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Biomedical subjects

P D Richardson

Publications and source records attributed to P D Richardson.

At least 19 recordsLinked to original sources
PubMed2005

Combined effects of pulsatile flow and dynamic curvature on wall shear stress in a coronary artery bifurcation model.

A three-dimensional model with simplified geometry for the branched coronary artery is presented. The bifurcation is defined by an analytical intersection of two cylindrical tubes lying on a sphere that represents an idealized heart surface. The model takes into account the repetitive variation of curvature and motion to which the vessel is subject during each cardiac cycle, and also includes the phase difference between arterial motion and blood flowrate, which may be nonzero for patients with pathologies such as aortic regurgitation. An arbitrary Lagrangian Eulerian (ALE) formulation of the unsteady, incompressible, three-dimensional Navier-Stokes equations is employed to solve for the flow field, and numerical simulations are performed using the spectral/hp element method. The results indicate that the combined effect of pulsatile inflow and dynamic geometry depends strongly on the aforementioned phase difference. Specifically, the main findings of this work show that the time-variation of flowrate ratio between the two branches is minimal (less than 5%) for the simulation with phase difference angle equal to 90 degrees, and maximal (51%) for 270 degrees. In two flow pulsatile simulation cases for fixed geometry and dynamic geometry with phase angle 270 degrees, there is a local minimum of the normalized wall shear rate amplitude in the vicinity of the bifurcation, while in other simulations a local maximum is observed.

Animals↗
PubMed2001

Nocardia asteroides lung abscess in acute ulcerative colitis treated with cyclosporine.

Cyclosporine is a potent suppresser of cell-mediated immunity that is mainly used in organ transplantation to prevent rejection. It is also being used increasingly outside of transplantation and probably is the only new treatment to have made an impact in acute ulcerative colitis (UC) resistant to steroid therapy. We describe a case of Nocardia asteroides lung abscess in a patient treated with cyclosporine for acute steroid resistant UC that was successfully managed with antibiotics and by discontinuing cyclosporine. With increasing use of cyclosporine for acute UC it is to be anticipated that opportunistic infections such as Nocardia will be more frequently encountered in the future.

Acute Disease↗
PubMed2001

Targeted gene correction strategies.

We are now approaching the reality of success in gene therapy as our knowledge of the genetic basis of disease continues to grow, coupled with improved delivery methods for therapeutic nucleic acid molecules. It is apparent that gene therapy can be divided into two specific and very different approaches in which gene replacement, or augmentation, is differentiated from gene repair. In fact, gene augmentation is characterized by the delivery of the coding sequence of the gene of interest in an expression cassette. In contrast, gene repair differs in that the process targets for correction of the mutation responsible for the genetic disorder. The in situ repair of a gene has many advantages over conventional replacement methods. This review will concentrate on the various strategies currently available for gene repair. The potential benefits of correction versus augmentation will be addressed and possible future developments outlined.

Cells, Cultured↗
PubMed2000

Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine.

BACKGROUND/AIM: Azathioprine is standard therapy for maintenance of remission in patients with autoimmune hepatitis. However, approximately 15% of patients are intolerant of therapy and 10% do not respond to it. There is a need for alternative therapies. We describe here the results of mycophenolate mofetil therapy in patients with autoimmune hepatitis. PATIENTS: We studied seven patients with type 1 AIH (six female). Three were intolerant of azathioprine and had elevated transaminases and liver histology showing active disease despite prednisolone therapy. Four had been on a dose of 2 mg per kg of azathioprine without complete normalisation of ALT, and had liver biopsies showing active disease. All were treated with mycophenolate 1 g bd and were followed for a median of 46 months (21-59). End points were improvement in histological inflammation, ALT and prednisolone dose. RESULTS: Five of the seven (71%) patients had normal transaminases after 3 months of treatment. The steroid dose fell from a median of 20 mg per day to 2 mg per day at 9 months (p=0.0001) and the hepatic activity index fell from median 11 to 3 (p=0.001) after 7 months of therapy. One patient required dose reduction because of a fall in white cell count. No other adverse effects were seen. CONCLUSIONS: Mycophenolate mofetil is effective and well tolerated in patients with type 1 AIH who are intolerant of, or do not respond to, azathioprine.

Adolescent↗
PubMed1996

Symptomatic and endoscopic duodenal ulcer relapse rates 12 months following Helicobacter pylori eradication treatment with omeprazole and amoxycillin with or without metronidazole.

