Biomedical subjects

J K McGavin

Publications and source records attributed to J K McGavin.

5 recordsLinked to original sources

PubMed2001

Comparison of a vitamin E-rich diet and supplemental vitamin E on measures of vitamin E status and lipoprotein profile.

OBJECTIVE: To determine whether dietary modification rather than use of supplements can raise indices of vitamin E status to potentially cardioprotective levels. DESIGN: Eight week randomised controlled trial with parallel treatments to compare increased use of vitamin E-rich foods, supplementation with 200 IU of vitamin E, and a placebo. SETTING: Dunedin, New Zealand. SUBJECTS: Ninety subjects were recruited, of whom 82 non-smoking, free-living individuals aged 22-72 y with plasma cholesterol <7.5 mmol/l completed the trial. MAIN OUTCOME MEASURES: Dietary intakes, plasma alpha tocopherol, plasma alpha tocopherol/cholesterol ratio and lipoprotein cholesterol. RESULTS: Consumption of an additional 12 mg of vitamin E (alpha tocopherol equivalents) from dietary sources was primarily achieved through the replacement of saturated fat-rich foods with unsaturated fats rich in vitamin E, nuts and vegetables. This resulted in a 3.4 micromol/l increase in plasma alpha tocopherol at week 6 (95% CI 1.6-5.3), and 0.9 micromol/mmol in plasma alpha tocopherol/cholesterol at weeks 4 and 6 (95% CI 0.3-1.4 and 0.4-1.4, respectively) when compared with the placebo group. In the supplement group, plasma alpha tocopherol and plasma alpha tocopherol/cholesterol were significantly increased within 2 weeks and remained so throughout the 8 week intervention. CONCLUSION: Increasing dietary vitamin E intake can increase plasma alpha tocopherol levels, although factors other than dietary intake are also important determinants. The extent of dietary modification required to achieve potentially cardioprotective levels of plasma alpha tocopherol is difficult in practice. SPONSORSHIP: The study was supported through the Otago Medical Research Foundation Laurenson Award.

Adult↗

PubMed2001

Inhaled budesonide/formoterol combination.

Current evidence suggests that the addition of the long acting inhaled beta2-agonist formoterol to low or moderate doses of the inhaled corticosteroid budesonide is effective in improving lung function and reducing the incidence of asthma exacerbations. Concurrent use of budesonide with formoterol does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles. The administration of combined budesonide/formoterol is effective in improving morning and evening peak expiratory flow rates in adults with persistent asthma. Control of asthma symptoms is also significantly improved. In children aged 4 to 17 years, combined budesonide/formoterol is effective in increasing both morning and evening peak expiratory flow rates and significantly improving forced expiratory volume in 1 second (FEV1). The most commonly encountered adverse effects in clinical trials with combination budesonide/formoterol therapy have been respiratory infection, pharyngitis and coughing. No adverse effects on pulse rate, blood pressure or serum potassium have been reported with combination therapy.

Adult↗

PubMed2001

Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients.

Ganciclovir is a nucleoside guanosine analogue which incorporates ganciclovir triphosphate (the active moiety) into DNA during elongation, thereby inhibiting viral replication. Comparative studies of pre-emptive and prophylactic ganciclovir therapies in bone marrow transplant (BMT) recipients have shown similar rates of cytomegalovirus (CMV) infection, disease and patient mortality. Long term prophylaxis with either oral, or sequential intravenous/oral, ganciclovir has shown efficacy in renal allograft recipients, including high risk patients or those receiving antilymphocyte antibody therapy. A preliminary study indicates that ganciclovir is more efficacious than aciclovir in paediatric patients. Both oral and intravenous prophylactic ganciclovir regimens have shown efficacy compared with no antiviral treatment in lung transplant recipients; initial reports have shown similar efficacy between pre-emptive and prophylactic ganciclovir. Oral ganciclovir monotherapy is as efficacious as sequential intravenous/oral ganciclovir therapy in liver transplant recipients. Pre-emptive treatment was equally as effective as long term ganciclovir prophylaxis in high risk patients. Ganciclovir prophylaxis for 4 weeks appears ineffective in heart allograft recipients treated with antithymocyte globulin. Long term sequential intravenous/ oral ganciclovir therapy has shown greater efficacy in preventing CMV disease than sequential ganciclovir/aciclovir therapy. in these patients. Initial reports indicate that pre-emptive therapy may be beneficial in this patient group. although this remains to be determined. Ganciclovir in therapeutic dosage regimens generally has acceptable tolerability with adverse effects usually of a haematological or neurological nature. Neutropenia, thrombocytopenia and anaemia are the primary dose-limiting toxicities associated with ganciclovir therapy. Overall, neutropenia occurs less frequently with administration of oral ganciclovir than with intravenous ganciclovir. Monitoring of renal function is recommended as serum creatinine levels may rise during ganciclovir therapy. In addition, ganciclovir prophylaxis appears more cost effective than the majority of other currently available therapies for CMV with oral ganciclovir more cost effective than intravenous ganciclovir. In conclusion, it is unlikely that a single strategy will be able to be applied to all transplant patients for the prevention of CMV disease. An optimal strategy will probably be arisk-adapted approach. Prophylactic treatment with ganciclovir appears the best strategy to implement in high risk patients: oral ganciclovir formulations may be best employed where lower toxicity is required. Pre-emptive treatment with ganciclovir appears most efficacious in patients identified as lower risk or, in the case of BMT recipients, where lower toxicity may be desirable. Ganciclovir remains an important therapeutic option for the prevention and treatment of CMV disease in transplant recipients.

