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Biomedical subjects

G A Young

Publications and source records attributed to G A Young.

At least 19 recordsLinked to original sources

Cholecystokinin octapeptide alters morphine-induced effects on EEG power spectra both quantitatively and qualitatively.

In the present study, EEG analysis was used to determine if cholecystokinin octapeptide (CCK-8) has an effect on the EEG spectral profile associated with morphine-induced bursting. Adult female Sprague-Dawley rats were implanted with cortical electrodes and indwelling i.c.v. and i.v. cannulas. On the day of the experiment, each rat received an i.c.v. injection of either H2O or one of four doses of CCK-8: 8.0, 16.0, 32.0 or 64.0 ng. Ten minutes after receiving the i.c.v. injection, each rat received a 10.0 mg/kg dose of morphine by i.v. injection. Neither the i.c.v. injections of H2O nor CCK-8 produced any EEG bursting or behavioral stupor. However, the i.v. injection of morphine produced high-voltage, slow-wave EEG bursts in all rats. Analysis of EEG recorded during bursting showed that both the 32.0 and 64.0 ng doses of CCK-8 increased absolute power associated with morphine-induced bursting, and comparison of the distribution of power across the range of frequency bands between the control (H2O) and the 32.0 ng dose of CCK-8 revealed that CCK-8 caused a significant change in the pattern of distribution of power. Furthermore, significant dose-related differences were found in the global (1-50 Hz) parameters absolute power, mean frequency, mobility, complexity and edge frequency. Significant differences among the five groups were not found in the parameter of peak frequency, or in either latency to slow-wave sleep or duration of morphine-induced bursting. These results demonstrate that CCK-8 caused both quantitative and qualitative changes in the EEG spectral profile associated with morphine-induced bursting.

Animals

Naltrindole retards tolerance development to morphine-induced effects on EEG and EEG power spectra.

In the present study, EEG and EEG power spectra were used to assess the effects of naltrindole, a selective delta opioid antagonist, on the development of tolerance to morphine. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling i.c.v. and i.v. cannulas. Twice daily for 7 days, rats were pretreated with either i.c.v. naltrindole (20 nmol) or i.c.v. water, 20 min before i.v. morphine (10 mg/kg) injections. The treatments produced EEG slow-wave bursts and associated behavioral stupor. The amount and duration of these effects decreased less rapidly over the 7 days in the naltrindole-pretreated rats than in the water-pretreated rats. I.c.v. naltrindole pretreatment also prevented significant decreases in latency to onset of slow-wave sleep that were seen in the i.c.v. water-pretreated group. EEG data were further analyzed on a Pathfinder II computer. The development of tolerance was reflected by decreases in the total absolute EEG spectral power (1-50 Hz) over the 7-day period. Rats that were pretreated with i.c.v. naltrindole (20 nmol) did not display a significant decrease in total absolute EEG spectral power by the 7th day, as did the i.c.v. water-pretreated group. Furthermore, significant differences were seen for complexity, mobility, and edge frequency between the two pretreatment groups. A delayed qualitative change in the EEG power spectra was also observed in rats pretreated with i.c.v. naltrindole. On day 1, EEG slow-wave bursts were associated with increases in EEG spectral power over the 1-10 Hz range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of chronic morphine administration and naloxone on EEG, EEG power spectra, and associated behavior in two inbred rat strains.

Utilizing behavioral and electroencephalographic (EEG) assessments, two inbred rat strains, Lewis (LEW) and Fischer 344 (F344), were exposed to morphine (IV) over a period of 7 days to discern differences in tolerance development. Following morphine injection, the LEW group demonstrated a greater mean total amount, as well as a greater rate of reduction, of stuporous behavior across the 7 days tested. Differences in patterns of latency to onset of slow-wave sleep between the two strains were also exposed. EEG analysis of spectral parameters utilizing an analysis of variance with repeated measures revealed that peak frequency, mean frequency, and edge frequency differed as a function of inbred rat strain. All spectral parameters differed as a function of duration of morphine injection; linear trends were indicated for both strains. Naloxone was administered (IV) following the 7 days of morphine to delineate dependence differences. LEW animals reflected a greater amount of behavioral responses, for example, wet-dog shakes, diarrhea, body stretch, and sluggish behavior. However, F344 rats demonstrated a greater alteration in two spectral parameters assessed: peak frequency and total power. Genetic variability appears to play a major role in both morphine tolerance and dependence as indicated by differences in EEG and behavioral responses.

