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Biomedical subjects

C J Gibson

Publications and source records attributed to C J Gibson.

At least 19 recordsLinked to original sources

The effects of propofol in the area postrema of rats.

UNLABELLED: Propofol has an antiemetic effect that may be mediated by gamma-aminobutyric acid (GABA) influences on the serotonin system, the mechanism of which is not known. We used three techniques, immunohistochemistry, High Performance Liquid Chromatography, and electrophysiology, to define propofol's effects on the rat's brainstem. Paired male Wistar rats received propofol, 20 mg/kg/hr, or Intralipid for 6 h. The brains were then subjected to immunohistochemical analysis of serotonin. In a separate experiment after a propofol or Intralipid infusion, cerebrospinal fluid (CSF) was extracted from the fourth ventricle and analyzed for the amount of serotonin and 5-hydroxyindoleacetic acid. Electrophysiological neuronal recordings were made in the area postrema (AP) in response to propofol with and without a GABA or serotonin antagonist. Results showed that immunohistochemical staining for serotonin in the propofol rats was significantly increased (28 +/- 12%) in the dorsal raphe and decreased in the AP (17 +/- 6%) compared with control. There were no significant changes in the isoflurane-anesthetized animals. Both serotonin and 5-hydroxyindoleacetic acid in the CSF of the fourth ventricle at the level of the AP were significantly reduced by 63% and 36%, respectively. Both propofol and pentobarbital injections reduce AP neuronal activity, but only the propofol response was blocked by bicuculline, a GABA antagonist. We conclude that the reduced levels of serotonin in the AP and the CSF may explain the antiemetic property of propofol. Propofol may also directly act on AP neurons via a GABA(A) receptor to reduce their activity. IMPLICATIONS: Propofol may produce its antiemetic effect by depleting the area postrema of serotonin as well as by a direct gamma-aminobutyric acid-mediated inhibition.

Anesthetics, Intravenous↗

Positive and negative modulation of the GABA(A) receptor and outcome after traumatic brain injury in rats.

Glutamate-mediated excitotoxicity has been shown to contribute to cellular dysfunction following traumatic brain injury (TBI). Increasing inhibitory function through stimulation of gamma-aminobutyric acid (GABA(A)) receptors may attenuate excitotoxic effects and improve outcome. The present experiment examined the effects of diazepam, a positive modulator at the GABA(A) receptor, on survival and cognitive performance in traumatically brain-injured animals. In experiment 1, 15 min prior to central fluid percussion brain injury, rats (n=8 per group) were injected (i.p.) with saline or diazepam (5 mg/kg or 10 mg/kg). Additional rats (n=8) were surgically prepared but not injured (sham-injury). Rats pre-treated with the 5 mg/kg dose of diazepam had significantly lower mortality (0%) than injured, saline-treated rats (53%). Also, diazepam-treated (5 mg/kg) rats had significantly shorter latencies to reach the goal platform in the Morris water maze test performed 11-15 days post-injury. In experiment 2, at 15 min post-injury, rats were given either saline (n=5) or 5 mg/kg diazepam (n=6). Rats treated with diazepam did not differ in mortality from injured rats treated with vehicle. However, rats treated with diazepam at 15 min post-injury had significantly shorter latencies to reach the goal platform in the Morris water maze than injured, vehicle-treated rats. In experiment 3, the post-injury administration of bicuculline (1.5 mg/kg, n=8), a GABA(A) antagonist, increased Morris water maze goal latencies compared to injured animals treated with saline (n=8). These results suggest that enhancing inhibitory function during the acute post-injury period produces beneficial effects on both survival and outcome following experimental TBI.

Animals↗

Tectal graft modulation of audiogenic seizures in Long-Evans rat.

Audiogenic seizure (AGS) activity can be induced in the seizure-resistant Long-Evans rat by postnatal priming. This study examined the effects of unilateral lesions of the inferior colliculus (IC) and implantation of tectal grafts on AGS components. Animals were primed with a 10-kHz tone burst at 120 dB on postnatal day 14 and tested for AGS susceptibility on day 28, and then two groups were unilaterally lesioned including animals receiving embryonic day 16-17 grafts of caudal tectum. Subsequently, animals were repeatedly tested for wild running and clonic-tonic convulsion components of AGS. The results demonstrate that unilaterally grafted animals with partial IC lesions showed significant reduction in the incidence of clonus expression with greater terminal uniphasic wild running behavior. These effects were stronger than in animals with comparable unilateral lesions alone. Many neurons in graft cases were in direct contact with host tissues to provide a substrate for tissue interactions previously demonstrated to promote neuron survival and remediate IC functions.

