Biomedical subjects

J H Campbell

Publications and source records attributed to J H Campbell.

At least 19 recordsLinked to original sources

PubMed1998

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma.

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.

Adult↗

PubMed1998

Effect of estrogen on vascular smooth muscle cells is dependent upon cellular phenotype.

To investigate the growth-regulating action of estrogen on vascular smooth muscle cells (SMC), effects of beta-17-estradiol (beta-E2) on phenotypic modulation and proliferation of rabbit aortic SMC were observed in vitro. At 10(-8)M, beta-E2 significantly slowed the decrease in volume fraction of myofilaments (Vv myo) of freshly dispersed SMCs in primary culture, indicating an inhibitory effect of beta-E2 on spontaneous phenotypic modulation of SMC from a contractile to a synthetic phenotype. Freshly dispersed SMCs treated with beta-E2 also had a relatively longer quiescent phase than control cells before intense proliferation occurred. This was in contrast to SMCs in passage 2 3 (synthetic state), where beta-E2-treated cells replicated significantly faster than untreated cells. beta-E2 also markedly enhanced the serum-induced DNA synthesis of synthetic SMCs in a concentration-dependent manner within physiological range (10(-10)to 10(-8)M). These findings indicate that the growth-regulating effect of estrogen on vascular SMC is dependent on the cell's phenotypic state. It delays the cell cycle re-entry of the contractile SMCs by retarding their phenotypic modulation: however, once cells have modulated to the synthetic phenotype, it promotes their replication.

Animals↗

PubMed1998

Changes in three-dimensional architecture of microfilaments in cultured vascular smooth muscle cells during phenotypic modulation.

To investigate changes in the three-dimensional microfilament architecture of vascular smooth muscle cells (SMC) during the process of phenotypic modulation, rabbit aortic SMCs cultured under different conditions and at different time points were either labelled with fluorescein-conjugated probes to cytoskeletal and contractile proteins for observation by confocal laser scanning microscopy, or extracted with Triton X-100 for scanning electron microscopy. Densely seeded SMCs in primary culture, which maintain a contractile phenotype, display prominent linear myofilament bundles (stress fibres) that are present throughout the cytoplasm with alpha-actin filaments predominant in the central part and beta-actin filaments in the periphery of the cell. Intermediate filaments form a meshed network interconnecting the stress fibres and linking directly to the nucleus. Moderately and sparsely seeded SMCs, which modulate toward the synthetic phenotype during the first 5 days of culture, undergo a gradual redistribution of intermediate filaments from the perinuclear region toward the peripheral cytoplasm and a partial disassembly of stress fibres in the central part of the upper cortex of the cytoplasm, with an obvious decrease in alpha-actin and myosin staining. These changes are reversed in moderately seeded SMCs by day 8 of culture when they have reached confluence. The results reveal two changes in microfilament architecture in SMCs as they undergo a change in phenotype: the redistribution of intermediate filaments probably due to an increase in synthetic organelles in the perinuclear area, and the partial disassembly of stress fibres which may reflect a degradation of contractile components.

Actin Cytoskeleton↗

PubMed1998

Arterial heparan sulfate proteoglycans inhibit vascular smooth muscle cell proliferation and phenotype change in vitro and neointimal formation in vivo.