Animals

Relationship between regulation of morphine-induced EEG effects and changes in naloxone sensitivity.

The present data indicate that pretreatment with i.c.v. injection of dynorphin, morphine and dynorphin/morphine resulted in quantitative and qualitative changes in EEG power spectra in rats given i.c.v. morphine 24 h later. Correlated changes in sensitivity to antagonism of these EEG effects by naloxone were also found. Rats were implanted with cortical EEG electrodes and i.c.v. and i.v. cannulas. I.c.v. injections of morphine (20 micrograms/rat) produced high-voltage, slow-wave EEG bursts (1-10 Hz) associated with behavioral stupor which lasted about 2 h. Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin (20 micrograms/rat), morphine (20 micrograms/rat) or dynorphin/morphine 24 h earlier, produced quantitative increases in absolute EEG spectral power. Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin/morphine 24 h earlier, also produced qualitatively different EEG power spectra with a predominant peak in the 4-6 Hz band, similar to the EEG power spectra seen after acute administration of kappa opioids. After 20 min of morphine-induced high voltage EEG bursts, i.v. naloxone was given in sequential doses (0.0025, 0.0125, 0.025, 0.050 mg/kg) every 3 min until the EEG bursts were suppressed for 20 min. Relatively low doses of naloxone suppressed morphine-induced EEG bursts in rats that received i.c.v. H2O/H2O pretreatment. Slightly higher, but significant, doses of naloxone suppressed morphine-induced EEG bursts in rats that received i.c.v. H2O/morphine or dynorphin/H2O pretreatment. Moreover, a 10-fold increase in naloxone dose was needed to suppress EEG bursts in rats that received dynorphin/morphine pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Long-term effects of biofeedback-induced facial relaxation on measures of asthma severity in children.

We studied the effects of electromyographic biofeedback on measures of asthma severity in children. Fifteen children received biofeedback training to reduce facial tension, and 14 children, who served as controls, received biofeedback training to maintain facial tension at a stable level. Assignment to experimental condition was random. As a result of training, electromyographic levels decreased in children trained in facial relaxation and remained fairly constant in children trained in facial tension stability. Biofeedback training was augmented for children in both groups by having them practice their facial exercises at home. Each child's condition was followed for a five-month period subsequent to biofeedback training. Throughout the experiment, the following measures of asthma severity were monitored: lung function, self-rated asthma severity, medication usage, and frequency of asthma attacks. In addition, standardized measures of attitudes toward asthma, self-concept, and chronic anxiety were recorded at regular intervals. As compared to the facial stability subjects, the facial relaxation subjects exhibited higher pulmonary scores, more positive attitudes toward asthma, and lower chronic anxiety during the follow-up period. Subjects in the two groups, however, did not differ on self-rated asthma severity, medication usage, frequency of asthma attacks, or self-concept. Based on the improvements we observed in pulmonary, attitude, and anxiety measures, we concluded that biofeedback training for facial relaxation contributes to the self-control of asthma and would be a valuable addition to asthma self-management programs.

Adolescent

Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study.

We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition.

Adolescent

An unusual cutaneous lymphoma with B and T cell characteristics showing gallium-67 positive benign thymic hyperplasia following intensive chemotherapy.

This case illustrates two interesting features. Firstly it describes an unusual cutaneous lymphoma in an adolescent girl. This lymphoma showed features of B and T cell lineages with rearrangements of both immunoglobulin heavy chain and T cell beta chain genes. Secondly it describes the development of gallium-67 citrate (67Ga) scan positive benign thymic hyperplasia, 15 months after diagnosis and three months after cessation of intensive chemotherapy.

