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Biomedical subjects

G Phillips

Publications and source records attributed to G Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1991

Relationship of clinical severity to packed cell rheology in sickle cell anemia.

There is wide variation in the clinical manifestations of sickle cell disease (SCD) from one affected individual to another. Many investigators have sought to discern parameters that would explain this variability. In the present studies we have attempted to correlate the frequency of painful events and the extent of end organ failure in SCD with rheologic properties of packed suspensions of sickle cells, using a magneto-acoustic ball microrheometer developed in our laboratory. Using this device we have measured the steady-state viscosity, and the viscous and elastic moduli of cell suspensions in 16 individuals with hemoglobin SS disease who were untransfused and in their steady state. The rheologic parameters were then correlated with clinical parameters. The clinical parameters measured were emergency department visits, hospitalizations, hemoglobin, reticulocyte count, age, and end organ failure (nephropathy, avascular necrosis of bone, stroke, retinopathy, resting hypoxemia after acute chest syndrome(s), leg ulcer, and priapism with impotence). The P value for the correlation between the steady state viscosity and end organ failure was .001 with a correlation coefficient (R value) of .73. The P value for the correlation between the viscous modulus of viscosity and end organ failure was .00006 with an R value of .83. The P value for the correlation between the elastic modulus of viscosity and end organ failure was .0006 with an R value of .76. However, there was no significant correlation between any component of packed cell rheology and emergency department visits or hospitalizations for pain.

Adult↗
PubMed1991

Effects of hydroxyurea on hemoglobin F and water content in the red blood cells of dogs and of patients with sickle cell anemia.

A rationale for clinical trials of hydroxyurea (HU) treatment in sickle cell disease is that the agent increases red blood cell (RBC) fetal hemoglobin content. However, an additional effect of HU is to raise the mean corpuscular volume (MCV). To investigate the action of HU in a species that makes no electrophoretically distinguishable fetal hemoglobin, we treated dogs with the drug and compared their response to that of five patients with sickle cell anemia. Both dogs and patients had an increase in MCV, but the effect of HU treatment on the mean corpuscular hemoglobin concentration (MCHC), density, and water content of the RBCs differed in the two species. The dog RBCs became low in MCHC, high in ion and water content, and low in mean density. Thus, HU can raise MCV and lower MCHC without influencing fetal hemoglobin synthesis. A different pattern was seen in the sickle cell patients during HU treatment. Although the MCV of their RBCs increased, there was no change in MCHC, ion content, or mean density. A notable change in the sickle cell patients' blood was that two subpopulations of cells were nearly eliminated during HU treatment; the hypodense reticulocyte fraction and the hyperdense fraction that contains irreversibly sickled cells. These findings lead us to suggest that trials of HU in sickle cell disease must recognize the possibility that any beneficial effect of this agent might be due not only to an increase in hemoglobin F alone, but perhaps also to the associated increase in MCV or the altered RBC density profile.

Administration, Oral↗
PubMed1991

Suppression or facilitation of operant behaviour by raclopride dependent on concentration of sucrose reward.

Rats responded under continuous reinforcement for 1%, 10% or 95% sucrose pellets, under food deprived or ad libitum access conditions. In both cases responding was highest for 10% sucrose reinforcement, and a small proportion of 95% sucrose was not consumed. Ad libitum food access reduced response rates for all sucrose concentrations. Responding for 10% and 95% sucrose pellets followed a parallel time-course; and accumulation of 95% sucrose pellets was immediate and nonprogressive. Extinction following availability of 95% sucrose pellets caused an increase in response rate, but removal of 10% sucrose led only to a decline in responding. Under both food deprived and non-deprived conditions, the dopamine D-2 antagonist raclopride dose-dependently decreased responding for 1% or 10% sucrose, but increased responding for, and consumption of, 95% sucrose reward. After eight sessions of responding under extinction conditions, the presentation of reward-associated cues increased response rate early in the session. Raclopride had no effect during this period, but decreased responding later in the session. We consider the implications of these results for theories of neuroleptic drug action.