PURPOSE: The aim of this study was to determine whether heparan sulfate proteoglycans (HSPGs) from the normal arterial wall inhibit neointimal formation after injury in vivo and smooth muscle cell (SMC) phenotype change and proliferation in vitro. METHODS: Arterial HSPGs were extracted from rabbit aortae and separated by anion-exchange chromatography. The effect of HSPGs, applied in a periadventitial gel, on neointimal formation was assessed 14 days after balloon catheter injury of rabbit carotid arteries. Their effect on SMC phenotype and proliferation was measured by point-counting morphometry of the cytoplasmic volume fraction of myofilaments (Vvmyo) and 3H-thymidine incorporation in SMCs in culture. RESULTS: Arterial HSPGs (680 microg) reduced neointimal formation by 35% at 14 days after injury (P=.029), whereas 2000 microg of the low-molecular-weight heparin Enoxaparin was ineffective. HSPGs at 34 microg/mL maintained subconfluent primary cultured SMCs with the same high Vvmyo (52.1%+/-13.8%) after 5 days in culture as did cells freshly isolated from the arterial wall (52.1%+/-15.1%). In contrast, 100 microg/mL Enoxaparin was ineffective in preventing phenotypic change over this time period (Vvmyo 38.9%+/-14.6%, controls 35.9%+/-12.8%). HSPGs also inhibited 3H-thymidine incorporation into primary cultured SMCs with an ID50 value of 0.4 microg/mL compared with a value of 14 microg/mL for Enoxaparin (P< .01). CONCLUSION: When used periadventitially in the rabbit arterial injury model, natural arterial HSPGs are effective inhibitors of neointimal formation. In vitro, the HSPGs maintain SMCs in a quiescent state by inhibiting phenotypic change and DNA synthesis. This study suggests that HSPGs may be a natural agent for the treatment of clinical restenosis.

Animals↗

PubMed1998

Antibiotic prophylaxis in dentistry: a common sense approach.

Current knowledge about potentially serious infections after dental treatment suggests that antibiotic prophylaxis is of benefit in their prevention. This article describes several regimens for preventing infectious sequelae in patients with heart disease, prosthetic joints, and other "high risk" medical conditions. The prudent dental practitioner will use them regularly.

Antibiotic Prophylaxis↗

PubMed1997

The effect of the aged garlic extract, 'Kyolic', on the development of experimental atherosclerosis.

The aged garlic extract 'Kyolic' lowers serum cholesterol levels in humans and experimental animals and thus is presumed to have a protective effect against atherosclerosis. However, to date no studies have examined the effect of this substance on the actual development of the disease. In the present study, the right carotid artery of 24 rabbits was de-endothelialized by balloon catheterisation in order to produce a myointimal thickening. After 2 weeks the rabbits were randomly assigned to four groups: Group I received a standard diet; Group II received the standard diet supplemented with 800 microl/kg body weight/day 'Kyolic'; Group III received a 1% cholesterol supplemented standard diet; and Group IV received a 1% cholesterol supplemented standard diet plus 'Kyolic'. After 6 weeks, the cholesterol diet caused a 6-fold increase in serum cholesterol level (Group III; 6.4 +/- 0.6 mmol/l) compared to normal diet (Group I; 1.2 +/- 0.4 mmol/l) (P < 0.05) with only a minor, non-significant reduction seen by the addition of 'Kyolic' (Group IV; 6.2 +/- 0.7 mmol/l). Group III rabbits developed fatty streak lesions covering approximately 70 +/- 8% of the surface area of the thoracic aorta, which was significantly reduced to 25 +/- 3% in the 'Kyolic'-treated Group IV. No lesions were present in Groups I and II. The hypercholesterolaemic diet caused an increase in aortic arch cholesterol (2.1 +/- 0.1 mg cholesterol/g tissue) which was significantly reduced by 'Kyolic' supplementation (1.7 +/- 0.2 mg cholesterol/g tissue) (P < 0.05). 'Kyolic' significantly inhibited the development of thickened, lipid-filled lesions in the pre-formed neointimas produced by balloon-catheter injury of the right carotid artery in cholesterol-fed rabbits (intima as percent of artery wall, Group III 42.6 +/- 6.5% versus Group IV 23.8 +/- 2.3%, P < 0.01), but had little effect in rabbits on a standard diet (Group II 18.4 +/- 5.0% versus Group I 16.7 +/- 2.0%). In vitro studies showed that 'Kyolic' has a direct effect on inhibition of smooth muscle proliferation. In conclusion, 'Kyolic' treatment reduces fatty streak development, vessel wall cholesterol accumulation and the development of fibro fatty plaques in neointimas of cholesterol-fed rabbits, thus providing protection against the onset of atherosclerosis.

