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Biomedical subjects

C M Hughes

Publications and source records attributed to C M Hughes.

At least 37 records · Page 2Linked to original sources

Changing profile in the use of anti-asthma drugs.

Data regarding the total number of anti-asthma drugs dispensed via community pharmacies within Northern Ireland from 1980 to 1997 were collected and analysed. The use of anti-asthma drugs within this population increased markedly over the study period from 19.84 DDDs/1000/day to 84.07 DDDs/1000/day. With the exception of the non-selective beta-agonists, there has been an overall increasing trend in the utilization of all of the anti-asthma drugs during the study period. Most of the increase is attributable to the increase in prescribing of the selective beta(2)-agonists and the glucocorticoids. This increase in the utilization of anti-asthma drugs may be explained by an increasing prevalence of the condition, increased adherence to asthma management protocols or to the prescribing of more intensive drug therapies. During the study period, a wider range of anti-asthma drugs and drug delivery devices have become available and hence have been prescribed. For example, in 1980, beclomethasone was the only inhaled steroid available, whilst in 1997, of all inhaled glucocorticoid products dispensed, 55.0% were beclomethasone-containing products, with budesonide (40.1%) and fluticasone (4.9%) products also being prescribed. With regard to drug delivery devices, there has been a move towards the use of dry powder inhalers in recent years. Prescribing of generic salbutamol products has also increased.

Journal Article↗

The importance that community pharmacists in Malta place on the introduction of pharmaceutical care.

The results from a study to assess the importance Maltese pharmacists placed on various aspects of pharmaceutical care and their willingness to provide such care are reported. A modified version of the Behavioural Pharmaceutical Care Scale (BPCS) questionnaire (consisting of three dimensions and 14 domains) was mailed to the 198 privately owned community pharmacies in Malta. A total of 99 questionnaires were returned following two reminder telephone calls. Pharmacists were asked to score the importance of each pharmaceutical care activity contained in the modified BPCS on a 6 point Likert scale ranging from 0 to 5. The overall score for the questionnaire, which illustrated the importance pharmacists attributed to various aspects of pharmaceutical care, ranged from 90 to 170 with a mean score of 134.8. There was little difference recorded between the scores for the three dimensions. The Referral and Consultation domain recorded a slightly higher score than the other two domains. Younger pharmacists obtained significantly higher scores (p < 0.05; Kruskal-Wallis test) in the Verification of Patient Understanding domain. Approximately 72% of respondents indicated that they were willing to provide pharmaceutical care, but remarked that a number of issues e.g. reimbursement, qualified support staff, GP-pharmacist co-operation, had to be addressed. A series of strategic steps are needed to help pharmacists resolve these issues before pharmaceutical care programmes could be offered by Maltese community pharmacists.

Age Factors↗

A self-reported work sampling study in community pharmacy practice.

Lack of time to implement pharmaceutical care has been cited as a barrier to the routine provision of this extended patient-care service. Using self-reported work sampling methodology, this study investigated how community pharmacists utilise their time. Pharmacists working in community pharmacies in the Greater Belfast area were found to spend approximately 49% of their time engaged in professional activities, 29% in semi-professional activities and 22% involved in non-professional activities. The activity to which pharmacists devoted the majority of their time was product assembly and labelling, this being a task which can be performed by trained technical staff. Only 9.5% of community pharmacists' time was devoted to counselling patients on their prescription medicines. Wide variation in the amount of time apportioned to each activity was observed between the participating community pharmacists (n = 30). Staffing levels within the community pharmacy were found to significantly influence pharmacists' involvement in a number of activities, with pharmacists who worked in pharmacies employing multiple pharmacists devoting more time to the assembly and labelling of products and less time to administrative tasks, non-professional encounters and to miscellaneous professional activities. Pharmacists working in pharmacies with a high prescription turnover were found to devote significantly less time to counselling patients regarding OTC products and in responding to patient symptoms.

Community Pharmacy Services↗

Abuse/misuse of non-prescription drugs.