Acoustic Stimulation↗
PubMed1991

Reward-dependent suppression or facilitation of consummatory behaviour by raclopride.

Rats were presented for 1 h with 0.7%, 7% or 34% sucrose solutions, either separately with water as an alternative (two-bottle test), or with all three concentrations concurrently available (three-bottle test). In trained animals, 7% sucrose produced the highest intakes in the two-bottle test, but 34% sucrose was preferred in the three-bottle test. In both tests the dopamine D-2 antagonist raclopride (100-400 micrograms/kg) reduced intake of 0.7% sucrose solution, but increased intake of 34% sucrose; both effects were apparent during the first 5 min of testing. In the two-bottle test, intake of the intermediate 7% concentration showed both effects: an immediate decrease and a later increase. In the three-bottle test, sucrose-naive animals showed a gradual onset of preference for 34% sucrose, and enhancements of intake by raclopride were not at first immediate; immediate enhancements required three sessions of exposure. Raclopride did not alter the consumption of a 0.001% solution of quinine. We consider the implications of these results for theories of neuroleptic drug action.

Animals↗
PubMed1991

Time-, schedule-, and reinforcer-dependent effects of pimozide and amphetamine.

Rats performed on two multiple random-interval schedules, in which sequences of ascending or descending reinforcement densities were balanced between the schedules and between the two halves of the session. Using a standard reinforcer (10% sucrose pellets), pimozide decreased response rates, while amphetamine increased responding. The effects of both drugs were schedule dependent: larger changes were evident in low response rate, reinforcement-lean components than in high response rate, reinforcement-rich components. Both effects were also time dependent, increasing over the course of the session; this casts serious doubt on the applicability of Herrnstein's matching law for studying agents acting on brain dopamine. Increasing the period of food deprivation increased response rates, while withdrawing food deprivation decreased responding. These effects were also schedule dependent, but were time dependent. Substituting 95% sucrose pellets for standard 10% sucrose pellets caused an immediate and sustained decrease in responding, and up to 10% of earned reinforcement was not consumed. Pimozide increased response rates within reinforcement-lean components and reinstated the complete consumption of earned reward typical of standard reinforcement. These apparently paradoxical effects may be consistent with a decrease in the rewarding properties of sucrose pellets. Despite low response rates, amphetamine did not affect responding maintained by 95% sucrose pellets but did further reduce the consumption of earned reward. These results call into question the generality of the rate-dependency principle in the action of psychomotor stimulants.

Amphetamine↗
PubMed1991

Sweetness-dependent facilitation of sucrose drinking by raclopride is unrelated to calorie content.

Previous studies have reported that dopamine receptor antagonists increase the intake of solid or liquid diets containing high concentrations of sucrose. In Experiment 1, different groups of rats were trained in two-bottle tests (sweet solution vs. water), using three concentrations of either sucrose (0.7, 7 or 34%) or saccharin (0.02, 0.2 or 0.8%). Both sweeteners showed an inverted-U-shaped concentration-intake function. Raclopride increased intake of 34% sucrose, but not of 0.8% saccharin. In Experiment 2, raclopride had similar effects in three-bottle tests (all 3 concentrations available concurrently). However, whereas 34% was the most preferred sucrose solution, 0.2% saccharin was preferred to 0.8%. Thus, 0.8% saccharin differs from 34% sucrose in two ways, being not only noncaloric, but also aversive. In Experiment 3, 34% sucrose was rendered aversive by the addition of 0.08% quinine. Intake of this cocktail was not increased by raclopride. These results suggest that the difference between sucrose and saccharin in the effects of raclopride is related to the aversive properties of a concentrated solution of saccharin, rather than to its lack of calories.

Animals↗
PubMed1991

Corynebacterium minutissimum infection.

Two cases of infection due to Corynebacterium minutissimum are described. On the basis of biochemical tests the organisms were thought at first to be Corynebacterium jeikeium. Methods of distinguishing between these species and the role of C. minutissimum in the pathogenesis of erythrasma and other skin infections are discussed.

