Biomedical subjects

G Patrick

Publications and source records attributed to G Patrick.

At least 19 recordsLinked to original sources

PubMed2001

A novel synthetic erionite fibre radiolabelled with (57)Co.

The aim was to produce a radiolabelled fibre suitable for long-term carcinogenesis studies. To this end, we have successfully synthesised erionite fibres by a method adapted to incorporate (57)Co into the crystal framework. Morphologically the fibres are straight, of median length 2.5 microm, with 11% of fibres > 8 microm long, and median width 0.32 microm. These values are comparable to natural Oregon erionite. Autoradiography confirmed that the (57)Co was associated with the fibres themselves. The stability of the radiolabel in vivo was examined by instilling 1 mg of synthetic erionite into the lungs of F-344 rats. About half of the thoracic content of (57)Co was cleared in the first week, and over the following 5 weeks the remainder was cleared slowly with a half-time of 120 days. After 6 weeks the urinary excretion of (57)Co was only 0.054% of the initial lung content per day. This represented fibre dissolution plus any leaching of (57)Co from the fibres. It can be concluded that the (57)Co is bound into the erionite fibres with sufficient stability in vivo for studying their effects in relation to translocation to the pleura.

Animals↗

PubMed2001

Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines.

BACKGROUND: In universal vaccination programs, when there is no postvaccination sero-1 logic assessment of response, there must be confidence that the vaccines used provide a high degree of seroprotection. OBJECTIVE: This parallel analysis of 2 recombinant hepatitis B vaccines (Engerix B and Recombivax/HB-Vax II) was conducted to review the seroprotective efficacy of each vaccine in defined populations. METHODS: Clinical studies of the 2 vaccines published as manuscripts or conference abstracts in the public domain between January 1986 and April 1999 were identified retrospectively by unrestricted screening of journals through BIOSIS, MEDLINE, and EMBASE and the Internet. Unpublished or internal company data were excluded to maintain impartiality. The studies were reviewed and analyzed. The studies were not assessed for quality other than a judgment of their eligibility for inclusion in the analysis. The primary outcome measure was the proportion of subjects in defined populations who showed an early seroprotective response to currently licensed vaccination schedules. Summary statistical analyses of seroprotective response rates and 95% CIs were calculated for each vaccine for each population. Seroprotective response was defined by an anti-hepatitis B surface antigen titer > or =10 IU/L measured between 1 and 3 months after the final vaccination. Because the study was designed specifically to review published immunogenicity data, safety data were not assessed. The study was not designed to demonstrate superiority of one vaccine over the other. RESULTS: A total of 181 clinical studies representing 32,904 vaccinated subjects were reviewed and analyzed, of whom 24,277 had been vaccinated with Engerix B and 8627 vaccinated with Recombivax/ HB-Vax II. Seroprotection was achieved in 20,060 subjects (95.8%) with Engerix B and in 7774 subjects (94.3%) with Recombivax/HB-Vax II in the normal population vaccinated according to currently licensed 3-dose schedules. In a subgroup analysis, response rates in health care workers were 6492 subjects (94.5%) for Engerix B and 3245 subjects (92.2%) for Recombivax/HB-Vax II. Children and adolescents (1-19 years) showed the highest response rates to vaccination (4612 [98.6%], Engerix B; 2292 [98.9%], Recombivax/HB-Vax II). A total of 2875 infants (<1 year) (95.8%) achieved seroprotection with Engerix B; 701 (88.5%) achieved seroprotection with Recombivax/ HB-Vax II. CONCLUSIONS: Hepatitis B vaccination programs using either Engerix B or Recombivax/HB-Vax II can achieve high seroprotective response rates, particularly in childhood and adolescence. Ideally, younger populations should be a primary target in current universal vaccination programs.

Adolescent↗

PubMed2001

Does EEG predict response to valproate versus lithium in patients with mania?

A number of factors may suggest that a patient with mania may respond to valproate or to lithium. However, prediction of which patients will respond to either medication remains difficult. In this study nonepileptiform EEG abnormalities in responders to each medication were investigated. Six of 20 patients (30%) responsive to lithium but not to valproate had nonepileptiform EEG abnormalities while 14 of 20 patients (70%) responsive to valproate but not to lithium had nonepileptiform EEG abnormalities. Patients presenting with mania and EEG abnormalities, particularly sharp activity, are statistically more likely (chi2 = 4.9, df = 1, p = .027) to respond to valproate than to lithium. Whether such a finding will also hold true for other anticonvulsants used to treat mania remains to be seen.

