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Biomedical subjects

G Phillips

Publications and source records attributed to G Phillips.

At least 109 records · Page 6Linked to original sources

Behavioural tests of the dopamine depletion hypothesis of neuroleptic-induced response decrement.

This study was carried out to test the hypothesis that neuroleptic-induced within-session response decrements reflect a fatigue process, resulting from dopamine depletion, that is present before the session begins but is masked briefly by activational cues present at the start of the session. Response decrementing effects of pimozide were examined in rats lever pressing on random interval schedules of food reinforcement. An initial experiment was carried out to rule out a pharmacokinetic explanation of the response decrement. In a second experiment, the response decrement was not exacerbated by an immediately preceding period of intense forced motor activity (wheel running). Experiments 3 and 4 tested two further predictions: that the pimozide-induced response decrement should be overcome by removing the animal to its home cage and then replacing it in the apparatus (thereby reinstating the activational cues present at the start of the session); and that response impairments should be present from the outset if the animal is confined in the apparatus prior to the start of the session (thereby allowing activational cues to dissipate). Neither prediction was confirmed. Overall, the results provide no support for the dopamine depletion hypothesis.

Animals↗

Hypothyroidism in adults with sickle cell anemia.

Persons with sickle cell anemia have several indications for transfusion of red blood cells. One of the complications of transfusion of red blood cells is iron overload. Iron overload has been associated with multiple endocrine abnormalities. We report herein three cases of hypothyroidism in adult individuals with sickle cell disease. All three patients were over the age of 45 years at the time of the diagnosis and had received multiple units of transfused red blood cells and had serum ferritin levels of greater than 6,000 ng/mL. All patients were diagnosed during times when they were critically ill. Replacement therapy was instituted in all cases; however, all three patients died shortly after the diagnosis of hypothyroidism was made. Congestive heart failure appeared to be a primary cause of death in all three patients. In the one patient in whom a postmortem examination was done, there was evident extensive fibrosis of the thyroid gland as well as extensive deposition of iron in the cells lining the thyroid follicles. We believe that this represents the first report of clinical hypothyroidism in patients with sickle cell anemia who have received multiple transfusions. Awareness of this condition is especially important given that congestive heart failure is common in sickle cell disease.

Anemia, Sickle Cell↗

Microbial growth and blockage of sub-floor drains in a renal dialysis centre: a problem highlighted.

The accumulation of microorganisms embedded in biofilm within the drainage pipework leading from individual dialysis monitors in a renal dialysis centre, represents a significant threat to the safe operation of the whole centre due to blockage of the pipes and overflow of waste water. Attempts to disperse the growth with chemicals and disinfectants have been unsuccessful. Only mechanical rodding has removed the deposit, and regrowth has occurred. Those planning new dialysis centres should ensure that effluent pipework is readily accessible with multiple rodding eyes and is made of material able to withstand rodding and chemicals.

Bacteria↗

Decreased reactivity to sweetness following chronic exposure to mild unpredictable stress or acute administration of pimozide.

Consumption of a palatable wet mash was examined in rats subjected chronically (4-10 weeks) to unpredictable mild stress. Intake of mash containing 0, 10%, or 20% additional sucrose was normal in stressed animals. In control animals, the addition of 30% or 40% sucrose caused a decrease in the quantity of mash consumed, but increased the rate of eating. Both the increase in eating rate and the decrease in intake, at high sucrose concentration, were markedly attenuated in stressed animals (which therefore had higher intakes of very sweet mash and lower rates of eating, relative to control animals). Like chronic mild stress, the dopamine receptor antagonist pimozide (0.2 mg/kg) also increased the intake of a wet mash with 30% added sucrose, while decreasing the rate of consumption. Stressed animals were relatively insensitive to pimozide, though there were significant additive effects on duration of eating (increased) and on postprandial resting (suppressed). The failure of stressed animals to adapt their intake to increases in sweetness, and the similarities between the effects of chronic mild stress and acute pimozide, are compatible with the hypothesis that animals exposed to chronic mild stress are anhedonic.

Animals↗

Sickle cell disease pain: 2. Predicting health care use and activity level at 9-month follow-up.