Animals↗

PubMed1997

Inhibition of neointimal formation by natural heparan sulfate proteoglycans of the arterial wall.

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Animals↗

PubMed1997

Effects of implantable biomaterials on radiation dosimetry.

BACKGROUND: It is generally known that radiation dose is enhanced in front of and reduced behind metallic plates. This study evaluates metallic, ceramic, and bioabsorbable facial-reconstruction materials for their differential effects on radiation dosimetry. METHODS: Commercially pure titanium (cpt), stainless steel (steel), titanium alloy (tia), hydroxyapatite (HA), and poly-L-lactide (PLA, a bioabsorbable polymer) were obtained for this study. The radiation doses distal (behind) and proximal (in front of) to the test material were measured with an ionization chamber placed at several distances from the test material. Therefore, transmission (proximal to plate) and backscattering (distal to plate) factors were generated at several distances for each material. RESULTS: Poly-L-lactide transmitted nearly 100% of the incident radiation beam. The metals had the greatest effect on transmission with steel, followed by cpt, tia, and HA showing the greatest reduction of incident beam. Poly-L-lactide revealed minimal backscattering. Greater backscatter of the incident radiation beam was seen from steel, followed by cpt and HA. Poly-L-lactide also behaved similar to water in transmission and backscatters properties during electron irradiation. CONCLUSIONS: Poly-L-lactide has a minimal effect on the radiation-dose distribution and may be beneficial as a reconstructive device for patients undergoing head and neck cancer radiotherapy. Hydroxyapatite showed a relatively minor effect, whereas the metals (steel, followed by cpt and tia) revealed the greatest detrimental effect on the radiation-dose distribution.

Alloys↗

PubMed1997

Inhibition of phenotype modulation, growth, and migration of vascular smooth muscle cells by a guanosine-rich 30-mer phosphorothioate oligodeoxynucleotide.

The testing of a 30-mer dG-rich phosphorothioate oligodeoxynucleotide (LG4PS) for effects on the behaviour of vascular smooth muscle cells (VSMC) in vitro and in vivo is described. LG4PS at 0.3 microM inhibited significantly the phenotype modulation of freshly isolated rabbit VSMC, and cell outgrowth from pig aortic explants was inhibited approximately 80% by 5 microM LG4PS. The growth of proliferating rabbit and pig VSMC was inhibited approximately 70% by 0.3 microM and 5 microM LG4PS, respectively. Though less marked, the antiproliferative effects of LG4PS on human VSMC were comparable to those obtained with heparin. The cytotoxic effects of LG4PS on VSMC in vitro were low. Despite these promising results, adventitial application of 2-200 nmol LG4PS in pluronic gel failed to reduce vascular hyperplasia in balloon-injured rabbit carotid arteries, and the highest dose caused extensive mortality.

Animals↗

PubMed1997

Lipid content and fatty acid composition of 11 species of Queensland (Australia) fish.

The fatty acid composition of 11 species of fish caught of the northeast coast of Australia was determined. No fatty acid profiles have been previously published for fish from this area nor for nine of these species. Although the percentage of polyunsaturated fatty acid (PUFA) was the same as the calculated average for Australian fish (42.3%), the percentage of n-3 fatty acids was lower (24.4 +/- 5.4% vs. 30.7 +/- 10.1%) and the n-6 fatty acids higher (16.5 +/- 4.5% vs. 11.2 +/- 5.9%), P < 0.001 in each case. The major n-3 PUFA were docosahexaenoic (15.6 +/- 6.3%) and eicosapentaenoic acid (4.3 +/- 1.1%) while the major n-6 PUFA were arachidonic (8.3 +/- 3.2%) and n-6 docosatetraenoic acid (3.1 +/- 1.3%). The second-most abundant class of fatty acid was the saturates (31.6 +/- 3.5%) while the monounsaturates accounted for 17.4 +/- 4.3% of the total fatty acids. The monounsaturate with the highest concentration was octadecenoic acid (11.8 +/- 2.6%). There was a positive correlation between the total lipid content and saturated and monounsaturated fatty acids (r = 0.675 and 0.567, respectively) and a negative correlation between the total lipid content and PUFA (r = 0.774).

