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S Downey

Publications and source records attributed to S Downey.

14 recordsLinked to original sources

Dimeric W3SO3 cluster complexes: synthesis, characterization, and potential applications as X-ray contrast agents.

Our continued research on the use of heavy metal cluster complexes as a new class of X-ray contrast agents in medical diagnostic imaging is described. A series of 2:3 cluster-ligand complexes, [(W(IV)3SO3)2L3]4- (L = linear polyaminopolycarboxylate ligands), were isolated from the reaction of aqua ion [W(IV)3SO3(H2O)9]4- (prepared in large quantities through an improved literature process) with respective ligands in refluxing DMF. The salts of [(W(IV)3SO3)2L3]4- complex anions were fully characterized using routine techniques such as elemental analysis, MS, HPLC, UV-vis, IR, and NMR. The solid structures of two complex anions, [(W(IV)3SO3)2(PDTA)3]4- and [(W(IV)3SO3)2(HO-PDTA)3]4-, were determined by X-ray crystallography. They are the first examples wherein two W(IV)3SO3 clusters are complexed and linked by three ligands that contain two terminal iminodiacetate (bis-IDA) groups. Complexation of the unstable aqua ion [W(IV)3SO3(H2O)9]4- with ligands has imparted desired biological compatibility to the tungsten metal cluster. These complexes are stable and highly soluble in H2O. The potential utility of such tungsten cluster complexes as X-ray contrast agents was evaluated in both in vitro and in vivo animal studies. In addition, the syntheses of several new linear polyaminopolycarboxylate ligands used in this study are reported.

Animals↗

Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen.

The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.

Adult↗

New endocrine therapies for breast cancer.

How do the new endocrine therapies stand up to the aims of modern endocrine therapy outlined in Table 1? We wish to see increased efficacy, decreased toxicity and improved general health in women taking a new agent. None of the new non-steroidal anti-oestrogens have shown unequivocal evidence of improved efficacy in the clinic to mirror their improved profiles over tamoxifen in preclinical studies. We know that toremifene is equivalent to tamoxifen, but we do not have any phase III data from the other four compounds in development. The specific steroidal antioestrogen, ICI 182,780, looks very promising, but is early in its developmental programme. The new aromatase inhibitors are likely to prove equal to tamoxifen or progestagens, but it is disappointing that improved oestrogen suppression has not led, to date, to improved efficacy. No comment can be made about adjuvant or preventative therapy for any of the new agents, although trials are planned for the new aromatase inhibitors in this clinical situation. Currently, the antiprogestins are disappointing and we will need to wait a considerable time for new agents in preclinical testing to reach the clinic. Many of the new agents are associated with decreased toxicity. It is likely that the NSAEs will be equitoxic with tamoxifen. The steroidal antioestrogen looks particularly non-toxic as do the new aromatase inhibitors, and thus we have an advance in terms of reduced toxicity. The effects of the new agents on the uterus, lipids and bone are in the early stages of testing. Raloxifene, ICI 182,780 and the new aromatase inhibitors are expected to have no proliferative effects on the endometrium, but only the new NSAEs are expected to have beneficial cardiovascular and skeletal effects. If the steroidal anti-oestrogens and new aromatase inhibitors become adjuvant therapies of choice, other agents to prevent osteoporosis and cardiovascular events may also have to be administered.

Animals↗

Bartonella (Rochalimaea) henselae in southern Africa--evidence for infections in domestic cats and implications for veterinarians.

Substantial evidence has recently accumulated showing domestic cats to be the principal reservoirs of Bartonella henselae, the aetiological agent of human diseases including cat-scratch disease, bacillary angiomatosis, bacillary peliosis and a febrile bacteraemia syndrome. To determine the prevalence of antibodies reactive with Bartonella henselae in cats from southern Africa, indirect fluorescent antibody assays were carried out on feline sera from South Africa and Zimbabwe. Overall, 23% (39/171) of cats had antibody titres > or = 1/64, with cats from Zimbabwe (24%; 28/119) having higher seroprevalences than those from South Africa (21%; 11/52) although this difference was not statistically significant. The implications of these findings for veterinarians in southern Africa are discussed.

Adolescent↗

A method for the production of iron-52 with a very low iron-55 contamination.

The production and radiochemical separation of 52Fe from 4He irradiation of enriched 50Cr target is described. Methods developed for the recovery of the target material (50Cr) are also described. The yield of 52Fe at 38 MeV incident 4He energy is 1667 +/- 133 MBq/C (163 +/- 13 microCi/microAh) at end of bombardment and the contamination of 55Fe is only 0.008%.

Chromium Isotopes↗

Production of gallium-66, a short-lived, positron emitting radionuclide.

The excitation functions for the production of 66Ga and some other radionuclides produced by the 4He-particle bombardment of a natural copper target have been measured up to 31 MeV incident energy. The radiochemical separation of 66Ga from the irradiated copper target as well as from the other radionuclides formed is described. The yield of 66Ga at 18 MeV incident energy is 708 microCi/microAh at end of bombardment and the contamination of 67Ga is 0.25%. The intended use of the 66Ga produced is to label monoclonal antibodies for PET scanning.

Gallium Radioisotopes↗

Production of cobalt-55, a short-lived, positron emitting radiolabel for bleomycin.

The production and radiochemical separation of 55Co from deuteron irradiation of enriched 54Fe target is described. Methods used for the recovery and reuse of the target material (54Fe) are also described. The yield of 55Co at 12 MeV incident deuteron energy is 1.7 mCi per mu Ah at end of bombardment and the contamination with 57Co is 0.016%. The 55Co produced is chelated to bleomycin and used for tumour imaging with a positron emission tomographic camera based on multi-wire proportional chamber detectors.

Bleomycin↗

Treatment of metastatic breast cancer with liver transplantation.

Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant.

Adult↗