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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
PubMed1996

A randomized study of high-dose cytarabine in induction in acute myeloid leukemia.

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC-3-7 and 74% with 7-3-7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3-7 and 12 months with 7-3-7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive longer with HIDAC-3-7 but there were no overall survival differences between the two arms. HIDAC-3-7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC-3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

Acute Disease↗
PubMed1996

Effects of cytosine arabinoside on human leukemia cells.

Cytosine arabinoside (Ara-C) is used to treat leukemias, with complete remission induced by combination chemotherapy in approximately 70% of cases of acute myelogenous leukemia (AML). Ara-CTP acts as a competitive inhibitor of DNA polymerase and may also be incorporated into DNA. Accumulation of deoxyribonucleoside triphosphates (dNTPs) induced by Ara-C may indicate disruption of DNA synthesis in susceptible leukemia cells. A procedure has been developed for the quantification of Ara-CTP and dNTPs from small samples of leukaemia cells from patients (4 x 10(7) cells) activated with concanavalin A (10 micrograms/ml, 48 hr) and grown in the presence of [32P]orthophosphate (1.1 microM, 9 x 10(6) Ci/mol, 16 hr). The susceptibilities to Ara-C of the human leukemia cell lines CCRF-CEM (IC50 = 6.30 nM), CCRF-HSB-2 (IC50 = 10.4 nM) and MOLT-4 (IC50 = 10.0 nM) may be correlated with their abilities to accumulate high concentrations of Ara-CTP (> 1000 amol/cell) with increases of between 1.3- and 3.4-fold in dATP, dGTP and dTTP for the four cell lines, while dCTP decreased between 0.23- and 0.78-fold. By contrast, an Ara-C-resistant derivative of HL-60 cells (IC50 = 400 nM) accumulated only low concentrations of Ara-CTP (71 amol/cell) without significant changes in dNTPs. High concentrations of Ara-CTP in leukemia cells induce accumulations of dATP, dGTP and dTTP due to inhibition of DNA synthesis, and depletion of dCTP. This imbalance in the pools of the four dNTPs could lead to genetic miscoding and cell death.

Aged↗
PubMed1996

Thalidomide responsive chronic pulmonary GVHD.

A 29-year-old male underwent allogeneic bone marrow transplantation for progressive multiple myeloma. His post-transplant course was complicated by severe chronic pulmonary graft-versus-host disease (GVHD) resistant to cyclosporin A, corticosteroids and azathioprine. The introduction of thalidomide resulted in a dramatic improvement in his lung function which has been maintained even after cessation of thalidomide. He remains well 40 months after transplantation.

Adrenal Cortex Hormones↗
PubMed1995

Acute interactive effects of MK-801 and morphine on cortical EEG and EEG power spectra in rats.

The interaction between MK-801 and morphine-induced effects on cortical electroencephalography (EEG) was investigated. Rats were administered one of five MK-801 doses (IP) prior to morphine (IV). MK-801 dose-dependently increased morphine-induced global spectral power, duration of morphine-induced EEG bursts and latency to sleep onset, and decreased morphine-induced mean frequency, mobility, complexity, and edge frequency. MK-801 pretreatment shifted the relative distribution of total power to the left. Significant interaction effects were found for all spectral parameters except peak frequency. A second group of rats was administered MK-801 prior to an increasing cumulative morphine dose. MK-801 increased maximal morphine effects on all spectral parameters except peak frequency. The results are in agreement with those of recent analgesia and in vitro studies in spinal neurons, and support observations of a synergistic interaction between effects of NMDA antagonism and morphine. These data further suggest that the component of cortical EEG that is produced by mu-opioid- and NMDA-receptor interactive effects may be dominated by an inhibitory effect of morphine on NMDA receptor activity.

Animals↗
PubMed1994

Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: I. Morphine tolerance development.

