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Biomedical subjects

M W Webster

Publications and source records attributed to M W Webster.

At least 73 records · Page 4Linked to original sources
PubMed1993

Culture of intraluminal thrombus during abdominal aortic aneurysm resection: significant contamination is rare.

The significance of positive bacterial cultures from intraluminal thrombus in patients undergoing repair of abdominal aortic aneurysm remains controversial. Over the last 4 years, thrombus was cultured during aneurysm repair in 116 patients. All patients received cephalosporin antibiotic before and for 48 h after operation. Although none of the aneurysms appeared to be clinically infected, six patients (5.2%) had positive cultures. Four groups were identified based on the bacteria cultured: group I, coagulase-negative staphylococci, light growth (three patients); group II, coagulase-negative staphylococci, light growth and 'Streptococcus viridans' (one patient); group III, Bacillus sp., heavy growth (Gram-negative stain) (one patient); group IV, Clostridium perfringens, occasional growth (one patient). One of the six patients died during resection; the other five are alive without graft infection at 5-24 (mean 12) months after operation. The absence of graft infection suggests that positive cultures were not clinically significant or were adequately covered by the antibiotic prophylaxis. The incidence of positive cultures was lower than previously reported. Routine culture of aneurysm thrombus in the absence of clinical infection is probably not cost-effective.

Aged↗
PubMed1993

Organization and development of a university multidisciplinary wound care clinic.

BACKGROUND: A multidisciplinary wound care clinic was established to diagnose and treat patients with nonhealing ulcers of the lower extremity. METHODS: The clinic was organized under the direction of the departments of vascular surgery and dermatology with support by the departments of plastic surgery, hyperbaric medicine, orthopedic surgery, and podiatry, and a research nurse. RESULTS: In the first 4 years and 3 months, 683 patients were evaluated. One hundred seventy-one patients underwent outpatient testing in the noninvasive vascular laboratory and 30 patients underwent angiography. Causes of the ulcers were venous stasis, 280 patients (41%); diabetic neuropathy, 182 patients (27%); arterial insufficiency, 119 patients (17%); rheumatologic disorders, 38 patients (6%); trauma, 15 patients (2%); and in 49 patients (7%) a variety of other disorders. One hundred seventy-nine operations were performed including 86 operating room debridements, 48 amputations (43 toe, 4 below knee, 1 above knee), 23 arterial bypasses, 1 venous bypass, 14 skin grafts, 2 pedicle flaps, and 5 excisions of tumor. Fifty-six patients with cellulitis were admitted to the hospital for intravenous antibiotics and 12 patients were treated with hyperbaric oxygen therapy. One-hundred thirty-two patients were entered into randomized prospective trials of topical growth factors on Institutional Review Board approved protocols. CONCLUSIONS: We concluded that a multidisciplinary approach to wound care is beneficial to patients with chronic wounds and provides a mechanism for clinical investigation on the healing of problem wounds.

Academic Medical Centers↗
PubMed1992

Directional coronary atherectomy in lesions unfavourable for balloon angioplasty: initial Green Lane and Mercy Hospitals experience.

AIMS: directional coronary atherectomy is a new percutaneous interventional technique in which coronary arterial stenotic material is shaved off to alleviate stenosis. This study presents the initial outcome of coronary atherectomy at Green Lane and Mercy hospitals where the major indications for atherectomy are lesions with angiographic appearances unfavourable for balloon angioplasty or where balloon angioplasty had been unsuccessful. METHODS: data on patients undergoing coronary atherectomy between February 1990 and December 1991 were analysed. No patient or procedure was excluded. RESULTS: for the first 28 lesions in 25 patients, procedural success, improvement in lumen diameter to less than 50% diameter loss stenosis, but freedom from myocardial infarction, death or emergency bypass surgery, was achieved in 27 of 28 lesions. In one patient there was acute thrombotic coronary arterial closure treated successfully by balloon angioplasty. Another patient developed an asymptomatic fistulous connection with an adjacent coronary vein which resolved spontaneously. CONCLUSIONS: although technically more difficult than balloon angioplasty, directional coronary atherectomy can be carried out in selected patients with a high initial success rate and low complication rate. The technique has allowed percutaneous treatment of a number of selected patients unsuitable for balloon angioplasty, and has turned an unsuccessful angioplasty into an initial procedural success in others.

