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Biomedical subjects

T Pilkington

Publications and source records attributed to T Pilkington.

5 recordsLinked to original sources
PubMed1992

Acitretin. A review of its pharmacology and therapeutic use.

Acitretin (etretin), a second generation monoaromatic retinoid for use in the treatment of severe psoriasis and other dermatoses, is the major active metabolite of etretinate and possesses a similar therapeutic index; i.e. a similar ratio of clinical efficacy to adverse effects. When used alone at a maintenance dosage of 30 to 50mg daily, acitretin is effective in the treatment of psoriasis, causing a reduction in the severity of scaling, erythema and induration. Efficacy appears to be further enhanced by combination with psoralen-ultraviolet A photochemotherapy (PUVA) or ultraviolet B irradiation (UVB). These combinations reduce the time to lesion clearance and reduce the total radiation dose, improving overall safety. Comparative studies have confirmed the equivalence of acitretin and etrtinate with regard to efficacy and toxicity. Adverse reactions are dose-related and generally typical of hypervitaminosis A. Alopecia and mucocutaneous symptoms such as cheilitis and drying of the mucous membranes are particularly prevalent. Hypertriglyceridaemia and elevation of cholesterol levels also occur. Examination of the pharmacokinetic profile of acitretin reveals its main advantage over etretinate. Acitretin is less lipophilic than etretinate, and its lack of sequestration into 'deep' fatty storage sites is reflected in a comparatively short terminal elimination half-life of 50 to 60 hours, compared with 120 days for etretinate. Due to its teratogenic potential, acitretin is strictly contraindicated in women of childbearing potential unless effective contraceptive measures are employed. Etretinate has been identified in plasma samples of some patients treated with acitretin. Thus, acetretin has an established place in the treatment of keratinising disorders, although its use in women of child-bearing potential must be accompanied by effective contraceptive measures, with a further 2-year contraceptive period after therapy completion.

Acitretin↗
PubMed1992

Skeletal muscle grids for assessing current distributions from defibrillation shocks.

This paper utilizes a structured and an unstructured grid representation of a torso with an anisotropic skeletal muscle to assess current distributions from defibrillation shocks. The results show that a finite-element solution on an unstructured grid of 400,000 elements (60,000 nodes) achieves comparable current distributions with a finite-difference solution on a structured grid that uses approximately the same number of nodes. Moreover, a finite-element solution on a 65,000-element (10,500 nodes) unstructured grid yielded fractional percent current results within 5% of the finer grids. The structured and unstructured grid models are used to investigate recent interpretations of experimental data that concluded that more than 80% of the total defibrillation current is shunted by the anisotropic skeletal muscle thoracic cage. It is concluded that these interpretations, which were based on a one-dimensional resistive network representation of the three-dimensional defibrillation situation, overestimate by 25% the current shunted by the anisotropic thoracic cage.

Animals↗
PubMed1992

The use of spectral methods in bidomain studies.

A Fourier transform method is developed for solving the bidomain coupled differential equations governing the intracellular and extracellular potentials on a finite sheet of cardiac cells undergoing stimulation. The spectral formulation converts the system of differential equations into a "diagonal" system of algebraic equations. Solving the algebraic equations directly and taking the inverse transform of the potentials proved numerically less expensive than solving the coupled differential equations by means of traditional numerical techniques, such as finite differences; the comparison between the computer execution times showed that the Fourier transform method was about 40 times faster than the finite difference method. By application of the Fourier transform method, transmembrane potential distributions in the two-dimensional myocardial slice were calculated. For a tissue characterized by a ratio of the intra- to extracellular conductivities that is different in all principal directions, the transmembrane potential distribution exhibits a rather complicated geometrical pattern. The influence of the different anisotropy ratios, the finite tissue size, and the stimuli configuration on the pattern of membrane polarization is investigated.

Algorithms↗
PubMed1991

Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer.

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.

Drug Evaluation↗