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Biomedical subjects

J T Powell

Publications and source records attributed to J T Powell.

At least 91 records · Page 5Linked to original sources
PubMed1993

The influence of smoking and lipids on restenosis after carotid endarterectomy.

Factors associated with restenosis were investigated in 107 patients undergoing carotid endarterectomy for symptomatic disease. The patients, 71 men and 36 women with mean age 68 +/- 8 years, were followed up for 1 year by serial Duplex scanning. Carotid restenosis of > or = 50% developed in 18 patients (17%), 11 men and seven women. Restenosis was not influenced by age, sex, diabetes or hypertension. Continuing smokers, serum cotinine > 200 nmol/l, had a significantly higher incidence of > or = 50% restenosis after 1 year (39%), compared with only 16% of non-smokers, p = 0.023. Restenosis > or = 50% also was associated significantly with below median body mass index (p = 0.027). Women undergoing carotid endarterectomy had higher levels of cholesterol (median 7.4 mmol/l) and apolipoprotein B (median 0.81 g/l) than men (median cholesterol 6.4 mmol/l, median apolipoprotein B 0.69 g/l), p < 0.01. For men only, restenosis of > or = 50% was associated with low levels of serum cholesterol (median 5.7 mmol/l), p = 0.002. For women cholesterol levels were higher (median 8.1 mmol/l) in those with > or = 50% restenosis. Smoking adversely influences early restenosis (1 year) after carotid endarterectomy. Hyperlipidaemia is not a risk factor for restenosis in men, but may be associated with restenosis in women.

Adult↗
PubMed1993

The magnitude of the hypercholesterolemia of hypothyroidism is associated with variation in the low density lipoprotein receptor gene.

To assess whether the variable extent to which patients with hypothyroidism become hypercholesterolemic was associated with variation in the genes for the low density lipoprotein (LDL) receptor or apolipoprotein-B, we investigated prospectively 52 patients with primary hypothyroidism treated with L-T4. There was significant reduction in cholesterol, high density lipoprotein cholesterol, LDL cholesterol, and apolipoprotein-A1 and -B after thyroid hormone replacement. The reduction in cholesterol was associated significantly with the magnitude in the reduction of serum TSH levels (P < 0.001) and the variable AvaII restriction site in exon 13 of the LDL receptor gene. For a given reduction in TSH, patients of genotype -/- (no restriction site) demonstrated a reduction in serum LDL cholesterol that was 4-fold greater than that of patients homozygous for the AvaII restriction site (genotype +/+), with heterozygous (+/-) patients showing an intermediate response. The hypocholesterolemic response was significantly greater in patients of the -/- genotype than in patients carrying the +allele (genotypes +/- and +/+; for LDL cholesterol, P < 0.01; for cholesterol, P < 0.05). No such relationship was observed with a variation at any other polymorphic site studied (four in the LDL receptor gene and two in the apolipoprotein-B gene). The magnitude of the decrease in high density lipoprotein cholesterol and apolipoprotein-A1 and -B was independent of the AvaII genotype, the effect of which was specific to LDL cholesterol. Variation within the LDL receptor gene appears to influence the magnitude of both the hypercholesterolemia of hypothyroidism and, consequently, the reduction of serum LDL cholesterol in response to L-T4. Thus, it may be possible to predict which hypothyroid patients are at greatest risk for coronary artery disease.

Adult↗
PubMed1993

Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium contained low levels of IGF-1 and the stimulation of type I collagen secretion was abolished when the conditioned medium was pre-incubated with antibodies to insulin-like growth factor 1 (IGF-1). There are important reciprocal interactions between alveolar type II cells and fibroblasts in co-culture. Direct contacts between alveolar type II cells and fibroblasts appear to have a trophic effect on cultured alveolar type II cells, increasing the levels of mRNA for SP-A. Rat lung alveolar type II cells appear to release a factor (possibly IGF-1) that stimulates type I collagen secretion by fibroblasts.

Animals↗
PubMed1993

Physiatrics at the forefront: physical medicine and rehabilitation in the 1990s.