AIM: To investigate the abuse of non-prescription (over-the-counter; OTC) products in Northern Ireland. METHOD: A structured questionnaire covering various aspects of OTC drug abuse was mailed to all 509 community pharmacies in Northern Ireland. RESULTS: 253 responses were received (response rate 49.7%) after two mailings. Pharmacists named 112 OTC products they perceived were being abused in Northern Ireland. These were classified into 8 groups, with opioids, antihistamines and laxatives the most frequently reported. The frequency of abuse of all product groups was perceived to be either increasing or static. The number of clients suspected of abuse over a three-month period ranged from 0 to 700 (median = 10, mode = 6) with 55% being regular customers. Pharmacists employed several methods to limit patient access to products of abuse. The most common technique was to keep the product out of sight. Others included additional client questioning, providing advice and limiting the quantity of product sold. The majority of respondents agreed their role could be extended to include other methods of dealing with abusers, including participation in harm-reduction programmes to wean abusers off products. Geographical region and location of pharmacy were not significant factors in the abuse of OTC products. CONCLUSIONS: Pharmacists in Northern Ireland perceive abuse and misuse of OTC products to be occurring in practice. Current methods employed for dealing with it are inadequate. Research into methods of effectively dealing with OTC abuse/misuse is required and has commenced on the basis of these findings.

Adult↗

Human sperm DNA integrity assessed by the Comet and ELISA assays.

DNA integrity in sperm is essential for the accurate transmission of genetic information and therefore the maintenance of good health in future generations. The ELISA and Comet assays, two techniques that detect DNA damage in cells, are compared in this study of DNA integrity in human sperm. Both techniques rely on alkaline unwinding for the release of single strands of DNA from the nucleus. The ELISA detects single strands immunochemically whereas the Comet assay measures single strands drawn out by electrophoresis, stained with ethidium bromide and quantified by image analysis. The two techniques, both modified for use with sperm, detect similar levels of baseline DNA damage along with similar dose-dependent patterns of induced damage by X-ray irradiation at 10 and 30 Gy (P < 0.05). The assays are also comparable in the detection of a significant protective effect by ascorbic acid (300 and 600 microM) and alpha-tocopherol (30 and 60 microM) on DNA integrity, both at baseline levels and following X-ray irradiation (p < 0.01). The advantages and disadvantages of each technique are discussed.

Antioxidants↗

Pharmaceutical care of patients with congestive heart failure: interventions and outcomes.

We evaluated a structured pharmaceutical care program for elderly patients (> 65 yrs) with congestive heart failure (CHF) based on objective measures of disease control, quality of life, and use of health care facilities in a randomized, controlled, longitudinal, prospective clinical trial. The 42 patients in group A received education from a pharmacist on the disease and its treatment, and lifestyle changes that could help control symptoms. Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy. If necessary, dosage regimens were simplified in liaison with hospital physicians. The 41 control patients (group B) received standard care. The following outcome measures were assessed in all patients at baseline (before the start of the trial) and at 3, 6, 9, and 12 months: 2-minute walk test, blood pressure, body weight, pulse, forced vital capacity, quality of life [disease-specific (Minnesota Living with Heart Failure questionnaire) and generic (SF-36)], knowledge of symptoms and drugs, compliance with therapy, and use of health care facilities (hospital admissions, visits to emergency room, emergency calls). Patients in group A showed improved compliance with drug therapy, which in turn improved their exercise capacity compared with those in group B; education on management of symptoms, lifestyle changes, and dietary recommendations were also of benefit. Group A patients significantly improved knowledge of their drug therapy over the 12-month study and had fewer hospital admissions compared with group B patients. They also had improved outcomes compared with group B, despite the small samples. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF.

Aged↗

Buccal absorption of enalapril and lisinopril.