AIM: To determine the effect of Helicobacter pylori eradication with omeprazole and amoxycillin, with or without metronidazole, on the 12-month course of duodenal ulcer disease. METHODS: In a randomized; double-blind study, conducted in 19 hospitals, 105 H. pylori positive duodenal ulcer patients were healed and symptom-free following either omeprazole dual therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s., OA, eradication rate 46%, n = 52) or omeprazole triple therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s.+metronidazole 400 mg t.d.s., OAM, eradication rate 92%, n = 53) for 2 weeks, followed by 2 weeks of omeprazole 20 mg o.m. and a 12-month untreated follow-up period, after which time all patients were endoscoped. Endoscopic and symptomatic relapse rates, and effect on H. pylori status measured using 13C-urea breath test, were determined. RESULTS: During the 12-month untreated follow-up period, the life-table endoscopic relapse rates were 12% (95% CI: 2-22%) and 2% (95% CI: 0-6%) for OA and OAM patients, respectively. By 12 months, life-table symptomatic relapse rates were 22% (95% CI: 13-37%) and 19% (95% CI: 8-30%) for OA and OAM, respectively. In the 12 months untreated follow-up period, 2/69 (3%, 95% CI: 0-7%) patients rendered H. pylori negative had an endoscopic relapse at the end of the 12-month follow-up period, compared with 5/31 (16%, 95% CI: 3-29%) patients remaining H. pylori positive (P = 0.03 between H. pylori positive and negative groups). Twelve of 69 (17%, 95% CI: 8-26%) patients rendered H. pylori negative relapsed symptomatically, compared with 9/31 (29%, 95% CI: 13-45%) patients remaining H. pylori positive (P = N.S. between groups). There was a significant improvement in epigastric pain (P = 0.0001), nausea and vomiting (P < 0.05) between entry to the study and 1, 6 and 12 months post-treatment for both treatment groups. CONCLUSIONS: OAM eradicates H. pylori in significantly more patients than OA, but successful H. pylori eradication with either OAM or OA predisposes to low endoscopic and symptomatic relapse rates for duodenal ulcer patients when followed up for 12 months.

Adult↗
PubMed1996

Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis.

BACKGROUND: As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis. METHODS: Patients (n = 209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily (n = 98) or placebo (n = 111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance. RESULTS: On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P < 0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P < 0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P < 0.01). A greater reduction in anxiety occurred in the omeprazole group (P < 0.05). CONCLUSION: Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.

Adult↗
PubMed1995

Omeprazole 10 mg or 20 mg once daily in the prevention of recurrence of reflux oesophagitis. Solo Investigator Group.

This study determined the optimal maintenance dose of omeprazole in reflux oesophagitis. One hundred and ninety three patients rendered asymptomatic and healed after four or eight weeks omeprazole were randomised double blind to 10 mg omeprazole once daily (n = 60 evaluable), 20 mg omeprazole once daily (n = 68), or placebo (n = 62) for one year or until symptomatic relapse. Each omeprazole regimen was superior to placebo in preventing both symptomatic relapse (life table analysis, p < 0.001) and endoscopically verified relapse (p < 0.001). At 12 months, the life table endoscopic remission rates (proportions of patients without grade > or = 2 oesophagitis) were: 50% (95% confidence intervals 34 to 66%) with 10 mg omeprazole once daily, 74% (62 to 86%) with 20 mg omeprazole once daily, and 14% (2 to 26%) with placebo. At 12 months, the life table symptomatic remission rates (proportions of patients asymptomatic or with mild symptoms) were: 77% (64 to 89%) with 10 mg omeprazole once daily, 83% (73 to 93%) with 20 mg omeprazole once daily, and 34% (16 to 52%) with placebo. Both 10 mg and 20 mg omeprazole once daily were effective in prolonging the remission of reflux oesophagitis: 10 mg may be appropriate to start longterm treatment, though the existence of a dose response relation means that 20 mg once daily may be effective in patients for whom 10 mg once daily is suboptimal.

Adult↗
PubMed1994

Lipid and cellular constituents of unstable human aortic plaques.

