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L Macdonald

Publications and source records attributed to L Macdonald.

At least 19 recordsLinked to original sources
PubMed2006

Intra-vascular glucocorticoid metabolism as a modulator of vascular structure and function.

The ability of glucocorticoids to directly alter arterial function, structure and the inflammatory response to vascular injury may contribute to their well-established link with the development of cardiovascular disease. Recent studies have emphasised the importance of tissue-specific regulation of glucocorticoid availability by the 11 beta-hydroxysteroid dehydrogenase (11HSD) isozymes, which inter-convert active glucocorticoids and their inactive metabolites. The expression of both type 1 and type 2 11HSDs in the arterial wall suggests that prereceptor metabolism of glucocorticoids may have a direct impact on vascular physiology. Indeed there is evidence that 11HSDs influence glucocorticoid-mediated changes in vascular contractility, vascular structure, the inflammatory response to injury and the growth of new blood vessels. Hence, inhibition of 11HSD isozymes may provide a novel therapeutic target in vascular disease.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2005

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome.

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7-12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery.

Age Factors↗
PubMed2003

A prospective audit of stomas--analysis of risk factors and complications and their management.

AIM: To prospectively audit stomas and to determine the nature and rate of complications and their relationship with various risk factors and their management. MATERIALS AND METHODS: The study was performed prospectively on 97 consecutive patients who had stomas formed between January 2000 to August 2000. Patients were followed up for one year. Risk factors including age, body mass index (BMI), preoperative siting, contour of the abdominal wall, smoking, grade of operating surgeon, emergency or elective procedure, diabetes, type of stoma and suture material used were noted. The type of surgery, and indications for surgery were also recorded. The complications were documented by two qualified stoma nurses and a photographic record taken. Statistical analysis comprising both univariate and multivariate methods, was performed by SPSS 10. RESULTS: The mean age was 65 years (standard deviation 16.01, range 16-99) and mean body mass index was 24.5 (standard deviation 4.66, range 15-37). Forty-nine of 97 (50.5%) stomas developed one or more complications. Twenty-three patients experienced retraction, 18 had stomas sited in a skin crease, 16 had early and 12 had late skin excoriation, 12 had detachments and a further 12 had parastomal hernia. Eleven further stoma complications were noted including prolapse, necrosis, ischaemia and sloughing. None of the risk factors achieved statistical significance when analysed against the overall complication rate. However, when the risk factors were analysed against individual complications using univariate logistic regression, a high body mass index was associated with more retractions (P = 0.003), early skin excoriation (P = 0.036) and poor siting (stoma in crease) occurred more commonly in emergencies (P = 0.022). Diabetes was associated with late skin excoriation (P = 0.02). Multivariate logistic regressions confirmed an independent association of body mass index, diabetes and emergency surgery with complications. Forty-five of 49 patients who had complications needed some conservative management such as a convexity appliance. Four patients needed refashioning. CONCLUSION: Body mass index, diabetes and emergency surgery were the significant risk factors identified in our study. Overall complications compare favourably with other series. We found that preoperative siting by stoma nurses and the grade of operating surgeon did not affect the outcome.

Adolescent↗
PubMed2001

Disagreement between height/weight classifications of underweight, normal weight, and obesity in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients are classified as underweight, normal weight, or obese by height/weight indices including body mass index (BMI) and the body weight/desired weight (W/DW) ratio. We compared these classifications of degree of obesity in 378 women and 555 men on PD. We used these cut-off values: for underweight, BMI < or = 18.5 and W/DW < or = 0.9; for obesity, BMI > or = 30.0 and W/DW > or = 1.2. The W/DW values were calculated assuming first a small frame, then a medium frame, and finally a large frame for all subjects. Regardless of sex or skeletal frame, BMI correlated highly with W/DW (r value between 0.98 and 0.99); however, the range of BMI values corresponding by linear regression to the normal range of W/DW (0.9-1.2) was narrower than the range of "normal" BMI (18.5-30.0). Consequently, regardless of sex or skeletal frame, smaller fractions of the patient population were classified as underweight or obese by BMI standards than by W/DW standards. The degree of agreement of the classifications of subjects as underweight, normal weight, or obese by BMI and W/DW was evaluated by Cohen's kappa ratio. The kappa ratio varied between 0.47 and 0.58, indicating a reasonable--but not high--degree of agreement beyond chance. The highest kappa ratios were obtained assuming a medium skeletal frame for both women and men. Substantial discrepancies are observed in the classification of PD patients as underweight, normal weight, or obese by BMI and W/DW. Further research is needed to identify the height/weight index that has the strongest association both with clinical outcomes and with other, more precise measurements of body fat content.

Body Constitution↗
PubMed2000

Low grade gliomas treated with adjuvant radiation therapy in the modern imaging era.

