PubMed Health⌕ Search

Biomedical subjects

David J Perry

Publications and source records attributed to David J Perry.

7 recordsLinked to original sources
PubMed2003

Veno-occlusive disease: cytokines, genetics, and haemostasis.

Hepatic veno-occlusive disease (VOD) is a major cause of morbidity and mortality following high dose cytotoxic therapy for stem cell transplantation (SCT). Pre-existing liver damage, SCT-related therapy, and genetic polymorphisms all appear to increase the risk of developing VOD. Studies of biological markers during SCT suggest that cytokines, haemostasis, and hepatic drug metabolism via the glutathione pathway are all involved in the pathogenesis of VOD. Until recently, treatment options were limited and experimental therapies directed at the pathogenesis of the disease were mostly unsuccessful. However, Defibrotide, a relatively new agent that has modulatory effects on vascular endothelium, cytokine release, and haemostasis, has been used with some success in the management and prophylaxis of VOD. In the future, a better understanding of genetic polymorphisms and biological markers which may be important in the pathogenesis of VOD, may enable us to predict which patients are most likely to be affected.

Animals↗
PubMed2002

Simple shifts in redox/thiol balance that perturb blood coagulation.

The biological chemistry that underlies and regulates the blood coagulation cascade is not fully understood. To begin to understand this, we performed clotting assays under various redox conditions. By varying the amount of oxidant and/or antioxidant in these assays, we observed that both the intrinsic/tenase complex and the extrinsic pathways were susceptible to shifts in the thiol/redox balance. We established a dichotomy where blood clotting via the intrinsic pathway was sensitive to oxidation whereas the tissue factor or extrinsic pathway was more sensitive to reduction. These differential inhibitory effects present a conceptual mechanism for selective modulation of the activities of clotting factors specific for the respective pathways. These data also suggest that blood clotting may be influenced by unidentified redox or thiol equilibria.

Blood Coagulation↗
PubMed2002

Immediate reconstruction after mastectomy for breast cancer does not prolong the time to starting adjuvant chemotherapy.

BACKGROUND: Immediate breast reconstruction is often performed after mastectomy for breast cancer. There has been concern that this will result in a delay in initiating chemotherapy and, as a consequence, may adversely impact survival. In this study we sought to determine whether immediate breast reconstruction affects the interval between surgery and adjuvant chemotherapy. METHODS: A single institution retrospective analysis was made using the institutional tumor registry and chart reviews. RESULTS: Forty-nine patients were identified who had undergone mastectomy with immediate reconstruction followed by adjuvant chemotherapy. They were compared with 308 patients undergoing mastectomy without reconstruction. Patients who underwent reconstruction were overall younger (46 versus 55, P <0.001), and had more advanced disease. The time to chemotherapy was significantly longer in the group receiving no reconstruction: 53 versus 41 days (P = 0.039). The type of reconstruction did not affect the time to chemotherapy. CONCLUSIONS: Immediate reconstruction after mastectomy does not increase the time to chemotherapy compared with mastectomy alone.

Abdominal Muscles↗
PubMed2002

Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency.

Factor X (FX) deficiency is a rare autosomal recessive disorder. The phenotype and genotype of 15 Iranian patients with FX deficiency from 13 unrelated families with a high frequency of consanguinity were analysed. Five different assays identified four patients from three families with a discrepancy between low-FX coagulant activity (FX:C) and higher-FX antigen (FX:Ag) (a type II deficiency). The remaining 11 patients had parallel reductions of FX:C and FX:Ag (a type I deficiency). Nine different homozygous candidate mutations were identified, of which eight were novel. The four type II cases were associated with an Arg(-1)Thr missense mutation in the prepropeptide: Arg(-1) is highly conserved in all vitamin K-dependent proteins. Four type I mutations (Gly78Asp, Cys81Tyr, Gly94Arg and Asp95Glu) were localized to the EGF-1 and EGF-2 domains, for which molecular views showed that the protein folding would be disrupted. The type I mutation Gly222Asp was localized in the catalytic domain of FX, and is sufficiently close to the Asp-His-Ser catalytic triad to disrupt its correct protein folding. The two type I splice site mutations were IVS1+3, A-->T and IVS2-3, T-->G. These novel homozygous FX mutations were consistent with their phenotypes and agree with experimental data from knockout mice, indicating that FX is an essential protein for survival.

Adolescent↗
PubMed2002

Factor X deficiency.

Factor X is one of the vitamin K-dependent serine proteases. It plays a crucial role in the coagulation cascade, as the first enzyme in the common pathway of thrombus formation. The gene for factor X maps to the long arm of chromosome 13, approximately 2.8 kb downstream of the factor VII gene. The gene consists of eight exons, each of which encodes a specific functional domain within the protein. Both the gene structure and the amino acid sequence show homology to other vitamin K-dependent clotting factors, suggesting their origin in a common ancestral protein. Factor X deficiency is one of the rarest of the inherited coagulation disorders. Inheritance is in an autosomal recessive manner. The clinical phenotype is of a variable bleeding tendency. Homozygous factor X deficiency has an incidence of 1:1,000,000 in the general population. Heterozygotes are often clinically asymptomatic. Acquired factor X deficiency is rare, but when it occurs it is usually in association with amyloidosis. Treatment of factor X deficiency involves replacement of the protein with either fresh frozen plasma or prothrombin complex concentrates, although the latter should be used with caution as infusion may be associated with an increased risk of thrombosis.

Amyloidosis↗
PubMed2002

Pharmacotherapy of hyperhomocysteinaemia in patients with thrombophilia.

Hyperhomocysteinaemia is often the result of inherited abnormalities of the enzymes involved in homocysteine metabolism or vitamin deficiencies (vitamins B12, B6 or folate) and is present in approximately 5% of the general population. High homocysteine levels in these individuals are associated with a significant increase in relative risk for both arterial and venous thromboembolic disease. Consequently, effective homocysteine-lowering therapeutic strategies have been extensively investigated. Folic acid represents the cornerstone of treatment. In daily doses of at least 0.4 mg, it effectively reduces homocysteine levels, even in non-folate-deficient patients. The addition of vitamins B12 and/or B6, to folic acid supplementation may provide a small further reduction in homocysteine levels in certain groups of patients. Renal impairment is an important cause of hyperhomocysteinaemia. Individuals with hyperhomocysteinaemia secondary to renal disease commonly require significantly higher doses of folic acid (5-40 mg) to achieve maximal therapeutic effect. The important question of whether effective homocysteine-lowering therapy translates into a reduction in vascular disease remains unknown but is being addressed in a series of ongoing prospective trials.

Folic Acid↗