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Biomedical subjects

G Patrick

Publications and source records attributed to G Patrick.

At least 19 recordsLinked to original sources
PubMed1999

Reduced P50 auditory gating response in psychiatrically normal chronic marihuana users: a pilot study.

BACKGROUND: Neurophysiological studies of marihuana (THC) often contain uncontrolled confounds [psychiatric diagnoses, polydrug use, central nervous system (CNS)-relevant injury, etc.] that can alter electrophysiological measures. This P50 sensory gating report is part of a larger neurophysiological and neurocognitive investigation of chronic THC exposure using rigorously screened medically and psychiatrically normal individuals without concurrent use of non-THC substances. METHODS: Following medical and psychiatric screening, including serial urine drug screens, technically adequate P50 paired auditory recovery tests were obtained on 19 chronic THC users and 14 control subjects. Fifty pairs of 80-dB auditory clicks (1 pair per 10 sec, 500-msec interclick separation) were delivered through earphones. The sensory gating measure was the ratio between the P50 amplitudes at the vertex elicited by the conditioning (first) and test (second) click. RESULTS: THC subjects had significantly higher sensory gating ratios (i.e., reduced suppression) than did control subjects. Among THC users, sensory gating ratios did not correlate with duration or frequency of THC use, although subjects with ratios above 40 had nearly twice the number of "joint-years" of THC exposure than did those with lower ratios. CONCLUSIONS: Reduced P50 suppression in the sensory gating paradigm may be a possible neurophysiological CNS sequela of long-term cumulative exposure to THC.

Acoustic Stimulation↗
PubMed1999

The effects of caffeine withdrawal on cognitive P300 auditory and visual evoked potentials.

Auditory and visual P300 cognitive evoked potentials were obtained in 13 individuals who regularly consumed caffeine prior to and during a 4 day period of abstinence from caffeine. During the period of caffeine abstinence auditory P300 evoked potentials showed significant decreases in amplitude measures but no significant changes in latency, while the visual P300 evoked potentials showed significant latency decreases but no significant changes in amplitude. The reason for these opposite effects is unclear and further research in this area is needed.

Adolescent↗
PubMed1999

Comparative hazards of chrysotile asbestos and its substitutes: A European perspective.

Although the use of amphibole asbestos (crocidolite and amosite) has been banned in most European countries because of its known effects on the lung and pleura, chrysotile asbestos remains in use in a number of widely used products, notably asbestos cement and friction linings in vehicle brakes and clutches. A ban on chrysotile throughout the European Union for these remaining applications is currently under consideration, but this requires confidence in the safety of substitute materials. The main substitutes for the residual uses of chrysotile are p-aramid, polyvinyl alcohol (PVA), and cellulose fibers, and it is these materials that are evaluated here. Because it critically affects both exposure concentrations and deposition in the lung, diameter is a key determinant of the intrinsic hazard of a fiber; the propensity of a material to release fibers into the air is also important. It is generally accepted that to be pathogenic to the lung or pleura, fibers must be long, thin, and durable; fiber chemistry may also be significant. These basic principles are used in a pragmatic way to form a judgement on the relative safety of the substitute materials, taking into account what is known about their hazardous properties and also the potential for uncontrolled exposures during a lifetime of use (including disposal). We conclude that chrysotile asbestos is intrinsically more hazardous than p-aramid, PVA, or cellulose fibers and that its continued use in asbestos-cement products and friction materials is not justifiable in the face of available technically adequate substitutes.

Air Pollution↗
PubMed1998

Investigation of lung tumour induction in C3H/HeH mice, with and without tumour promotion with urethane, following paternal X-irradiation.