This study examined 9-month follow-up data obtained from adults with sickle cell disease (SCD) participating in a longitudinal study of pain-coping strategies. Of 99 subjects completing the baseline assessment of pain-coping strategies, 89 (90%) completed a structured pain interview assessing health care use and activity reduction during painful episodes over the follow-up period. Regression analyses controlling for demographics and disease severity revealed that baseline Negative Thinking and Passive Adherence was associated with greater activity reduction and more frequent health care contacts during the subsequent 9 months. Additional correlational analyses revealed that if levels of Negative Thinking and Passive Adherence increased from baseline to follow-up, this increase was associated with even further reductions in activity level during painful episodes. Changes in disease severity were not associated with any of the follow-up measures. Comparing pain-coping strategies assessed at baseline to pain-coping strategies measured at follow-up revealed that, without intervention, pain-coping strategies were relatively stable over time.

Activities of Daily Living↗

Stress, coping, and psychological adjustment of adults with sickle cell disease.

A transactional model of psychological adjustment to chronic illness was examined with 109 African-American adults with sickle cell disease (SCD). Good psychological adjustment was associated with lower levels of perceived daily stress and stress regarding SCD illness tasks, higher efficacy expectations, less use of palliative coping methods, less use of negative thinking/passive adherence pain-coping strategies, and family functioning characterized by high levels of support and low levels of conflict and control. Overall the underlying stress and coping conceptual model accounted for 44-50% of the variance in psychological adjustment.

Adaptation, Psychological↗

Attributions and relapse in opiate addicts.

This study investigated whether attributions of opiate addicts would predict both their ability to abstain from future use and their reactions to abstinence violations. Measures of generalized beliefs about responsibility for positive and negative outcomes and specific attributions about relapse episodes were elicited from 80 addicts at the time of admission for inpatient detoxification and treatment. Addicts who at admission attributed to themselves greater responsibility for negative outcomes and who attributed relapse episodes to more personally controllable factors were subsequently (at 6-month follow-up) more likely either to be completely abstinent or to contain the effects of temporary lapses into opiate use.

Adaptation, Psychological↗

Urine transparency as an index of absence of infection.

A visual assessment of the clarity of urine was used as an exclusion test to indicate the absence of infection; verified by dipslide culture, it was applied to 363 urine samples collected from patients attending 2 adult nephrology clinics over a period of 6 months. The crimped aluminium bowl used for collection of samples assisted the assessment of clarity. The sensitivity of the method compared with dipslide culture was 73%, with specificity and efficiecy both 58%. The predictive value of a negative test (clarity) was 97% with a false negative rate of 3%, enabling this simple examination to be used as an exclusion test for further testing. In simple terms, a clear urine is unlikely to be infected. It is also an advantage to have an immediate indicator of the absence of infection available at the clinic. Analysis of only those urines assessed as cloudy could result in financial savings and, from the clinics, a 56% reduction in workload.

Adolescent↗

Use of telephone enquiries to a microbiology laboratory as a proxy measure of reporting efficiency.

AIMS: To assess the efficacy of a bacteriology service in respect of the time interval between collection of specimen and receipt of final report using the number and type of incoming telephone enquiries as a proxy measure. METHODS: For three months, all incoming telephone enquiries regarding the results of bacteriology specimens were monitored. Specimen type, date of sampling, the sender's location and the reason for making the telephone enquiry were recorded. RESULTS: The number of telephone enquiries made during the study was 1170, about 5% of the total number of samples received. Most enquiries related to results of urine cultures. These accounted for 33.9% of the calls, but only 5% of the total number of urines cultured. Enquiries relating to blood cultures were the next largest group accounting for 14.9% of calls, but 11% of the blood cultures received resulted in a telephone enquiry. The most frequent reason for making the telephone call was that the sender had not received the final report. CONCLUSIONS: Clinicians may have unrealistic expectations of the time taken to examine a specimen. A requirement for reporting sterile blood cultures after a shorter incubation period was found, and the value to patient management of earlier reporting of negative urine samples was identified.

Bacteriology↗

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↗

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↗

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↗

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↗

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↗

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↗