This study investigated a potential interaction between MK-801 and morphine tolerance using electroencephalography (EEG), EEG spectral parameters and behavior in the rat. Rats were treated for 7 days with morphine alone or with morphine and MK-801. Control groups received chronic MK-801 alone or saline. On day 8 all rats received morphine alone. Co-treatment significantly accelerated the development of tolerance to morphine-induced total power and latency to sleep onset. Co-treatment, but not morphine alone, produced tolerance to morphine-induced complexity and edge frequency, and produced tolerance equal to that from morphine alone in duration of EEG bursting. MK-801 co-treatment decreased, where chronic morphine alone increased, the excitatory response to morphine. Our results support recent reports that chronic morphine treatment produces supersensitivity to glutamate in the rat cortex and alteration in mesolimbic dopamine levels that are modulated by glutamatergic activity.

Animals↗
PubMed1994

Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: II. Morphine dependence.

A potential interaction between MK-801 and the cortical electroencephalographic (EEG) and behavioral expressions of morphine dependence in female Sprague-Dawley rats was assessed. Rats were treated chronically (7 days) with either morphine alone, morphine and MK-801, MK-801 alone or saline vehicle alone. On day 8 all rats received morphine alone followed by naloxone. An additional group received chronic (7 days) morphine alone, followed by MK-801 on day 8 prior to morphine and naloxone. Naloxone-induced EEG complexity in morphine-dependent rats was significantly lower than in chronic saline-treated rats. Total power, mobility, mean frequency, complexity and edge frequency in response to naloxone-induced withdrawal in morphine-dependent rats were significantly altered from those in chronically MK-801 alone-treated rats. No differences were found in the EEG and behavioral responses to naloxone between rats that received chronic MK-801 and those that didn't during chronic morphine treatment. Acute MK-801 prior to naloxone in morphine-dependent rats attenuated the behavioral, but not the EEG response to naloxone-induced withdrawal.

Animals↗
PubMed1994

Dynorphin A-(1-13)-morphine interactions: quantitative and qualitative EEG properties differ in morphine-naive vs. morphine-tolerant rats.

The effects of dynorphin A-(1-13) on cumulative IV morphine-induced EEG and EEG power spectra were studied in naive and morphine-tolerant rats. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling ICV and IV cannulae. In naive rats, dynorphin A-(1-13) quantitatively decreased cumulative IV morphine-induced EEG spectral power as well as qualitatively shifting the relative distribution of spectral power to predominantly faster frequencies. In morphine-tolerant rats, the quantitative and qualitative EEG properties were identical to those in dynorphin A-(1-13) pretreated morphine-naive rats. Thus, dynorphin A-(1-13) pretreatment apparently produced instantaneous acute morphine tolerance. Furthermore, in morphine-tolerant rats, dynorphin A-(1-13) pretreatment quantitatively increased morphine-induced EEG power without qualitatively changing the relative distribution of EEG spectral power. This latter effect may be due to a summation of increased endogenous levels of dynorphin A-(1-13) associated with the development of morphine tolerance and the experimentally administered dynorphin A-(1-13). These results indicate that dynorphin-induced quantitative and qualitative EEG changes of morphine may reflect different underlying processes. That is, quantitative changes may reflect the number of receptors that are activated, while qualitative changes may reflect the nature of the receptor-effector coupling.

Animals↗
PubMed1993

Interactions between U-50,488H and sigma receptor antagonists: EEG, EEG power spectral and behavioral correlates.

I.v. administration of U-50,488H after i.v. saline pretreatment produced occasional high-voltage EEG slow-wave bursts that were associated with relatively small increases in spectral power in the 2.5-7.5 Hz band as a spectral peak and with behavioral incidents of sedation, ataxia, ptosis, straub tail, hunching of the back, and backing-up. After pretreatment with the sigma antagonists rimcazole and DuPont Merck S-7389-4, U-50,488H administration produced significantly larger increases in absolute EEG spectral power, both over the 1-50 Hz range and in the 2.5-5.0 and 5.0-7.5 Hz bands, than after saline pretreatment; rimcazole pretreatment eliminated U-50,488H-induced incidents of ataxia, ptosis, hunching of the back and backing-up. In summary, effects of U-50,488H on EEG, EEG power spectra and behavior may reflect interactions between kappa opioid and sigma (non-opioid) receptor-effector systems.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Genetic profiles of morphine-induced EEG, EEG power spectra, and behavior in two inbred rat strains.