Adolescent

Exercise-induced CD8 lymphocytosis: a phenomenon associated with large granular lymphocyte leukaemia.

This report describes a patient with a large granular lymphocyte leukaemia (CD8 + lymphoproliferative disease) and severe neutropenia (less than 0.5 x 10(9)/l) in whom exercise resulted in a marked lymphocytosis, a phenomenon which has not previously been recorded. The lymphocyte count at rest was within normal limits (2.2 x 10(9)/l), then fell to the resting level within 15 min of cessation of exercise. The peripheral blood mononuclear cells showed the morphology of large granular lymphocytes (LGL) by light and electron microscopy both at rest (30%) and to a much greater extent during exercise (70%). Immunophenotyping of these lymphocytes during exercise demonstrated that the predominant cell was CD3+, CD8+, CD57+ (Leu7)/CD4-, CD16-, CD25-. In the resting state, despite a total lymphocyte count within the normal range, surface marker studies indicated an excess of cells with the CD8+/CD57 + T cell phenotype (26%; cf. normal range less than or equal to 10%). Functional assays revealed a minimal increase in natural killer (NK) activity during exercise. T cell receptor beta chain gene rearrangement was demonstrable in the peripheral blood at rest and during exercise. Although severe neutropenia was present, the growth of normal colony forming units, granulocyte-macrophage (CFU-GM) was not inhibited by patient lymphocytes and no anti-neutrophil antibodies were demonstrated. Finally, hyposplenism has developed and the relationship of this to the LGL leukaemia is discussed. In summary, the findings demonstrated large granular lymphocyte leukaemia as the primary disorder for which the primary manifestation, apart from the neutropenia, was a marked exercise-induced lymphocytosis.

Antigens, Differentiation, T-Lymphocyte

Effect of intrarenal renin inhibition on renal hemodynamics and excretory function.

This study was designed to investigate in sodium-depleted monkeys the renal hemodynamic and excretory effects resulting from blockade of the renin-angiotensin system induced by intrarenal infusion of the primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317 (n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4 ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4 ml/min, with no significant changes in mean arterial pressure (MAP) or plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a recovery period, the intrarenal infusion dose of A-65317 was increased to 0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/- 3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4% inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte excretion remained at control levels. Intrarenal infusion of vehicle (n = 6) had no significant effect on any of the variables studied. In a separate group of monkeys, intravenous (iv) infusion of A-65317 at 0.01 microgram.kg-1.min-1 (n = 5) did not result in significant changes from control.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Plasma and dialysate immunoglobulin G in continuous ambulatory peritoneal dialysis patients: a multicenter study.

Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.

Ascitic Fluid

Amino-acid-based continuous ambulatory peritoneal dialysis (CAPD) fluid over twelve weeks: effects on carbohydrate and lipid metabolism.

Aspects of lipid and carbohydrate metabolism were studied in 8 patients established on continuous ambulatory peritoneal dialysis (CAPD) with plasma albumin less than 35 g/L, before, during, and after substitution of 1 of the daily glucose exchanges by a commercial 1% amino acid dialysis fluid for 12 weeks. The amount of glucose absorbed from the dialysis fluid was consequently reduced by about 25%, hence total energy intake decreased by about 100 Kcal/day, but peritoneal glucose transfer kinetics were unaffected. Glucose was lost into amino acid dialysate as expected (2 g/day). Excluding 1 patient with a large rise in calorie intake, total and LDL cholesterol fell at 8 and 12 weeks (LDL cholesterol week 0, 5.26 +/- 1.13; week 8, 4.32 +/- 0.74; week 12, 4.30 +/- 1.22; mean +/- SD, p less than 0.01 for both), but returned to baseline 2 weeks after the restoration of glucose fluid (LDL 4.91 +/- 1.22, p less than 0.05 vs. week 12). Apolipoprotein B concentration also fell at 12 weeks (p less than 0.01). No changes were seen in body weight, body fat, arm muscle circumference, fasting plasma glucose, insulin, growth hormone, triglyceride, nonesterified fatty acids, or HDL cholesterol. The response of these biochemical indices to single 8-h glucose and amino acid morning exchanges at 0 and 12 weeks were studied. After 12 week's use of amino acid dialysis fluid, plasma cholesterol and apolipoprotein B were significantly lower throughout the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Longitudinal study of proteins in plasma and dialysate during continuous ambulatory peritoneal dialysis (CAPD).