Acoustic Stimulation↗

Detection of viral pathogens by reverse transcriptase PCR and of microbial indicators by standard methods in the canals of the Florida Keys.

In order to assess the microbial water quality in canal waters throughout the Florida Keys, a survey was conducted to determine the concentration of microbial fecal indicators and the presence of human pathogenic microorganisms. A total of 19 sites, including 17 canal sites and 2 nearshore water sites, were assayed for total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, enterococci, coliphages, F-specific (F(+)) RNA coliphages, Giardia lamblia, Cryptosporidium parvum, and human enteric viruses (polioviruses, coxsackie A and B viruses, echoviruses, hepatitis A viruses, Norwalk viruses, and small round-structured viruses). Numbers of coliforms ranged from <1 to 1, 410, E. coli organisms from <1 to 130, Clostridium spp. from <1 to 520, and enterococci from <1 to 800 CFU/100 ml of sample. Two sites were positive for coliphages, but no F(+) phages were identified. The sites were ranked according to microbial water quality and compared to various water quality standards and guidelines. Seventy-nine percent of the sites were positive for the presence of enteroviruses by reverse transcriptase PCR (polioviruses, coxsackie A and B viruses, and echoviruses). Sixty-three percent of the sites were positive for the presence of hepatitis A viruses. Ten percent of the sites were positive for the presence of Norwalk viruses. Ninety-five percent of the sites were positive for at least one of the virus groups. These results indicate that the canals and nearshore waters throughout the Florida Keys are being impacted by human fecal material carrying human enteric viruses through current wastewater treatment strategies such as septic tanks. Exposure to canal waters through recreation and work may be contributing to human health risks.

Clostridium↗

Chromogranin A inhibits dopamine release from rat striatal slices.

Chromogranin A (CGA), a prohormone and a protein component of endocrine and neural secretory granules, neuritic plaques in Alzheimer's disease and Lewy bodies in Parkinson's disease, inhibited the release of dopamine (DA) from perfused rat striatal slices. Dopamine release was stimulated by a pulse of high potassium (40mM) medium introduced at 20 minutes (K1) and 55 minutes (K2) following equilibration. The ratio of K2/K1 was 0.80+/-0.04 in control tissues, but fell significantly to 0.26+/-0.08 when 100nM purified CGA was added prior to the second potassium pulse. This reduction in DA release was equivalent to that seen when calcium was excluded from the buffer (0.19+/-0.05). Pancreastatin, a centrally active peptide product of CGA, had no effect on stimulated DA release (0.77+/-0.06), although it, as well as the other treatments, did reduce basal DA release. It is likely that the parent molecule itself, CGA, or an as yet unidentified product is responsible for inhibition of K-stimulated striatal DA release.

Animals↗

Risk assessment of waterborne protozoa: current status and future trends.

Throughout the past decade much research has been directed towards identifying the occurrence, epidemiology, and risks associated with waterborne protozoa. While outbreaks are continually documented, sporadic cases of disease associated with exposure to low levels of waterborne protozoa are of increasing concern. Current methodologies may not be sensitive enough to define these low levels of disease. However, risk assessment methods may be utilised to address these low level contamination events. The purpose of this article is to provide an introduction to microbial risk assessment for waterborne protozoa. Risk assessment is a useful tool for evaluating relative risks and can be used for development of policies to decrease risks. Numerous studies have been published on risk assessment methods for pathogenic protozoa including Cryptosporidium and Giardia. One common notion prevails: microbial risk assessment presents interesting complications to the traditional chemical risk assessment paradigm. Single microbial exposures (non-threshold) are capable of causing symptomatic illness unlike traditional chemical exposures, which require a threshold to be reached. Due to the lack of efficient recovery and detection methods for protozoa, we may be underestimating the occurrence, concentration and distribution of these pathogenic micro-organisms. To better utilize the tool of microbial risk assessment for risk management practices, future research should focus in the area of exposure assessment.

Animals↗

The significance of variations in the angular correction factor in in situ gamma spectrometry.

In situ gamma spectrometry is a powerful method of assessing radioactive contamination in soil. The most widely adopted calibration methodology relates the overall sensitivity of the detector system to the product of three calibration factors: (a) the flux at the detector per unit activity in the ground phi/S(A), (b) the detected count-rate per unit flux incident normally at the detector N0/phi and (c) a correction factor to take into account the angular non-uniformity in response of the detector (Nf/N0). The dependence of the latter factor on the activity distribution with soil depth is generally neglected despite the lack of published evidence to support this. By (i) modelling and (ii) use of published experimental profiles, this work examines the range of Nf/N0 values likely to be encountered in the field. It was found that the use of a fixed angular correction factor is justified given that the maximum errors in the derived activity concentration do not exceed 5% and are far outweighed by other uncertainties.