Physiatry, a specialty title derived from the word "physical," is the second-fastest-growing medical specialty in the United States. The interdisciplinary team-management system is the key to the success of physiatric services. The goal is to maximize functional outcome for physically challenged patients who have any of a broad scope of disorders causing disabilities or pain. Rehabilitation of these patients is cost-effective and provides improved quality of life for those treated. The job of the four excellent Physical Medicine and Rehabilitation (PM&R) training programs in Texas is to educate young physicians with knowledge regarding medicine, general science, electrodiagnostics, and allied health-care science. Young physiatrists may gravitate towards various subspecialties in the field or choose to provide a variety of services to assist other physicians in the management of patients over a prolonged period. In the age of managed competition, costs versus access, and quality-of-care issues, physiatrists must educate physicians, the public, legislators, and insurance carriers (federal, state, workers' compensation, and third-party) as to why rehabilitation should be included in any and every health-care plan.

Education↗
PubMed1993

Risk factors for atherosclerosis in men with stenosing or aneurysmal disease of the abdominal aorta.

Risk factors associated with atherosclerosis were compared in 2 groups of men: with aneurysmal dilatation (AAA) or stenosing disease (SAD) of the infrarenal aorta. In the AAA group (N = 114) the median aortic diameter was 6.9 cm and 89% of patients had undergone elective or emergency surgical repair. In the SAD group (N = 57) an equal proportion had had an aortobifemoral bypass, the median aortic diameter was 1.8 cm. Men with AAA were older (73 years vs 68 years; p < 0.001). There were no differences in total cholesterol and triglycerides between the two but men with AAA had a higher HDL-cholesterol concentration (1.22 mmol/l vs 1.08 mmol/l; p = 0.019). Tobacco consumption in the 2 groups was similar (36.5 pack years vs 35.0 pack years; p = 0.387). After correction for age, diastolic blood pressure was significantly higher in the AAA group. In both groups there is extensive aortic atherosclerosis but differences between the two groups indicate that stenosing and dilating disease are distinct pathological entities.

Age Factors↗
PubMed1992

The uptake and expression of the factor VIII and reporter genes by vascular cells.

The conditions and efficacy of transfection of vascular cells in primary culture using DEAE-dextran, calcium phosphate and lipofectin have been investigated using chloramphenicol acetyltransferase and luciferase as reporter genes. Subsequently factor VIII was expressed in endothelial and smooth muscle cells. Both reporter genes could be expressed after transfection of umbilical vein endothelial cells, umbilical artery smooth muscle cells and fibroblasts. The expression of both reporter genes in endothelial and smooth muscle cells was highest using lipofectin. After transfection of smooth muscle cells with both full-length and mutant factor VIII genes, factor VIII activity and antigen were secreted into the culture medium, the secretion remaining stable to serial cell passage. The secretion of factor VIII from transfected smooth muscle cells was confirmed by the immunoprecipitation of [35S]methionine labelled protein. Endothelial cells also were successfully transfected with the mutant factor VIII gene.

Cells, Cultured↗
PubMed1992

Selection for screening for familial aortic aneurysms.

The reported familial clustering of abdominal aortic aneurysm (AAA) indicates the possible rewards of family-based screening programmes with respect both to the number of asymptomatic aneurysms detected and to identifying associated genes. Ultrasonographic screening of 28 families (25 brothers and 28 sisters) was carried out together with collecting a history and a blood sample for analysis of the cholesterol level and genetic markers. Among the screened siblings six (11 per cent), all > 60 years old, had an AAA > or = 3.0 cm in diameter. A further 11 siblings (21 per cent), six of whom were < 60 years old, had a wide (2.5-2.9 cm) aorta. The presence of an aneurysmal or wide aorta was significantly associated with smoking (P = 0.027), male sex (P = 0.008) and a proband age of < 60 years (P = 0.031). Polymorphic genetic markers for type III collagen and haptoglobin were not informative in these families. These results indicate that the efficiency of screening siblings of patients with AAA could be improved by limiting it to brothers with a smoking history and/or siblings of younger patients. The familial component appears to be greatest in these younger patients.

Adult↗
PubMed1992

Mechanical properties of the aneurysmal aorta.