Unstable plaques are undergoing thrombosis which, in most instances, is due to fissuring and rupture of the plaque cap. This process (deep intimal injury) is a complication of plaques with a lipid-rich core. The cap tear allows blood to enter the core from the lumen, leading initially to intraplaque thrombosis and, subsequently, in some cases intraluminal thrombosis. Cap tears reflect the interplay between the force exerted on the tissue and its inherent mechanical strength. Factors which elevate and concentrate circumferential wall stress on the cap during systole include an increasing proportion of the total plaque volume occupied by the lipid core, thinning of the cap and a loss of internal collagen struts within the core. Factors which lead to an inherent reduction in the mechanical strength of cap tissue include a reduction in collagen and glycosaminoglycan concentrations, an increase in the number and density of macrophages, and a concomitant reduction in smooth muscle cells in the cap tissue. It is therefore possible to define a vulnerable plaque as one in which the lipid core is disproportionately large, the cap thin, and in which monocytes preponderate over smooth muscle cells.

Arteriosclerosis↗
PubMed1994

Pulmicort Turbohaler once daily as initial prophylactic therapy for asthma.

In a double-blind, randomized, parallel-group clinical trial, 340 asthmatic patients aged 12-70 years received budesonide 400 micrograms once daily in the morning, budesonide 400 micrograms once daily in the evening, budesonide 200 micrograms twice daily or placebo, for 12 weeks in addition to inhaled short-acting beta 2-agonists used as required (p.r.n.). Budesonide was given as Pulmicort Turbohaler. Peak expiratory flow rate (PEFR) increased by 20 to 30 1 min-1 in each of the active treatment groups, significantly more than in the placebo group (P < 0.01). There were no significant differences between the active treatment groups. Symptom improvement and decreased beta 2-agonist use reflected the PEFR data. Incidences of adverse events in the active treatment groups were similar to those observed in the placebo group. Budesonide 400 micrograms given once daily morning or evening is equieffective with the same total daily dose given twice daily in the treatment of mild to moderate stable asthmatics.

Adolescent↗
PubMed1994

Intracorporeal oxygenation.

The dominant problem in the design of an intracorporeal oxygenator is achieving gas transfer rates sufficient for physiological needs in the space available with acceptably low flow resistance to blood. Design problems still to be solved, when configurations with sufficient gas transfer effectiveness are well identified, are biological tolerance (including adequate blood compatibility), ease of manufacture, and prolonged function.

Animals↗
PubMed1994

Gas transport in the intracorporeal oxygenator with woven tubes.

The woven tubes membrane oxygenator is a suitable configuration for the intracorporeal membrane oxygenator because of a high gas exchange performance and a compact packing of tubing. In this study the oxygen transfer performance of woven tubes was evaluated by an in vitro experiment with an external perfusion mode; the blood flow is outside of the tubes in order to reveal the feasibility of designing the intravascular oxygenator (IVOX) by the woven tubes. The oxygen transfer efficiency of the external perfusion mode is superior to that with the internal perfusion mode because of the larger convective mixing effect on the external surface of the tubes. Thus the use of the external perfusion mode results in the shorter necessary tube length for the rated condition, which enables making the oxygenator unit more compact. All of these features encourage the adoption of the woven tubes for use in the intravascular oxygenator.

Animals↗
PubMed1993

Testing of small connective tissue specimens for the determination of the mechanical behaviour of atherosclerotic plaques.

The tearing of the cap of atheromatous plaques is the commonest cause of thrombosis in human coronary arteries. It has been proposed that tearing arises because of structural weakening of the cap's connective tissue around the tear. To test this hypothesis we compared the mechanical properties of the intact edges of torn plaque caps and unbroken caps. Owing to limitations in plaque size, a purpose-built tensometer was developed to study stress-strain relationships of the small connective tissue specimens. The design of the tensometer is reported and was shown to detect accurately, minor differences in connective tissues and to generate complete stress-curves with computer-assisted image analysis.

Animals↗
PubMed1993

Does 40 mg omeprazole daily offer additional benefit over 20 mg daily in patients requiring more than 4 weeks of treatment for symptomatic reflux oesophagitis?