Calibration↗

Heterotopic ossification as a complication of toxic epidermal necrolysis.

The development of heterotopic ossification (HO) as a complication of toxic epidermal necrolysis (TEN) has not been previously reported. TEN, also known as Lyell's syndrome, is a rare but serious skin disorder that typically occurs after the administration of drugs, especially sulfonamides, barbiturates, phenytoin, and nonsteroidal anti-inflammatory agents. TEN is characterized by the development of large fluid-filled bullae with separation of large sheets of skin. Complications of TEN can include extensive denudation of skin with dehydration and electrolyte abnormalities, gastrointestinal hemorrhage, acute tubular necrosis, secondary infection of denuded skin, pneumonia, bacterial conjunctivitis, keratitis, and septic infarcts of internal organs. We report a case of HO in a patient with TEN after treatment with trimethoprim-sulfamethoxazole. A 49-year-old man developed an erythematous rash, bullae, fever, and extensive skin loss consistent with a diagnosis of TEN. He was intubated for complications of TEN (pneumonia) and maintained on bed rest for several weeks. In addition, he developed HO that resulted in multiple joint contractures. He was treated with aggressive range of motion by physical therapy, surgical resection of the HO followed by radiation to both elbows, right hip, and right knee. Postoperative outpatient rehabilitation enabled improved function in his mobility and activities of daily living. HO is known to occur after spinal cord and brain injuries and burns. It has not been reported to occur after TEN. Our experience with this case suggests that HO may merit inclusion into the list of complications of TEN.

Anti-Infective Agents↗

Release of dopamine in the nucleus accumbens caused by stimulation of the subiculum in freely moving rats.

Stimulation of the ventral subiculum of the hippocampus activates the hippocampal-accumbens pathway and increases locomotor activity. Dopaminergic terminals in the nucleus accumbens have also been implicated in initiation of locomotor activity, and the release of dopamine in the nucleus accumbens is critical for locomotor responses initiated from the subiculum to occur. We have demonstrated release of dopamine in the nucleus accumbens using in vivo microdialysis after stimulation of the ventral subiculum with NMDA. Extracellular dopamine level in the nucleus accumbens was significantly increased by 40% over baseline as a result of NMDA stimulation of the ventral subiculum. This stimulation also caused more than a 40-fold increase in horizontal activity and total distance covered by the rats. Injection of saline into the subiculum caused neither a change in the dopamine level nor an increase in animal's activity. The dynamics of the measured changes in dopamine overflow correlated with the time course of locomotor changes. The results demonstrate that stimulation of the ventral subiculum causes release of dopamine in the nucleus accumbens which parallels the increase in locomotor activity.

3,4-Dihydroxyphenylacetic Acid↗

Outdoor ultraviolet exposure of children and adolescents.

The weekday and weekend outdoor ultraviolet exposure of young people from primary and secondary schools in three geographically distinct regions of England was determined over a 3-month period in summer. Ultraviolet exposure was measured using personal film badges worn by each young person, and time spent outdoors, in hourly intervals, assessed using exposure records. In each area a class of 9-10-year-old children from a primary school and a class of 14-15-year-old adolescents from a secondary school took part, giving a total of 180 subjects. We found that primary school children received higher outdoor ultraviolet exposure than young people in secondary schools, and geographical differences in exposure could not be accounted for solely by differences in ambient ultraviolet. There was little difference between the exposure of males and females. Children and adolescents did not behave as homogeneous groups with regard to exposure.

Adolescent↗

Inpatient rehabilitation: physiatric and nurse practitioner admission assessment of stroke patients and their rehabilitation outcomes.

The purpose of this study was to compare outcomes in stroke patients with two different methods of admission to an inpatient unit. Patients' outcomes were studied for 3 years. Admission screening was performed either by a physiatrist (group I, n = 93) or by a nurse practitioner (group II, n = 100). All admission decisions were made solely by the physiatrist. The outcome measures used were appropriateness of admission, discharge to home versus nursing home and functional gains measured on the Functional Independence Measure. The average length of stay was 28 days for group 1 patients and 29 days for group II. Ninety-seven per cent of group I and 94% of group II patients were considered appropriate for admission. The difference is not statistically significant (Z = 1.02). Ninety-six per cent of patients in each group were discharged home. Ninety-six per cent of group I and 89% of group II patients met the functional goals. Group I fared better than group II, and the difference between the groups (Z = 1.85) is statistically significant at p < 0.04.

