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Biomedical subjects

P C Stone

Publications and source records attributed to P C Stone.

At least 19 recordsLinked to original sources
PubMed2006

Predicting prognosis in patients with advanced cancer.

BACKGROUND: Patients with advanced cancer and their carers frequently wish to know how long they can expect to live. Improved prognostication would enable patients and their carers to be better prepared for their impending death, and would allow clinicians to make better informed decisions about place of care. However, clinician estimates of survival are inaccurate and systematically overoptimistic. Recently, attempts have been made to improve upon clinician estimates of survival by devising prognostic scales incorporating clinical information with biochemical and haematological results. DESIGN: A descriptive and critical review of palliative prognostic scales, on the basis of the recommendations of the European Association of Palliative Care prognosis working group (2005) supplemented by an Ovid Medline search 1966-March 2006 using the key words 'prognosis', 'neoplasms', 'palliative care' and 'terminal care'. RESULTS: This paper reviews the advantages and limitations of the palliative prognostic score, the palliative prognostic index, the Chuang prognostic scale, the terminal cancer prognostic score and the poor prognostic indicator. CONCLUSIONS: All the currently available prognostic scales have limitations, but nonetheless offer an improvement on unadjusted clinician estimates of survival. Further research is required to systematically develop a prognostic scale on the basis of all the known prognostic variables in patients with advanced cancer.

Advance Care Planning↗
PubMed2001

Differential effect of cold acclimation on blood composition in rats and hamsters.

Male rats and hamsters were exposed to a progressively lower air temperature and shorter photoperiod to simulate the onset of winter. Normothermic hamsters had a higher haematological oxygen carrying capacity (OCC) and coagulability (shorter prothrombin time and activated partial thromboplastin time) than rats. Cold acclimation significantly increased the OCC of rats, which parallels an increased metabolic rate, while no differences were observed in hamsters. Red cell transit time through filters was faster in the acclimated rats but not in hamsters, reflecting the lower mean cell volume due to a decreased rate of clearance from the circulation. Platelet counts were significantly lower in both cold-acclimated rats and hamsters, and there was a significant leucopenia in rats, which would reduce the degree of microvascular blockade. Whole blood viscosity, plasma viscosity, and serum osmolarity showed little change in either species. However, whole blood viscosity was significantly lower in cold-acclimated hamsters than control hamsters at the lowest shear rate tested (0.95 s(-1)). Interestingly, plasma viscosity and serum osmolarity were significantly lower in hamsters exposed to low temperatures for a shorter period (4 weeks), and may reflect the development of a reduced coagulability. These data suggest that blood composition in hamsters contributes to an innate tolerance of low temperatures, maintaining tissue perfusion under hypothermic conditions and aiding arousal from hibernation.

Acclimatization↗
PubMed1999

Conditions under which immobilized platelets activate as well as capture flowing neutrophils.

Immobilized activated platelets present P-selectin and efficiently capture flowing neutrophils. We investigated how the treatment of the platelets affected whether adherent neutrophils rolled continuously or became immobilized. Washed platelets were maintained in a 'resting' state by Ca++ chelation, prostacyclin and theophylline. When these platelets were adhered to glass that had been coated with aminopropyltriethoxysilane (APES) they retained discoidal morphology. Compared to a confluent surface of spread platelets prepared by allowing heparinized platelet-rich plasma to settle on APES-glass, 'resting' platelets captured far fewer flowing neutrophils, which rolled rapidly. However, if neutrophils were perfused along with thrombin (>/= 0.2 U/ml), then the resting platelets rapidly changed shape, neutrophil binding increased markedly, rolling velocity decreased, and 40-70% of the neutrophils were immobilized via beta2-integrins. Similar effects could be induced using ADP perfused with the neutrophils. Thrombin did not itself activate neutrophils, and stationary adhesion could also be induced if platelets were treated with thrombin before addition of neutrophils. After thrombin treatment of platelets, rolling adhesion was only fully re-established after a prolonged period of washout. Thus, platelets presented a stable surface-bound agent able to activate neutrophils. Blockade of platelet-activating factor receptor, leukotriene B4 receptor, or CXC-chemokine receptor 1 (CXCR1) on neutrophils did not inhibit conversion from rolling to stationary adhesion, but blockade of CXCR2 maintained a higher proportion of rolling adhesion. Thus, platelets attached to damaged vessels may capture flowing neutrophils, but the stability of neutrophil deposition will depend on the scale of the local generation of platelet agonists such as thrombin and ADP.

Blood Platelets↗
PubMed1996

Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells.

