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P C Stone

Publications and source records attributed to P C Stone.

12 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Serum levels of acute phase and cardiac proteins after myocardial infarction, surgery, and infection.

C-reactive protein and four other acute phase reactant proteins of non-cardiac, origin (orosomucoid, alpha 1- antitrypsin, heptoglobin, and alpha 2- macroglobulin) were studied serially by laser immunonephelometric assay in sera from 17 patients with myocardial infarction. A similar comparison was made in 57 patients undergoing surgery and 72 patients with acute infection. C-reactive protein was consistently the most sensitive acute phase reactant in all three conditions. After myocardial infarction, a raised serum C-reactive protein level was found on admission in four patients before a rise in creatine kinase MB isoenzyme (CK MB). The peak C-reactive protein level was reached on the third post-infarct day and it then declined over seven days with a half-life similar to myocardial tropomyosin. Serial monitoring of serum C-reactive protein, in parallel with cardiac proteins of short half-life (CK MB) and long half-life (tropomyosin), provides maximal information for diagnosis and for detecting post-infarct complications.

Alpha-Globulins

Response of crickets to amount of forage in the diet.

Three replicated tests were to define the conditions needed to use house crickets (Acheta domesticus) to evaluate forages. Crickets were placed on various proportion of forage-to-concentrate mixtures to determine the relative proportions best suited for cricket survival, growth, and maturity. The concentrate portion alone was adequate to support nominal cricket performance. Forages used were timothy, alfalfa, and alfalfatimothy (1:1). Forages replaced from 0 to 100%, in increments of 10% of the concentrate portion. A diet of 40% concentrate and 60% roughage was suitable for evaluating growth and survival effects. The 28-day tests were not long enough to evaluate fully the effects of diet on maturity.

Animal Feed