Adult↗
PubMed1992

Acute hemodynamic effects of converting enzyme inhibition in children with intracardiac shunts.

The short-term hemodynamic effects of intravenous enalaprilat were assessed in 26 infants and children, aged 6 months to 15 years, with intracardiac shunts undergoing cardiac catheterization. Pulmonary and systemic pressure, flow, and resistance indices were measured by the direct Fick method before and 30 min after enalaprilat at 0.06 mg/kg. Aortic and pulmonary artery pressure decreased 15 and 20%, respectively, by 10 min, with little further change at 30 min. The heart rate did not change significantly and there was no reduction in systemic flow. In those with a large ventricular septal defect and normal or near-normal pulmonary resistance (less than 3.5 u.m2, n = 8), the mean pulmonary-systemic flow ratio decreased from 2.9 +/- 0.3 to 2.4 +/- 0.3 (p less than 0.05) and the mean left-to-right shunt from 7.4 +/- 0.8 to 5.9 +/- 0.7 L/min/m2 (p less than 0.02). Those with an elevated pulmonary vascular resistance (greater than 5 u.m2, n = 8) showed a varied response. Two children, both with Down's syndrome, an atrioventricular canal defect, and reversible pulmonary hypertension (as assessed by an infusion of isoproterenol), had no decrease in pulmonary vascular resistance with enalaprilat. There were no adverse effects. Converting enzyme inhibitors may benefit "heart failure" associated with large ventricular septal defects and normal or mildly elevated pulmonary resistance.

Adolescent↗
PubMed1992

Antithrombotic efficacy of low-molecular-weight heparin in deep arterial injury.

Low-molecular-weight heparin subfractions more specifically inhibit factor Xa than thrombin, and they may have advantages over unfractionated heparin in arterial thrombosis. The antithrombotic efficacy of four dosages of a low-molecular-weight heparin (CY216 at 100, 200, 400, or 500 Institute Choay units/kg) was compared with unfractionated calcium heparin (100 US Pharmacopeia units/kg) and placebo during deep arterial injury produced by balloon dilatation of the carotid artery in the pig. The acute thrombotic end points were 111In-labeled platelet and 125I-labeled fibrinogen/fibrin deposition and macroscopic mural thrombosis; these were related to the anti-factor Xa and antithrombin effects of the heparin preparations. Platelet deposition in segments with deep arterial injury was 42 +/- 28, 22 +/- 5, 29 +/- 12, 9 +/- 2, 9 +/- 2, and 11 +/- 3 x 10(6)/cm2 (mean +/- SEM) for pigs treated with placebo, with 100, 200, 400, and 500 units/kg CY216, and with 100 units/kg unfractionated heparin, respectively. Fibrinogen/fibrin deposition was 35 +/- 8, 19 +/- 2, 19 +/- 4, 21 +/- 3, 14 +/- 4, and 12 +/- 3 molecules x 10(12)/cm2, respectively; deposition was significantly reduced in pigs given 100 units/kg unfractionated heparin compared with placebo (p less than 0.05). Mural thrombosis was present in 74%, 45%, 30%, 14%, 5%, and 9% of deeply injured arterial segments, respectively (p = 0.02). Plasma anti-factor Xa activity and prolongation of the activated partial thromboplastin time (aPTT) with 100 units/kg unfractionated heparin were similar to that produced by 200 units/kg and 500 units/kg CY216, respectively. Thus, low-molecular-weight heparin, which predominantly inhibits factor Xa activity, was only moderately effective at reducing platelet thrombus deposition. It was less effective than 100 units/kg unfractionated heparin, except at high dosages, producing similar prolongation of the aPTT and the thrombin time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo.