Abnormal adhesion of sickle cells to vascular endothelium may be a factor in the initiation of painful vaso-occlusive crisis. The sickle cell population contains an unusually large number of less dense reticulocytes that are known to be more adhesive than mature red cells, but there is contradictory evidence regarding the adhesiveness of dense sickle cells. We used a flow-based assay of adhesion to cultured human umbilical vein endothelial cells to test the properties of density fractions of sickle cells, prepared either by density gradient or by centrifugation of packed cells. We also examined the effects of incubating sickle cells with or without cyclical deoxygenation on their adhesion. After fractionation on a Percoll-isopaque gradient, the less dense 10% (reticulocyte-rich) cells and the most dense 10% cells adhered in greater number than the remainder (by about twofold). However, after centrifugation of packed cells, the less dense 10% were again more adhesive than the "middle" cells, but the most dense were not. Exposing sickle cells to constituents of the gradient had no consistent effect on adhesion, while centrifugal packing induced a degree of hemolysis, and tended to reduce adhesiveness of the dense fraction previously obtained from a gradient. Incubation in air at 37 degrees C for 15 hr reduced the number of reticulocytes and the adhesiveness of less dense sickle cells compared to those held at 4 degrees C. On the other hand, incubation at 37 degrees C for 15 hr with cyclical deoxygenation caused formation of dense cells and increased adhesiveness compared to incubation without cyclical deoxygenation. We conclude that young, less dense sickle cells are unusually adhesive, but that this adhesiveness is reduced during maturation. However, repeated sickling in vivo causes formation of an abnormally dense subpopulation of cells which either redevelop an increased tendency to adhere to endothelial cells or preserve their initial adhesiveness. Both adhesive cell populations may be implicated in promoting vascular obstruction.

Adult↗
PubMed1994

Additive in vitro effects of anti-sickling drugs.

To study the effect of anti-sickling drugs on cellular dehydration induced by entry of Ca, sickle cells were subjected to cyclical oxygenation-deoxygenation for 15 h in Ca-containing buffer. The consequential loss of cation (K) via the Ca-dependent K efflux (Gardos) channel caused cell dehydration and loss of deformability. Inhibition of a specific fraction of Ca entry by verapamil had no rheologically protective effect, whereas inhibition of the Gardos channel by clotrimazole or nitrendipine had a marked protective effect. When Gardos channel inhibition (by either clotrimazole or nitrendipine) was combined with stabilization of the oxy-conformation of sickle haemoglobin (by the substituted benzaldehyde 12C79), an additive protective rheological effect was achieved with 60-78% reduction in clogging rate of 5 microns diameter pores when compared with no drug. Therapeutic use of anti-sickling compounds in combination may achieve increased efficacy with lower toxicity.

Anemia, Sickle Cell↗
PubMed1994

Monitoring the acute phase response to vaso-occlusive crisis in sickle cell disease.

AIMS: To identify suitable acute phase proteins as objective markers of tissue ischaemia during painful vaso-occlusive crises in sickle cell disease. METHODS: The prodromal and established phases of 14 vaso-occlusive crises were studied longitudinally in 10 patients with sickle cell anaemia. Automated solid phase enzyme immunoassays were used to measure the fast responding acute phase proteins C-reactive protein and serum amyloid A protein. Slower responding glycoproteins (fibrinogen, orosomucoid, sialic acid and concanavalin-A binding) were measured in parallel. RESULTS: C-reactive protein and serum amyloid A protein increased early in crisis, sometimes within the early (prodromal) phase. Crises that resolved within 24 hours in hospital showed a minor and transient rise compared with crises that required treatment for four days or more. In eight crises treated by patients at home the acute phase response ranged from minor to a level consistent with extensive tissue ischaemia. CONCLUSIONS: Sensitive enzyme immunoassays for C-reactive protein and serum amyloid A protein are of potential value for monitoring the onset of tissue ischaemia in sickle cell crisis and for confirming subsequent resolution.

Acute-Phase Proteins↗
PubMed1992

Substituted benzaldehydes (12C79 and 589C80) that stabilize oxyhaemoglobin also protect sickle cells against calcium-mediated dehydration.

Reversibly sickled cells from patients with homozygous sickle-cell disease were prepared by Percoll-Isopaque density gradient separation and subjected to 15 h of cyclical deoxygenation-reoxygenation in the presence of Ca. After 15 h the sickle cells became dehydrated, losing volume secondary to K efflux via the Ca-activated (Gardos) channel, and showed impaired filterability through 5 microns diameter pores. The substituted benzaldehydes 12C79 and 589C80, which stabilize the oxy-conformation of sickle haemoglobin, showed an additional protective effect at pharmacological concentration by maintaining the K concentration, mean cell volume, and deformability of sickle cells. Drugs that increase the oxygen affinity of sickle haemoglobin may be more effective than specific inhibitors of Ca entry or K efflux in preserving the cation homeostasis and deformability of sickle cells during sickling in vivo.