In series of papers Nomura has reported that parental irradiation can lead to an enhanced incidence of lung and other tumours. However, in a recent study with BALB/cJ mice, using optimum conditions as defined by Nomura, we were unable to confirm this. We have now repeated the investigation using a different inbred strain, C3H/HeH, with and without tumour promotion in the F1 by urethane, again using protocols defined by Nomura. In a series of replicate studies spanning over 2 years, males were exposed to single, acute doses of 0, 250 and 500 cGy X-rays and thereafter placed with two females each in each of two consecutive weeks. Half the offspring from each treatment group and each week of mating were given 5 mmol/kg body weight of the urethane, while the remainder remained untreated. Most of the offspring produced were killed and scored for lung tumours at 6 months of age, while the rest were examined at 12 months of age. The proportion of fertile females and litter size provided evidence of a dose-dependent mutational response to the paternal irradiation, but no trace of a radiation-enhanced lung tumour incidence was detected among the progeny, whether in the urethane or non-urethane groups at 6 or 12 months of age, and whether assessed by numbers of mice with tumours, clusters of tumours, or cluster size. As seen in the BALB/cJ study, significant differences among different replicates were found, again suggesting a cyclical or seasonal variation in tumour incidence, but the variations seen with the two strains were not the same. The need for concurrent controls for tumour work was, nevertheless, again indicated. The overall findings do not therefore accord with those of Nomura. Furthermore, they do not support the causal association between the raised incidence of childhood leukaemia and non-Hodgkins lymphoma near Sellafield and the father's recorded radiation exposure during employment in the nuclear industry, as suggested by the Gardner report.

Animals↗
PubMed1998

Possible EEG sequelae of very long duration marihuana use: pilot findings from topographic quantitative EEG analyses of subjects with 15 to 24 years of cumulative daily exposure to THC.

In previous work we demonstrated and replicated a significant association between increased absolute and relative power and interhemispheric coherence of EEG alpha activity over the bilateral frontal-central cortex ("alpha hyperfrontality") in daily marihuana users as contrasted with nonusers. In this report we focused our analyses on subjects who reported smoking marihuana on a daily basis for 15 to 24 consecutive years. Compared to nonuser controls and subjects who had used marihuana on a daily basis for shorter periods of time, subjects with excessively long cumulative exposures to THC were found to have significantly elevated absolute power of theta activity over bilateral frontal-central cortex, as well as significantly increased interhemispheric coherence of theta activity across central and posterior regions. Concurrent reaction time studies conducted in our laboratory suggest that very long duration cumulative marihuana exposure might be associated with slowed cognitive processing.

Adult↗
PubMed1997

Early and middle latency evoked potentials in medically and psychiatrically normal daily marihuana users: a paucity of significant findings.

The use of evoked potentials to study CNS effects of marihuana (THC) have produced inconsistent findings. Our previous pilot studies suggested that auditory P300 latencies and amplitudes, auditory P50 and somatosensory P30 amplitudes and brainstem auditory evoked potential latencies were altered in THC users. Because these findings were flawed by uncontrolled psychiatric diagnostic and medication variables, we undertook a controlled investigation of screened medically and psychiatrically normal THC users and controls. When age effects were controlled, THC related alterations of brain stem and both auditory and visual P300 responses could not be seen. This report extends our analyses to other auditory, somatosensory and visual evoked potentials. With the possible exception of an elevated auditory P50 amplitude, significant evoked potential correlates to daily THC use were not seen when normals were studied and age effects controlled.

Adolescent↗
PubMed1997

Decreased multi-band posterior interhemispheric coherence with a lipoma on the corpus callosum: a case report of a possible association.

The corpus callosum plays a role in mediating interhemisphere communication. Coherence may be a quantitative EEG-based measure of this communication. The present report is of a female schizophrenic patient with a marked coherence deficit in the temporal-parietal-occipital region involving multiple frequency bands. An MRI scan of her brain revealed a lipoma involving the splenium of the corpus callosum. It is speculated that this lipoma may have caused a physical impingment on or developmental aberration of adjacent callosal fibers, resulting in the observed coherence deficit. Further studies of coherence measures in patients with collosal lipomas are proposed.

Adult↗
PubMed1997

Somatic dysfunction increase during caffeine withdrawal.

The authors studied the effects of caffeine withdrawal on 14 subjects at baseline and during a 4-day period of abstinence from caffeine. They studied the results from quantitative electroencephalograms performed on these subjects and gauged any changes that may have been evoked during this withdrawal period. The participants were also evaluated for the occurrence of somatic dysfunctions. Examinations for the presence of somatic dysfunctions were performed on the participants before caffeine cessation and on Days 1, 2 and 4 of abstinence. Results showed that the number of somatic dysfunctions increased significantly during the process of caffeine withdrawal.

Adult↗
PubMed1996

Zipeprol: preclinical assessment of abuse potential.