The mechanical properties of the abdominal aorta were investigated non-invasively in 30 patients with aortic aneurysm and 11 with peripheral arterial disease. The distensibility of the aorta was measured using M-mode ultrasonography, permitting non-invasive assessment of the pressure--strain elastic modulus or aortic stiffness, Ep. The median Ep value increased from 4.0 N/cm2 in control subjects in their third decade of life (n = 10) to 10.4 N/cm2 in middle age (n = 11) to 14.0 N/cm2 in the elderly (n = 13). In the presence of a normal diameter, peripheral arterial disease with aortic atherosclerosis had little effect on aortic stiffness, median Ep being 16.0 N/cm2. Aneurysmal dilatation was associated with a significant increase in aortic stiffness, median Ep being 31.3 N/cm2 (P < 0.001). For aortas of normal diameter, Ep was at all ages dependent on mean arterial pressure. In patients with aortic aneurysms there was no clear relationship between Ep and mean arterial pressure or aortic diameter. Of the patients studied, 15 underwent aortic reconstruction; increasing aortic stiffness (log Ep) was associated with a decreased medial elastin content of the aortic biopsy (r = -0.63, P < 0.02). This study demonstrates the marked stiffness or inelasticity of dilated or aneurysmal vessels, part of which is attributable to the loss of elastin.

Adult↗
PubMed1992

On the accumulation of D-aspartate in elastin and other proteins of the ageing aorta.

Ageing and degenerative changes of the human aorta are associated with medial thinning and a reduced dry weight content of elastin. The metabolic stability of cross-linked elastin was investigated by measuring the accumulation of D-aspartate with ageing in insoluble elastin isolated from human aorta. D-Aspartate accumulation in elastin was compared with D-aspartate accumulation in aortic collagen and an elastin bound glycoprotein fraction. The D-aspartate content of elastin, purified from infrarenal aorta; increased linearly with age from 3% of the total aspartate in youth to 13% in the mid 80s. In contrast the D-aspartate content of aortic collagen remained invariant (3-5% of the total aspartate) from youth to old age. The apparent first order rate constant for the racemization of L-aspartate in elastin was 1.14 x 10(-3). The D-aspartate content of the elastin bound glycoproteins increased by only a small amount, from 3% in the mid 30s to 6% in the mid 80s. These results argue for the metabolic stability of aortic elastin as compared with the fibrillar collagens of the human aorta. Both the rate of racemization and the specific accumulation of D-aspartate in elastin, but not collagen, indicates that mature cross-linked elastin is not synthesized in the adult aorta.

Aged↗
PubMed1992

Gene transfer into specific vascular cells.

Gene transfer therapy in vascular surgery is on the horizon and will include the insertion of genes for anti-clotting proteins into the endothelial lining of vascular grafts and for genes controlling the proliferation of smooth muscle cells after endovascular intervention. Here we address the possibility of targeting genes to specific vascular cells using non-infectious methods, DEAE-dextran or lipofectin complexes of reporter genes, to aid transfection of endothelial cells, smooth muscle cells and fibroblasts cultured from human umbilical veins or arteries. For these studies we used the firefly luciferase gene under control of several different promoters including those for the Rous sarcoma virus (RSV) and for tissue plasminogen activator type 1 (PAI-1). DEAE-dextran mediated transfections resulted in low level, transient (2-5 days) expression of RSV-luciferase in all three cell types. Lipofectin mediated transfections resulted in a four-to-five-fold higher expression of RSV-luciferase in endothelial and smooth muscle cells, expression remaining fairly stable for up to 14 days. One particular PAI-1 promoter construct of 800 bp was only half as effective as the RSV promoter in the expression of luciferase from smooth muscle cells, 82 +/- 9 and 35 +/- 11 ng mg-1 respectively (p less than 0.02). In contrast these two promoters resulted in very similar expression of luciferase in endothelial cells, 64 +/- 8 and 67 +/- 10 ng mg-1 respectively. These experiments demonstrate the possibilities of augmenting cultured vascular cells with foreign genes using lipofectin, a cationic lipid, for insertions into endothelial and smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prevalence, progression and natural history of asymptomatic carotid stenosis: is there a place for carotid endarterectomy?