Anemia, Sickle Cell↗
PubMed1992

Mode of action and comparative efficacy of pharmacological agents that inhibit calcium-dependent dehydration of sickle cells.

1. Selected Ca-channel antagonists were tested at 20 microM as inhibitors of Ca(2+)-uptake in human sickle red cells. Nitrendipine, fendiline, and bepridil (and its stereoisomers), were found to be as effective as methoxyverapamil (D-600) in inhibiting a fraction (25%) of Ca(2+)-uptake. In contrast cetiedil and Org 30701 were ineffective. 2. The drugs were subsequently tested as inhibitors of Ca(2+)-induced K+ efflux (Gardos) from sickle cells. They all showed inhibitory activity, with the order of efficacy nitrendipine greater than fendiline greater than bepridil greater than cetiedil greater than Org 30701. 3. With a 15 h programme of deoxygenation/reoxygenation cycles in a gas exchanger, it was shown that the inhibitors protected against cellular dehydration and loss of filterability in the order nitrendipine greater than fendiline greater than bepridil greater than cetiedil greater than Org 30701. However, significant stomatocytosis occurred at high concentrations of cetiedil, and bepridil (including its stereoisomers and analogues) impairing cell deformability. 4. It is concluded that Ca-antagonists may partially block both Ca(2+)-uptake and Ca(2+)-induced K+ efflux. The latter pathway is significant in contributing to sickle cell dehydration and nitrendipine is the most effective inhibitor of this route.

Anemia, Sickle Cell↗
PubMed1992

Medicolegal aspects of emergency department radiology.

This article reviews the current legal environment in which radiologists practice medicine and some of the key problems radiologists may experience. Particular attention is given to the need for accurate communication, complete charting, and carefully performed procedures. Information is also provided about the requirements for informed consent. Recommendations are made for dealing with patient grievances and with patients' attorneys after a lawsuit has arisen.

Communication↗
PubMed1991

Rheological action of drugs that prevent erythrocyte dehydration.

The water content of the human erythrocyte is a major determinant of its cytoplasmic viscosity and thus deformability. Loss of cell water may be either primary or secondary to loss of erythrocyte cations (K+). Several existing drugs (cetiedil citrate, pentoxifylline and piracetam) have recently been shown to inhibit K+ loss from erythrocytes and thus have the potential to prevent erythrocyte dehydration. Further studies of cation flux pathways in the erythrocyte membrane are of importance for the development of new drugs that maintain cell hydration.

Azepines↗
PubMed1987

Comparison of serum cardiac specific troponin-I with creatine kinase, creatine kinase-MB isoenzyme, tropomyosin, myoglobin and C-reactive protein release in marathon runners: cardiac or skeletal muscle trauma?

Problems arise in distinguishing skeletal from cardiac muscle trauma on the basis of serum enzyme tests following severe muscle exercise. The contributions of cardiac and skeletal sources have been assessed in eleven marathon runners by measuring pre- and post-race serum levels of cardiac-specific myofibrillar troponin-I together with total creatine kinase, creatine kinase-MB isoenzyme, myoglobin, myofibrillar tropomyosin and C-reactive protein. Total creatine kinase, creatine kinase-MB isoenzyme, tropomyosin and myoglobin were significantly elevated above pre-race levels in all runners between 1 h and 128 h post-race. Neither mean cardiac troponin-I nor C-reactive protein was elevated post-race. Nine out of sixty-three samples fulfilled conventional positive criteria for cardiac muscle damage on the basis of combined creatine kinase and creatine kinase-MB isoenzyme levels. Six runners had one or more positive samples. No samples had levels above twice the upper normal limit for either cardiac troponin-I or C-reactive protein. Correlation analysis of levels in each sample indicated skeletal and not cardiac muscle as the source of raised serum protein.

Athletic Injuries↗
PubMed1987

Oxpentifylline and cetiedil citrate improve deformability of dehydrated sickle cells.

Erythrocytes from 14 patients with homozygous sickle cell anaemia were treated with the calcium ionophore A23187 to induce loss of cellular potassium and water. The dehydrated cells showed a decrease in filterability (loss of deformability) through pores of 5 micron diameter. Oxpentifylline and cetiedil citrate, which preserve erythrocyte cation and water content, had a significant (p less than 0.01) protective effect against loss of deformability at a concentration of 1 mumol/l. Oxpentifylline showed no adverse effect on the rheology, morphology, or haemolysis of sickle cells at concentrations up to 500 mumol/l. Drugs that act on the erythrocyte membrane to maintain cell hydration are of potential rheological benefit in sickle cell anaemia.