The purpose of this study is to evaluate tumor control and failure patterns in patients with low grade gliomas treated with surgery and conventional adjuvant radiation therapy. Twenty-eight patients with low grade gliomas (7 grade I, 21 grade II) were retrospectively evaluated. Extent of resection was gross total (3), subtotal (17), and biopsy alone (8). All grade I tumors underwent subtotal resection. Median radiation therapy dose was 54 Gy delivered to localized fields. Tumor control and patterns of failure were determined from follow-up computed tomography and/or magnetic resonance scans. Median follow-up was 86 months (range, 2.4-177 months). Thirteen patients (46%) (four grade I, nine grade II) developed tumor progression. The 5-year actuarial progression-free survival rates for grade I and grade II patients were 86% and 51%, respectively. Corresponding 5-year actuarial survival rates were 100% and 70%. All recurrences were within the treated volume. Our results reveal that conventional adjuvant radiation therapy is associated with high rates of local tumor progression in both grade II and incompletely resected grade I low grade gliomas. Alternative strategies need to be explored in these patients in an effort to improve tumor control and outcome.

Actuarial Analysis↗
PubMed1999

Peptide based cytotoxic T-cell vaccines; delivery of multiple epitopes, help, memory and problems.

Synthetic CD8+ cytotoxic T-lymphocyte (CTL) peptide epitope based vaccines are being developed against a number of human diseases. Here we describe extensive preclinical testing of peptide epitope vaccines formulated with a protein as a source of CD4 help and Montanide ISA 720, an adjuvant currently in human clinical trials. Such water-in-oil formulations could effectively co-deliver several peptide epitopes and simultaneously induce multiple independent CTL responses. The efficiency of CTL induction by some peptides was, however, dependent on the aqueous buffer conditions, with poor performance correlating with non-covalent peptide oligomerisation. Any of a number of proteins currently used in human vaccines could supply CD4 help and no difference in CTL induction was obtained if the CD4 response was amnestic or a primary. Peptide immunisation was found to induce long term CTL memory and the recall of protective responses did not depend on an amnestic CD4 response. Slow pyroglutamic acid formation and rapid oxidation of methionine residues was observed in water-in-oil formulations, however, the latter had no effect on CTL induction. These data highlight the need to monitor for potential deleterious chemical events and interpeptide interactions, but illustrate that peptide based vaccination can effectively deliver multiple epitopes, in conjunction with any protein, and induce protective memory.

Adjuvants, Immunologic↗
PubMed1996

Effect of P2-purinoceptor antagonists on hemolysate-induced and adenosine 5'-triphosphate-induced contractions of dog basilar artery in vitro.

OBJECTIVE: To test the hypothesis that the vasoactive effects of hemolysate of dog erythrocytes on dog basilar artery in vitro are caused by adenosine 5'-triphosphate (ATP). METHODS: Dog erythrocyte hemolysate was assayed for ATP by high-pressure liquid chromatography. Dog basilar arteries were cut into rings and studied under isometric tension to determine the effects of the P2-purinoceptor antagonists suramin, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, and reactive blue 2 on contractions induced by hemolysate, prostaglandin F2 alpha (PGF2 alpha), KCl, uridine 5'-triphosphate, and ATP. RESULTS: Dog erythrocyte hemolysate contained 34 mumol/L of ATP. Hemolysate produced concentration-dependent contractions of dog basilar artery. Suramin (100 mumol/L) significantly inhibited contractions to hemolysate, ATP, and uridine 5'-triphosphate but not to PGF2 alpha and KCl (P < 0.05). Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (100 mumol/L) caused a small but significant reduction of the contractions to hemolysate and did not affect contractions to PGF2 alpha and KCl. Reactive blue 2 (30 mumol/L) produced significant inhibition of contractions to hemolysate and PGF2 alpha but did not affect contractions to KCl. CONCLUSION: These findings suggest that ATP mediates a smooth muscle contractile response of hemolysate on dog basilar artery. Because erythrocyte cytosol is known to be important in the pathogenesis of vasospasm, these results suggest that ATP may contribute to the vasoconstriction that occurs in vasospasm.

Adenosine Triphosphate↗
PubMed1995

Hormone replacement therapy, sleep quality and psychological wellbeing.

OBJECTIVE: To examine the effect of hormone replacement therapy upon sleep quality and duration in postmenopausal women. DESIGN: Randomised, single-blind, placebo-controlled trial. SETTING: Sleep research laboratory. SUBJECTS: Thirty-three healthy postmenopausal women. INTERVENTIONS: Continuous 0.625 mg conjugated equine oestrogens with 0.15 mg cyclic norgestrel taken for 12 days per 28 day cycle. MAIN OUTCOME MEASURES: Occurrence of vasomotor symptoms, polysomnographic sleep stage measures, Stanford sleepiness questionnaire, Crown-Crisp experiential index and the cognitive failures questionnaire. RESULTS: Hormone replacement therapy results in an improvement in menopausal symptoms but not in parameters of sleep quality. Despite this, certain measures of psychological wellbeing showed significant improvement in the hormone replacement therapy group. CONCLUSION: Hormone replacement therapy results in a measurable improvement in physical and psychological welfare, the latter being independent of improvement in sleep quality.