Acute Disease↗

PubMed2000

Neurobehavioral activity in mice of N-vanillyl-arachidonyl-amide.

We studied the cannabimimetic properties of N-vanillyl-arachidonoyl-amide (arvanil), a potential agonist of cannabinoid CB(1) and capsaicin VR(1) receptors, and an inhibitor of the facilitated transport of the endocannabinoid anandamide. Arvanil and anandamide exhibited similar affinities for the cannabinoid CB(1) receptor, but arvanil was less efficacious in inducing cannabinoid CB(1) receptor-mediated GTPgammaS binding. The K(i) of arvanil for the vanilloid VR(1) receptor was 0.28 microM. Administered i.v. to mice, arvanil was 100 times more potent than anandamide in producing hypothermia, analgesia, catalepsy and inhibiting spontaneous activity. These effects were not attenuated by the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide.HCl (SR141716A). Arvanil (i.t. administration) induced analgesia in the tail-flick test that was not blocked by either SR141716A or the vanilloid VR(1) antagonist capsazepine. Conversely, capsaicin was less potent as an analgesic (ED(50) 180 ng/mouse, i.t.) and its effects attenuated by capsazepine. The analgesic effect of anandamide (i.t.) was also unaffected by SR141716A but was 750-fold less potent (ED(50) 20.5 microg/mouse) than capsaicin. These data indicate that the neurobehavioral effects exerted by arvanil are not due to activation of cannabinoid CB(1) or vanilloid VR(1) receptors.

Analgesics↗

PubMed2000

Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres.

A method for culturing primary rat alveolar macrophages (AMs) for 14 days was used to compare their responses to crocidolite and chrysotile asbestos fibres. Exposure to crocidolite increased production of tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta), whereas exposure to chrysotile did not; neither fibre altered the production of interleukin 6 (IL-6). IL-1beta production increased progressively, while TNF-alpha was fully elevated from day 1. Conversely, chrysotile, but not crocidolite, increased production of superoxide anion and nitric oxide (NO) radicals. These differential responses were only observed by extending the culture beyond the usual 1-3 days.

Animals↗

PubMed2000

Different cytotoxic response to gadolinium between mouse and rat alveolar macrophages.

The cytotoxicity of gadolinium (Gd) chloride was investigated in alveolar macrophages (AM) cultured in vitro. A marked difference in the cytotoxic response to Gd was found between mouse and rat AM. The viability of rat AM was decreased by exposure to Gd at doses more than 3 microM, while mouse AM appeared to be resistant even up to 1000 microM Gd exposure. The decrease in the viability of rat AM exposed to Gd at doses up to 1000 microM was mitigated by centrifugation and filtration of the culture medium containing Gd, or by the treatment of AM with lysosomotropic agents such as NH(4)Cl or chloroquine, suggesting that the cytotoxic response of rat AM to Gd at doses up to 1000 microM was dependent on the intracellular uptake and subsequent dissolution of Gd present in the culture medium in colloidal form. The phagocytic activity of mouse AM, evaluated by the uptake of latex particles, was higher than that of rat AM. Furthermore, quantitative analysis of Gd with inductively coupled plasma-mass spectrometry revealed that mouse AM took up a larger amount of Gd than rat AM. Therefore, the marked difference in the cytotoxic response to Gd between mouse and rat AM could not be attributed to the phagocytic activities for the colloidal form of Gd. The cytotoxic sensitivity of AM to Gd present in non-colloidal form was almost the same between mouse and rat AM. Therefore, it is suggested that the extent to which Gd-colloid phagocytosed is dissolved in the phago-lysosome or the subsequent process to exhibit the cytotoxicity may be different between mouse and rat AM.

Ammonium Chloride↗

PubMed2000

Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres.

Asbestos fibres have been shown to stimulate the mitogen-activated protein kinase signalling cascade in rat pleural mesothelial (RPM) cells after autophosphorylation of the epidermal growth factor receptor (EGFR). We examined if mineral fibres with known carcinogenicity can be discriminated from materials with less or no carcinogenicity by their ability to up-regulate expression of EGFR protein in RPM cells in vitro. Crocidolite and erionite, two fibrous preparations with marked potential to induce mesothelioma, were associated with increases in EGFR protein expression over sham controls, whereas chrysotile asbestos and milled (non-fibrous) crocidolite did not. Intense patterns of EGFR protein expression were linked to RPM cells phagocytosing long fibres. To determine the role of EGFR expression in these cells, we assessed cell proliferation using an antibody against proliferating cell nuclear antigen (PCNA) in combination with an antibody against EGFR. In these co-localization studies, cells showed intense staining for EGFR protein 24 h before being PCNA positive at 48 h. These results suggest that carcinogenic fibres induce EGFR and initiate cell signalling cascades in mesothelial cells, leading to cell proliferation and carcinogenesis.