Activities of Daily Living↗

Inpatient rehabilitation: the correlation between functional gains and appropriateness of admissions.

All admissions to an acute rehabilitation unit were later critiqued by the rehabilitation team to determine appropriateness of admissions. The physiatrist alone evaluated the patient for admission. From the team which worked with the patient, a physical therapist, occupational therapist and a nurse were asked to evaluate the appropriateness of the admission; a decision on appropriateness had to be supported by at least two of these three. The team scored patients with the Functional Independence Measure (FIM) on admission, weekly, and at discharge. In a six-month period there were 60 appropriate admissions and ten inappropriate admissions. The average length of stay was 38.3 days for appropriate and 17.3 days for inappropriate admissions. The appropriate gorup had an average initial FIM score of 40.6 and discharge score of 66.6. The inappropriate group started with high FIM scores, with an average of 61.0, and did not significantly improve their scores. Their average discharge score was 70.0. The rate of progress (efficiency ratio), in points per day, was 0.81 for the appropriate and 0.36 for the inappropriate group. Thus, there is a strong positive correlation between the rate of progress and appropriateness as assessed at discharge by the multidisciplinary team [corrected].

Activities of Daily Living↗

Pharmacological characterization of grooming induced by a selective NK-1 tachykinin receptor agonist.

Bilateral intranigral administration of the selective NK-1 tachykinin receptor agonist [AcArg6, Sar9, Met(O2)11]SP6-11 (0-1 nmol total bilateral dose) selectively induced grooming in rats. This response was blocked by concurrent intranigral administration of the NK-1 tachykinin receptor antagonist RP 67580 (2 nmol), but not by NK-2 (L-659,877) or NK-3 ([Trp7, beta-Ala8]NKA4-10) antagonists. Pretreatment with systemic opioid (naloxone 1.5 mg/kg) and D1 dopamine (SCH 23390 100 micrograms/kg) receptor antagonists also attenuated tachykinin-induced grooming, which was unaffected by D2 dopamine (sulpiride 30 mg/kg) or 5-HT2A+C (ritanserin 2 mg/kg) antagonists. Grooming induced by intranigral [AcArg6, Sar9, Met(O2)11]SP6-11 was also attenuated by bilateral 6-hydroxydopamine lesions of the substantia nigra. These findings indicate that grooming induced by intranigral tachykinins reflects activation of NK-1 receptors and is dependent upon endogenous dopamine and consequent selective stimulation of D1 dopamine receptors.

Animals↗

Effectiveness of bran supplement on the bowel management of elderly rehabilitation patients.

1. Constipation is a common problem in the elderly that affects up to 20% of those 65 years and older. 2. Patients receiving the fiber supplement had a significantly lower number of bowel agents per day as compared to the control patients. 3. Side effects from the additional fiber occurred in a subgroup of patients; thus, institution of additional fiber to the diets of ill, physically dependent patients is best done gradually and with close monitoring.

Aged↗

The practice of ultraviolet phototherapy in the United Kingdom.

A survey, using a postal questionnaire, was carried out to examine the current practice of UVB phototherapy in dermatology centres in the U.K. The questionnaire was sent to 115 dermatology departments, and sought information regarding the type and age of each machine used for ultraviolet B (UVB) phototherapy, methods of prescribing, recording and terminating patient exposure, and the skin conditions treated. Completed questionnaires were received from 87 of the 115 centres, giving a response rate of 76%. The survey showed that an appreciable number of U.K. phototherapy centres are using equipment which is both old, and suboptimal in producing a therapeutic response. There appeared to be a wide variation in the approach to phototherapy, both in terms of prescribing initial and incremental exposure, and in terminating treatment. The findings suggest that effectiveness and efficiency might be improved, and the risk/benefit ratio of phototherapy further reduced, by some rationalization of treatment protocols.

Dermatology↗

Chromogranin A inhibits retinal dopamine release.

Chromogranin A (CGA), a peripherally active prohormone, is a soluble component in the secretory granules of many endocrine tissues and is cosecreted with their peptide or amine hormones. Using an antibody prepared against purified rat adrenal CGA, immunostaining was localized to the inner and outer plexiform layers of the rat retina and to selected ganglion cells. Exogenous CGA (purified from human adrenals) when applied to perfused rat retina potently inhibited the potassium-induced release of endogenous dopamine (DA). This action was dose-dependent, with an IC50 of 3 nM; at 100 nM CGA retinal DA release was completely abolished.

Animals↗