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Biomedical subjects

B O'Connor

Publications and source records attributed to B O'Connor.

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

Does cyclosporin increase lipoprotein(a) concentrations in renal transplant recipients?

Cyclosporin, the immunosuppressant of choice for renal transplant recipients, has been implicated as the cause of abnormalities in serum lipid concentrations in these patients. We have measured serum lipoprotein(a) concentrations and analysed the distribution of apoprotein(a) isoforms in 90 renal transplant recipients receiving cyclosporin and prednisolone (with or without azathioprine), 59 patients receiving azathioprine and prednisolone alone, and 146 non-hyperlipidaemic controls. Cyclosporin-treated patients had significantly higher lipoprotein(a) concentrations (median 170 [interquartile range 55-382] mg/L) than those receiving azathioprine and prednisolone (64 [10-204] mg/L, p = 0.001) or the healthy controls (94 [18-280] mg/L, p = 0.008). The difference between the azathioprine and prednisolone group and the controls was not significant. Although the time since transplantation was significantly shorter for the cyclosporin-treated group, there was no correlation between lipoprotein(a) concentration and time since transplantation (r = -0.13, p = 0.18). Apoprotein(a) phenotyping showed no significant differences in the distribution of apoprotein(a) isoforms between the treatment groups or between patient and control groups. Lipoprotein(a) concentrations are higher in renal transplant recipients treated with cyclosporin than in those maintained on azathioprine and prednisolone. The mechanisms underlying this abnormality remain to be elucidated.

Adult↗
PubMed1993

The effect of nicotinic acid and acipimox on lipoprotein(a) concentration and turnover.

This study examines the effect of nicotinic acid (1 g t.d.s.) on serum Lp(a) concentration in a group of patients with type II hyperlipidaemia selected on the basis of a plasma Lp(a) concentration greater than 30 mg/dl. Reductions in total cholesterol, triglyceride, LDL-cholesterol and Lp(a) were 16.3%, 25.5%, 23.7% and 36.4%, respectively, with an increase in HDL cholesterol of 37.3%. The reduction in Lp(a) concentration did not correlate with any other lipoprotein changes. In order to establish the mechanism of the fall in Lp(a) concentration, in vivo turnover of autologous Lp(a) was studied in three subjects before and whilst taking nicotinic acid. The fractional catabolic rate in Lp(a) was unaltered in the subjects on therapy, indicating that nicotinic acid did not increase catabolism of Lp(a) but decreased the synthetic rate. Since nicotinic acid was poorly tolerated we examined the effect of acipimox, an analogue of nicotinic acid on lipoproteins using a placebo controlled double-blind crossover design in a group of hyperlipidaemic patients again selected with plasma Lp(a) concentration greater than 30 mg/dl. Acipimox was better tolerated than nicotinic acid but the percentage changes in lipoprotein concentrations were smaller.

Adult↗
PubMed1993

Identification of a specific radioligand for the cardiac rapidly activating delayed rectifier K+ channel.

Class III antiarrhythmic drugs show promise as effective treatments for the suppression of potentially lethal cardiac arrhythmias. Dofetilide (UK-68,798), is a potent class III antiarrhythmic agent that is presently under clinical investigation. The objective of this study was to determine whether [3H]dofetilide could be used as a specific radioligand for the rapidly activating delayed rectifier K+ channel of the heart. We find that [3H]dofetilide binds to high-affinity sites on guinea pig cardiac myocytes. Competition studies using unlabeled dofetilide indicate that binding is characterized by an IC50 of 100 +/- 30 nM (mean +/- SD, n = 13). Scatchard analyses of binding indicate a Kd of 70 +/- 6 nM and a maximal binding capacity of 0.30 +/- 0.02 pmol/mg protein. [3H]Dofetilide is displaced from guinea pig myocytes by dofetilide, clofilium, quinidine, sotalol, and sematilide with a rank order of potency that correlates with functional blockade of the rapidly activating delayed rectifier K+ current (correlation coefficient, 0.951; slope, 0.99 +/- 0.19; p = 0.014). High-affinity [3H]dofetilide binding is not detected in rat myocytes, which are devoid of delayed rectifier K+ current. We conclude that [3H]dofetilide specifically binds to sites associated with the rapidly activating delayed rectifier K+ channel of guinea pig myocardium.

