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Biomedical subjects

R Gibb

Publications and source records attributed to R Gibb.

At least 19 recordsLinked to original sources
PubMed2002

Microsatellite instability, MLH1 promoter methylation, and loss of mismatch repair in endometrial cancer and concomitant atypical hyperplasia.

OBJECTIVE: MLH1 methylation is associated with the microsatellite instability (MSI) phenotype in endometrial cancer and atypical endometrial hyperplasia, a premalignant precursor to carcinoma. The observation that methylation is also seen in atypical endometrial hyperplasia without MSI suggests that methylation is an early event in endometrial tumorigenesis. Our objective was to determine if methylation is always present in MSI-positive atypical hyperplasia concomitant with MSI-positive, methylation-positive carcinoma. METHODS: We used laser capture microdissection to study MLH1 methylation and MSI in a large series of endometrial cancer cases that had previously been shown to have methylation and the MSI-high (MSI-H) phenotype. We resampled areas of carcinoma from 27 patients along with 51 foci of concomitant atypical endometrial hyperplasia. RESULTS: Consistent with previous reports, we saw MLH1 methylation in areas of atypical endometrial hyperplasia that did not show MSI. In addition, we noted that 18% of the MSI-H atypical endometrial hyperplasia DNAs lacked methylation of critical cytosines in the MLH1 promoter. Immunohistochemistry studies showed that these MSI-H unmethylated foci of atypical endometrial hyperplasia failed to express MLH1, as did regions of simple hyperplasia. CONCLUSION: Methylation of the MLH1 promoter is an early event in endometrial tumorigenesis. Given that not all MSI-positive tissues had methylation at cytosines -229 and -231, it appears that methylation may not be required for MLH1 silencing and loss of mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Neural compensations after lesion of the cerebral cortex.

Functional improvement after cortical injury can be stimulated by various factors including experience, psychomotor stimulants, gonadal hormones, and neurotrophic factors. The timing of the administration of these factors may be critical, however. For example, factors such as gonadal hormones, nerve growth factor, or psychomotor stimulants may act to either enhance or retard recovery, depending upon the timing of administration. Nicotine, for instance, stimulates recovery if given after an injury but is without neuroprotective effect and may actually retard recovery if it is given only preinjury. A related timing problem concerns the interaction of different treatments. For example, behavioral therapies may act, in part, via their action in stimulating the endogenous production of trophic factors. Thus, combining behavioral therapies with pharmacological administration of compounds to increase the availability of trophic factors enhances functional outcome. Finally, anatomical evidence suggests that the mechanism of action of many treatments is through changes in dendritic arborization, which presumably reflects changes in synaptic organization. Factors that enhance dendritic change stimulate functional compensation, whereas factors that retard or block dendritic change block or retard compensation.

Animals↗
PubMed2000

The identification and treatment of opiate users in police custody.

All detainees admitted to seven London police stations were observed over a six-month period (n=2,947). Four per cent were identified as opiate users, although the actual percentage is likely to be much higher. Compared to the general population of detainees there were significantly more women among known opiate users and this group also contained a higher percentage of white detainees and people born in the British Isles. People born in continental European countries were also over-represented. A little more than half of known users did not reveal their use on arrival at the police station. At least 60% of known opiate users remained well throughout their detention, 30% were intoxicated through drugs at the time of their arrest, but only 13% displayed signs or symptoms of withdrawal during their detention. Overall, 65% of the known opiate users were seen by a police surgeon and of these 52% were given medication. All of those withdrawing were given drug treatment, but most of those who were intoxicated by opiates, or who remained well throughout their detention, received no medication. Of those given medication 86% received an opiate, dihydrocodeine being the commonest preparation, usually in association with a benzodiazepine. Despite the adoption of differing management paradigms among police surgeons, the actual medical treatment of opiate-using detainees was pragmatic and determined by individual need.

Adult↗
PubMed2000

Cortical plasticity and the development of behavior after early frontal cortical injury.

It has been known for over 100 years that frontal lobe injury in children is often associated with considerably more functional recovery than after similar injury in adulthood. Systematic study of frontal cortical injury in laboratory animals has shown that this recovery is tightly tied to developmental age: There is a brief window of time during cortical development during which the brain is able to compensate. Simply being young is not sufficient because injury prior to this critical period leads to miserable behavioral outcomes. For humans, the least favorable time for cortical injury is likely at the end of the gestational period, perhaps including the 1st month or so of life whereas the most favorable time is around 1 to 2 years of age. In addition to age, the extent of behavioral recovery is influenced by age at assessment, the nature of the behavioral assessment, sex, and lesion size. Anatomical studies have shown that functional recovery following early cortical injury is correlated with a reorganization of remaining cortical circuitry, including increased dendritic arborization and increased spine density. Recovery, and the compensatory anatomical changes, can also be potentiated by application of different treatments including behavioral therapy, trophic factors, and neuromodulators. Finally, there is preliminary evidence in laboratory animals to suggest that it may be possible to induce neural regeneration in the injured brain and that the regenerated brain functions to support functional recovery.

