Biomedical subjects

D L Steed

Publications and source records attributed to D L Steed.

At least 37 records · Page 2Linked to original sources

PubMed1995

Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group.

PURPOSE: The purpose of this study was to investigate the efficacy and safety of recombinant human platelet-derived growth factor (rhPDGF-BB) in a double-blind, placebo-controlled, multicenter study of patients with chronic diabetic ulcers. METHODS: Patients with chronic, full-thickness, lower-extremity diabetic neurotrophic ulcers of at least 8 weeks' duration, free of necrotic and infected tissue after debridement, and with transcutaneous oxygen tensions of 30 mm Hg or greater were studied. A total of 118 patients were randomized to receive either topical rhPDGF-BB (2.2 micrograms/cm2 of ulcer area) or placebo until the ulcer was completely resurfaced or for a maximum of 20 weeks, whichever occurred first. RESULTS: Twenty-nine (48%) of 61 patients randomized to the rhPDGF-BB group achieved complete wound healing during the study compared with only 14 (25%) of 57 patients randomized to the placebo group (p = 0.01). The median reduction in wound area in the group given rhPDGF-BB was 98.8% compared with 82.1% in the group given placebo (p = 0.09). There were no significant differences in the incidence or severity of adverse events between the rhPDGF-BB and placebo groups. CONCLUSIONS: Once-daily topical application of rhPDGF-BB is safe and effective in stimulating the healing of chronic, full-thickness, lower-extremity diabetic neurotrophic ulcers.

Administration, Topical↗

PubMed1995

Compromised cerebral blood flow reactivity is a predictor of stroke in patients with symptomatic carotid artery occlusive disease.

PURPOSE: The purpose of this study was to determine whether the hemodynamic consequences of extracranial carotid disease correlate with the risk of subsequent cerebral infarction. METHODS: In 95 patients with symptoms who had greater than or equal to 70% stenosis (31 patients) or who had occlusion (64 patients) of the ipsilateral carotid artery, cerebral blood flow was measured by the stable xenon/computed tomography technique both at baseline and after vasodilatory challenge with intravenous acetazolamide. Patients were stratified into group 1, 43 patients with no more than a 5% decrease in flow in any vascular territory, and group 2, 52 patients with greater than a 5% decrease in one or more vascular territories after an acetazolamide challenge. RESULTS: In group 2, 15 (28.9%) of 52 patients had a new stroke, but only one (2.3%) of 43 patients in group 1 did (p = 0.0005). Of patients with total carotid occlusion 10 (26%) of 38 in group 2 and none (0%) of 26 in group 1 had a new stroke (p = 0.003). Of patients with greater than or equal to 70% stenosis, five (36%) of 14 in group 2 and only one (6%) of 17 in group 1 had a stroke (p = 0.067). CONCLUSION: The loss of cerebral reactivity in patients with symptoms who had greater than or equal to 70% carotid stenosis or occlusion is an important predictor of impending cerebral infarction.

Acetazolamide↗

PubMed1995

Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease.

Proteolytic imbalance may play a role in the pathogenesis of abdominal aortic aneurysms (AAA). CLG4B, which encodes the 92-kDa form of type IV collagenase, is a candidate gene for AAA. We genotyped a polymorphic dinucleotide repeat in the 5' flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight alleles were detected in 188 control chromosomes with an observed heterozygosity of 0.68. There was no significant difference in allele distribution between cases and controls. We genotyped the dinucleotide repeat in 10 CEPH reference pedigrees and performed pairwise linkage analysis with markers on each of the 22 human autosomes. Lod scores between 10.45 and 20.29 were observed with markers spanning chromosome region 20q11.2-q13.1. Further support for assignment of CLG4B to chromosome 20 was provided by analysis of human-rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assigns this gene to chromosome 20.

Aortic Aneurysm↗

PubMed1995

Promotion and acceleration of diabetic ulcer healing by arginine-glycine-aspartic acid (RGD) peptide matrix. RGD Study Group.