Animals↗
PubMed1993

Potent leukotriene D4 receptor antagonist ICI 204,219 given by the inhaled route inhibits the early but not the late phase of allergen-induced bronchoconstriction.

ICI 204,219 is a potent and specific leukotriene D4 receptor antagonist that blocks both the early and late responses to allergen challenge in humans when given orally at a dose of 40 mg. Here we report our findings with an inhaled formulation of ICI 204,219 against allergen-induced bronchoconstriction. A group of 10 atopic subjects (mean age 25.6 +/- 4.2; 6 females; FEV1 > 90% of predicted; on inhaled beta 2-agonists only) were studied on 2 separate days 2 to 3 wk apart. In a randomized placebo-controlled trial they inhaled eight puffs of a standard metered dose inhaler containing either ICI 204,219 (200 micrograms/puff, total dose 1,600 micrograms) or propellant alone. They underwent bronchial allergen challenge 30 min later using a single concentration of allergen previously shown to lower the FEV1 by > or = 15%. FEV1 was monitored hourly for 10 h, and urine was collected for LTE4 determination. Inhalation of ICI 204,219 was well tolerated, with no adverse clinical or biochemical effects. There was no significant effect of ICI 204,219 inhalation on basal airway caliber (change in FEV1 30 min after inhalation was -149 +/- 67 ml after placebo versus 3 +/- 38 ml after ICI 204,219; p = 0.08). The early response to allergen was significantly inhibited by ICI 204,219 (the maximum fall in FEV1 was -21.2 +/- 6.1% after ICI 204,219 compared with -38.8 +/- 6.5% on placebo; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Lipoprotein (a) in patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis.

Lipoprotein (a) concentrations and apoprotein (a) isoforms were measured in 99 haemodialysis and 79 peritoneal dialysis patients and compared with a normal population. Peritoneal dialysis patients demonstrated a threefold and haemodialysis a twofold increase in median Lp(a) values compared to controls (P < or = 0.001). The peritoneal dialysis group had significantly more patients with Lp(a) values greater than 30 mg/dl compared to controls, (53% versus 22% P < or = 0.001). In addition both patient groups demonstrated significant hypertriglyceridaemia (P < or = 0.001), reduction in HDL (P < or = 0.001) and elevation of the cholesterol/HDL ratio (P < or = 0.001) compared with controls. Peritoneal dialysis patients also demonstrated significant hypercholesterolaemia (P < or = 0.003). Lipoprotein (a) concentrations are considerably elevated in patients on maintenance dialysis and this occurs in addition to the typical lipoprotein disturbances. This elevation may increase vascular risk, particularly in the peritoneal dialysis group who also have hypercholesterolaemia and reduced HDL.

Arteriosclerosis↗
PubMed1992

Plasma lipids and lipoproteins and the prevalence of risk for coronary heart disease in Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report population reference values for blood lipids, to determine the prevalence of lipid risk factors and to assess their association with other risk factors. DESIGN: Population-based cross-sectional surveys. Survey participants were interviewed at home and provided a blood sample at a clinic. All blood lipid analyses were done in the Lipid Research Laboratory, University of Toronto. The laboratory is standardized in the National Heart, Lung Blood Institute-Centres for Disease Control Standardization Program. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 was selected from the health insurance registers for each province. Blood samples were obtained from 16,924 participants who had fasted 8 hours or more. OUTCOME MEASURES: Concentration of total plasma cholesterol, triglycerides and high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in blood samples from fasting participants. MAIN RESULTS: Of the study population, 46% had total plasma cholesterol levels above 5.2 mmol/L, 15% had LDL-cholesterol levels above 4.1 mmol/L, 15% had triglyceride levels above 2.3 mmol/L and 8% had HDL-cholesterol levels below 0.9 mmol/L. Total plasma cholesterol, LDL-cholesterol and triglyceride levels rose with age in men to a maximum in the 45-54 age group; in women there was little change with age up to ages 45 to 54, at which time the level of each of these lipids increased appreciably. The age-standardized prevalence of obesity was positively associated with elevation of total plasma cholesterol. CONCLUSION: The results suggest the need for a multifactorial approach in health promotion efforts to lower blood cholesterol levels and reduce other risk factors in the population. A considerable number of adults were found to be at risk at all ages in both sexes. In the short term, men aged 34 and older and women aged 45 and older might benefit most from prevention programs.