The purpose of the present study was to examine and compare the effects of morphine at doses of 3, 10, and 30 mg/kg, IV, on EEG, EEG power spectra, and behavior in two inbred rat strains, Lewis and Fischer 344. Duration of morphine-induced EEG slow-wave bursts and associated behavioral stupor was greater in Lewis rats. Latency to slow-wave sleep increased in a dose-related manner for both strains; differences were not significant between the two groups. The analog EEG signal was transformed by fast Fourier analysis; six power spectral quantities were examined: peak frequency, complexity, mobility, mean frequency, edge frequency, and total power. With the exception of peak frequency and edge frequency, all differed as a function of inbred rat strain. Regarding morphine dose, all spectral parameters differed except peak frequency. Factor analysis on morphine-induced EEG revealed a unique factor for each strain that was bipolar in nature and may be associated with the burst and interburst periods that occur in EEG after opiate administration. Genetic variability appears to play a role in the behavioral, EEG, and derived power spectral responses of both LEW and F344 inbred rat strains following acute morphine administration. These results may reflect differences in neurosensitivity and/or opioid receptor populations between Lewis and Fischer 344 inbred rat strains.

Animals↗
PubMed1993

EEG, EEG power spectral, and behavioral differences in response to acute ethylketocyclazocine administration in two inbred rat strains.

Differences in response to behavioral and electroencephalographic parameters were delineated between two inbred rat strains, Lewis (LEW) and Fischer 344 (F344), upon acute exposure to IV administration of ethylketocyclazocine (EKC) at doses of 1.25, 2.5, and 5 mg/kg. Duration of EKC-induced EEG slow-wave bursts and associated behavioral stupor increased in a dose-related manner, and was greater in duration for the LEW animals; a less robust, quadratic trend was displayed by the F344 group. For both rat strains, latency to onset of slow-wave sleep increased proportionately with EKC dose. Duration of EKC-induced EEG bursts and interbursts were greater in duration for the F344 rats. Assessment of six power spectral parameters (peak frequency, complexity, mobility, mean frequency, edge frequency, and total power) revealed no differences between groups when EKC-induced burst and interburst periods were analyzed simultaneously. Separation of the phases revealed rat strain differences; overall, the LEW animals displayed a greater dose-related EEG response. Except for total power, the F344 group displayed little variation across the three doses tested in the burst phase; the interburst phase reflected more dose-related differences for this group but to a lesser degree than the LEW animals. These results may reflect differences in opioid-related receptor populations between Lewis and F344 inbred rat strains.

Animals↗
PubMed1993

Complement activation during CAPD.

Complement activation was monitored in 20 CAPD patients and 20 normal individuals using markers of the alternative (Bb fragment), classical (C4d fragment), common (iC3b) and terminal pathways (SC5b-9, the soluble form of the membrane attack complex, MAC), together with C3, C4 and factor B. CAPD plasma SC5b-9 was higher than normal although this was not due to increased complement activation in the plasma. The calculated cleavage for C3, C4 and factor B to iC3b, C4d and Bb respectively, due to spontaneous activation, was similar in both groups. C3, C4 and factor B in dialysate were less than 1% of plasma concentration, consistent with vascular leakage, whereas iC3b, Bb and SC5b-9 were at higher concentrations, suggesting generation in the peritoneum by the alternative pathway. 2.4% C4d is consistent with leakage of this small molecule but may indicate slight classical activation. It is concluded that complement activation occurs in the peritoneum during CAPD. MAC and the anaphylatoxins which are also generated may contribute to an increased risk of infection and other inflammatory complications.

Blood↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