Adult↗
PubMed1999

Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities.

The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant.

Abnormalities, Drug-Induced↗
PubMed1999

Multicenter evaluation of the Abbott LCx Mycobacterium tuberculosis ligase chain reaction assay.

Four Australian hospital laboratories evaluated the performance of the Abbott LCx Mycobacterium tuberculosis assay with 2,347 specimens (2,083 respiratory and 264 nonrespiratory specimens) obtained from 1, 411 patients. A total of 152 specimens (6.5%) were culture positive for Mycobacterium tuberculosis complex (MTBC); of these, 79 (52%) were smear positive. After resolution of discrepant data, the overall sensitivity, specificity, and positive and negative predictive values for the LCx assay were 69.7, 99.9, 99.1, and 97.7% respectively. For smear-positive respiratory specimens that were culture positive for MTBC, the values were 98.5, 100, 100, and 98.4%, respectively, while the values for smear-negative respiratory specimens were 41.5, 99.9, 96.4, and 98%, respectively. Relative operating characteristic curves were constructed to demonstrate the relationship between sensitivity and specificity for a range of possible cutoff values in the LCx assay. These graphs suggested that the assay sensitivity for respiratory samples could be increased from 70.2 to 78.6%, while the specificity would be reduced from 99.9 to 99.4% by inclusion of a grey zone (i.e., LCx assay values of between 0.2 and 0.99). An algorithm is presented for the handling of specimens with LCx assay values within this grey zone.

DNA Ligases↗
PubMed1998

Age, experience and the changing brain.

In this review, various aspects of how environmental experience effects the structure of the cortex at different times in the age of the animal are summarized. The interactions of brain injury and sex on the age-dependent plastic changes in the cortex are also considered. Finally, we have attempted to reach some general conclusions that describe the effects of age, experience, sex, and injury on the cortex.

Aging↗
PubMed1998

Possible regeneration of rat medial frontal cortex following neonatal frontal lesions.

The experiments described here show that the cavity left by midline frontal cortex removals at 10 days of age (P10) fills in with neural tissue. Similar changes are not found at earlier and later ages. This neuronal filling is blocked by prior pretreatment by administration of Bromodeoxyuridine (BrdU) on embryonic day 13. Administration of BrdU following the P10 lesion does not interfere with regrowth. Subsequent immunohistochemical staining for BrdU demonstrates the regrown area to be composed of newly generated cells. which include pyramidal and nonpyramidal neurons. Injections of a retrograde tracer into the striatum or posterior parietal cortex shows that the new neurons have connections similar to those of undamaged brains. The regrowth of this tissue is correlated with recovery of function in a test of forelimb use. Thus, the mammalian brain, during some privileged postnatal stages of growth. is capable of extensive reorganization that includes regeneration of lost neurons. These results are discussed in relation to the proximity of the lesion to the stem cells in the lateral ventricle and their postnatal migrational activities.

Animals↗
PubMed1997

The role of a specialist team in implementing continuing health care guidelines in hospitalized patients.

BACKGROUND: Assessment of continuing health care needs is unstandardized and often undertaken by professionals not trained in the management of complex disability. METHODS: A 6 month prospective study to evaluate the role of a specialist team in implementing continuing care guidelines in hospitalized patients. The team was responsible for assessment and facilitation of access to continuing health care throughout the hospital between hospital and community on a non-age-related basis. It had access to six inpatient beds and a budget to purchase health care after discharge for 7 days. Patients with complex disability were referred to the team if their continuing health care needs could not be assessed, improved or provided within routine practice. RESULTS: Of the 93 patients included in the study, 34 (37%) were from geriatric wards and 59 (63%) from other specialties. Twenty-six (44%) of the patients from other specialties had been inappropriately referred (no continuing health care needs) and 24 (41%) appropriate patients had not been referred because of inadequate assessments. It was possible to facilitate discharge and continuing care provision in 26 patients without transfer to dedicated beds. Thirty-two patients were transferred for further management (median length of stay 17 days). Three (9%) patients died, 20 (63%) were discharged home and six (19%) were discharged to institutional care. Three patients had to be transferred to acute care. A high level of satisfaction with support and post-discharge arrangements was reported by 26 (81%) patients, 25 (78%) carers and 26 (81%) general practitioners for patients transferred to specialist beds. CONCLUSIONS: Specialist intervention, using a team approach, facilitates effective implementation of continuing care guidelines in hospitalized patients.

