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Biomedical subjects

C Grey

Publications and source records attributed to C Grey.

At least 19 recordsLinked to original sources
PubMed2001

GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry.

GABA receptors within the mesolimbic circuitry have been proposed to play a role in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat. However, the precise GABA(A) receptor subunit(s) mediating the reinforcing properties of EtOH remains unknown. We examined the capacity of intrahippocampal infusions of an alpha5 subunit-selective ( approximately 75-fold) benzodiazepine (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)] to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v) and a saccharin solution (0.05% w/v). Bilateral (1.5-20 microgram) and unilateral (0.01-40 microgram) RY dose-dependently reduced EtOH-maintained responding, with saccharin-maintained responding being reduced only with the highest doses (e.g., 20 and 40 microgram). The competitive BDZ antagonist ZK 93426 (ZK) (7 microgram) reversed the RY-induced suppression on EtOH-maintained responding, confirming that the effect was mediated via the BDZ site on the GABA(A) receptor complex. Intrahippocampal modulation of the EtOH-maintained responding was site-specific; no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and intraventral tegmental [ventral tegmental area (VTA)] infusions was observed. Because the VTA and NACC contain very high densities of alpha1 and alpha2 subunits, respectively, we determined whether RY exhibited a "negative" or "neutral" pharmacological profile at recombinant alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors expressed in Xenopus oocytes. RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a neutral efficacy was not sufficient to explain the failure of RY to alter EtOH responding in the NACC or VTA. The results provide the first demonstration that the alpha5-containing GABA(A) receptors in the hippocampus play an important role in regulating EtOH-seeking behaviors.

Animals↗
PubMed2001

An evaluation of short-term oxygen therapy: the prescription of oxygen to patients with chronic lung disease hypoxic at discharge from hospital.

The provision of domiciliary oxygen to patients hypoxic at hospital discharge has been termed short-term oxygen therapy (STOT). This practice appears widespread, although there is a paucity of literature and no evidence-based guidelines. We undertook this audit to examine the prescription of STOT and determine the proportion fulfilling for long-term oxygen therapy (LTOT) 2 months post-discharge. STOT was defined prospectively: resting PaO2 < or = 7.3 kPa (55 mmHg) or PaO2 between 7.3 and 8.0 kPa (60 mmHg) with any of the following: clinical evidence of cor pulmonale (pedal oedema or jugular venous distension), ECG evidence of pulmonale, echocardiogram evidence of pulmonary hypertension, haematocrit > 0.55 (adapted directly from LTOT criteria). Patients were evaluated for LTOT 2 months post-discharge when clinically stable on optimal medical management. All referrals to the Auckland Regional Oxygen Service between July 1998 and 1999 were systematically reviewed. The majority 289/405 (71%) of new referrals were for the prescription of STOT/LTOT in patients with chronic lung disease: 160/289 (55%) derived from hospitalized patients with the majority 130 (81%) fulfilling criteria for STOT, median age 73, range 24-96 years. Mean hospital stay was 10.2 days. Two months after discharge 22/127 (17%) of STOT patients had died, comparable with 4/22 (18%) not fulfilling criteria for STOT. A total of 123 patients were assessed for LTOT at 2 months; 76 (62%) fulfilled criteria for LTOT. The prescription of oxygen at hospital discharge represented a considerable proportion of our referral load. There was a high mortality in the 2-month follow-up period. A significant proportion of STOT patients did not subsequently fulfill criteria for LTOT. Further prospective studies are required in order to develop evidence-based guidelines.

Adolescent↗
PubMed2000

Parasite community similarity between four Irish lakes.

A total of 140 trout were examined from four lakes in north west Ireland, Loughs Craghy, Waskel, Meela and Owennamarve. Eleven species of metazoan parasite were recorded, ten of which were of freshwater origin and Anisakissp. was the only marine species. No acanthocephalan species were found. Diphyllobothrium ditremum, D. dendriticum and Anisakissp. were the only allogenic species. Lough Owennamarve had the largest component community with nine species recorded. Lough Meela, the only brackish water lake had the smallest component community with six species recorded. Lough Waskel and Craghy had intermediate component community values. Lough Meela showed the lowest levels of similarity to any of the other lakes. Values for the Shannon-Wiener diversity index were highest for Lough Owennamarve and lowest for Lough Meela and intermediate for the other two lakes. Lough Meela had the highest values for the Simpson's dominance index and the Berger-Parker index. Lough Owennamarve had the highest Brillouin's index and Lough Meela had the lowest. The use of multiple regression techniques to control for the potentially confounding effect of geographical distance as a predictor of community similarity was discussed. No parasite species found could be considered as regionally and locally abundant and therefore described as a core species. The helminth community appears to have some degree of predictability, but chance colonization events are also important.