OBJECTIVE: The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects. METHODS: The partitioning of enalapril and lisinopril into n-octanol was examined over the pH range of 3 9 at room temperature. RESULTS: Enalapril exhibited maximal partitioning into the organic phase at pH 4 5; minimal partitioning was recorded at pH values 8 and 9. The partitioning of lisinopril into n-octanol was found to be maximal at pH 9 and minimal at pH 3. Using the buccal absorption technique, the partitioning of enalapril and lisinopril (0.5 mg), was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8 and 9). In the case of enalapril, lowest buccal partitioning occurred at pH 3, 8 and 9, while maximal partitioning occurred at pH 5; absorption of lisinopril was not extensive at any pH, but was greatest at pH 6. These results, in addition to the n-octanol partition coefficients, indicated that enalapril obeyed the normal lipid partition hypothesis with respect to buccal absorption. The buccal absorption of lisinopril also obeyed the lipid partition hypothesis over the pH range 3-7. These findings are in direct contrast to those for captopril. The buccal partitioning experiments were repeated at the maximal pH for absorption for each angiotensin converting enzyme (ACE) inhibitor, but with the addition of cephradine (0.05 mmol x l(-1)). CONCLUSION: The data indicated that the presence of this peptide transport inhibitor had no effect on the buccal absorption of enalapril (0.06 mmol x l(-1)) and lisinopril (0.057 mmol x l(-1)), which suggests that both drugs do not share a common buccal absorption pathway with cephradine.

Administration, Buccal↗

Societal perceptions of community pharmaceutical services in Malta.

OBJECTIVE: To assess the views of the Maltese general public on services provided by community pharmacies in Malta and their opinions on the proposed extended role for pharmacies. METHOD: An interviewer-administered structured questionnaire was used to interview 912 members of the public (395 males, 517 females). RESULTS: The majority of respondents (70.8%) visited a pharmacy at least once a month, with females visiting more frequently than males (P< 0.01). Almost 31% stated that the main reason for visiting a pharmacy was to purchase prescribed medication, while 23-3% said that it was to obtain over-the-counter products. Women were more likely than men to be influenced by the pharmacist's advice when selecting an over-the-counter product (P< 0.05). The majority of respondents (62.8%) said that they usually bought their medicines from the same pharmacy and loyalty to a particular pharmacy increased with age. When treating minor ailments, respondents were more likely to consult their doctor or self-treat rather than seek advice from the pharmacist. The proposed extended role of the community pharmacist found support with the public, e.g. 90.2% felt that the pharmacist should promote health education, with the preferred method suggested being through individual advice; 85-7% were in favour of screening and monitoring services and 85.6% felt that the keeping of patient medication records would be useful. Almost three-quarters (74.6%) of respondents said that they would be willing to participate in pharmaceutical care programmes. When asked to suggest new activities for community pharmacy, respondents were most in favour of the pharmacist offering more advice on the treatment of minor ailments. CONCLUSION: Overall, the results obtained are encouraging and Maltese pharmacists should plan to provide new services to the community in the future.

Adolescent↗

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity.

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.

Acetylcysteine↗

Two potential clinical applications of the alkaline single-cell gel electrophoresis assay: (1). Human bladder washings and transitional cell carcinoma of the bladder; and (2). Human sperm and male infertility.

Part 1: The alkaline single-cell gel electrophoresis (comet) assay was used to analyse the integrity and DNA content of exfoliated cells extracted from bladder washing specimens from 9 transitional cell carcinoma patients and 15 control patients. DNA damage, as expressed by % tail DNA and tail moment values, was observed to occur in cells from both control and bladder cancer samples. The extent of the damage was, however, found to be significantly greater in the cancer group than in the control group. Comet optical density values were also recorded for each cell analysed in the comet assay and although differences observed between tumour grades were not found to be statistically significant, the mean comet optical density value was observed to be greater in the cancer group than in the control population studied. These preliminary results suggest that the comet assay may have potential as a diagnostic tool and as a prognostic indicator in transitional cell carcinoma. Part 2: Baseline DNA damage in sperm cells from 13 normozoospermic fertile males, 17 normozoospermic infertile males and 11 asthenozoospermic infertile males were compared using a modified alkaline comet assay technique. No significant difference in the level of baseline DNA damage was observed between the 3 categories of sperm studied; however the untreated sperm cells were observed to display approximately 20% tail DNA. This is notably higher than the background DNA damage observed in somatic cells where the % tail DNA is normally less than 5%. Sperm from the 3 groups of men studied were also compared for sensitivity to DNA breakage, using the modified alkaline comet assay, following X-ray irradiations (5, 10 and 30 Gy) and hydrogen peroxide treatments (40, 100 and 200 microM). Significant levels of X-ray-induced damage were found relative to untreated control sperm in the two infertile groups following 30 Gy irradiation. Significant damage in hydrogen peroxide-treated sperm was observed in sperm from fertile samples, at 200 microM and in infertile samples at 100- and 200-microM doses relative to controls. These results therefore indicate that fertile sperm samples are more resistant to X-ray- and hydrogen peroxide-induced DNA breakage than infertile samples. Further studies involving greater numbers of individuals are currently in progress to confirm these findings.