Adult↗
PubMed1995

Persistent nocturnal cough in childhood: a population based study.

A cross sectional epidemiological study was carried out to investigate the validity of persistent nocturnal cough (PNC) as an independent marker of childhood asthma. A screening questionnaire on respiratory symptoms was applied to 4003 children attending primary schools in Aberdeen, after which 799 symptomatic children and a random selection of 229 asymptomatic children were invited to attend for a diagnostic interview. Six hundred and seven (359 boys and 248 girls) symptomatic children and 135 asymptomatic children (57 boys and 78 girls) were selected from the screening questionnaires. Of 607 children with respiratory symptoms when interviewed, 27 (nine boys and 18 girls) had isolated PNC, and 97 (51 boys and 46 girls) had multiple symptoms (polysymptomatic asthma). The incidence of prematurity was highest in the group with PNC (19%). The prevalence of hay fever in children with PNC (11%) was similar to that of the asymptomatic group (15%) and less than that in the group with polysymptomatic asthma (41%). Eczema was twice as common in the PNC (19%) as in the asymptomatic children (10%) but only half as common in the polysymptomatic asthma group (35%). The prevalence of a parental history of hay fever was similar in all three groups. The prevalence of a parental history of eczema was similar in the PNC (7%) and asymptomatic (7%) groups but higher in the polysymptomatic asthma group (22%). The prevalence of a history of parental asthma was 30% in children with PNC, 13% in the asymptomatic group, and 42% in those with polysymptomatic asthma. The parents of three (11%) children with PNC were aware of a diagnosis of asthma; two of these children (7%) were on inhaled bronchodilator treatment and one (4%) was on a slow release theophylline preparation. Using a stepwise discriminant analysis procedure, in 18 (67%) children with PNC predicted membership was in the asymptomatic group and only nine (33%) children with PNC were grouped into the polysymptomatic asthma category. It is concluded that the clinical features of children with PNC resembled those of the asymptomatic population more closely than those of the polysymptomatic asthmatic population. In this age group PNC, in the absence of wheeze, shortness of breath or tightness in the chest, is likely to be a manifestation of atypical or hidden asthma in only a minority of cases.

Asthma↗
PubMed1991

Internal image (Ab2 beta) anti-idiotype vaccines. Theoretical and practical aspects.

Anti-idiotype antibodies that carry an internal image of an antigen epitope (Ab2 beta antibodies) can be used in vaccine preparations to favourably manipulate the immune network. These vaccines have been shown to induce protective immunity in animals that have not been intentionally exposed to the native antigen epitope. This review attempts to define certain theoretical and practical aspects of immunological network manipulations and their relevance to Ab2 beta internal image anti-idiotype antibody vaccine design.

Adult↗
PubMed1991

The immune response to anti-idiotype antibodies bearing an internal image epitope of tetanus toxin/toxoid. I. Induction of the humoral immune response.

Primary immune responses to tetanus toxoid (TT) and primary and secondary immune responses to a rabbit TT internal image bearing anti-idiotype antibody (Ab2 beta 1) inoculated in Freund's complete adjuvant (FCA), saline (SAL) or syntex adjuvant formulation vehicle (SAF) via the intraperitoneal or subcutaneous route, were examined in mice. High anti-TT antibody (Ab3) titres are reported although the titre and persistence of the antibody response varied according to the adjuvant used in the priming and challenge inocula of Ab2 beta 1. Mouse Ab3 antibodies were elicited in mice inoculated with rabbit Ab2 beta 1 antibodies which in turn were elicited by an inoculum of mouse monoclonal anti-TT Ab1 antibody. Ab3 was shown to be identical to Ab1 by immunoblot analysis. Primary and secondary immune responses elicited by rabbit Ab2 beta 1 antibody protected mice against a lethal dose of tetanus toxin.

Animals↗
PubMed1991

The immune response to anti-idiotype antibodies bearing an internal image epitope of tetanus toxin/toxoid. II. Comparison of the primary humoral immune response to xenogeneic Ab2 beta 1 and Ab2 beta 2 internal image anti-idiotype antibodies.

Mouse monoclonal (Ab1) anti-tetanus toxin/toxoid antibodies were used to raise Ab2 beta (tetanus toxin/toxoid internal image bearing) anti-idiotype antibodies in rabbits. Those rabbit serum antibodies (Ab2 beta) that did not bind to mouse serum proteins on an affinity column gave rise to an Ab3 anti-tetanus toxin/toxoid antibody response in mice. Rabbit serum antibodies that did bind to the affinity column, when eluted and used to inoculate mice also gave rise to an Ab3 anti-tetanus toxin/toxoid antibody response. It is suggested that one population of rabbit Ab2 beta anti-idiotype antibodies (unbound fraction) bears a partial or complete internal image of a tetanus epitope (Ab2 beta 1) while others (bound fraction) bear a complete or partial mirror image of a mouse immunoglobulin epitope as well (Ab2 beta 2).

Animals↗