OBJECTIVE: To determine the effectiveness and safety of arginine-glycine-aspartic acid (RGD) peptide matrix in the treatment of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: This randomized placebo-controlled investigator- and patient-blinded prospective multicenter investigation was conducted at three institutional and three private U.S. clinics providing ambulatory care. Sixty-five diabetic patients with chronic full-thickness neurotrophic foot ulcers were enrolled. Six discontinued the study because of adverse events. RGD peptide matrix (Argidene Gel; formerly Telio-Derm Gel) was applied topically twice weekly for up to 10 weeks in patients who otherwise received standard care. Control group patients received topical saline as a placebo plus standard care. The primary method of assessment was the incidence and rate of ulcer closure. All patients enrolled were included in the data analysis. RESULTS: The percentage of patients whose ulcers healed completely in the RGD peptide matrix group (35%; 14 of 40 patients) was over fourfold greater (P = 0.02) than that in the placebo group (8%; 2 of 25 patients). By the study end point (either day of healing or week 10), 30 of 40 (75%) RGD peptide matrix patients had achieved > 50% ulcer closure compared with 12 of 25 (48%) placebo patients (P = 0.03). RGD peptide matrix also significantly (P = 0.03) increased the rate of ulcer closure over the 10 weeks of the study. CONCLUSIONS: RGD peptide matrix treatment promoted and accelerated the healing of chronic diabetic foot ulcers to a significant degree.

Administration, Cutaneous↗

PubMed1994

The effect of arm exercise on regional cerebral blood flow in the subclavian steal syndrome.

Reversed vertebral blood flow distal to a subclavian obstruction is not uncommon and rarely leads to stroke. A small subgroup of these patients have obstruction in other portions of the extracranial or intracranial circulation, however, and cerebrovascular symptoms are induced by arm exercise, which may decrease regional cerebral blood flow--at times to critical levels--indicating a true "steal" syndrome. We evaluated six patients with symptomatic subclavian steal syndrome using stable xenon with computed tomography cerebral blood flow mapping. A decrease in flow from 13% to 90% in one or more regional vascular territories was found after arm exercise. Patients with a true "steal" syndrome may be at higher risk for stroke. Measuring regional cerebral blood flow may be a means of detecting patients who have a critical loss of flow reserves and who will be symptomatically improved by cerebral revascularization.

Acetazolamide↗

PubMed1994

Thrombosed aneurysm of the cervical carotid artery: avoiding a retrospective diagnosis.

Two patients with neck masses were evaluated, one with computed tomography (CT) and the other with magnetic resonance (MR) imaging. Each mass was correctly identified within the carotid sheath. The correct diagnosis-thrombosed cervical carotid aneurysm--was not considered, necessitating unexpected repair of the aneurysm or artery. Although rare, aneurysm of the cervical carotid artery should be considered in the differential diagnosis of a carotid sheath mass between the jugular vein and carotid artery. Peripheral calcification or enhancement on CT scans and a peripheral signal void on MR images are especially suggestive of the diagnosis.

Aged↗

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

Changing etiology of iliopsoas abscess.

Over a 5-year period, iliopsoas abscesses were found in 11 patients. Although the most common underlying condition was Crohn's disease (3 of 11 patients), 5 abscesses resulted from hematogenous spread from a distant site. Each of these five patients was elderly, severely malnourished, or had an underlying chronic disease. Fever was a presenting sign in 8 of 11 patients, whereas all 4 patients who presented with back pain had nontuberculous lumbar osteomyelitis or disk space infections. No patient presented with the classic triad of fever, back pain, and anterior thigh or groin pain. Computed tomographic (CT) scans accurately established the clinical diagnosis in 10 of 11 patients. Two of the patients died. One patient was an intravenous drug abuser, whereas the other patient was being treated with steroids for systemic lupus erythematosus. Elderly patients, diabetics, and patients with chronic disease are susceptible to this kind of occult infection and may present with minimal clinical findings. Aggressive diagnosis using CT scanning and treatment with resection of involved bowel, complete drainage of the abscess, and prolonged antibiotics are required to salvage these patients.

Abscess↗

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↗

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

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

Alterations in erythrocyte rheology in patients with severe peripheral vascular disease: 1. Cell volume dependence of erythrocyte rigidity.

The erythrocyte rigidity of patients suffering from severe peripheral vascular disease (PVD) was measured by a filtration method using 3 microns pore size filters. Filtration pressures for both PVD patients and normal subjects showed a cell volume dependency, and patient filtration pressures were normalized to cell volume to evaluate intrinsic, ie, nonvolume dependent, abnormalities in erythrocyte deformability. A significant (p less than 0.001) increase in cell rigidity was found in 44 of 54 PVD patients in comparison with volume-matched normal controls. No significant difference was found between patient mean corpusculer hemoglobin (MCH) and normal MCH at any given mean corpuscular volume (MCV), indicating that observed increases in erythrocyte rigidity are not attributable to changes in patient MCH. Therefore, the mechanism of increase in erythrocyte rigidity for PVD patients still needs further investigation into such parameters as levels of adenosine triphosphate,2,3-DPG, and membrane fluidity (calcium- and/or protein-binding membrane, cholesterol and phospholipid content of membrane, etc), as well as other aspects of erythrocyte physiology.

Adult↗