Anemia, Sickle Cell↗
PubMed1986

Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus.

Erythrocyte deformability was studied in a total of 83 poorly controlled diabetics (mean blood glucose 12.2 mmol/l) who were divided into three groups, each with matched healthy controls. There was no appreciable difference between diabetics and matched controls regarding the filtration of erythrocytes through 3 micron diameter straight channel pores (25 diabetics) or tortuous channel pores (28 diabetics), or for the measurement of erythrocyte elongation over a range of osmolalities in the Ektacytometer (30 diabetics). When erythrocytes from 17 additional diabetics and 17 healthy controls were incubated for two hours at 37 degrees C in hyperglycaemic (50 mmol glucose/l) buffer, however, there was a considerable reduction in erythrocyte filterability for both diabetics and controls in parallel with an increase in erythrocyte sorbitol concentration. This loss of filterability was prevented by the addition of an aldose reductase inhibitor (Sorbinil). High glucose concentrations (congruent to 50 mmol/l) impair the filterability of erythrocytes through 3 micron pores, and the intracellular accumulation of sorbitol in poorly controlled outpatients is therefore unlikely to have a major adverse effect on erythrocyte rheology in diabetes mellitus.

Adult↗
PubMed1985

Erythrocyte deformability in peripheral occlusive arterial disease.

A rheological study of 32 patients with peripheral occlusive arterial disease (POAD), compared with 32 matched healthy controls, has shown no loss of erythrocyte deformability as measured by filtration methods (using initial flow rate and positive pressure instruments, polycarbonate and silver membranes, and 3 microns and 5 microns diameter pores) or by viscometry (using laser visco-diffractometric and high shear rate viscosity methods). Erythrocyte ATP concentration in POAD was also normal. Patients with POAD showed a small (4 fl) increase in mean erythrocyte volume, associated with a raised serum gamma-glutamyl transpeptidase concentration, which correlated with erythrocyte filtration and viscometric measurements. Previous reports of impaired blood filterability in POAD probably reflect the effects of accompanying leucocytosis, plasma hyperfibrinogenaemia, or an increase in erythrocyte size, but not an intrinsic loss of erythrocyte deformability.

Adenosine Triphosphate↗
PubMed1984

Endotoxaemia as a cause of fever in immunosuppressed patients.

Using a recently developed chromogenic substrate assay sensitive to 10 pg/ml Escherichia coli endotoxin in plasma, systemic endotoxaemia was found in 52% of 21 episodes of fever in patients with a haematological malignancy who were infected. Endotoxaemia was also found in 27% of 22 episodes of fever of unknown origin. In 45 afebrile patients neither neutropenia nor cytotoxic chemotherapy was a cause of endotoxaemia. Passage of endotoxin from portal blood into the systemic circulation can contribute to unexplained fever in immunosuppressed patients.

Chromogenic Compounds↗
PubMed1984

C reactive protein rapid assay techniques for monitoring resolution of infection in immunosuppressed patients.

Three rapid assay techniques (latex agglutination, laser nephelometry, and EMIT enzyme immunoassay) have been evaluated for serial monitoring of the serum C reactive protein (CRP) concentration in immunosuppressed patients with fever. Radial immunodiffusion assay was used as a reference method. Latex agglutination reliably distinguished between normal and raised serum CRP concentrations. Enzyme immunoassay also provided a result within minutes, showed particularly close correlation (r = 0.967) with the reference method, and was free from interference by lipaemic or icteric sera. In 27% of 55 episodes of fever studied serially in immunosuppressed patients, the enzyme immunoassay provided clinically useful information by indicating incomplete resolution of infection despite resolution of fever.

Bacterial Infections↗
PubMed1983

Quantitative cytochemistry of blood neutrophils in myelodysplastic syndromes and chronic granulocytic leukaemia.

Quantitative cytochemistry of components of blood neutrophil azurophilic granules (myeloperoxidase, chloroacetate esterase, beta-glucuronidase, and acid phosphatase) and specific granules (lactoferrin) has been performed by scanning and integrating microdensitometry in 13 patients with a myelodysplastic syndrome and 11 patients with chronic granulocytic leukaemia. Both patient groups showed a reduction of enzyme activity in azurophilic granules, and also of lactoferrin, consistent with abnormal development of neutrophil granules. These cytochemical changes in blood neutrophils are similar to those found in acute myeloid leukaemia, are consistent with a leukaemic maturation defect, and may be of diagnostic value.

Acid Phosphatase↗