Zipeprol was evaluated in a number of in vitro and in vivo assays predictive of stimulant, depressant, or opioid abuse potential. Zipeprol had affinity for mu and kappa opioid binding sites as well as sigma binding sites. However, it failed to exert opioid-like agonist actions in rodents, and did not attenuate withdrawal signs in morphine- or pentobarbital-dependent rats. Zipeprol did not substitute for either amphetamine or pentobarbital in drug discrimination assays in rhesus monkeys. On the other hand, it suppressed morphine withdrawal signs in rhesus monkeys in two assays, and it acted as a quadazocine-sensitive reinforcer in monkeys trained to self-inject alfentanil. Zipeprol also acted as a reinforcer in monkeys trained to self-inject methohexital. In a dose range of 10-18 mg/kg, zipeprol induced convulsions in monkeys. Zipeprol appears to have abuse potential and a novel spectrum of action involving both opioid and non-opioid effects.

Animals↗
PubMed1996

Does caffeine cessation increase firing rates of diffuse paroxysmal slowing dysrhythmia? A serendipitous observation.

As part of a quantitative EEG study of caffeine withdrawal a serendipitous observation suggested that individuals with Diffuse Paroxysmal Slowing (a minor EEG dysrhythmia) in their baseline resting EEGs had an increased firing rate of this pattern while undergoing a period of caffeine abstinence. For all EEGs, individual bursts of Diffuse Paroxysmal Slowing were identified by consensus rating and the firing rate for this pattern expressed as the number of bursts per 10 minutes of alert waking activity. The firing rate of this pattern was seen to increase markedly during 4 days of verified abstinence and to return to baseline or lower than baseline levels following reintroduction of caffeine. Some possible implications of this phenomenon are discussed.

Adult↗
PubMed1995

Auditory and visual P300 event related potentials are not altered in medically and psychiatrically normal chronic marihuana users.

Attempts to use Event Related Potentials, particularly the cognitive or P300 evoked potential, as measures of CNS effects of THC use have been infrequent and have produced inconsistent results. We published a pilot study in which psychiatric patient THC users had significantly prolonged auditory P300 latencies and reduced amplitudes as contrasted with non-users. Because psychiatric diagnoses and medication effects could not be controlled, we repeated the study with medically and psychiatrically normal subjects selected with extremely stringent exclusion criteria and screening procedures. P300 latency differences between THC users and controls were not detected. Using all subjects, THC users displayed reduced auditory and visual P300 amplitudes. However, when age differences between THC users and controls were removed, all significant P300 amplitude differences were removed as well. The contaminating effect of using psychiatric patients in THC research is discussed and the importance of using carefully screened normal subjects in studies of neurophysiological abuse drug effects is stressed.

Adolescent↗
PubMed1995

Investigation of lung tumour induction in BALB/cJ mice following paternal X-irradiation.

Evidence of an enhanced incidence of lung tumours (benign adenomas and adenocarcinomas) was sought in the BALB/cJ mouse following paternal germ cell X-irradiation. In a series of replicate studies spanning approximately 1 year, males were exposed to single, acute X-ray doses of 0, 250 and 500 cGy. In each of the 2 consecutive weeks immediately thereafter they were placed with two females to generate progeny that were derived from irradiated post-meiotic cells (spermatozoa to late spermatids). These animals were then examined at 8 or 12 months for lung tumours. While the proportion of fertile females and mean litter size was affected by the radiation, showing a dose-dependent, dominant lethal response, and while cases of mutant offspring were detected, the paternal radiation did not affect lung tumour incidence in the offspring. The incidence did not vary significantly between germ cell stages irradiated (week of mating), sex of offspring, or radiation dose. However, significant differences between lung tumour incidence (mostly representing benign adenomas) were found between different replicates, these being high at the start of the study, declining and then rising to yet higher levels at its close. The finding that lung tumour incidence in BALB/cJ mice is not affected by paternal germ cell irradiation does not accord with Nomura's reports using other strains of mice. This, in turn, weakens biological support for a causal association between the raised incidence of childhood leukaemia and non-Hodgkin lymphoma near Sellafield and the father's recorded radiation exposure during employment by the nuclear industry.

Adenoma↗
PubMed1995

Topographic quantitative EEG measures of alpha and theta power changes during caffeine withdrawal: preliminary findings from normal subjects.

Neurophysiological consequences of withdrawal from caffeine are poorly understood. In particular, quantitative studies of EEG changes that may occur during the period of caffeine abstinence in caffeine dependent individuals have not been reported. In this pilot study, 13 physically- and psychiatrically-normal caffeine users were asked to abstain from caffeine for a period of 4 days. Quantitative EEGs were obtained prior to stopping caffeine and on Days 1, 2, and 4 of the caffeine abstinence period. Results indicated that significant increases in alpha and theta absolute power accompany the caffeine withdrawal process with return to the pre-abstinent EEG levels when caffeine usage is resumed. The implications of these findings are discussed with special reference to the possible need to control for the variable of caffeine usage in quantitative EEG studies of other phenomena.