Animals↗

PubMed1997

Growth factors released into the coronary circulation after vascular injury promote proliferation of human vascular smooth muscle cells in culture.

OBJECTIVES: This study sought to 1) assess in vivo release of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) into the coronary circulation after vascular injury in human subjects; and 2) evaluate mitogenic effects of PDGF and bFGF on the patient's own vascular smooth muscle cells (VSMCs). BACKGROUND: Circumstantial evidence suggests involvement of PDGF and bFGF peptides in the neointimal response to vascular injury. To date, no study has shown biologically active growth factors within the coronary circulation after vascular injury in human subjects. METHODS: In 18 patients, plasma PDGF AB, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) levels were measured in coronary sinus blood obtained before and up to 30 min after angioplasty. In five patients undergoing atherectomy, coronary sinus serum was added to cultured VSMCs derived from atherectomy tissue to assess the mitogenic potential of the serum. Mitogenicity attributable to PDGF and bFGF was determined using neutralizing antibodies to these factors. PDGF A, PDGF B and bFGF were localized within the atherectomy tissue using immunocytochemical analysis. RESULTS: Before angioplasty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patients scheduled for angioplasty compared with those in control patients (p < 0.01). Within 5 min of angioplasty, PDGF AB levels increased twofold and returned toward preangioplasty levels at 30 min; PF4 and beta-TG levels remained elevated. Serum obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity compared with preatherectomy serum (p = 0.01). This increase in mitogenicity was reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF, bFGF and PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized within the intima of the atherectomy tissue. CONCLUSIONS: The change in plasma PDGF level is consistent with first-phase release of PDGF after vascular injury. The increase in mitogenicity of serum suggests that PDGF and bFGF are biologically active.

Adult↗

PubMed1997

The cell biology of atherosclerosis--new developments.

In the development of atherosclerotic lesions, three basic processes occur: 1) invasion of the artery wall by leucocytes, particularly monocytes and T-lymphocytes; 2) smooth muscle phenotypic modulation, proliferation, and synthesis of extracellular matrix; and 3) intracellular (macrophage and smooth muscle) lipoprotein uptake and lipid accumulation. Invasion of the vessel wall by leucocytes is mediated through the expression of adhesion molecules on both leucocytes and the endothelium making them 'sticky'. The adhesion molecules are induced by inflammatory mediators released from leucocytes and endothelium, and these in turn are induced by high serum cholesterol levels or complement fragments. Leucocytes which have adhered to the endothelium are chemo-attracted into the vessel wall by cytokines produced by early arriving leucocytes or by low density lipoprotein which has passively passed into the wall, in the process being trapped and oxidised. The oxidised low density lipoprotein is taken up by scavenger receptors (which are not subject to down-regulation) on both macrophages and smooth muscle cells. The overaccumulation of lipid is toxic to the cells and they die contributing to the central necrotic core. The macrophages and T-lymphocytes produce substances which induce smooth muscle cells of the artery wall to change from a 'contractile' (high volume fraction of myofilaments [Vvmyo]) to a 'synthetic' (low Vvmyo) phenotype. In this altered state they respond to growth factors released from macrophages, platelets, regenerating endothelial cells and smooth muscle cells; produce large amounts of matrix; express lipoprotein scavenger receptors; express adhesion molecules for leucocytes; and express HLA-DR following exposure to the T-lymphocyte product, IFN-delta, suggesting that they can become involved in a generalised immune reaction.