This study was designed to establish whether 40 mg omeprazole once daily exhibits sufficient additional efficacy over that of 20 mg omeprazole once daily in patients with symptomatic reflux oesophagitis requiring more than an initial 4-week course of 20 mg omeprazole once daily (o.m.) to warrant routine use of the higher dose. Three hundred and thirteen patients were randomized to receive either 20 mg omeprazole (4 weeks) then 20 mg (second 4 weeks if not both healed and symptom-free after 4 weeks), or 20 mg omeprazole (4 weeks) then 40 mg omeprazole o.m. (second 4 weeks). One hundred and twenty-seven patients were healed and symptom-free after 4 weeks and left the study at that point. Taking the second treatment period in isolation, the healing rate (64% vs. 45%, P < 0.02) and relief of heartburn (72% vs. 60%, P < 0.002) were greater among patients receiving 40 mg omeprazole o.m., demonstrating the existence of a dose-response relationship for omeprazole. However, on completion, there were no significant differences between the patients randomized to the 20/20 mg (healed 65%, asymptomatic 69%) or the 20/40 mg (healed 74%, asymptomatic 74%: both not significant differences compared with 20/20 mg) regimens. The magnitude of the difference in efficacy between 20 and 40 mg omeprazole in symptomatic reflux oesophagitis is insufficient to warrant the routine use of 40 mg in patients requiring more than 4 weeks' treatment with 20 mg omeprazole o.m.; continued treatment with 20 mg omeprazole for 4-8 weeks is the preferred option.

Adolescent↗
PubMed1993

Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content.

OBJECTIVE: To assess the size of the lipid pool and the number of smooth muscle cells and monocyte/macrophages in human aortic plaques that were intact and to compare the results with those in aortic plaques undergoing ulceration and thrombosis. DESIGN: The lipid pool was measured as a percentage of the total cross sectional area of the plaque. Immunohistochemistry was used to identify cell types (monocytes/macrophages (M phi) by EBM11 and HAM56, smooth muscle cells by alpha actin). The area of the tissue occupied by each cell type was measured by quantitative microscopy in the peripheral (shoulder) area of the plaque and the plaque cap. Absolute counts of each cell type were expressed as the ratio of SMC:M phi. MATERIAL: Aortas were obtained at necropsy from men aged less than 69 years who died suddenly (within 6 hours of the onset of symptoms) of ischaemic heart disease. 155 plaques from 13 aortas were studied. Four aortas showed intact plaques only (group A, n = 31). Nine aortas showed both intact plaques (group B, n = 79) and plaques that were undergoing thrombosis (group C, n = 45). RESULTS: In 41 (91.1%) of the 45 plaques undergoing thrombosis (group C) lipid pools occupied more than 40% of the cross sectional area of the plaque. Only 12 (10.9%) of the 110 intact plaques (groups A + B) had lipid pools of this size. The mean size of the lipid pool in plaques of groups A, B, and C was 12.7%, 27.3% and 56.7% respectively. Compared with intact plaques those undergoing thrombosis contained a smaller volume of smooth muscle cells (2.8% v 11.8%) and a larger volume of monocyte/macrophages (13.7% v 2.9%) in the plaque cap. The ratio of the number of smooth muscle cells to monocytes/macrophages was 7.8 in group A plaques, 4.1 in group B plaques, and 1.0 in group C plaques. This gradient was the result of an absolute increase in monocyte/macrophages and an absolute decrease in smooth muscle cells. CONCLUSIONS: In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of their volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smooth muscle cells in the cap.

Aged↗
PubMed1992

Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: span-wise variations.

Measurements of total collagen, of the ratio of collagen types III/(I+III) and of sulphated glycosaminoglycans (GAGs) were compared with mechanical strength for individual ulcerated and non-ulcerated human aortic plaque caps and with intima adjacent to the plaques. The distributions of the collagen type ratio were similar for both ulcerated and non-ulcerated plaque caps but different from that of the adjacent intima. The proportions of different collagen types were not related to fracture stress and are thus unlikely to affect the potential to ulcerate. The distributions of the sulphated GAGs showed lower amounts for the plaque caps compared with the nearby intima, with the centres of ulcerated plaque caps having the lowest values. Total collagen had higher values in the peripheries of plaque caps compared with the nearby intima, but was distinctly lower in the centres of ulcerated plaque caps. Plaque caps appeared to require a higher collagen content than adjacent intima to support a given level of mechanical strength, suggesting that while collagen production had occurred in the plaque caps it was not as efficiently organized to resist fracture as a similar amount of collagen in the adjacent intima. Ulcerated plaque caps are notable for much larger transverse (centre vs. periphery) gradients of connective tissue constituents than for non-ulcerated plaque caps. The development of these transverse gradients may be a critical aspect in determining the propensity of a plaque to ulcerate.

Aortic Diseases↗