Animals↗

PubMed2000

Reduction of auditory P50 gating response in marihuana users: further supporting data.

This report attempts to replicate our recent finding of a significantly reduced sensory gating response in medically and psychiatrically normal chronic marihuana users. After exclusions, 10 normal heavy marihuana users (> or = 3 times per week) and 10 normal non-user controls were tested with the paired auditory P50 sensory gating procedure. Sensory gating ratios were significantly higher (i.e., impaired suppression) for THC users as compared to controls. Using combined data from the current and previous report, the degree of sensory gating impairment among THC users was significantly correlated with the frequency of marihuana use per week. Suggestions for further research are offered.

Acoustic Stimulation↗

PubMed2000

Topographic quantitative analysis of the intrinsic alpha rhythm in chronic obstructive pulmonary disease.

Twenty-two patients with documented COPD and no other significant illnesses were studied to assess the effect of varying degrees of COPD on the intrinsic alpha rhythm. The severity of COPD was determined by spirometry with assessment of FEV1, FVC, and FEV1/FVC. The alpha frequency for COPD patients was slower than that which characterizes age equated normals and averages 1.6 S.D. below normative data base mean values (range -0.43 S.D. to -1.85 S.D.). Impairment of pulmonary functioning significantly correlated with the degree of alpha frequency slowing over the posterior cortical regions, and the slowest alpha frequencies occurred in those COPD patients with the lowest FEV1/FVC ratios. Impairment of cognitive functioning is thus an important clinical consideration in treatment of patients with COPD but may go unrecognized until late in the course of the disease.

Aged↗

PubMed2000

Inadequacies of self-report data for exclusion criteria detection in marihuana research: an empirical case for multi-method direct examination screening.

Stringent exclusion criteria in drug abuse research are necessary to protect against methodological confounds compromising the interpretation of findings. However, reliance on self-report screening may fail to detect important exclusion variables. We compared three levels of exclusion criteria screening in a study of neurophysiological/neurocognitive sequelae of chronic marihuana use in normals. LEVEL 1 (self-report) consisted of telephone pre-screening. LEVEL 2 (also self-report) involved in-depth personal interviews. LEVEL 3 consisted of several direct examination assessments including a medical/psychiatric examination by a board certified psychiatrist, eight weeks of twice per week urine drug screens, an EEG exam and eight hours of neuropsychological testing. Results indicated that 39.0% of subjects passing self-report screening had significant exclusion criteria findings that were only detected through LEVEL 3 direct examination procedures. Of all subjects found to have exclusion criteria after being provisionally accepted following LEVEL 1 telephone pre-screening, 55.7% were detected only through more rigorous LEVEL 3 direct examination screening methods.

Adolescent↗

PubMed2000

Cannabinoid properties of methylfluorophosphonate analogs.

Methylarachidonylfluorophosphonate (MAFP) and related analogs have been shown to inhibit fatty acid amidohydrolase activity (FAAH), the enzyme responsible for hydrolysis of the endogenous cannabinoid ligand anandamide. To fully characterize this class of compounds, methylfluorophosphonate compounds with saturated alkyl chains ranging from C8 to C20 along with C20 unsaturated derivatives were synthesized and evaluated for their ability to interact with the CB1 receptor, inhibit FAAH, and produce in vivo pharmacological effects. These analogs demonstrated widely varying affinities for the CB1 receptor. Of the saturated compounds, C8:0 was incapable of displacing [(3)H]CP 55,940 binding, whereas C12:0 exhibited high affinity (2.5 nM). The C20:0 saturated analog had low affinity (900 nM), but the introduction of unsaturation into the C20 analogs restored receptor affinity. However, none of the analogs were capable of fully displacing [(3)H]CP 55,940 binding. On the other hand, all compounds were able to completely inhibit FAAH enzyme activity, with the C20:0 analog being the least potent. The most potent FAAH inhibitor was the short-chained saturated C12:0, whereas the other analogs were 15- to 30-fold less potent. In vivo, the C8:0 and C12:0 analogs were highly potent and fully efficacious in producing tetrahydrocannabinol (THC)-like effects, whereas the other analogs were either inactive or acted as partial agonists. None was capable of attenuating the agonist effects of THC. Conversely, the C20:0 analog potentiated the effects of anandamide but not those of 2-arachidonoyl-glycerol and THC. The high in vivo potency of the novel short-chain saturated MAFP derivatives (C8:0 and C12:0) underscores the complexity of manipulating the endogenous cannabinoid system.

