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Biomedical subjects

K Downes

Publications and source records attributed to K Downes.

7 recordsLinked to original sources
PubMed2005

Common VKORC1 and GGCX polymorphisms associated with warfarin dose.

We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.

Adult↗
PubMed2001

Massive blood transfusion.

Pediatricians in the hospital setting must frequently treat children who require massive transfusion (MT) in a variety of clinical situations ranging from major trauma to neonatal hyperbilirubinemia. After identifying the need for massive transfusion, the pediatrician must select the appropriate blood components. Different blood components have specific temperature, preservative, and time requirements for their storage. Changes, termed storage lesions, occur over time in blood components during storage; biochemical changes include decreased levels of 2,3-DPG, a decrease in pH, and an increase in supernatant potassium (K+) with a concurrent decrease in intracellular K+. These changes may affect the function and the viability of components. Additionally, physical changes such as deformation of the red cell membrane occur during storage. Knowledge of these storage lesions is necessary for the pediatrician to make the most appropriate decisions regarding the preparation and selection of components during MT. Serious complications of MT include hemostatic abnormalities, biochemical/metabolic abnormalities, hypothermia, mechanical injury and the effect of Rh incompatibility, each of which has a specific management response. Pediatricians need to be aware of the potential complications associated with massive transfusion, to take measures to prevent them when possible, to anticipate additional transfusion requirements, and to know how to manage them in the pediatric patient.

Blood Coagulation Disorders↗
PubMed1986

The treatment of subacute sclerosing panencephalitis with interferon: a case report.

A child with subacute sclerosing panencephalitis (SSPE) received intraventricular alpha interferon (IFN) as experimental treatment. The course was monitored by colleagues in pediatric neurology, neuro-opthalmology and clinical psychology, also by monthly EEGS and brain CT scans. Two courses of IFN were administered. During the first course, improvement occurred nearly to the premorbid level of function. About 1 month after this trial was stopped, a severe recrudescence rapidly produced a thalamic state. A second trial of IFN resulted in less improvement. When the brain CT showed severe degeneration, the second trial was stopped. Intraventricular administration of alpha IFN was well tolerated in both courses of therapy. Alpha IFN has promise in the treatment of SSPE but the optimal dosage and duration of treatment are undetermined.

Adolescent↗