Adult↗
PubMed1992

Lipid and lipoprotein (a) concentrations in renal transplant patients.

Lipid and lipoprotein concentrations, including lipoprotein (a), were measured in 67 clinically stable renal allograft recipients and compared with age- and sex-matched controls. Median lipoprotein (a) concentrations were significantly elevated in the transplant group (P = 0.048), with the distribution of apoprotein (a) isoforms being similar between the two groups. The transplant group also demonstrated significant elevations in cholesterol (P less than 0.0001), triglycerides (P = 0.0007) and low-density lipoprotein cholesterol (P less than 0.0001). There was no significant difference in high-density lipoprotein cholesterol concentrations between the groups although there was the expected tendency for higher values in females. Lipoprotein abnormalities are common following renal transplantation and these patients also demonstrate elevated lipoprotein (a) values. This unique lipoprotein is known to be atherogenic and may contribute to the development of vascular disease, which is a common mode of death in these patients.

Adolescent↗
PubMed1992

Continuing evolution of the pelvic pouch procedure.

The results of the pelvic pouch procedure were reviewed to assess the surgical complication rate and outcome of patients who had had the procedure performed with a stapled ileo-anal anastomosis with and without a defunctioning ileostomy. Between December 1982 and March 1992, 483 patients underwent a pelvic pouch (PP) procedure. Patients were divided into three groups: group I consisted of 325 patients (178 men and boys and 147 women and girls) who underwent a PP procedure with a handsewn ileoanal anastomosis (IAA) with a defunctioning loop ileostomy. In group II, there were 87 patients (47 men and boys and 40 women and girls) who had a stapled IAA with a defunctioning ileostomy. Group III patients consisted of 71 patients (43 men and boys and 28 women and girls) who had a stapled IAA with no covering ileostomy. Assessment was made of the IAA leak rate, the surgical complications, the reoperation rate, and functional outcome. Early surgical complications included 40 (12%) IAA leaks in group I patients compared with only six (7%) leaks in group II patients who had a stapled IAA (p < 0.05). In group III patients, who had a stapled IAA but no covering ileostomy, there were 13 leaks (18%). Eleven of these 13 leaks healed spontaneously with tube drainage; one patient remains with a rectal tube in place 6 weeks after operation, and only one patient has required a reoperation (defunctioning ileostomy). Functionally, all patients with a healed IAA after a leak have had an excellent result comparable to those without a leak. Patients who were male, older than age 40, on steroids, and had had a true one-stage PP procedure, had a greater risk of developing an IAA leak. In two patients, there was intraoperative difficulty, and one of these patients had an IAA leak after operation. Disease activity at the resection margin and patient weight did not affect the leak rate. Our results suggest that the IAA leak rate is significantly reduced in patients with a stapled IAA with an ileostomy compared with those with a handsewn IAA. Omission of the defunctioning ileostomy is associated with a higher IAA leak rate, but spontaneous healing occurs in almost all patients without impairment of functional results. In patients in whom the ileostomy is omitted, the IAA leak rate is greatest in male patients who have undergone a true one-stage PP procedure, are on steroids, and are older than age 40.

Adenomatous Polyposis Coli↗
PubMed1991

N omega-nitro-L-arginine attenuates the accumulation of aortic cyclic GMP and the hypotension produced by zaprinast.

