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Biomedical subjects

C M Hughes

Publications and source records attributed to C M Hughes.

At least 19 recordsLinked to original sources
PubMed2006

Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N.

Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes with AQ4N and radiation inhibits tumor growth. Here we examine the ability of other CYPs, in particular CYP1A1, to metabolize AQ4N, and to enhance radiosensitization. Metabolism of AQ4N was assessed using microsomes prepared from baculovirus-infected cells transfected with various CYP isoforms. AQ4N metabolism was most efficient with CYP1A1 (66.7 nmol/min/pmol) and 2B6 (34.4 nmol/min/pmol). Transient transfection of human CYP1A1+/-CYP reductase (CYPRED) was investigated in hypoxic RIF-1 mouse cells in vitro using the alkaline comet assay. There was a significant increase in DNA damage following transient transfection of CYP1A1 compared to non-transfected cells; inclusion of CYPRED provided no additional effect. In vivo, a single intra-tumoral injection of a CYP1A1 construct in combination with AQ4N (100 mg/kg i.p.) and 20 Gy X-rays caused a 16-day delay in tumor regrowth compared to tumors receiving AQ4N plus radiation and empty vector (P=0.0344). The results show the efficacy of a CYP1A1-mediated GDEPT strategy for bioreduction of AQ4N.

Animals↗
PubMed2006

The hidden costs of IVF.

Whether the payment is personal or funded via a third party, IVF is expensive. Clinical and drug costs are known and if necessary can be budgeted for. But, indirect expenses involved in participation also need to be considered. In order to find out what these latter might be, women attending Human Assisted Reproduction Ireland at the Rotunda Hospital Dublin completed prospectively a detailed questionnaire on all likely areas of extra expense during a single IVF cycle from down-regulation to zygote transfer. Four groups participated, divided according to their distance from the clinic. Group A were within Dublin and Group B within a 50 mile radius. Group C were between a 50-130 mile radius and Group D a 130-200 mile radius. Mean levels of costs increased with distance:- Group A 104 euros. to Group D 703 euros. Food, meals and accommodation were the main contributors. Travel time and time-off work also increased with distance. These were respectively, Group A to Group D 15hrs to 139hrs: 35hrs to 75hrs. The study demonstrates that significant extra expense in time and money can be spent in an IVF cycle over and above medical and drug costs. This must be advised prior to commencement. All other issues being equal, geographical location should be part of the decision as to which clinic to attend.

Adult↗
PubMed2005

Prevalence of over-the-counter drug-related overdoses at Accident and Emergency departments in Northern Ireland--a retrospective evaluation.

BACKGROUND AND OBJECTIVES: One major concern associated with misuse/abuse of over-the-counter (OTC) products is the potential for over-dosage. The aim of this research study was to evaluate, over a 3-month period, OTC medicine-related overdoses (those involving OTC drugs only and OTC drugs in combination with other drugs) that led to patients presenting at the Accident and Emergency (A & E) departments in four Belfast hospitals. METHODS: A data collection sheet was designed to capture the information required from the A & E records in each hospital. A retrospective week-by-week data collection, reviewing A & E records, took place over a 3-month period (starting on 1 December 2002). All data related to cases presenting at the A & E departments because of drug overdoses (either accidental or deliberate according to Read Clinical Classification) were included in the study. Data were coded and entered into a custom designed SPSS database for analysis, using Chi square and Fisher exact tests. RESULTS: OTC drug-related overdoses comprised 40.1% of all overdoses, of which 24.0% were OTC-only overdoses. Those who overdosed on OTC drugs (solely or combined with other drugs) were mainly female (62.3%) and in the age category 31-50 years (44.9%; P <0.05). The majority (n=215) of OTC-related overdoses were intentional, whereas only 28 were accidental. Of those who attended the A & E departments and had an overdose history, one-third overdosed on OTC-related products and two-thirds overdosed on OTC drugs only. CONCLUSIONS: OTC drugs accounted for a significant proportion of overdose presentations at the A & E departments in Northern Ireland. Higher awareness of the potential of OTC product use in overdose cases (intentional or accidental) is recommended for both the public and health care professionals.

Acetaminophen↗
PubMed2005

Exercise and mononuclear cell DNA damage: the effects of antioxidant supplementation.

