Publications by authors named "Cooke T"

Angiotensin II (AT-II) has been used to target regionally-administered cytotoxic microspheres in patients with intrahepatic tumours. The optimisation of vasoconstrictor targeting requires a knowledge of the blood flow changes induced by agents such as AT-II. We therefore assessed duplex/colour Doppler sonography (DCDS) as a means of evaluating the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with intrahepatic tumours.

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Previous studies have shown that the delivery of cytotoxic microspheres to liver tumours may be improved by manipulating the tumour to normal liver blood flow ratio using angiotensin II (AT-II). The optimization of this targeting requires the assessment of the temporal blood flow changes induced by agents such as AT-II. Duplex/colour Doppler sonography (DCDS) was evaluated as a means of studying the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with colorectal liver metastases.

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Image-directed Doppler ultrasonography has been used to measure changes in hepatic arterial and portal venous blood flows in 22 controls and 88 patients with colorectal cancer. Doppler Perfusion Index, (DPI, ratio of hepatic arterial to total liver blood flow) and Doppler Flow Ratio (DFR, ratio of hepatic arterial to portal venous blood flow) of controls and patients with overt liver metastases were clearly separated (p < 0.0001).

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Both high resolution (10 MHz) ultrasound and 201-thallium/99m-technetium subtraction scanning (Tl/Tc) were carried out preoperatively in 25 patients with primary hyperparathyroidism. Operative findings were the standard against which these two imaging methodologies were compared. Tl/Tc scanning showed a sensitivity of 42% and a specificity of 97%.

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The population dynamics of developing somatic embryos of carrot (Daucur carota L.) was investigated in batch and fed-batch cultures using modified Murashige and Skoog medium. These substrate limitations coincided not only with stoppage of biomass increase, but also with the increase in total concentration of embryos as well as the advancement of the embryo into a more mature stage.

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Abnormalities in liver blood flow are known to occur in patients and animals with overt hepatic tumour. This study investigated the changes in liver blood flow associated with the development of overt hepatic tumour in two different models. Hepatic tumour was induced by intraportal inoculation of either 300 LV10 sarcoma cells or 10(5) MC28 sarcoma cells in rats.

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Previous studies using dynamic scintigraphy have shown that the measurement of changes in hepatic perfusion may be exploited to detect liver metastases. Similar hepatic haemodynamic changes also occur in cirrhosis, however, thereby reducing the diagnostic power of the technique. The ability of duplex colour Doppler sonography (DCDS) to differentiate between the changes in liver perfusion in patients with cirrhosis and those with hepatic metastases was assessed.

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The use of lasers has made a significant impact on surgery. Various types of lasers are available for use in orthopedics. A successful laser program identifies perioperative considerations, applications/modalities, and reimbursement issues.

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The expression of the protease cathepsin-D has been evaluated using an immunohistochemical technique with a polyclonal antibody in paraffin-embedded tissue from 359 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and twenty seven patients (35%) have strongly positive, granular staining, 138 (38%) are intermediately stained in the cytoplasm, and in 94 (26%) no staining is observed. There is a strong positive association between expression of cathepsin-D and the presence of tumour in axillary lymph nodes (P < 0.

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A method and apparatus for quantitative measurement of the alignment and motion of the joints of the hand in three dimensions has been developed using stereoradiogrammetric principles. Alignment in planes of flexion-extension and radial-ulnar deviation can be determined to within 2.5 degrees; rotation about the long axis of the metacarpals or phalanges is more difficult to determine, and can be measured to within 7 degrees.

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A possible role for immune complexes in the degradation of cartilage (rheumatoid arthritis and antigen induced arthritis) has been modelled in vitro by studying interactions between cultured bovine chondrocytes and monomeric (M) or heat aggregated (HA) IgG. Concentrations of IgG used were within the range of values reported in the synovial fluids of rheumatoid joints. ELISA and rosetting assays revealed Fc receptor mediated binding of MIgG and HAIgG to chondrocytes that had been cultured, but not to freshly isolated cells.

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Cartilage from patients with rheumatoid arthritis and from animals with antigen-induced arthritis is frequently contaminated with complement-containing immune complexes. A possible role for complement activation in cartilage degradation was modeled in vitro by exposing cultured bovine chondrocytes to homologous serum, and determining cytotoxicity by monitoring the release of intracellular 51Cr. Complement activation was found to be cytotoxic, having maximal effect at 20-30% serum by 18 h.

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2,4-Dichlorophenoxyacetic acid (2,4-D) promotes the accumulation of tryptophan-derived indole-3-acetic acid (IAA) in carrot cell cultures during callus proliferation by a biosynthetic pathway that is apparently not active during somatic embryo formation. The effects of 2,4-D were examined by measuring the isotopic enrichment of IAA due to the incorporation of stable isotope-labeled precursors (deuterium oxide, [(15)N]indole, and (2)H(5)-l-tryptophan). Enrichment of IAA from deuterium oxide is similar in both cultured hypocotyls and cell suspension cultures in the presence and absence of 2,4-D, despite the large differences in absolute IAA concentrations.

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Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (AI) on tumour blood flow in ten patients with colorectal liver metastases.

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DNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model.

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Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients.

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Fifty-five consecutive patients, with colorectal metastases confined to the liver, underwent surgical placement of a hepatic artery catheter. At angiography, abnormal hepatic arterial anatomy was present in 33% of patients. In the majority of patients, the hepatic artery catheter was inserted in the conventional manner.

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Lipoprotein(a) [Lp(a)], which combines structural elements of the lipid and fibrinolytic systems, is a major independent risk factor for the development of coronary heart disease. Eighty-four consecutive patients with peripheral vascular disease (of whom 42 had concomitant ischaemic heart disease) and 43 healthy controls were enrolled in a case-control study. We found that the mean Lp(a) concentration in male patients with peripheral vascular disease (PVD) was almost threefold higher than that of controls, while in female patients the Lp(a) concentration was more than twice that of controls.

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Patients with hepatic metastases derived from colorectal carcinoma have a poor prognosis. Regional chemotherapy, either alone, or combined with agents such as degradable starch microspheres (DSM) that reduce or abolish intrahepatic arterial flow and potentiate the delivery of cytotoxics to hepatic metastases, have not significantly improved survival. We have investigated one positive mechanism, namely the effect of portal venous washout of cytotoxics, for the poor efficacy of drugs administered either alone or in combination with DSM via the hepatic artery in the rat.

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The relationship between hepatic arterial albumin microsphere distribution and hepatic arterial blood flow and the effects of regional angiotensin II were studied in a rat liver metastases model. Hooded-Lister rats were inoculated subcapsularly with 2 x 10(6) HSN sarcoma cells. At 20 days, hepatic arterial blood flow was measured using the reference microsphere technique.

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A phase I study was undertaken in order to establish the maximum tolerated dose of intra-hepatic arterial 5-fluorouracil (5-FU) when given in combination with systemic folinic acid. Patients with colorectal liver metastases (n = 10) received escalating doses of 5-FU as a 24 h infusion with a fixed dose (400 mg m-2) of intravenous folinic acid once per week. Dose limiting toxicity (WHO grade greater than 2) was encountered at 2 g m-2 5-FU.

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