To determine if N omega-nitro-L-arginine (NNA), an inhibitor of the synthesis and/or release of endothelium-derived relaxing factor (EDRF), alters the response to zaprinast, a selective inhibitor of cyclic GMP (cGMP) phosphodiesterase, zaprinast (3-30 mg/kg) or vehicle (1 ml/kg) was given to conscious, spontaneously hypertensive rats (SHR) in a cumulative i.v. dose-response manner 30 min after pretreatment with NNA (1 or 3 mg/kg) or saline (1 ml/kg). Mean arterial pressure (MAP) was measured 5 min after each dose of zaprinast. Five minutes after the last dose of zaprinast (30 mg/kg), the rats were anesthetized with pentobarbital (25 mg i.v.). A segment of the abdominal aorta was freeze-clamped in situ and removed for the determination of cGMP levels. NNA (3 mg/kg) decreased basal aortic cGMP levels by 54% and increased MAP by 37 +/- 2 mm Hg. Zaprinast (30 mg/kg) increased aortic cGMP by 187% and decreased MAP by 49 +/- 4 mm Hg. NNA (3 mg/kg) reduced the accumulation of cGMP in aortic tissue (from 4.1 +/- 0.4 to 1.3 +/- 0.1 fmol/microgram protein) and attenuated the depressor response (from -49 +/- 4 to -31 +/- 4 mm Hg) produced by zaprinast. These data are consistent with the hypothesis that NNA inhibits the tonic release of EDRF and that the depressor effects of zaprinast are due, at least in part, to the potentiation of the vasodilator effects of EDRF in vivo. Moreover, since the changes in MAP produced by NNA and zaprinast were significantly correlated with cGMP levels in aortic tissue, the concentration of cGMP in vascular tissue may be a determinant of blood pressure in SHR.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

Circulating autoantibodies to recombinant lipocortin-1 in asthma.

One of the postulated mechanisms of corticosteroid action is through the de novo synthesis and release of lipocortins. We assayed circulating antibodies to lipocortin-1 in sera obtained from normal (n = 67) and asthmatic (n = 57) subjects using an ELISA technique. Asthmatic subjects with a wide range of severity, with the mildest needing only occasional inhaled beta-agonist therapy to the most severe needing maintenance oral corticosteroid treatment, were recruited from our Asthma Clinic and classified into five categories according to the need of therapy. Median values of IgM and IgG lipocortin-1 antibody for normal subjects were 19.3 (interquartile range (r) = 11.0-30.4) and 16.9 (r = 10.54-29.4) ELISA units (EU) ml-1 respectively. These levels were significantly elevated in asthmatic subjects: IgM = 43.9 EU ml-1 (r = 31.7-64.5) and IgG = 29.0 EU ml-1 (r = 21.2-44.7) (P less than 0.001). There was no significant relationship between the levels of lipocortin antibody and the clinical severity of asthma. Asthmatics with significantly raised levels of antibody were found within all five categories of severity. We conclude that the level of this antibody is not related to severity of asthma, to previous or current corticosteroid therapy or to the development of corticosteroid resistance.

Adolescent↗
PubMed1991

Isolation and identification of bacteria from subgingival plaque with low susceptibility to minocycline.

Twenty subgingival plaque samples from patients with chronic periodontitis were screened for the presence of three periodontal 'pathogens'--Porphyromonas gingivalis, Fusobacterium nucleatum and Eikenella corrodens. Nineteen of the samples were found to contain at least one of the three organisms and six samples contained all three. The subgingival plaque samples were cultured in the presence of various concentrations of minocycline, and those organisms which appeared to be least susceptible to the antibiotic were isolated and identified. A total of 40 isolates were obtained and these consisted of 18 different species, only one of which, Fusobacterium nucleatum, is generally recognized as being associated with chronic periodontitis. The minimum inhibitory concentrations of minocycline for many of the organisms isolated were greater than the concentration of attainable in gingival crevicular fluid following routine parenteral administration of the antibiotic.

Adult↗
PubMed1991

Longitudinal evaluation of neuropsychological function in homosexual men with HIV infection: 18-month follow-up.

Subjects were 21 men with persistent generalized lymphadenopathy (PGL, n = 13) or AIDS-related complex (ARC, n = 8), who were not receiving anti-retroviral medication, and 21 controls. At baseline, mild cognitive impairment was detected in language, memory, attention, and visual and auditory processing, primarily in patients with ARC. On follow-up, the ARC group showed continued impairment and abnormalities on new measures of distractibility and activities of daily living. Although mild decline in verbal memory was noted for some patients, overall neuropsychological profiles did not show deterioration. Nomenclature for the pattern of mild, stable neuropsychological changes in patients with cognitive symptoms is discussed. Two interdisciplinary panels have recommended the term HIV-1-associated minor cognitive/motor disorder. Unlike the term AIDS dementia, it does not imply progression or a diagnosis of AIDS.

AIDS Dementia Complex↗