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Biomedical subjects

P T Murphy

Publications and source records attributed to P T Murphy.

At least 19 recordsLinked to original sources

Octa- and nonaprenylhydroquinone sulfates, inhibitors of alpha1,3-fucosyltransferase VII, from an Australian marine sponge Sarcotragus sp.

Alpha1,3-fucosyltransferase (Fuc TVII) is a key enzyme in the biosynthesis of selectin ligands. We have isolated two inhibitors of Fuc TVII from a marine sponge Sarcotragus sp. They were characterized as octa- and nonaprenylhydroquinone sulfates on the basis of spectral data. These compounds inhibited Fuc-TVII with IC50 values of 3.9 and 2.4 microg/mL, respectively.

Animals

Paroxysmal cold haemoglobinuria caused by non-Hodgkin's lymphoma.

Paroxysmal cold haemoglobinuria is an autoimmune haemolytic anaemia characterized by a biphasic polyclonal IgG autoantibody, the Donath-Landsteiner (D-L) antibody. Although classically described in association with chronic syphilis, it is most commonly seen after acute viral infections in children. We describe a case of high-grade B-cell non-Hodgkin's lymphoma which presented with paroxysmal cold haemoglobinuria. The lymphoma responded promptly to combination chemotherapy whilst, at the same time, the haemolytic process rapidly resolved. Subsequent investigations showed that the D-L antibody originated from the lymphoma cells.

Aged

Primary cardiac lymphoma: death from cardiac asystole after attaining second complete remission.

A patient with primary high grade cardiac lymphoma, diagnosed by pericardial fluid cytology, achieved complete remission with chemotherapy. After a relapse 11 months later, a second complete remission was attained with radiotherapy and chemotherapy but the patient suffered a fatal cardiac asystole during intensification therapy. A review of the recent literature suggests that prognosis for this rare extra nodal lymphoma has markedly improved as a result of early diagnosis and prompt institution of aggressive antilymphoma therapy.

Death, Sudden, Cardiac

Audit of patients on oral anticoagulants with International normalized ratios of eight or above.

We reviewed retrospectively the medical records of all patients (n = 77, mean age 74.2) on oral anticoagulants with an International normalized ratio (INR) of eight or above in a 12-month period in the Leicestershire District Health Authority (DHA). From a total of 55,625 INRs, 131 (0.24%) were > or = 8. A major cause of over-anticoagulation was unsatisfactory dose loading during in-hospital commencement of oral anticoagulation. The incidence of major bleeding was 12.9% of total episodes of INR > or = 8 with two haemorrhage-related fatalities. Therapy of major haemorrhage with fresh frozen plasma (FFP) and intravenous (i.v) vitamin K proved effective but was not given in a majority of such cases. In conclusion, improvements in initial dose loading of oral anticoagulation and in the management of major haemorrhage are required. Severely over-anticoagulated patients without obvious bleeding should nevertheless receive small dose vitamin K therapy to reduce the risk of haemorrhage related morbidity and mortality without compromising subsequent oral anti-coagulant control.

Adult

Lymphoma associated bone marrow necrosis with raised anticardiolipin antibody.

A case of high grade B cell lymphoma presented with bone marrow necrosis, followed by development of extensive marrow fibrosis, the evolution of which was documented by serial magnetic resonance imaging and bone marrow trephine histology. A markedly raised anticardiolipin antibody titre at diagnosis suggests that lymphoma associated antiphospholipid syndrome may have contributed to the aetiology of the bone marrow necrosis.

Aged

Interleukin-4 and tumour necrosis factor-alpha produce non isotype specific partial differentiation of peripheral blood B-cells in myeloma.

In a previous study, culture of peripheral blood mononuclear cells (PBMC) from myeloma patients with interleukin(IL)-4 and tumour necrosis factor(TNF)-alpha resulted in the appearance of clonal plasma cells, thus suggesting the presence of circulating myeloma cell precursors in the peripheral blood. Using the same cytokine combination, we cultured PBMC and purified peripheral blood B-cells from myeloma patients. In nearly all cases, partial differentiation of B-cells occurred but, similarly to results for normal controls, both kappa and lambda light chain (L.C.) cytoplasmic positive lymphoid and lymphoplasmacytoid cells were detected rather than clonal plasma cells. These results suggest that IL-4 and TNF-alpha cause partial differentiation of residual normal polyclonal B-cells rather than of circulating myeloma cell precursors in the peripheral blood of myeloma patients.

B-Lymphocytes

Adjunctive treatment of compartment syndrome with hyperbaric oxygen.

Trauma-induced compartment syndrome and other acute traumatic peripheral ischemias have been effectively treated with hyperbaric oxygen therapy. We describe a case of compartment syndrome associated with an acute exertional injury. After surgical decompression, hyperbaric oxygen therapy reduced edema and improved tissue viability. The mechanisms of hyperbaric oxygen applicable to the pathophysiology of compartment syndrome are described. We believe that hyperbaric oxygen is a useful intervention in the management of compartment syndrome.