Animals↗

PubMed1997

Human leukemia inhibitory factor upregulates LDL receptors on liver cells and decreases serum cholesterol in the cholesterol-fed rabbit.

In a previous study, we found that the cytokine (human) leukemia inhibitory factor (hLIF) significantly reduced plasma cholesterol levels and the accumulation of lipid in aortic tissues of cholesterol-fed rabbits after 4 weeks of treatment. The mechanisms by which this occurs were investigated in the present study. This involved examining the effect of hLIF on (1) the level of plasma cholesterol at different times throughout the 4-week treatment and diet period; (2) smooth muscle cell (SMC) and macrophage-derived foam cell formation in vitro; and (3) LDL receptor expression and uptake in the human hepatoma cell line HepG2. At time zero, an osmotic minipump (2-mL capacity; infusion rate, 2.5 microL/h; 28 days) containing either hLIF (30 micrograms kg-1.d-1) or saline was inserted into the peritoneal cavity of New Zealand White rabbits (N = 24). Rabbits were divided into four groups of six animals each. Group 1 received a normal diet/saline; group 2, a normal diet/hLIF; group 3, a 1% cholesterol diet/saline; and group 4, a 1% cholesterol diet/hLIF. hLIF had no effect on the plasma lipids or artery wall of group 2 rabbits (normal diet). However, in group 4 rabbits, plasma cholesterol levels and the percent surface area of thoracic aorta covered by fatty streaks was decreased by approximately 30% and 80%, respectively, throughout all stages of the 4-week treatment period. In vitro, hLIF failed to prevent lipoprotein uptake by either SMCs or macrophages (foam cell formation) when the cells were exposed to beta-VLDL for 24 hours. In contrast, hLIF (100 ng/mL) added to cultured human hepatoma HepG2 cells induced a twofold or threefold increase in intracellular lipid accumulation in the medium containing 10% lipoprotein-deficient serum or 10% fetal calf serum, respectively. This was accompanied by a significant non-dose-dependent increase in LDL receptor expression in hLIF-treated HepG2 cells incubated with LDL (20 micrograms/mL) when compared with controls (P < .05) incubated in control medium alone (P < .05). We suggest that the hLIF-induced lowering of plasma cholesterol and tissue cholesterol levels (inhibition of fatty streak formation) in the hyperlipidemic rabbit is due in part to upregulation of hepatic LDL receptors, with resultant increased clearance of lipoprotein-associated cholesterol from the circulation. There is an additional and as-yet-unknown mechanism acting at the level of the vessel wall that appears to be affecting the process of arterial cholesterol accumulation.

Animals↗

PubMed1996

Incidence and significance of cardiac arrhythmia in geriatric oral surgery patients.

We recorded heart rhythms of 40 older patients (20 medicated for cardiovascular disease and 20 not medicated for cardiovascular disease) during an outpatient oral surgery visit to determine overall arrhythmia incidence and severity, differences in incidence associated with cardiovascular medication status, and the impact of surgical intervention on arrhythmia incidence. We hypothesized that both groups would show similar arrhythmia numbers and types during surgical visits and that a history of medication for cardiovascular disease would not be an indicator of cardiac arrhythmia. Enrollment remained open until 20 patients older than 60 years of age from each group agreed to participate. Data were analyzed using the chi square statistic and Fisher's exact test (2-tailed). Included in the study were 24 women and 16 men; their mean age was 70.5 years (range, 60 to 86 years). Arrhythmias were detected in 17 patients and 33 of the 160 recorded rhythms. None of the detected arrhythmias were considered life-threatening. Significantly more arrhythmias occurred before administration of anesthesia than during administration of epinephrine-containing local anesthetics (p = 0.0001), and a greater number of rhythm disturbances were seen during the surgical procedure when compared with anesthesia administration (p = 0.0170). No differences in arrhythmia incidence were seen with increasing age, when male patients were compared with female patients, or when patients pharmacologically treated for cardiovascular disease were compared with patients not taking cardiovascular therapeutic medications. We conclude that although arrhythmias in this ambulatory population are common, they are typically benign in character and cardiovascular medication status is not indicative of their presence. In addition, minor oral surgery intervention with local anesthetics used in recommended dosages has no effect on cardiac arrhythmia status in the ambulatory geriatric population.