The aim was to evaluate plasma proteins during continuous ambulatory peritoneal dialysis (CAPD) in relation to dialysis losses, membrane permeability, renal insufficiency, and time on CAPD. Ten male patients, established on CAPD for at least 14 months, were studied every 8 weeks for 56 weeks. Blood and dialysate from the morning exchange were analysed for urea, creatinine, and 7 proteins, and used to calculate dialysate to plasma concentration ratios (D/P). These ratios were not significantly changed suggesting that permeability remained constant. However, there was a trend for beta 2-microglobulin, creatinine, and urea to increase progressively. After 56 weeks, beta 2-microglobulin had increased from 27.9 to 31.3 mg/L (p less than 0.05) and creatinine 1006 to 1099 mumoL/L (p less than 0.05) and both correlated with time on CAPD (p less than 0.001). Plasma alpha 1-acid glycoprotein, albumin, transferrin, IgG, IgA, and complement C3 were not significantly changed, although IgA and complement C3 were each negatively correlated with time on CAPD (r = -0.70 and -0.67, respectively), creatinine (r = 0.51 and -0.54), and urea (r = -0.61 and -0.61) (p less than 0.001 for all). It is concluded that increases in beta 2-microglobulin, creatinine, and urea are not due to loss of membrane permeability but reflect a slight increase in uraemia. Long-term decreases in immunological proteins may be caused by uraemia or progressive depletion.

Adult

Renal hemodynamic and excretory responses to renin inhibition induced by A-64662.

Experiments were conducted in sodium-depleted anesthetized monkeys to determine the effects of the primate-selective renin inhibitor A-64662 on renal function. Five groups of monkeys were examined with each group receiving an i.v. infusion of vehicle or A-64662 at doses (bolus plus continuous infusion) of 0.1 + 0.01, 1.0 + 0.1, 10 + 1.0 or 100 micrograms/kg + 10 micrograms/kg/min (n = 6/dose). Plasma renin activity was inhibited (P less than .05) at all infusion doses ranging from 33 +/- 8% at the lowest dose to 95 +/- 3% at the highest dose. Inhibition of plasma renin activity was accompanied by renal vasodilation as renal blood flow (RBF) increased (P less than .05) in a dose-dependent manner beginning at the dose of 1.0 microgram/kg + 0.1 micrograms/kg/min. RBF increased 36 +/- 7% at the highest dose of A-64662 examined. Associated with the increments in RBF, renal vascular resistance progressively decreased (P less than .05) by 12 +/- 3, 31 +/- 3 and 40 +/- 6%, respectively, with increasing doses of A-64662. Glomerular filtration rate was unchanged at all doses of A-64662. As a result, a significant (P less than .05) fall in the filtration fraction was observed as the dose of A-64662 increased. Mean arterial pressure was unaffected by the two lowest doses of A-64662, but decreased (P less than 0.05) by 13 +/- 1 and 18 +/- 4 mm Hg, respectively, at the two highest doses of A-64662 infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Haloperidol pretreatment unmasks the kappa opioid effects of U-50, 488H on cortical EEG and EEG power spectra in rats.

Adult female Sprague-Dawley rats were implanted with chronic cortical EEG electrodes and intravenous cannulae. U-50, 488H injection (5.0 mg/kg) produced initial EEG desynchrony and EEG spectral power that was mainly distributed over the zero to 10 Hz range, including a relatively small spectral peak in the 4-6 Hz band. In contrast, following haloperidol pretreatment (0.1 mg/kg), U-50, 488H injection produced high-voltage EEG bursts and a predominant EEG spectral peak in the 4-6 Hz band. These effects of U-50, 488H after haloperidol pretreatment were identical to those previously demonstrated with the benzomorphan kappa agonist ethylketocyclazocine. Thus, haloperidol pretreatment unmasked the kappa opioid effects of U-50, 488H.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Dissociation of naloxone-sensitive and naloxone-insensitive effects of U-50,488H.