Adult↗
PubMed1991

The effect of whole body disinfection on intraoperative wound contamination.

As part of a large whole body disinfection (WBD) trial two small sub-groups of patients who showered preoperatively with either a 4% chlorhexidine (CHX: N = 29) or placebo (N =27) detergent were studied to assess intraoperative wound contamination. The groups were well matched for age, sex and length of surgery. A membrane filter contact technique was used for bacterial recovery from the wounds after the initial skin incision and before wound closure. The membrane filters were incubated aerobically on blood agar plates with a CHX neutralizer for 48 h at 37 degrees C and colonies were counted. The results show a significant difference, between the bacterial counts at the start and end of surgery in the CHX and placebo groups. There was no difference in bacterial counts at the start of surgery between the CHX and placebo groups. There was a significant difference in the bacterial counts at the end of surgery between the CHX and placebo groups. These results indicate that preoperative WBD with CHX reduces intraoperative wound contamination but the effect of this on postoperative wound sepsis rates awaits the results of a large WBD trial.

Adult↗
PubMed1991

Effects of whole body disinfection on skin flora in patients undergoing elective surgery.

Bacterial skin flora were studied in two groups of patients having three showers with either a 4% chlorhexidine detergent solution (Group A, N = 57) or a placebo detergent (Group B, N = 58). Previous reports on the efficacy of chlorhexidine in decreasing bacterial counts on the skin were confirmed and the time taken to recolonization (median 5 days; range 1-10 days) was in broad agreement with previous reports. However, concern regarding the colonization of the skin of the patients in the chlorhexidine group by potential pathogens during the recolonization period appears unfounded as there was no significant difference in the incidence of non-resident skin flora between the chlorhexidine (17/57; 30%) and the placebo (14/58; 24%) groups. These non-residents are generally lost from the skin before discharge in the chlorhexidine group but nine patients in the placebo group had abnormal skin flora at discharge from hospital. All those patients tested after discharge had lost the non-resident flora within 2 weeks of discharge. The results of this study indicate that recolonization of the skin after whole body disinfection does not present a clinical problem.

Adolescent↗
PubMed1990

Regulation of tissue plasminogen activator in sickle cell anemia.

Evidence of activation of the clotting system in individuals with sickle cell anemia (SCA) has been observed by several investigators. It has been suggested that the clotting and fibrinolytic systems may play a role in the pathophysiology of vaso-occlusion in SCA. We reported previously evidence of abnormal fibrinolytic activity as reflected in decreased releasable tissue plasminogen activator (t-PA) using a functional assay. We have examined the mechanism of the decreased functional releasable t-PA in individuals with SCA. We studied 12 patients with respect to releasable t-PA, fast acting inhibitor to t-PA (or PAI-1), and immunoreactive or antigenic t-PA. These SCA individuals were at their baseline states and not taking medications known to interfere with the fibrinolytic or clotting systems. We found that the mean releasable t-PA for the SCA individuals was 0.01 IU/ml of plasma with a standard error of mean (SEM) of 0.01. The mean releasable t-PA of 118 healthy normal controls was 0.70 IU/ml with SEM 0.10 (P less than .001). The mean level of fast-acting inhibitor to t-PA in unoccluded circulation of the SCA patients' plasma was 16.5 IU/ml with SEM of 3.54. The mean plasma levels of fast-acting inhibitor to t-PA in 56 healthy controls was 2.56 IU/ml with SEM of 0.29 (P less than .0001). The SCA patients had a mean baseline t-PA antigen level of 5.98 ng/ml with SEM of 1.72. The mean level of t-PA antigen of 78 healthy controls using the same technique was 4.3 ng/ml with SEM of 2.7 (not significant). The mean baseline functional t-PA for SCA individuals was 0.15 IU/ml with SEM 0.01 and the mean baseline functional t-PA for 118 controls was 0.17 IU/ml with SEM 0.10. These data suggest that the mechanism of decreased releasable t-PA in sickle cell anemia is related to an elevation of fast-acting inhibitor to t-PA and that antigenically t-PA is present in normal quantities in the baseline plasma in this population.