The purpose of this investigation was to determine the effects of antioxidant supplementation on DNA damage following exercise. Fourteen subjects were randomly assigned to one of two groups and required to ingest either antioxidants (400 mg alpha-lipoic acid, 200 mg co-enzyme Q10, 12 mg manganese, 600 mg vitamin C, 800 mg N-acetyl cysteine, 400 microg selenium, and 400 IU alpha-tocopherol per day) or placebos for 7 d. Exercise increased DNA damage, PS, FRAP, and LDH (P < 0.05), but not selectively between groups. LDH and PS concentration decreased 1 h post-exercise (P < 0.05), while LH concentration decreased 1 h post-exercise in the antioxidant group only (P < 0.05). The antioxidant group had a higher concentration of LH (P < 0.05), perhaps due to a selective difference between groups post-exercise (P < 0.05). The main findings of this investigation demonstrate that exhaustive aerobic exercise induces DNA damage, while antioxidant supplementation does not protect against damage.

Adult↗
PubMed2003

The separation of codeine from nonprescription combination analgesic products.

In the United Kingdom number of products containing codeine in combination with nonopioid analgesics are available from pharmacies for purchase without a prescription. These products may be abused and it has been reported that in order to avoid nonopioid toxicity, some users may attempt to separate the components of combination analgesics, by mixing the dosage form in water and passing it through a coffee filtration apparatus (coffee filters). The present research sought to test the ease of separation of products available in the United Kingdom. The results obtained indicated that separation was possible; however, the extent of separation was influenced by the volume of water used and the product chosen. Healthcare professionals must be aware that separation may be attempted by those wishing to abuse codeine; however, significant nonopioid toxicity could still arise in the abuser.

Analgesics↗
PubMed2001

The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N.

AQ4N is a bioreductive drug that can significantly enhance the anti-tumour effect of radiation and cyclophosphamide. The aim of this study was to examine the ability of AQ4N to potentiate the anti-tumour effect of cisplatin and to compare it to the chemopotentiation effect of tirapazamine. In the T50/80 murine tumour model, AQ4N (50-100 mg/kg) was administered 30 min, 2.5 or 6 h prior to cisplatin (4 mg/kg or 8 mg/kg); this produced an anti-tumour effect that was approximately 1.5 to 2 times greater than that achieved by a single 4 or 8 mg/kg dose of cisplatin. Tirapazamine (25 mg/kg) administered 2.5 h prior to cisplatin (4 mg/kg) resulted in a small increase in anti-tumour efficacy. AQ4N was also successful in enhancing the anti-tumour effect of cisplatin in the SCCVII and RIF-1 murine tumour models. This resulted in an increased cell kill of greater than 3 logs in both models; this was a greater cell kill than that observed for tirapazamine with cisplatin. Combination of cisplatin with AQ4N or tirapazamine resulted in no additional bone marrow toxicity compared to cisplatin administered alone. In conclusion, AQ4N has the potential to improve the clinical efficacy of cisplatin.

Animals↗
PubMed2001

The role of the community pharmacist in drug abuse: a comparison of service provision between Northern Ireland and England/Wales.

AIM: The aim of the present research was to establish the current extent of pharmacists' contact with illicit drug users in Northern Ireland, their willingness to provide services for this group and to compare the findings with data from a 1995 national survey of community pharmacies in England and Wales. METHOD: The questionnaire developed by the National Addiction Centre for research in England/Wales was used to collect data. It was mailed on two occasions (March and April 1999) together with a covering letter and a prepaid return envelope to all community pharmacies in Northern Ireland (n = 507). A final reminder letter was included in the local wholesalers' medical delivery for the attention of the pharmacist in May 1999. MAIN OUTCOME MEASURE: The extent to which Northern Ireland pharmacists had contact with and provided services to illicit drug users compared to pharmacists in England/Wales. RESULTS: A response rate of 67.5% was achieved. Respondents in Northern Ireland were providing fewer services to drug users than those in England/Wales. Respondents reported dispensing methadone for the treatment of addiction/misuse to only 9 patients, while only 17 pharmacists had been asked to sell injecting equipment in the previous week and no pharmacist was participating in a needle exchange scheme. However, most respondents indicated their willingness to provide such services. Barriers towards the provision of services were, however, highlighted e.g. the need for training and the establishment of support systems. CONCLUSION: Pharmacists in Northern Ireland are in a position to contribute to the policy agenda in Northern Ireland for drug misuse, prevention, treatment and harm minimisation--roles which the survey indicates they are willing to embrace. However, training programmes, support systems and adequate remuneration packages must be established before they will be in a position to participate fully.

England↗
PubMed2001

Nursing and residential care for the elderly in Northern Ireland: the contribution of the pharmacist.