This study was designed to compare the dose-related effects of U-50,488H on the cortical electroencephalogram (EEG) and behavior, following either saline or naloxone pretreatment. Adult female Sprague-Dawley rats were implanted with chronic cortical EEG and temporalis muscle electromyographic (EMG) recording electrodes and with permanent cannulae in the external jugular vein. U-50,488H injection produced initial "psychotomimetic-like" EEG and behavioral effects for about 10-20 min, followed by a predominance of behavioral stupor and associated EEG slow-wave bursts for about 20 min. Naloxone pretreatment completely antagonized the behavioral stupor and associated EEG slow-wave bursts. However, the "psychotomimetic-like" effects were not antagonized by naloxone pretreatment. Thus, dissociation between naloxone-sensitive and naloxone-insensitive effects of U-50,488H was demonstrated.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Metabolic changes in human liver associated with preoperative intravenous nutrition.

1. This study examined the influence of pre-operative intravenous nutrition upon carbohydrate stores, glucose metabolism and protein synthesis in the liver of patients undergoing laparotomy. 2. Thirty patients with gastrointestinal cancer and weight loss (greater than 5 kg in 3 months) were randomized to receive a hospital diet only or a hospital diet plus intravenous nutrition (0.18 g of N + 125 kJ day-1 kg-1) for 3 or 7 days before laparotomy. Patients who had not lost weight received the hospital diet only and formed a control group. 3. Wedge biopsies of liver were obtained at laparotomy and analysed for glycogen concentration, the activity of three key enzymes of glucose metabolism, 6-phosphofructokinase (EC 2.7.1.11), fructose bisphosphatase (EC 3.1.3.11) and hexokinase (EC 2.7.1.1), and the capacity for protein synthesis. 4. Compared with controls and the hospital diet group, both phosphofructokinase and fructose bisphosphatase activity were reduced in patients who received intravenous nutrition, suggesting the utilization of glucose for glycogen synthesis with a reduction in the glycolytic flux. Consistent with these changes, patients who received intravenous nutrition had a significantly higher glycogen concentration compared with the control and hospital diet groups. 5. Maximal rates of protein synthesis were achieved after only 3 days of intravenous nutrition. 6. The provision of intravenous nutrition was associated with changes in hepatic metabolism suggestive of repletion of energy stores and a higher capacity for protein synthesis.

Aged

A longitudinal study of the effects of amino acid-based CAPD fluid on amino acid retention and protein losses.

During the evaluation of 1% amino acid solution as an alternative osmotic agent to glucose, we measured amino acids and proteins in dialysate, urine and plasma to evaluate the uptake of amino acids and their effects on membrane permeability. Eight patients (plasma albumin less than 35 g/l) were on 21 exchanges of glucose fluid for 4 weeks before and after 12 weeks, during which a solution of 15 amino acids (Baxter '151') was used for the morning exchange. The absorption of amino acids from the single daily '151' exchange increased during the study: 16.4 g at 4 weeks and 17.1 g after 12 weeks (P less than 0.01) with increases in eight amino acids. Amino acid uptake was related to the permeability characteristics of the patients. Following each '151' exchange, 1% of the amino acids absorbed were dialysed into subsequent glucose exchanges. Consequently the net daily gain was 15.0 g increasing to 15.6 g, whereas daily depletion during glucose exchanges was 1.8 g both before and after '151'. Clearance of five proteins increased both at the start and after 12 weeks of '151'. Total protein and prealbumin loss into dialysate increased by about 20%, and when glucose was restored loss of transferrin, albumin and immunoglobulin G decreased. Urinary concentrations were similar throughout. Amino acid uptake from '151' greatly exceeded all losses although our results suggest small reversible increases in macromolecular permeability of the peritoneum.

Absorption