Adolescent↗
PubMed1994

Brainstem auditory response (BAER) in polydrug abuse.

Based on preliminary data suggesting that polydrug abuser subjects may have delayed wave V BAER latencies, we contrasted BAER latency and amplitude measures between a group of polydrug users and six different comparison groups of subjects drawn from our laboratory files. A series of analyses showed that BAER latencies were, in fact, prolonged for psychiatric polydrug users as compared with groups of medically screened and unscreened normals not using drugs and normals using marijuana only. However, further analyses which compared polydrug abusers with nondrug users or marijuana-only users drawn from a psychiatric patient population failed to confirm these differences, thus suggesting that psychiatric status was more important than polydrug abuse in producing BAER alterations. Furthermore, subsidiary analyses using wave I latency as statistical covariate suggested that wave V latency prolongations could, under certain circumstances, be epiphenomena or reflections of earlier wave I alterations.

Acoustic Stimulation↗
PubMed1994

Persistent topographic quantitative EEG sequelae of chronic marihuana use: a replication study and initial discriminant function analysis.

In a previous pilot study using psychiatric patients we reported that daily marihuana users had significant elevations of (1) Absolute Alpha Power, (2) Relative Alpha Power, and (3) Interhemispheric Alpha Coherence over both frontal and frontal-central areas when contrasted with subjects who did not use marihuana. We referred to this phenomenon as Hyperfrontality of Alpha. The study presented here is a successful replication of our previous findings using new samples of subjects and identical methods. Post hoc analyses based on the combined sample from both studies suggest that variables of psychiatric diagnoses and medication did not bias our results. In addition, a discriminant function analysis using quantitative EEG variables as candidate predictors generated a 95% correct THC user versus nonuser classification accuracy which received a successful jackknife replication.

Adult↗
PubMed1993

The role of glutamine and glucose analogues in metabolic inhibition of human myeloid leukaemia in vitro.

1. Glutamine analogues L-[alpha S,5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) and 6-diazo-5-oxo-L-norleucine (DON) have been shown to possess cytotoxic activity against a wide variety of animal and human xenografted solid tumours, however their potential in man has been limited by toxicity. 2. We have analysed the effects of acivicin and DON on glutamine utilization to determine whether the reason for the disappointing therapeutic profile is solely due to the inefficient inhibition of glutamine metabolism. 3. Human myeloid leukaemic cells treated with acivicin inhibited ribonucleotide biosynthesis but not energy production via glutaminolysis and had little effect on viability, whereas treatment with DON inhibited both ribonucleotide biosynthesis and glutamine oxidation and resulted in reduced viability. 4. Treatment of the myeloid leukaemic cells with the glucose analogue 2-deoxy-D-glucose in addition to DON potentiated the inhibition of de novo nucleotide biosynthesis, glutaminolysis and glycolysis, and caused a further reduction in cell viability. 5. These results provide further support for the essential role of glutamine in cellular metabolism, and indicate that use of the glutamine analogue DON in the treatment of acute myeloid leukaemia may be more clinically effective if used in combination with 2-deoxy-D-glucose.

Acute Disease↗
PubMed1992

Transport of particles of colloidal gold within and from rat lung after local deposition by alveolar microinjection.

Because inhalation and intratracheal instillation deposit particles throughout the respiratory tract, these methods of administration give little information on the movement of particles within the lung and no direct information on the clearance kinetics from locally defined sites within alveolar tissue. Approximately 0.05 microL of 195Au-labeled gold colloid was administered to 32 rats by microinjection into a small volume of subpleural alveoli. Its fate was studied by whole-body counting and serial sacrifice over 15 months. The kinetics of clearance from the subpleural deposition site showed that there was no rapid removal of particles, and the main clearance process was defined by an exponential term with a half-time averaging 583 days. There was a wide variation between individual animals. The distribution of 195Au at sacrifice showed that the gold colloid was nearly all retained within the respiratory tract. The particles were not appreciably redistributed throughout the lung volume, so most of the material not cleared from the lung remained close to the deposition site. At the later times after microinjection, much of the gold colloid was associated with thickened pleura and adjoining septae.

Animals↗