The purpose of this study was to determine the prevalence, progression and prognosis of asymptomatic carotid artery stenosis in a population of 1198 patients with peripheral arterial disease (n = 986) or aortic aneurysm (n = 212), mean age 67.7 (S.D. = 10.0) years. Patients were recruited from 1985 to 1989 with annual assessment of carotid artery stenosis of over 50% using Doppler peak frequency analysis. Patients were followed up annually until 1990 or their first event, transient ischaemic attack (TIA), amaurosis fugax (AFx), stroke without antecedent TIA, or death (mean follow up 20 months). Life tables were used to determine risk of events in different patient groups. Only 164 (13.7%) patients had a stenosis of over 50% in either of the common or internal carotid arteries, disease was bilateral in 33 (2.8%) patients. A total of 33 patients (2.8%) had over 80% stenosis in common or internal carotid arteries. During follow up 37 (3.1%) patients developed a stenosis greater than 50%. Only 27 (2.3%) patients developed a stroke, 11 of which were fatal. A further 33 (2.8%) suffered a TIA or AFx and a total of 155 patients died during follow up. The total neurological event rate (TIA, AFx and stroke) was significantly associated with the presence of over 50% stenosis, [relative risk (RR) = 2.98, 95% confidence interval (95% C.I.) 1.68-5.29, p less than 0.001] and carotid bruit (RR = 1.16, 95% C.I. 1.23-3.81, p = 0.010). Although risk of stroke was higher in patients with a 50% stenosis, this failed to achieve statistical significance (RR = 1.78, 95% C.I. 0.66-4.80, p = 0.275).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Aneurysm↗
PubMed1992

Aspirin usage and its influence on femoro-popliteal vein graft patency. The Femoro-popliteal Bypass Trial Participants.

As part of the Femoro-popliteal Bypass Trial patients undergoing femoro-popliteal vein bypass were randomised to aspirin 300 mg and dipyridamole 150 mg twice daily or identical placebo tablets. Blood was taken from a subgroup of 145 patients (mean age 66.3 years) with patent grafts at 6 months. Serum salicylate analysis revealed that of the 65 randomised to receive placebo 18 (28%) had evidence of salicylate in their sample (greater than 50 ng ml-1). Similarly, in those randomised to active treatment and considered to be good compliers 16/61 (26%) had no evidence of salicylate in their serum sample (less than 50 ng ml-1). Analysis of primary graft patency by "intention to treat" failed to detect a difference by life table, the risk being slightly higher in the group assigned to placebo (RR = 1.33, 95% confidence internal C.I. 0.64-2.78, p = 0.438). When comparing patients with no detectable serum concentration (less than 50 ng ml-1) with patients with serum salicylate over 50 ng ml-1 there was a significant difference in graft patency at 66 versus 83% respectively at 3 years (RR = 2.38, 95%C.I. 1.08-5.26, p = 0.024). When corrected for a number of possible risk factors this significant difference was maintained (RR = 2.78, 95%C.I. 1.15-6.67, p = 0.017). Although these findings are based on observational data they provide indirect evidence of an improvement in graft patency with aspirin. This result combined with the finding of a significant reduction in cardiovascular events in the main trial results support the use of aspirin and dipyridamole in patients undergoing femoro-popliteal vein bypass.

Aged↗
PubMed1991

Limitations of ultrasonography in surveillance of small abdominal aortic aneurysms.

The repeatability, observer bias and instrument bias of aortic diameter measurement by ultrasonography, were investigated in ten patients with small (3-6 cm by computed tomography) infrarenal abdominal aortic aneurysm. The repeatability of maximum aortic diameter measurement by ultrasonography was much better for anterior-posterior than transverse diameter, with coefficients of repeatability 3.0-7.5 mm and 10-15 mm respectively. The repeatability of suprarenal aortic diameter measurement was poor. Surprisingly, maximum diameter using ultrasonography was larger than that using computed tomography, the difference being least for anterior-posterior measurements. At best a single, experienced observer, using the same instrument may provide aortic diameters using ultrasonography accurate to within 5 mm, but more commonly such aortic diameter is only accurate to within 8 mm.

Aorta, Abdominal↗
PubMed1991

Influence of apolipoproteins on the anatomical distribution of arterial disease.