Adult↗
PubMed1990

A matching law analysis of the effects of dopamine receptor antagonists.

Herrnstein's matching equation was used to analyze drug effects on performance in random interval reinforcement schedules. Pimozide caused effects compatible with both motor and motivational impairments, in a 5-component multiple schedule, a 3-schedule 3-day cycle (ALT-3), and a 2-schedule 2-day cycle (ALT-2). However, at low doses, both sulpiride and SCH-23390, tested in the ALT-3 and ALT-2 procedures, caused effects compatible with selective motivational impairments. In experiments using the non-multiple schedules, motivational effects increased during the course of the experimental session, under all three drugs. The interpretation of "motor" and "motivational" deficits in the ALT-2 procedure was validated by experiments in which the response-force and deprivation level were systematically varied. The results support the view that dopamine may be involved in the maintenance of rewarded behaviour, but not differentially implicate the D1 or the D2 receptor subtype.

Animals↗
PubMed1990

Behavioural analysis of the anorectic effects of fluoxetine and fenfluramine.

Two sets of experiments were carried out to compare the effects of fenfluramine and fluoxetine on consummatory and operant behaviour. In food-deprived rats allowed access to a 35% sucrose solution, an initial period of sucrose consumption was followed by a short period of grooming and exploratory behaviour, later superceded by resting. This "behavioural satiety sequence" was advanced by fluoxetine, but disrupted by dl-fenfluramine, which suppressed post-prandial resting, even at sub-anorectic doses. Fluoxetine also elicited resting behaviour following water drinking. However, this did not appear to be a non-specific sedative effect, since fluoxetine increased post-prandial grooming. In rats performing on random interval schedules of food reinforcement, fluoxetine caused proportionally greater decreases in responding on a reinforcement-lean schedule (RI-300s), as compared to a reinforcement-rich schedule (RI-7.5s); this effect is similar to that of a reduction in level of food deprivation. By contrast, fenfluramine reduced responding equally on both schedules. In both paradigms, the effects of fluoxetine were compatible with an increase in postprandial satiety, but the effects of fenfluramine were not.

Animals↗
PubMed1990

Pimozide does not impair sweetness discrimination.

In an initial experiment pimozide decreased preference for a weak sucrose solution but increased preference for a strong solution on the descending limb of the concentration-intake function. As these effects resemble those of dilution, we therefore investigated whether pimozide decreases the perceived intensity of sweet stimuli. Rats were trained to perform a conditional discrimination in a T-maze. A correct response was rewarded by access to a 10% sucrose solution; an incorrect response was punished by confinement in the non-rewarded arm. In the first part of this experiment the discriminative stimulus, located at the choice point of the T-maze, was either water or sucrose, initially a 10% solution, but reduced gradually to 0.0003%. In the second part of the experiment, the discriminative stimulus was either 1% sucrose or a weaker solution, which was initially 0.0001% then raised gradually to 0.5%. Performance fell below 75% accuracy at 0 versus 0.0012% and at 1% versus 0.1%. Pimozide (0.5 mg/kg) administered at these (and other) levels of difficulty decreased running speed but had no effect on discrimination accuracy. As pimozide did not affect either the threshold for sweetness perception or the discrimination of a just noticeable difference, the decreased responsiveness of neuroleptic-treated rats to sweet rewards cannot be explained by a change in the perception of sweetness.

Animals↗
PubMed1990

Clinical study of herpes simplex virus infection in leukemia.

Twenty-nine patients with leukemia were observed for the development of and recovery from oral herpes simplex virus (HSV) lesions. In patients with seropositive test results, lymphocyte and monocyte counts may provide a guide to predict the onset of HSV infections and to indicate when to institute acyclovir prophylaxis. When HSV developed, acyclovir was effective in preventing progression of the lesions, which did not resolve until white cell counts had recovered.

Acyclovir↗