OBJECTIVE: To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS: Thirteen patients entered a randomized, double-blind trial of topically applied CT-102 APST vs. placebo (normal saline) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers. CT-102 APST (Curative Technologies, Setauket, NY) was prepared from homologous platelets and contained multiple growth factors including PDGF, PDAF, EGF, PF-4, TGF-beta, aFGF, and bFGF. Inclusion criteria for subjects included diabetes, ulcer of > 8 wk duration, peri-wound transcutaneous oxygen tension > 30 mmHg, platelet count > 100,000/mm3, and no wound infection. Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume, < 100 cm2 in area, and involved subcutaneous tissue. RESULTS: In the CT-102 group, 5 of 7 ulcers were healed (100% epithelialized) by 15 wk, but only 1 of 6 ulcers was healed by 20 wk with placebo (P < 0.05). Average percent reduction in ulcer area at 20 wk was 94% for CT-102 vs. 73% for placebo. Daily reduction in ulcer volume was 73.8 +/- 42.4 mm3/day (mean +/- SE) for CT-102 vs. 21.8 +/- 8.1 mm3/day for placebo (P < 0.05). Daily reduction in ulcer area was 6.2 +/- 1.8 mm2/day for CT-102 vs. 1.8 +/- 0.4 mm2/day for placebo (P < 0.05). CONCLUSIONS: CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers.

Chronic Disease↗
PubMed1992

Antithrombotic therapy and progression of coronary artery disease. Antiplatelet versus antithrombins.

Coronary artery disease develops and progresses over decades with lipid incorporation and coalescence into the arterial wall, leading to recurrent plaque disruption, thrombosis, and organization into fibromuscular lesions. The role of thrombin in arterial thrombosis is documented by observations that specific thrombin inhibition can completely prevent intraluminal mural thrombus in vivo, even though other factors that activate platelets are not inhibited. Platelet-rich thrombi associated with deep injury have a high thrombin content and require blood levels of specific thrombin inhibition with hirudin that are eight to 10 times those required to prevent thrombi associated with lesser injury or stasis. Total prevention of mural thrombus in deeply injured arteries is impossible with aspirin or conventional antithrombotic therapy, which can reduce occlusive thrombus. Thus, conventional antithrombotic therapies can reduce clinical events but are not effective in reducing progression of coronary artery disease. Whether newer antithrombins that can totally prevent mural thrombus after deep injury can be developed and administered orally and chronically without high risk of bleeding and will be able to reduce progression of coronary artery disease is unknown. Lesion growth, vascular injury, acute coronary syndromes, and principles of thrombus formation on ruptured plaque are discussed elsewhere in this issue. This article extends these findings and discusses the prevention and treatment of mural thrombosis, the pivotal role of thrombin in arterial thrombosis, and antithrombotic therapy for the prevention and the progression of coronary artery disease.

Aspirin↗
PubMed1992

Endothelium and atherosclerosis.

PURPOSE: To review the effect of damaged endothelium on the development of atherosclerotic disease. BACKGROUND: Atherosclerotic cardiovascular disease is a complex problem involving lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance and thrombogenic factors. The loss of functional, if not structural, integrity of the vascular endothelium is closely related to the initiation of atherosclerosis. The endothelium contributes to local vascular regulation. Normal endothelial cells are thrombo-resistant; they prevent leukocyte adhesion and control vascular tone by converting angiotensin I into angiotensin II, inactivating bradykinin, norepinephrine, serotonin and ADP, and by secreting vasodilator substances, such as prostacyclin and endothelium-derived relaxing factor (EDRF), and contracting factors such as endothelin. Endothelin is a potent vasoconstrictor peptide that increases intracellular calcium, causing a rapid and transient increase in c-fos and c-myc messenger (m)RNA levels and DNA synthesis in rat vascular smooth muscle cells. In isolated vessel segments, altered endothelial vasoreactivity is usually demonstrated following mechanical trauma to the endothelium. METHODS AND RESULTS: We investigated the function of normal and damaged endothelium in pigs, following superficial balloon injury, which produces a significant alteration in endothelium-dependent coronary vasoreactivity. The anesthetized pigs were given an intracoronary (left anterior descending artery) infusion of acetylcholine. The balloon injury caused a local transient spasm while the distal uninjured vessel did not change. When acetylcholine was given before the balloon injury, the diameter of the left anterior descending artery did not change, even after preconstriction in vivo with prostaglandin (PG) F2 alpha, but acetylcholine given after the balloon angioplasty caused dose-dependent vasoconstriction. It is known that vasoconstriction in arteries can reduce blood flow and increase arterial wall-shear forces, which increase platelet deposition in injured arteries and may precipitate rupture of atherosclerotic plaques. CONCLUSION: The intact endothelium is one of the greatest sources of protection from arterial thrombosis, atherosclerosis and vasoconstriction.