Absorption↗

PubMed2001

Gemtuzumab ozogamicin.

Gemtuzumab ozogamicin is a humanised monoclonal IgG4 antibody, linked to a cytotoxic calicheamicin derivative. It effects cell necrosis by specifically targeting the CD33 antigen which is expressed on the surface of leukaemic cell blasts in more than 90% of patients with acute myeloid leukaemia (AML), but is not present on normal stem cells. Therapy with gemtuzumab ozogamicin (2 doses of 9 mg/m2) in 3 noncomparative studies produced complete remission in 16% of adult patients with AML in first relapse, and complete remission with incomplete platelet recovery in an additional 13% of patients. Rates of remission did not differ between those aged less than 60 years and older than 60 years. Many patients were able to receive both doses of gemtuzumab ozogamicin therapy as outpatients. Survival duration was similar between those treated as outpatients and those requiring hospitalisation. About one-third of 11 children and adolescents treated with 2 doses of 9 mg/m2 gemtuzumab ozogamicin in a phase I study showed <5% bone marrow blasts after completion of therapy. The most commonly encountered adverse events in clinical trials with gemtuzumab ozogamicin were myelosuppression, increased levels of hepatic enzymes, infection, fever, bleeding, chills, nausea and vomiting and dyspnoea. No treatment-related renal failure or alopecia was reported.

Adolescent↗

PubMed2001

Capecitabine: a review of its use in the treatment of advanced or metastatic colorectal cancer.

Capecitabine is an orally administered fluoropyrimidine which is selectively activated in tumour tissue to the active moiety fluorouracil and is cytotoxic through inhibition of DNA synthesis. In patients with advanced or metastatic colorectal cancer, first-line therapy with intermittent capecitabine achieved significantly higher objective tumour response rates than therapy with fluorouracil plus leucovorin in pooled analysis. Response rates were also higher in patients pretreated in the adjuvant setting and whose primary site of metastasis was the lung. However, no significant differences between the two treatment groups were seen in the time to disease progression, time to treatment failure or overall survival. Preliminary data suggest response may be improved by combining capecitabine with other anticancer therapies such as oxaliplatin, irinotecan and radiotherapy. Capecitabine in therapeutic dosage regimens generally has acceptable tolerability. Diarrhoea and hand-and-foot syndrome are the major dose-limiting toxicities associated with capecitabine therapy, with adverse effects generally of a gastrointestinal nature. Overall, diarrhoea, stomatitis, nausea and alopecia were significantly less common with capecitabine than with bolus fluorouracil and leucovorin. In addition, capecitabine recipients experienced significantly less myelosuppression, although more capecitabine recipients discontinued therapy because of adverse events. Importantly, patients spent less time in hospital after capecitabine than after bolus fluorouracil and leucovorin therapy, and the oral route of administration of capecitabine is likely to be preferred. In conclusion, capecitabine has shown superior tumour response and less myelosuppression, although more grade 3 hand-and-foot syndrome, in comparison with the 'Mayo Clinic' regimen of fluorouracil therapy, but is unlikely to improve survival. Significantly, its oral route of administration is likely to be preferred by patients. Future strategies to improve patient response may involve selection of those patients likely to respond best to capecitabine, through determination of relevant enzyme levels and combination of capecitabine with various antineoplastic agents. Data on the effect of the drug on quality of life would help establish its role. In the meantime, capecitabine appears to offer an effective and more convenient alternative to fluorouracil as first-line monotherapy for the treatment of metastatic colorectal cancer.

Absorption↗