Aged↗

Reproducibility of human sperm DNA measurements using the alkaline single cell gel electrophoresis assay.

The single cell gel electrophoresis (SCGE) assay is a simple visual technique used to assess DNA integrity in individual cells by measuring damage reflected as strand breaks under alkaline conditions. Cells are embedded in agarose on glass slides followed by lysis of the cell membranes after which damaged DNA strands are electrophoresed away from the nucleus towards the anode and deposited to one side giving the appearance of a tail. DNA damage may be measured by assessing the relative amounts of DNA remaining in the head as opposed to those strands which have formed the tail. The assay has been used to determine DNA quality in human sperm (Hughes, C.M., S.E.M. Lewis, V.J. McKelvey-Martin, W. Thompson, A comparison of baseline and induced DNA damage in human sperm from fertile and infertile man, using a modified comet assay. Mol. Human Reprod., in press) by measuring fifty cells on one slide for each individual. Coefficients of variation between three control slides prepared for ten individuals were less than 4% and less than 9% for three slides prepared using irradiated sperm. Ten readings of fifty sperm each from a single slide showed a coefficient of variation of less than 6% for ten individuals studied. These results indicate that the measurement of fifty sperm from a single slide is sufficient to assess the DNA damage within a sperm population. Coefficients of variation of less than 5.4% for repeated analysis of individual cells were obtained which demonstrates the reproducibility of the image analysis software.

DNA↗

A pharmacokinetic and pharmacodynamic evaluation of buffered sublingual captopril in patients with congestive heart failure.

OBJECTIVE: The pharmacokinetics and pharmacodynamics of buffered sublingual captopril were assessed in patients with congestive heart failure (CHF). METHODS: The study was carried out in a randomised single-blind cross-over fashion (n = 6, 4 males and 2 females) and involved two study days, at least 7 days apart. Baseline measurements were carried out for plasma renin activity (PRA), blood pressure (B.P.) and heart rate (H.R.). Captopril (12.5 mg) was administered sublingually with dibasic potassium phosphate which maintained salivary pH at 7, or perorally with 100 ml of water. Further B.P., H.R. measurements and venous blood samples were taken over a 3 hour period post-drug administration. Blood samples were analysed for captopril and PRA levels. RESULTS: tmax after buffered sublingual administration of captopril, which ranged from 40-60 min (median = 40 min), was significantly shorter than after peroral administration (range 60-120 min, median = 90 min). Cmax was slightly greater after buffered sublingual than after peroral administration with mean values of 108.2 vs. 94.0 ng.ml-1. AUC values were similar after both routes of administration. Systolic and diastolic B.P. vs. time profiles for each administration method were significantly different i.e. sublingual administration produced an earlier reduction in B.P., however, HR did not differ significantly between the two routes. CONCLUSION: The data indicate that this novel administration method of captopril leads to an increased rate, but an unchanged extent of captopril absorption, suggesting a modest therapeutic advantage with the use of buffered sublingual captopril if a rapid reduction in blood pressure is required.

Administration, Sublingual↗

A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay.