AIM OF THE STUDY: To gain more detailed information on the current pharmaceutical service provision in nursing and residential homes in Northern Ireland and to assess the views of care staff on future pharmacy services. METHOD: A structured questionnaire was developed and mailed to all nursing and residential homes (n = 586) in Northern Ireland on two occasions. RESULTS: A response rate of 68% (n = 396) was obtained. The most frequent services currently provided by community pharmacists were the supply of medication and the collection of unwanted, discontinued or out-of-date medicines. The majority of respondents also reported receiving advice on safe-keeping, correct administration of medicines, advice on more appropriate formulations and advice on patient medication records from the community pharmacist. Over a third of all the respondents received advice on compliance devices. A similar proportion stated that their care staff were trained by the pharmacist on broad medication management issues. Over 90% of all homes strongly supported staff training by pharmacists on the recognition of medication-related problems as a future service. Over 70% of all respondents thought additional guidelines and advice for missed dosages and the use of home remedies would be beneficial. A review of patient medication records to assess drug-drug interactions and possible adverse drug reactions by pharmacists was supported by over 65% of all respondents. CONCLUSIONS: This work has demonstrated that those responsible for care in nursing and residential facilities strongly support further involvement by the pharmacist in these care facilities; pharmacy policy makers must ensure that such services are developed to meet the needs of these vulnerable elderly residents.

Aged↗
PubMed2001

Effect of triplicate prescription policy on benzodiazepine administration in nursing home residents.

OBJECTIVE: To estimate the effect of a triplicate prescription policy on administration of benzodiazepines and possible substitute drugs in nursing home residents during 1994-1995. DESIGN: Retrospective cross-sectional study SETTING: Medicare- and Medicaid-certified nursing homes in five states: New York, which has a policy requiring triplicate prescription forms for certain drugs, and four states without such a policy. SUBJECTS: A total of 211,177 nursing home residents. MEASUREMENTS AND MAIN RESULTS: Data were collected using the Minimum Data Set; logistic regression provided an estimated effect of the policy on prescribing benzodiazepines. We also estimated possible substitute drugs for benzodiazepines (e.g., barbiturates, antidepressants, antipsychotics, and miscellaneous sedative-hypnotics) while adjusting simultaneously for potential confounders. New York nursing home residents were less likely to be receiving benzodiazepine therapy than those in nonpolicy states (odds ratio 0.42; 95% confidence interval 0.41-0.44). No increases occurred in administration of benzodiazepine substitute drugs in New York versus states without a triplicate prescription policy. CONCLUSION: Policy did affect prescription and administration of benzodiazepines in nursing homes in states with versus without a triplicate prescription policy Lack of substitution with other drugs makes it unclear whether overprescribing occurred in states without a policy, or undertreatment occurred in the state with a policy.

Affect↗
PubMed2001

Assessment of a community pharmacy-based program for patients with asthma.

STUDY OBJECTIVE: To implement and assess a community-based pharmaceutical care program for patients with asthma. DESIGN: Prospective, randomized, controlled trial. SETTING: Community pharmacies (11 control, 11 intervention) in Malta. PATIENTS: Community-dwelling patients with asthma. INTERVENTIONS: A comprehensive asthma education and monitoring program was implemented. Intervention patients received verbal counseling, an educational video, an information leaflet, and subsequent monitoring with reinforcement; control patients received routine dispensing services. MEASUREMENTS AND MAIN RESULTS: Parameters assessed at baseline and at 4, 8, and 12 months were health-related quality of life, peak expiratory flow (PEF), inhaler technique, compliance with therapy, hospitalization rates, days lost from work, asthma symptoms, and patient satisfaction. Health-related quality of life of the intervention patients improved at 12 months (p=0.044). In the same time period, PEF significantly decreased in control patients compared with intervention patients (p=0.009) whereas inhaler technique improved in the intervention group (p=0.021). There were significantly fewer self-reported hospitalizations in intervention patients. CONCLUSIONS: A community-based pharmaceutical care program was appreciated by the participants and had a positive impact on the vitality of patients with asthma, inhaler technique, and PEE.

Adolescent↗
PubMed2001

Benefits and risks of self medication.

Self medication is becoming an increasingly important area within healthcare. It moves patients towards greater independence in making decisions about management of minor illnesses, thereby promoting empowerment. Self medication also has advantages for healthcare systems as it facilitates better use of clinical skills, increases access to medication and may contribute to reducing prescribed drug costs associated with publicly funded health programmes. However, self medication is associated with risks such as misdiagnosis, use of excessive drug dosage, prolonged duration of use, drug interactions and polypharmacy. The latter may be particularly problematic in the elderly. Monitoring systems, a partnership between patients, physicians and pharmacists and the provision of education and information to all concerned on safe self medication, are proposed strategies for maximising benefit and minimising risk.

Drug Therapy↗
PubMed2000

Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine.