Analgesics, Opioid↗

PubMed1999

Mammalian Cdk5 is a functional homologue of the budding yeast Pho85 cyclin-dependent protein kinase.

Mammalian Cdk5 is a member of the cyclin-dependent kinase family that is activated by a neuron-specific regulator, p35, to regulate neuronal migration and neurite outgrowth. p35/Cdk5 kinase colocalizes with and regulates the activity of the Pak1 kinase in neuronal growth cones and likely impacts on actin cytoskeletal dynamics through Pak1. Here, we describe a functional homologue of Cdk5 in budding yeast, Pho85. Like Cdk5, Pho85 has been implicated in actin cytoskeleton regulation through phosphorylation of an actin-regulatory protein. Overexpression of CDK5 in yeast cells complemented most phenotypes associated with pho85Delta, including defects in the repression of acid phosphatase expression, sensitivity to salt, and a G(1) progression defect. Consistent with the functional complementation, Cdk5 associated with and was activated by the Pho85 cyclins Pho80 and Pcl2 in yeast cells. In a reciprocal series of experiments, we found that Pho85 associated with the Cdk5 activators p35 and p25 to form an active kinase complex in mammalian and insect cells, supporting our hypothesis that Pho85 and Cdk5 are functionally related. Our results suggest the existence of a functionally conserved pathway involving Cdks and actin-regulatory proteins that promotes reorganization of the actin cytoskeleton in response to regulatory signals.

Actins↗

PubMed1999

Topographic quantitative EEG sequelae of chronic marihuana use: a replication using medically and psychiatrically screened normal subjects.

In two previous studies it was reported that chronic marihuana (THC) use was associated with unique quantitative EEG features which were present in the non-intoxicated state. THC users, as contrasted with controls, had significant elevations of Absolute Power, Relative Power, and Coherence of alpha activity over the bilateral frontal cortex. Furthermore, a quantitative EEG discriminant function analyses permitted a 95% correct user versus non-user classification. However, because all of the THC users and 58% of the non-user controls were psychiatric inpatients, diagnostic and medication effects, if any, were uncontrolled. In the present study the same quantitative EEG methods were used to study daily THC users and non-user controls who underwent a rigorous screening process to insure that they were medically and psychiatrically healthy. The results of previous studies were replicated and an additional EEG correlate of chronic THC exposure (reduced alpha frequency) was identified.

Adolescent↗

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

Auditory and visual P300 cognitive evoked responses in patients with COPD: relationship to degree of pulmonary impairment.

Twenty-two subjects with documented COPD and no other significant illnesses were studied to assess the effect of varying degrees of COPD on cognitive P300 auditory and visual evoked potentials. The severity of COPD was determined by spirometry with assessment of FEV1, FVC, and FEV1/FVC. Auditory P300 latency was significantly correlated with the FEV1/FVC ratio (Pearson Product Moment correlations r = -.56, N = 20, probability level = 0.1), indicating that increasingly severe airflow impairment is associated with longer auditory P300 latencies. There was no significant association of FEV1/FVC with visual P300 latency or with auditory or visual evoked potential amplitude measures. Progressive impairment of the auditory P300 evoked potential latency occurs with increasing severity of COPD. This impairment is present even in patients with mild COPD, suggesting some degree of accompanying cognitive decline early in the course of COPD with worsening as the disease progresses.

Electroencephalography↗

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↗

PubMed1999

The effects of donepezil on the P300 auditory and visual cognitive evoked potentials of patients with Alzheimer's disease.

Donepezil is a cholinesterase inhibitor used for the treatment of patients with mild to moderately severe Alzheimer's disease (AD). The purpose of this study was to determine the effect of treatment with donepezil 5 mg qd on cognitive evoked potentials (EPs) of patients with AD. Although treatment with donepezil did not normalize EP latencies, treatment was associated with a significant decrease in the auditory P300 latency (mean latency pretreatment=401. 5 msec; posttreatment=392.7 msec.; P=0.04), and the visual P300 latency (mean latency pretreatment=605.7 msec; posttreatment=580.3 msec; P=0.04). Treatment with donepezil had no discernible effect on auditory or visual P300 EP amplitudes.

Aged↗