Baseline DNA damage in spermatozoa from fertile and infertile men was compared using a modified alkali single cell gel electrophoresis (comet) assay. Semen from normozoospermic fertile, normozoospermic infertile and asthenozoospermic infertile (World Health Organization criteria, 1992) samples were studied. No significant difference was observed in levels of baseline damage between the three groups. A median value for baseline damage of approximately 20% (80% head DNA) was obtained in all samples. Irradiation with X-rays (5-30 Gy) produced no additional damage in fertile samples when median values were examined. However, irradiation with 30 Gy X-rays produced significant damage in both infertile groups. Hydrogen peroxide (40 microM) treatment induced significant damage in the asthenozoospermic group, whereas 100 microM H2O2 was required to cause significant damage in the normozoospermic fertile and infertile samples. Within the fertile population a subgroup in which percentage head DNA was greater than 80% was observed in both treated and untreated specimens. This subgroup significantly decreased with treatment in both infertile groups. We conclude that the asthenozoospermic infertile group is more susceptible to damage than the normozoospermic infertile group, which in turn is more susceptible than the fertile group. The fertile group contains a resistant subpopulation of spermatozoa with relatively intact DNA.

DNA↗

c-erbB3 protein expression in ovarian cancer.

Aims-To study the prevalence of overexpression of c-erbB3 growth factor receptor in ovarian carcinomas and to analyse its relation to histological subtype, stage and grade of the tumours.Methods-Ninety eight ovarian carcinomas were evaluated immunohistochemically using the RTJ1 monoclonal antibody raised against a synthetic peptide, the sequence of which was derived from the cytoplasmic domain of the c-erbB3 protein.Results-Of the tumours, 16% (16/98) overexpressed c-erbB3 protein relative to normal ovarian epithelium, whereas 22% (22/98) were completely negative. There was a statistically significant association between overexpression and well differentiated grade.Conclusions-These findings suggest that c-erbB3 protein overexpression occurs in a significant proportion of ovarian cancers and is correlated with differentiation. Overexpression may merit further investigation as a potential prognostic indicator and as a target for new treatment.

Journal Article↗

The effect of three H2 receptor antagonists on the disposition of cyclosporin A in the in situ perfused rat liver model.

The in situ perfused rat liver model was used to investigate the effect of three H2 receptor antagonists on the disposition of cyclosporin A (CyA) and the major human metabolite, AM1. Perfusion experiments, using standard techniques, were carried out on four groups (one control and three H2-receptor antagonist-treated groups) of male Sprague-Dawley rats (300-350 g). All animals received CyA, 2.5 mg; the three treated groups received cimetidine (8 mg), ranitidine (3 mg), or famotidine (0.4 mg). Perfusate and bile samples were collected and assayed for CyA, AM1, and the H2 receptor antagonists by HPLC. Results indicated that CyA perfusate concentrations in the controls and cimetidine and ranitidine-treated groups were not significantly different, although levels in the famotidine group were significantly higher at all times (p < 0.05), except 30 min, compared to the controls. However, examination of the AM1 perfusate and bile data and the apparent metabolic clearance data indicated that CyA metabolism was still occurring, despite the presence of the H2 receptor antagonist. It is suggested that the absence of a interaction may be attributed to a lack of specificity of the H2 receptor antagonists for CYP3A, the isoenzyme responsible for CyA metabolism.

Analysis of Variance↗

The effect of pH on the buccal and sublingual absorption of captopril.

The effect of pH on the buccal and sublingual absorption of captopril was evaluated using in vitro techniques and human studies. Partitioning of captopril into n-octanol was lowest over the pH range 5 to 8 and highest at pH values 3, 4 and 9. Using the buccal absorption technique, the partitioning of captopril (2 mg) was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8, and 9). Lowest buccal partitioning occurred at pH 3 while maximal buccal partitioning occurred at pH 7. These data clearly indicated that the buccal absorption of captopril pharmacokinetic and pharmacodynamic parameters were determined after administration of buffered sublingual captopril (pH 7, optimal hP for absorption as determined from the buccal partitioning data) and unbuffered sublingual captopril. The study was performed in eight healthy volunteers in a randomised single-blind cross-over fashion. The tmax for captopril was found to be approximately 11 minutes earlier after buffered versus unbuffered sublingual administration and AUC0-30 min increased by approximately 30% in the case of buffered captopril. Cpmas, AUC0-180 min and relative bioavailability did not differ between the buffered and unbuffered administration. Pharmacodynamic parameters (BP, heart rate and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration. The increased rate of captopril absorption after buffered sublingual administration was small and is likely to offer little therapeutic advantage over conventional sublingual formulation.

1-Octanol↗