The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50-150 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 200 mg kg 1 dose of cyclophosphamide. Tirapazamine (25 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 150 mg kg(-1) dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50-200 mg kg(-1)); AQ4N (50-200 mg kg(-1)) produced a more effective combination than tirapazamine (12.5-50 mg kg(-1)). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg(-1)) 6 h prior to cyclophosphamide (100 mg k(-1)) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg(-1)).

Animals↗
PubMed2000

Influence of facility characteristics on use of antipsychotic medications in nursing homes.

OBJECTIVES: This study investigated the effect of facility and resident characteristics on the use of antipsychotic medications in the long-term care setting. RESEARCH DESIGN: This research used data available from the On-Line Survey and Certification of Automated Records (OSCAR) for all Medicare/Medicaid-certified nursing homes in the contiguous United States in 1997. The data consisted of 14,631 facilities. MEASURES: A multiple linear regression model was used to determine the effects of selected facility and resident characteristics on antipsychotic drug use while simultaneously controlling for the effects of resident characteristics and stratifying by ownership type. beta-Coefficients provided measures of effect and represented the per-unit change in the prevalence of antipsychotic use corresponding to the per-unit change in each independent variable. RESULTS: In for-profit facilities, both the presence of special care units and mental health professionals were associated with increased antipsychotic use (beta = 1.70, SE = 0.23; beta = 0.24, SE = 0.17, respectively), while other facility factors such as increasing size, being part of a chain, and higher occupancy rate were associated with decreased antipsychotic drug use. In the nonprofit environment, facility characteristics (eg, increasing occupancy rate, certified nurses' aides per 100 beds) were associated with decreasing antipsychotic use. Increasing percentages of residents covered by Medicare, those with dementia, and residents with mental retardation (beta = 0.05, SE = 0.01; beta = 0.03, SE = 0.01; beta = 0.08, SE = 0.08, respectively) were predictive of increased drug use. CONCLUSIONS: Facility and resident characteristics are associated with use of antipsychotic medications, although the extent to which these factors explain variability in use of anti-psychotics may vary on the basis of the underlying financial incentives of the institution.

Antipsychotic Agents↗
PubMed2000

The impact of legislation on psychotropic drug use in nursing homes: a cross-national perspective.

OBJECTIVES: To quantify the impact of legislation on nursing home residents, psychotropic drug use, and the occurrence of falls in the US compared with five countries with no such regulation. DESIGN: A retrospective cross-sectional study SETTING: Nursing homes in five US states and selected nursing homes in Denmark, Iceland, Italy, Japan, and Sweden. PARTICIPANTS: Residents in nursing homes in five US states and the aforementioned countries during 1993-1996. MAIN OUTCOME MEASURES: Using data collected using the Minimum Data Set, logistic regression provided estimates of the legislative effects on the use of antipsychotics and antianxiety/hypnotics while simultaneously adjusting for potential confounders. The occurrence of falls was evaluated similarly. RESULTS: Prevalence of antipsychotic and/or antianxiety/ hypnotic use varied substantially across countries. After adjustment for differences in age, gender, presence of psychiatric/neurologic conditions, and physical and cognitive functioning, residents in Denmark, Italy, and Sweden were at least twice as likely to receive these drugs (Denmark Odds Ratio (OR)=2.32; 95% Confidence Intervals (CI), 2.15-2.51; Italy OR=2.05; 95% CI, 1.78-2.34; Sweden OR=2.50; 95% CI, 2.16-2.90); in Iceland, the risk was increased to greater than 6 times (OR=6.54; 95% CI, 5.75-7.44) that of the US. Residents were less likely to fall in Italy, Iceland, and Japan compared with the US, despite more extensive use of psychotropic medication, whereas residents in Sweden and Denmark were more likely to fall. CONCLUSIONS: Policy has had an impact on the prescribing of psychotropic medication in US nursing homes compared with other countries, but it is unclear if this is translated into better outcomes for residents.

Accidental Falls↗
PubMed2000

Primary schoolteachers' knowledge of asthma: the impact of pharmacist intervention.

The Newcastle Asthma Knowledge questionnaire was used to determine primary schoolteachers' knowledge of asthma. The mean score achieved (20.71 +/- 3.20), was representative of a reasonable degree of knowledge. However, knowledge of symptoms associated with asthma and of medications used to manage the condition was poor. Teachers who had contact with an asthmatic individual or who had received previous training on asthma had a significantly greater knowledge of asthma. An asthma training session, delivered by a pharmacist, was found to significantly improve primary schoolteachers' knowledge of the condition, however, the extent of the improvement was low.

Adult↗