Animals↗
PubMed1998

The opioid receptor antagonist nalmefene reduces responding maintained by ethanol presentation: preclinical studies in ethanol-preferring and outbred Wistar rats.

Nalmefene, the 6-methylene derivative of naltrexone, was examined after subcutaneous (s.c.) (0.0001 to 8.0 mg/kg) and oral (10 to 80.0 mg/kg) administration in ethanol (EtOH)-preferring rats whose responding (i.e., lever pressing) was maintained by the presentation of EtOH. Naltrexone (0.01 to 40 mg/kg) was used as a reference opioid antagonist. EtOH (10% v/v) and saccharin (0.025 to 0.1% w/v) solutions were concurrently available for 1 hr each day under a two-lever, fixed-ratio schedule in which four responses on one lever produced the EtOH solution and four responses on the other lever produced the saccharin solution. When basal response rates for saccharin were 10% that of EtOH, all routes of nalmefene administration reduced control levels of responding maintained by EtOH by 38 to 84%. When basal response rates for saccharin-maintained responding were 60% or 82% that of EtOH, only lower s.c. naltrexone (e.g., 0.01 to 0.025 mg/kg) and nalmefene (e.g., 0.01 to 0.10 mg/kg) doses produced a selective dose-dependent suppression of EtOH-maintained responding. Higher nalmefene (0.25 to 8.0 mg/kg) and naltrexone (1.0 to 20.0 mg/kg) doses failed to produce a dose-dependent suppression on EtOH or saccharin maintained responding. Both antagonists suppressed responding maintained by EtOH primarily during the initial 10-min period, with little additional suppression occurring across the remainder of the 60-min period. Subcutaneous nalmefene was 3200- to 6400-fold more potent than oral nalmefene, suggesting bioavailability was optimized using the s.c. route. Nalmefene (0.5 mg/kg, s.c.) treatment for 10 consecutive days produced mild tolerance development, whose effects dissipated by day 8. Naltrexone (10 to 40 mg/kg) and nalmefene (1.5 to 3.0 mg/kg), given 8 to 24 hr before the test session, reduced control levels of responding maintained by EtOH by 82%. Thus, immediate opioid receptor occupancy was not required to observe antagonism. These data demonstrate that, under a variety of experimental conditions, nalmefene is an effective antagonist of responding maintained by EtOH and lend support to clinical reports that nalmefene may function as an alternative pharmacotherapy to naltrexone to reduce EtOH-motivated behavior and prevent relapse.

Alcohol Drinking↗
PubMed1996

Rates of bone loss in peri- and postmenopausal women: a 4 year, prospective, population-based study.

1. Age-related bone loss is well established but reported rates of bone loss in the spine and femur vary widely. The aim of the present study was to investigate changes in bone mineral density in the lumbar spine and proximal femur in healthy postmenopausal women. 2. One hundred and thirty-eight population-based women, aged 45-65 years, recruited from general practice registers in 1990, were assessed at baseline; 108 returned for repeat assessment 4 years later, of whom 31 had taken hormone replacement therapy for 12 months or more of the 4-year study period. Bone densitometry of the lumbar spine and proximal femur was performed by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D and oestradiol were measured by RIA and serum intact parathyroid hormone by radio-immunometric assay. 3. The mean age at follow-up was 62 years (mean of 13.6 years after menopause). Lumbar spine bone mineral density was significantly higher in women who had received hormone replacement therapy for more than 12 months during the study period than in those who had not (P < 0.01). There was no difference between these two groups in the femoral neck or trochanteric bone mineral density. In the lumbar spine, the annual change in bone mass in untreated women was -0.39% (95% confidence intervals -0.60 to -0.09; P < 0.02) whereas there was a small gain in women receiving hormone replacement therapy [+0.36% (-0.12 to 0.84; P not significant)]. The annual change in bone mass in the femoral neck and trochanter was -0.51 and -0.45 respectively in untreated women (P < 0.01 and P < 0.02), and -0.16 and -0.15 in those receiving hormone replacement therapy (P not significant). 4. Our results demonstrate relatively low rates of bone loss in the spine and proximal femur in these healthy, population-based peri- and postmenopausal women. Hormone replacement therapy appeared to be associated with a significant protective effect on spinal, but not femoral, bone mineral density.

Absorptiometry, Photon↗
PubMed1996

Vertebral deformity in the thoracic spine in post-menopausal women: value of lumbar spine bone density.