The association of raised triglyceride levels with peripheral arterial disease has indicated that different interactions of environmental, biochemical and genetic risk factors promote atherosclerosis in particular sites. This hypothesis was investigated in patients presenting with atherosclerotic disease in the carotid (n = 23) or peripheral arteries (n = 94) before the age of 50 years; symptomatic coronary artery disease was also present in some patients (n = 35). Patients presenting with carotid disease had the highest levels of cholesterol (mean 7.6 mmol/l, P less than 0.05), apolipoproteins B (mean 1.02 g/l) and CIII (median 22.8 mg/dl, P less than 0.05) but normal levels of apolipoprotein AI. Patients presenting with peripheral arterial disease were the heaviest smokers and this was the only group where hypertriglyceridaemia was observed. Patients with coronary artery disease had the lowest levels of apolipoprotein AI (mean 1.15 g/l, P less than 0.05). Although polymorphic variation in the apolipoprotein genes did not appear to influence the distribution of symptomatic disease, genetic variation at two polymorphic sites in the apolipoprotein AI-CIII-AIV gene cluster was associated with differences in triglyceride levels. The control of the metabolism of triglyceride rich particles by apolipoproteins may predispose to atherosclerosis in specific sites, low levels of apolipoprotein AI selectively promoting coronary artery atherosclerosis and high levels of apolipoprotein CIII selectively promoting carotid artery atherosclerosis.

Adult↗
PubMed1991

Genetic variants of collagen III and abdominal aortic aneurysm.

Collagens provide the tensile strength of the aortic wall. Variations in collagen structure are recognised in Ehlers Danlos syndrome type IV and could also be associated with a predisposition to aortic aneurysm. The frequency of some minor genetic variants of type III collagen, present in the normal population, can be detected by restriction enzyme digestion of genomic DNA from peripheral leucocytes. The frequency of a minor collagen type III allele demonstrated with the restriction enzyme Ava II was compared in patients with abdominal aortic aneurysm (n = 70) and aortoiliac stenosis (n = 47). The frequency of the minor allele was significantly higher in aneurysm patients (0.30) compared with patients with aortoiliac stenosis (0.17), p less than 0.05. The presence of the minor allele was associated with a less elastic aneurysm wall (median pressure strain elastic modulus 4575, n = 7), compared with patients homozygous for the common allele (median pressure strain elastic modulus 1990, n = 6), p less than 0.05. These results indicate that genetic variants of type III collagen may influence the extensile properties of the aortic wall and that mutations in the type III collagen gene may be associated with aortic aneurysms.

Aged↗
PubMed1991

Metalloproteinases in degenerative aortic disease.

1. Atherosclerosis and aneurysm of the abdominal aorta are associated with thinning of the medial connective tissue. We have investigated the presence of the connective-tissue-degrading metalloproteinases in homogenates prepared from atherosclerotic, aneurysmal and control aortic media. 2. Gelatinase activity was much increased in homogenates from atherosclerotic and aneurysmal aorta [10.9 +/- 1.8 and 13.3 +/- 3.3 micrograms of gelatin hydrolysed h-1 (mg of protein)-1 respectively]. This gelatinase activity was highest at the luminal aspect of the aortic media, where the activity increased three- to five-fold after the destruction of alpha 2-macroglobulin. Zymograms demonstrated the principal gelatinase in atherosclerotic aorta to have a molecular mass of about 92 kDa, whereas in aneurysmal aorta there was a spectrum of gelatinase activity from 92 to 55 kDa. 3. Collagenase and stromelysin (proteoglycanase) could be detected by immunoblotting in homogenates of aneurysmal aorta, but rarely in atherosclerotic aorta and never in control aorta. Collagenase and stromelysin activities were low, but increased two- to three-fold after the destruction of tissue inhibitor of metalloproteinases. Collagenase and stromelysin activities were highest at the adventitial aspect of aneurysmal media. 4. The secretion of gelatinase by inflammatory cells at the intima of diseased aorta could have a pathological role in establishing atherosclerotic plaques and medial thinning. Secretion of collagenase, gelatinase and stromelysin from the adventitia could accelerate connective tissue degradation in the media of aneurysmal aorta.

Aged↗