portions of standardized 300-g meals were administered on four different study days to eight healthy subjects in an attempt to define the range of inter- and intrasubject variability in gastric emptying. Meal half emptying times, analysis of variance, and intraclass correlations were computed and compared within and between subjects. The mean solid half emptying time was 58 +/- 17 min (range 29-92), while the mean liquid half emptying time was 24 +/- 8 min (range 12-37). A nested random effects analysis of variance showed moderate intrasubject variability for solid emptying and high intrasubject variability for liquid emptying. The variability of solid and liquid emptying was comparable and relatively large when compared with other reports in the literature. The isotopic method for measuring gastric emptying is a valuable tool for investigating problems in gastric pathophysiology, particularly when differences between groups of subjects are sought. However, meal emptying time is a variable phenomenon in healthy subjects with significant inter- and intraindividual day-to-day differences. These day-to-day variations in gastric emptying must be considered in interpreting individual study results.

Adult↗

Monitoring platelet interactions with prosthetic graft implants in a canine model.

This study shows that prosthetic arterial grafts stimulate platelets for as long as 1 year after implantation in a canine model. Carotid-to-distal aorta Dacron (DuPont, Wilmington, DE) grafts (0.8 x 50.0 cm) were tunneled subcutaneously over the right dorsal side, allowing for percutaneous arterial sampling. Thromboxane B2 (TxB2) levels were evaluated at the proximal anastomosis (w), 5.0 (x), 25.0 (y), and 50.0 (z) cm distal from w, and platelet counts and mean platelet volumes were monitored at sites w and z. TxB2 levels increased after blood entered the graft and progressively increased until the blood exited at the distal anastomosis. Platelet counts did not significantly change across the graft. Over time, systemic platelet counts decreased to approximately 50% of each dog's pregraft baseline levels and remained depressed over a 1 year period. Mean platelet volumes peaked 1-3 weeks after implant and remained greater than pregraft levels. Examination of the graft luminal surface showed a developed pseudointima characteristically similar to that which develops in mature human vascular grafts. These results suggest that healed vascular grafts in canines continue to stimulate platelet release of TxB2, reduce systemic platelet counts, and increase mean platelet volumes over 1 year. These data further suggest that platelets are stimulated by the graft and consumed.

Animals↗