Differential bone loss in the thoracic and lumbar spine is known to occur in some patients with osteoporosis. However, the discriminant value of lumbar spine bone densitometry in the detection of thoracic spine fractures in healthy, population-based women has not been established. The relationship between lumbar spine bone mineral density and thoracic spine vertebral deformities in a prospective study of 79 post-menopausal population-based women aged 45-65 years has been investigated. Lumbar spine bone mineral density was measured using dual energy X-ray absorptiometry, and vertebral morphometry was assessed from lateral thoracic spine radiographs. Seven women (9%) were found to have one or more vertebral deformities in the thoracic spine (reduction in anterior or posterior height > 25%). Only one of these had a lumbar spine bone mineral density T score below -2.5, whilst the T score was between -1 and -2.5 in three and greater than -1 in three. Two of these women also had lumbar spine vertebral deformity but lumbar spine radiographs were normal in the remaining five. There were no significant differences in age, height, weight, hormone replacement therapy use or bone mineral density between women with and without thoracic spine fractures. These results demonstrate that vertebral deformities in the thoracic spine occur in a proportion of healthy post-menopausal women in the absence of densitometric or radiographic evidence of osteoporosis in the lumbar spine. Although often asymptomatic, the significance of these fractures lies in the increased risk of further fractures. In the future, morphometric X-ray absorptiometric techniques may prove valuable in the detection of these fractures and avoid the need for conventional radiography.

Absorptiometry, Photon↗
PubMed1991

Naloxone modulates the behavioral effects of cholinergic agonists and antagonists.

Peripheral glucose administration enhances memory in rodents and humans. Recent findings suggest that glucose may affect behavior, in part, by augmenting central cholinergic functions and by attenuating central opiate functions. The present experiments examined interactions between an opiate antagonist, naloxone, and cholinergic agents to determine whether the effects would parallel those found with glucose. Three behavioral measures were assessed: tremors, hyperactivity, and spontaneous alternation. Naloxone (1 mg/kg) significantly augmented tremors elicited by physostigmine (0.3 mg/kg). Naloxone (1 mg/kg) also attenuated increases in locomotor activity and impairments in spontaneous alternation performance elicited by scopolamine (1 and 3 mg/kg for activity and alternation measures, respectively). Thus, across three diverse measures, naloxone produced effects similar to those previously reported for glucose. These findings are consistent with the hypothesis that release of cholinergic activity from opiate inhibition may contribute to glucose effects on behavior.

Animals↗
PubMed1986

Psychosocial factors in outcome in two opiate addiction treatments.

Thirty naltrexone and 30 methadone patients in outpatient opiate addiction treatment were compared on pretreatment somatization, stress, and family support. Also, the relationship between these pretreatment variables and outcome in terms of drug abuse and retention was examined. In the methadone group, drug abuse was correlated significantly with somatization, stress, and family support. In the naltrexone group, retention was correlated significantly with somatization and stress. Treatment and research considerations were discussed.

Adult↗
PubMed1986

Influence of lid position on astigmatism.

The influence of 3 different lid positions on the astigmatism of 50 young healthy eyes was investigated with an autorefractor. The results showed that a significant amount of astigmatism may be induced when the palpebral aperture is voluntarily narrowed.

Adolescent↗
PubMed1986

Psychosocial adjustment, modality choice, and outcome in naltrexone versus methadone treatment.

Thirty naltrexone and 30 methadone patients in outpatient opiate addiction treatment were compared on pretreatment psychosocial adjustment and on short-term outcome in terms of drug abuse and retention. Also, the relationship between pretreatment psychosocial adjustment and outcome for the total sample was assessed. The naltrexone and methadone groups were generally not significantly different in pretreatment psychosocial adjustment. The two groups differed significantly in retention, but not in drug abuse outcome. Pretreatment drug abuse was significantly related to drug abuse outcome. No aspect of pretreatment psychosocial functioning was related to retention outcome. Treatment and research implications are discussed.

Adult↗
PubMed1985

The Arden gratings in optometric practice.

The use of the Arden gratings (AO contrast sensitivity system) in optometric practice is evaluated. A total of 320 patients presenting for eye examination were screened with the gratings. Sixty-four eyes (10%) gave abnormal grating scores although results from conventional examination techniques revealed no abnormality. Of the 110 abnormal eyes detected by routine examination techniques, 8 presented with normal grating scores, 6 with "borderline suspect" scores and 96 with abnormal scores. Used in isolation, the failure rate of the Arden gratings to detect ocular abnormality in the patient population was 1.3% and the "false positive" referral rate was 10%.

Adolescent↗