Adult

Australian deliberations on access to its terrestrial and marine biodiversity.

The predominantly developed country business principle that the natural resource is effectively free, or of very low monetary value, has been significantly challenged in recent years, not only through the recognition of the accelerated rate of depletion of native forest resources and of the space and food demands of increasing populations, but also through international conventions which deal with a wide range of topics from the rights of indigenous people to the Law of the Sea Convention. Australia, classified as a developed country, but located in a geographic region of many developing countries, has, in the past 25 years, demonstrated particular concern for the rights of the people of those countries, as well as for the rights of indigenous people of Australia. The practical international aspects were clearly exemplified in the time, from 1985, when the Australian Institute of Marine Science (AIMS) negotiated, within the National Cancer Institute (NCI) contract, that collections of biological samples in developing countries would be accompanied by an agreement to provide benefits arising from field work, and from any commercial product developments, to those countries. Australia, as a signatory to the Convention on Biological Diversity (Appendix I), continues to analyze the challenge presented by the need to freely exchange genetic resources of common value, e.g. food crops, while insuring an appropriate reward to developing and developed countries, should discoveries be made from their biological resources, which lead directly or indirectly, to high value commercial non-food products. The Prime Minister's Coordinating Committee on Science and Technology established a special working group to recommend on access to Australia's biodiversity. The report arising from the study, and other related issues, are discussed.

Animals

POEMS syndrome and Waldenström's macroglobulinaemia.

A 58 year old man presented with a three year history of impotence, night sweats and ankle swelling. On examination, the patient fulfilled the diagnostic criteria for POEMS syndrome, but was unusual in that he also had underlying Waldenström's macroglobulinaemia with IgM kappa paraproteinaemia. The patient was treated with intermittent chlorambucil and made a good recovery. POEMS syndrome has been described in association with osteosclerotic myeloma and Castleman's disease. The paraprotein involved is usually IgG or IgA with lambda light chains. This case indicates that the presence of lambda light chains is not essential for the pathogenesis of POEMS syndrome. It also emphasises the diversity of plasma cell dyscrasias that can manifest as POEMS syndrome.

Humans

Successful use of topical retinoic acid in severe dry eye due to chronic graft-versus-host disease.

Topical retinoic acid has proved to be of variable benefit in a number of dry eye disorders of disparate aetiology, in which squamous metaplasia with keratinization of ocular epithelium is present. Its exact role in patients with dry eye however remains in dispute. We describe a case of severe dry eye due to chronic graft-versus-host disease, which was refractory to conventional therapy but which responded remarkably to topical retinoic acid with reversal of conjunctival keratinization and marked resolution of symptoms.

Administration, Topical

Acute lymphoblastic transformation of essential thrombocythaemia.

Essential thrombocythaemia is a myeloproliferative disorder which may transform to acute myeloid leukaemia, especially following therapy with alkylating agents or radioactive phosphorus. We describe the rare occurrence of acute lymphoblastic leukaemia transformation in a patient with known essential thrombocythaemia.

Humans

The distribution of brominated long-chain fatty acids in sponge and symbiont cell types from the tropical marine sponge Amphimedon terpenensis.

The tropical marine sponge Amphimedon terpenensis (family Niphatidae, order Haplosclerida) has previously been shown to possess unusual lipids, including unusual fatty acids. The biosynthetic origin of these fatty acids is of interest as the sponge supports a significant population of eubacterial and cyanobacterial symbionts. The total fatty acid composition of the sponge was analyzed by gas chromatography/mass spectrometry of the methyl esters. Among the most abundant of the fatty acids in intact tissue were 16:0, 18:0 and 3,7,11,15-tetramethyl-hexadecanoic (phytanic) acid. In addition, three brominated fatty acids, (5E,9Z)-6-bromo-5,9-tetracosadienoic acid (24:2Br), (5E,9Z)-6-bromo-5,9-pentacosadienoic acid (25:2Br) and (5E,9Z)-6-bromo-5,9-hexacosadienoic acid (26:2Br) were also present. The three brominated fatty acids, together with phytanic acid, were isolated from both ectosomal (superficial) and choanosomal (internal) regions of the sponge. Analysis of extracts prepared from sponge/symbiont cells, partitioned by density gradient centrifugation on Ficoll, indicated that phytanic acid and the three brominated fatty acids were associated with sponge cells only. Further, a fatty acid methyl ester sample from intact tissue of A. terpenensis was partitioned according to phospholipid class, and the brominated fatty acids were shown to be associated with the phosphatidylserine and phosphatidylethanolamine fractions that are commonly present in marine sponge lipids. The phosphatidylcholine and phosphatidylglycerol fractions were rich in the relatively shorter chain fatty acids (16:0 and 18:0). The association of brominated long-chain fatty acids (LCFA) with sponge cells has been confirmed. The findings allow comment on the use of fatty acid profiles in chemotaxonomy and permit further interpretation of LCFA biosynthetic pathways in sponges.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals