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Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.

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PURPOSE: Orthotopic liver transplantation is typically associated with large volume blood loss. Technological and pharmacological advances permit liver transplantation in patients who formerly were not candidates for this surgery because of strict limitations on blood product administration. We describe a liver transplant in a Jehovah's Witness with ankylosing spondylitis. CLINICAL FEATURE: A 49-yr-old Jehovah's Witness with ankylosing spondylitis and end stage liver disease secondary to sclerosing cholangitis underwent orthotopic liver transplantation. Recombinant human erythropoietin (4,000 IU sc every two days for four weeks, then 4,000 IU sc every week) established a normal hemoglobin concentration preoperatively (> 140 g x L(-1) compared with 120 g x L(-1) baseline). Intraoperatively, strategies for reducing risk of blood product transfusion included avoidance of hypothermia (T>35 degrees C), minimal blood sampling (four 1 ml samples), normovolemic hemodilution (two units), administration of Aprotinin (2 million units bolus dose followed by infusion of 500,000 u x hr(-1)), and return of blood (1,500 ml) scavenged from the operative field. Estimated blood loss was 2,200 mi. The preoperative and postoperative hemoglobin concentration was 147 g x L(-1) (hematocrit 0.45) and 123 g x L(-1) (hematocrit 0.37), respectively. No blood products were required and he was discharged three weeks postoperatively without complication. CONCLUSION: Technological and pharmacological advances allow patients to undergo surgery traditionally associated with large volume blood loss with reduced risk of blood product administration.

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For those giving and receiving health care there will always be problems and queries which occur outside of normal office hours. Palliative care is no exception. It was found that Queenscourt Hospice in Southport was being used as an accessible point of contact for specialist palliative care advice by patients, relatives and health professionals. In response, an audit was undertaken to monitor the frequency and substance of the many drop-in visits and telephone calls to the hospice. The results showed that almost half of the calls/visits received are outside office hours. This article describes the nature of the calls and the advice offered by the staff taking the call. As the majority of the 'out-of-hours' calls/visits were taken by nursing staff, it was necessary for them to draw on their specialist palliative care knowledge and communication skills to make an assessment of how best to deal with each situation. As a result of the audit, several organizational and educational initiatives have been developed to further improve the service offered.

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The effects of 3C intermediates of the photosynthetic carbon reduction (PCR) cycle (glyceraldehyde 3 phosphate [G3P], dihydroxyacetone phosphate and 3 phosphoglyceric acid) on the activity of phosphoenol pyruvate (PEP) carboxylase from Pennisetum purpureum (a C4 plant) have been investigated. Addition of these compounds, at concentrations greater than about 3 mM, to standard assay mixtures (5 mM concentrations of PEP, HCO3 (-) and Mg(2+)) reduced the observed activity. The extent of inhibition was greater at lower (<5 mM) concentration of Mg(2+). G3P was the most potent inhibitor. During studies of saturation kinetics with PEP as variable substrate it was found that addition of these 3C compounds (2mM) reduced the sigmoid nature of Michaelis-Menten plots and reduced the value of n obtained from Hill plots from about 3 to near one. The results are disussed in terms of the possible regulation of C4 photosynthesis by intermediates of the PCR cycle which are easily leaked from chloroplasts.

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The effects of ATP, ADP and AMP on the activity of PEP carboxylase from Pennisetum purpureum (a C4 plant) have been investigated. AMP caused slight changes in activity. Both ATP and ADP were inhibitory. The extent of inhibition was related to the concentration of Mg(2+). Kinetics of inhibition (with PEP as variable substrate) were investigated at limiting concentrations of Mg(2+) (2 mM); with excess Mg(2+) (5 mM); or with the concentration of Mg(2+) buffered at about 8 mM. At low Mg(2+) parabolic competitive-kinetics were observed. With higher Mg(2+) concentration linear competitive kinetics of inhibition were observed with a K i (slope) of 1.25 mM ATP. This was increased to 2.03 mM on addition of the allosteric activator glucose-6-P (5 mM). With Mg(2+) buffered ATP was an activator at low concentrations of PEP.Response to enegery charge was investigated using either calculated concentrations of all adenylates or mixtures of AMP and ATP pre-incubated with adenylate kinase. Inhibition at high charge could be reduced by increasing the concentration of Mg(2+) or by addition of the activator glucose-6-P. With enzyme-generated charge series and Mg(2+) buffered at 8 mM an increase in activity was observed at high charge values.These results are discussed in terms of a possible regulatory role of adenylates in the C4 dicarboxylic acid pathway of photosynthesis.

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Phosphoenol pyruvate (PEP) carboxylase has been partially purified from leaves of the C-4 tropical grass Pennisetum purpureum and shown to have allosteric properties. When initial velocities of incorporation of (14)C from NaH(14)CO3 into oxaloacetate were determined as a function of concentration of either HCO3-or Mg(2+) typical Michaelis-Menten kinetics were observed. Both Lineweaver-Burk and Hill plots were linear with values of n (interaction coefficients) of about one. Sigmoid Michaelis-Menten plots were obtained with PEP as the variable substrate. Following (NH4)2SO4 fractionation and DEAE-cellulose chromatography Lineweaver-Burk plots were concave upwards and Hill plots gave n values of two. With enzyme purified further by Sephadex G-200 chromatography Lineweaver-Burk plots were concave downwards and Hill plots gave values of n of 0.5 at low concentrations of PEP increasing to about 4 at high concentrations of PEP. Enzyme activity was modified by inclusion of glucose-6-phosphate (G6P) in the assay mixtures. When the eoncentration of G6P exceeded that of PEP, the initial velocity tended towards zero. When the concentration of G6P equalled that of PEP activity was increased. When the concentration of PEP exceeded that of G6P, the velocity approached that recorded in control samples at saturating concentrations of PEP. The rate of reaction was also increased on addition of NADH, and decreased by oxaloacetate and malate.