Aged↗

PubMed1996

Angiotensin-converting enzyme inhibitors and atherosclerosis: relevance of animal models to human disease.

1. Most studies examining the effect of angiotensin-converting enzyme (ACE) inhibitors on atherosclerosis in experimental animals have used doses well in excess of those given clinically. 2. Using a rabbit model of cholesterol-induced atherosclerosis characterized by subendothelial lipid accumulations ('juvenile fatty streaks') in the aorta and atheromatous lesions in the pre-injured carotid artery, we examined the effect of perindopril (at doses approaching clinical relevance) on the development, progression and regression of atherosclerosis. 3. Administration of perindopril during the 6 weeks of cholesterol feeding reduced lipid accumulation in developing atheromatous plaques of the carotid artery and in fatty streaks of the aorta. In animals with pre-existing fat-filled lesions, perindopril inhibited progression of the disease in both vessels and aided lesion regression following return to a normal diet for up to 10 months. The protective effect of perindopril was not related to a decrease in blood pressure nor to an influence on serum cholesterol levels. 4. The bradykinin B2 receptor antagonist Hoe140 did not alter the effectiveness of perindopril in inhibiting either the development of atherosclerosis or vessel wall ACE activity, indicating that the anti-atherogenic effect of perindopril is not mediated through the B2 receptor. 5. The angiotensin II (AngII) receptor antagonist losartan had no effect on the development of atherosclerotic plaques in this rabbit model, indicating that inhibition of AngII production is not the mechanism by which perindopril exerts its antiatherogenic effects.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Foot function in diabetic patients after partial amputation.

The function of partially amputated feet in 10 patients with diabetes mellitus was studied. First-step bilateral barefoot plantar pressure distribution and three-dimensional kinematic data were collected using a Novel EMED platform and three video cameras. Analysis of the plantar pressure data revealed a significantly greater mean peak plantar pressure in the feet with transmetatarsal amputation (TMA) than in the intact feet of the same patients. The heels of the amputated feet had significantly lower mean peak plantar pressures than all the forefoot regions. A significantly greater maximum dynamic dorsiflexion range of motion was seen in the intact compared with the TMA feet. However, no difference was noted in the static dorsiflexion range of motion between the two feet and there was, therefore, a trend for the TMA feet to use less of the available range of motion. Given the altered kinematics and elevated plantar pressures noted in this study, careful postsurgical footwear management of feet with TMA would appear to be essential if ulceration is to be prevented.

Aged↗

PubMed1995

Effect of extracellular matrix proteins on vascular smooth muscle cell phenotype.

The effect on phenotypic expression of rabbit vascular smooth muscle cells (SMC) of the interstitial matrix proteins collagen I and fibronectin, the basal lamina proteins collagen IV and laminin, and the serum adhesion protein vitronectin was examined in culture. Experiments were performed in foetal calf serum stripped of fibronectin and vitronectin to eliminate their confounding effects. All the proteins promoted adhesion to the plastic culture dish (in a concentration dependent manner) of SMC freshly isolated from the artery wall. These cells had a high volume density of myofilaments (Vvmyo) in their cytoplasm. Laminin was best at maintaining SMC with a high Vvmyo (Vvmyo = 49.8%) followed by collagen IV (41.7%). Cells plated on vitronectin showed the lowest Vvmyo (31.3%). The results support the concept that the SMC basal lamina has a role in maintaining cells in the high Vvmyo phenotype.

Actin Cytoskeleton↗

PubMed1995

Effect of extracellular matrix proteins on vascular smooth muscle cell phenotype.

Actin Cytoskeleton↗