Acetylcholine↗
PubMed1991

Computed tomographic scan confirmation of paraprosthetic enteric fistula.

Aortoenteric anastomotic fistulae and paraprosthetic graft infections are rare but devastating complications following aortic graft surgery. Although the incidence of these complications is reported to be less than 2%, the difficulty in diagnosis and management has led to high mortality rates and extensive morbidity. The majority of patients present with either groin infection or significant gastrointestinal tract bleeding. There is, however, a subset of patients with nonspecific clinical findings in whom routine studies are not diagnostic. Computed tomography was a useful adjunct to the diagnosis of retroperitoneal infection in these patients by demonstrating small collections of periaortic gas or "black dots." The presence of periaortic gas in each instance proved to be a specific sign of a paraprosthetic-enteric fistula, as opposed to a graft infection without intestinal communication.

Aged↗
PubMed1991

Collagen stability and collagenolytic activity in the normal and aneurysmal human abdominal aorta.

Two issues were addressed in this study. The first was whether a bona fide collagenase exists within the wall of the aorta. The second was whether the activity of this putative collagenase is greater in aneurysmal tissue. No collagenase could be extracted from the wall of the aorta under nondenaturing conditions. However, hydroxyproline was liberated from tissue samples allowed to autolyze at neutral pH under reaction conditions favoring the activity of collagenase. Such an activity was probably enzymic as it occurred in a time- and temperature-dependent fashion and was suppressed by chelators. In normal and stenotic tissue, activity was increased by adding aminophenylmercuric acetate, an activator of latent collagenase. Examination of the blanks revealed that the collagen of aneurysmal aorta was more soluble than normal. Furthermore, its digestion kinetics differed in a way that suggested that aneurysmal aorta possessed a labile component that was absent from normal tissue. Although the activity of the putative aortic collagenase was higher than normal in the aneurysmal tissue, our assays do not distinguish between changes in the amount or activity of the enzyme and alterations in the collagen.

Adult↗
PubMed1991

Inducible synthesis of collagenase and other neutral metalloproteinases by cells of aortic origin.

In view of the possible link between collagenase and the formation of aortic aneurysms we have determined whether cells within the aorta are able to synthesize this enzyme. Explanted cells obtained from fragments of lapine abdominal aorta secreted little or no collagenase. Two related metalloproteinases, gelatinase and stromelysin, were also produced at very low levels. Treatment with purified human monocyte interleukin-1 beta, partially purified lapine, synovial IL-1 or phorbol myristate acetate strongly induced the synthesis of all these enzymes. These activators also increased synthesis of prostaglandin E2. The identity of collagenase was confirmed by detection of the characteristic TCA and TCB breakdown fragments of collagen and by demonstration of collagenase mRNA within activated aortic cells. Unactivated aortic cells contained no detectable collagenase mRNA, suggesting a pretranslational level of regulation. Aortic cells thus possess the ability to express several neutral metalloproteinases and, if a sufficient inflammatory stimulus was present, they might do so in arteries undergoing aneurysmal degeneration.

Animals↗
PubMed1991

Coronary restenosis: what have we learned from angiography?

Coronary restenosis remains a major problem for interventional cardiology not only by virtue of its frequency, but also because of the current inability to prevent it. Symptomatic status and non-invasive evaluation have been used to study restenosis, but both lack specificity and sensitivity, particularly in patients with multivessel disease. Angiography remains the reference standard. Several arbitrary definitions have been used, some related to visual estimates of coronary stenosis and others to quantitative angiographic techniques. In another approach, linear modeling is used to assess minimal luminal diameter of lesions on restudy. Although angiographic studies have been essential in the study of restenosis, questions concerning the underlying mechanism and pathophysiology remain. The development of animal models that closely resemble human restenosis should allow evaluation of pathophysiologic mechanisms and development of new strategies to prevent the problem.

Angioplasty, Laser↗
PubMed1991

Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model.

A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap. The right common iliac artery was divided in 15 rabbits. In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group). In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group). After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals. The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005). Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb. The augmentation in perfusion provided by these connections can be quantified.