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The enzymes NAD-specific malate dehydrogenase (E.C.1.1.1.37) and malic enzyme (E.C. 1.1.1.40) have been partially purified from leaves of P. purpureum and their kinetic properties examined. With malate dehydrogenase, assayed in the direction of malate synthesis, Lineweaver-Burk plots with either oxaloacetate or NADH as variable substrate were parallel to one another, indicating an ordered reaction mechanism of the ping-pong type. Studies of end-product inhibition suggested that the mechanism was iso-ping-pong-bi-bi. Michaelis constants were about 5×10(-5) M for NADH and 3×10(-4) M for oxaloacetate. With the malic enzyme Michaelis constants were about 2×10(-6) M for NADP(+), 4×10(-4) M for malate and 8×10(-6) M for Mn(2+). Results are discussed in terms of the roles of these enzymes in the metabolism of carbon through the C-4 pathway of photosynthesis.

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The anatomical structure of leaf tissue of P. purpureum, and the short term labelling pattern following exposure to (14)CO2 in the lighht, have been investigated. Both the arrangement of photosynthetic tissue in two layers around the vascular tissue, and the early labelling of malate and aspartate, characteristic of C-4 plants were observed. The structure of the epidermis and the arrangement of stomata is such that CO2 must pass through non-chloroplast-containing tissue before reaching the chloroplasts. At 0.05% CO2 in air the rate of photosynthetic CO2 assimilation was about 70 µmoles/mg chl·h. This increased to over 700 µmoles/mg chl·h at saturating concentrations of CO2. At 0.05% CO2 negative slopes were obtained from percentage plots for malate, which was the major product. As the CO2 concentration was increased, sugar phosphates became the major product. At saturating concentrations of CO2, both malate and aspartate had positive initial slopes and a negative slope was observed for phosphoglyceric acid. These results are discussed in relation to the contribution of C-4 metabolism to photosynthesis in P. purpureum.

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The progressive release of protein, chlorophyll, phenol oxidase activity and phenolic compounds during the mechanical disruption of sugar cane leaves has been correlated with the release of carboxylating enzymes. Enzymes of the photosynthetic carbon reduction cycle were released in parallel with chlorophyll, the bulk of which was recovered in grana-containing chloroplasts. PEP carboxylase activity followed the release of total protein. Increased activities of the carboxylating enzymes were obtained in the presence of thioglycollate. There is evidence that PEP carboxylase resides in the cytoplasm rather than in either type of chloroplast. These results are discussed in relation to the possible localisation of carboxylation reactions in the sugar cane leaf.

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Sugar cane chloroplasts isolated in simple media possessed little photochemical activity, but showed rapid O2 uptake, independent of light. A similar rapid consumption of O2 was observed with brei prepared from cane leaves. This was not observed in brei of spinach leaves. Authentic polyphenols and cane leaf extracts stimulated the consumption of O2 by cane preparations and inhibited photosynthesis in chloroplasts isolated from spinach. Chlorogenic acid and caffeic acid were the major o-diphenols in extracts of cane leaves. These compounds inhibited reactions associated with CO2 fixation by the photosynthetic carbon reduction cycle. Assimilation of CO2 due to phosphoenol pyruvate carboxylase activity was less sensitive to inhibition by o-diphenols. Mechanisms are discussed whereby o-diphenols may inhibit cane chloroplasts during their isolation.

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A number of additives have been tested for their effects on o-diphenol: O2 oxidoreductase activity of cane leaves. The most inhibitory compounds were thioglycollate, ß-mercaptoethanol, polyethylene glycol and bovine serum albumin. Sulphydryl (SH) compounds did not affect rates of photosynthetic CO2 assimilation when used at concentrations below 10(-2) M. However, in the presence of Mn(++) ions they contributed to an O2 consumption which masked photosynthetic O2 evolution. Addition of SH compounds or of polymers to the grinding media increased rates of enzymic CO2 assimilation in crude enzyme preparations from cane leaves, but did not affect rates of CO2 assimilation in similar spinach preparations. Strong reducing agents, copper chelators, low O2 tension and high pH were effective in reducing phenoloxidase activity, but presented problems in the isolation and assay of chloroplasts. The results are discussed in relation to (a) design of suitable media for preparation of active cane chloroplasts and (b) comparative studies of enzyme levels in plants of various genera.

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A simplified procedure (involving disruption in sorbitol-pyrophosphate mixtures) permits the separation of spinach chloroplasts which retain the ability to catalyze the photosynthetic assimilation of carbon dioxide and its associated oxygen evolution.

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Photosynthetic carbon assimilation by isolated chloroplasts and its associated oxygen evolution were measured simultaneously in a single simplified reaction mixture. Each showed an initial lag prior to the attainment of the maximal rate and the photosynthetic quotient was unity during the period of illumination. Following illumination an oxygen uptake was observed in the dark which was not accompanied by any net release of newly fixed carbon dioxide.

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1. The orthophosphate inhibition of photosynthesis by isolated spinach chloroplasts can be reversed by 3-phosphoglycerate, dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate. 2. Metabolically related compounds such as ribulose 1,5-diphosphate, glucose 6-phosphate, 6-phosphogluconate and phosphoenolpyruvate are ineffective. 3. The kinetics of reversal are characteristic of the intermediate used, but, in each instance, the onset of oxygen evolution is accompanied by a carbon dioxide fixation and except with 3-phosphoglycerate the stoicheiometry is close to unity. 4. The nature of orthophosphate inhibition and its reversal is discussed in relation to metabolic control of photosynthesis.

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