Animals↗
PubMed1991

Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm.

The pedigrees were constructed of 43 patients (probands) who underwent resection of an abdominal aortic aneurysm. Seven probands (16.2%) had a first-degree relative (parent, sibling, child) known to have had an abdominal aortic aneurysm (multiplex family). To determine the prevalence of undiagnosed abdominal aortic aneurysm, ultrasound screening of first-degree relatives over age 40 years was undertaken. Of 202 eligible relatives, 103 (51.0%) were screened. An occult abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than 1.5. An incipient abdominal aortic aneurysm was defined as a clear focal bulge of the infrarenal aorta, which was less than 3.0 cm in greatest diameter. Four of 103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient abdominal aortic aneurysm (age/sex: 56M, 60M, 67F). These smaller abdominal aortic aneurysms were in patients younger than the operated probands (average age men, 67 years; women, 69 years). Six of seven individuals were in families previously considered simplex, increasing the actual multiplex family frequency from 16.2% to 27.9%. All seven new abdominal aortic aneurysms were found in the 49 siblings age 55 years or older. There were no abdominal aortic aneurysms found in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in one parent. Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and 2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

Probability of rupture of an abdominal aortic aneurysm after an unrelated operative procedure: a prospective study.

It has been assumed by some authors that patients with abdominal aortic aneurysms may be at increased risk of rupture after unrelated operations. From July 1986 to December 1989, 33 patients (29 men, 4 women) with a known abdominal aortic aneurysm underwent 45 operations. Twenty-eight patients had an infrarenal abdominal aortic aneurysm, and five patients had a thoracoabdominal aneurysm. The abdominal aortic aneurysm ranged in transverse diameter from 3.0 to 8.5 cm (average 5.6 cm). Twenty-seven patients underwent a single operation, and six patients had two or more (range of 1 to 6). Operations performed were abdominal (13); cardiothoracic (9); head/neck (2); other vascular (11); urologic (7); amputation (2); breast (1). General anesthesia was used in 29 procedures, spinal/epidural in 6, and regional/local in 10. One postoperative death occurred from cardiopulmonary failure. One patient died of a ruptured abdominal aortic aneurysm at 20 days after coronary artery bypass (1/33 patients [3%]; 1/45 operations [2%]). Fourteen patients had repair of their abdominal aortic aneurysm at a later date, an average of 18 weeks after operation. Four patients had abdominal aortic aneurysm considered too small to warrant resection (average 3.6 cm). Four patients were considered at excessive risk for elective repair. The five thoracoabdominal aneurysm were not repaired. Four patients are awaiting repair. During this same 40-month period, two other patients, not known to have an abdominal aortic aneurysm, died of a ruptured abdominal aortic aneurysm after another operative procedure, at 21 days and 77 days. All three ruptured abdominal aortic aneurysms were 5.0 cm or greater in transverse diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Abdominal aortic aneurysm: results of a family study.

Data pertaining to abdominal aortic aneurysm among first-degree relatives of 91 patients with abdominal aortic aneurysm are presented. The percentage of families with at least one affected first-degree relative of the proband (multiplex families) was 15.4%. In 21.4% of multiplex families parent-offspring transmission of abdominal aortic aneurysm was noted; in the remaining families only siblings were affected. The mean age at onset among probands was 67.3 years; that among all affected was 67.4 years. No statistically significant difference in the mean ages at onset between genders was noted. Among affected siblings of probands, the sex ratio, male:female, was 1.33:1, which is not significantly different from 1:1. The relative risk of developing an abdominal aortic aneurysm was 3.97 for fathers, 4.03 for mothers, 9.92 for brothers, and 22.93 for sisters.

Age Factors↗
PubMed1991

Antithrombotic therapy for deep arterial injury by angioplasty. Efficacy of common platelet inhibition compared with thrombin inhibition in pigs.

BACKGROUND: Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis. METHODS AND RESULTS: Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (x 10(6)/cm2) was 68.8 +/- 12.3 and 48.1 +/- 16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80% in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (less than 10 x 10(6)/cm2, a single layer) and was not changed by any therapy, including hirudin. CONCLUSIONS: These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.

Angioplasty, Balloon↗