Aged↗
PubMed1996

Unilateral lesions of the forelimb area of rat motor cortex: lack of evidence for use-dependent neural growth in the undamaged hemisphere.

Unilateral lesions of the forelimb area of the motor cortex have been reported to produce enhanced dendritic outgrowth in the undamaged hemisphere in response to the behavioral asymmetry produced by the lesions (e.g. Jones, T.A. and Schallert, T., Use-dependent growth of pyramidal neurons after neocortical damage, J. Neurosci, 14 (1994) 2140-2152). We attempted to replicate this result and to determine if there were sex differences in cortical plasticity using the Jones and Schallert model. Animals were given either unilateral aspiration or electrolytic lesions of the forelimb area of the motor cortex or a sham operation. Use of the forelimb ipsilateral to the lesion for postural support was assessed pre- and postsurgery. Eighteen days after surgery the animals were sacrificed. and the brains processed for Golgi-Cox staining or a series of other stains for acetylcholine, astrocytes (glial fibrillary acidic protein), and microglia (OX-42). Although the lesions produced significant behavioral asymmetry and enhanced glial response on the lesioned side, there was little evidence for use-dependent neural growth in the undamaged hemisphere in either sex.

Acetylcholine↗
PubMed1996

Does dendritic growth underly recovery from neonatal occipital lesions in rats.

Rats were given lesions of visual cortex on postnatal day 4 or 10, or in adulthood. Ninety days later they were trained on a horizontal-vertical stripes discrimination task and a visual-spatial navigation task. None of the operated rats acquired the tasks. The brains were processed for Golgi-Cox staining and dendritic arborization was quantified in the layer III pyramidal cells in somatosensory cortex. Relative to normal control brains, the neurons of the day 4 and adult operates showed a reduction in dendritic branching, whereas the neurons of the day 10 operates had a significant increase in dendritic arborization. This arborization may be related to enhanced somatosensory function but does not support recovery of visually-guided behavior.

Animals↗
PubMed1996

The entry of mentally disordered people to the criminal justice system.

BACKGROUND: The police are the gatekeepers to the criminal justice system (CJS). It is agreed that where possible mentally ill people should be diverted to psychiatric care. The purpose of this investigation was to determine what factors were associated with the entry of obviously mentally ill people into the CJS. METHOD: The population of all detainees arrested in seven London police stations was observed to determine the presence of obvious mental illness. All detainees regarded as ill or known to have significant psychiatric histories were followed through the CJS to court disposal. Defendants diagnosed as psychotic by court liaison psychiatrists were identified and the circumstances of their arrest and detention examined. RESULTS: Of all police detainees observed, 1.4% were found to be acutely ill. Diversion of obviously ill detainees was common practice. The factor most strongly associated with entry to the CJS was the presence of violence at time of arrest. Other factors were the persistence of (petty) offending and the operation of court warrants issued as a result of the person's failure to appear at court when required to do so. CONCLUSIONS: Both police and courts are well aware of the inappropriateness of custody for acutely ill people and efforts are made to divert such people out of the CJS. Persistent petty offenders are often being recycled from the street to police station to court and back to the street without the benefit of care. A dedicated facility is recommended in central London to meet this need.

Criminal Law↗
PubMed1996

Human performance during exposure to toluene.

PURPOSE: The purpose of this research was to examine the effects of inhalation of toluene on respiratory function and neuropsychological performance of humans. METHODS: We exposed six healthy adults to 100 ppm toluene or air (control) for 6 h, in a double-blind, randomized fashion, with exposures separated by at least 14 d and including 30 min of exercise at a level that quadrupled minute ventilation. Blood and exhaled air toluene levels were measured before, during, immediately, and 1 and 2 h post-exposure. Lung function was measured before and immediately after exposure. Three repetitions of two computerized neuropsychological tests were performed, including a brief standard neuropsychological battery (ANAM) and a 1-h complex performance test (SYNWORK). Statistical analysis of the psychological data was conducted as a repeated measures ANOVA. FINDINGS: Following exercise, the mean blood and exhaled air toluene levels averaged 1.5 micrograms and 28 ppm, respectively. Lung function was unchanged post-exposure. On the SYNWORK test, the Composite score obtained over time during toluene exposure was lower than that during room air (F = 29.20, p = 0.005), with the score from the final hour reduced by 10%. On standard neuropsychological tests, latency but not accuracy proved the sensitive measure for five of the seven subtests presented. CONCLUSIONS: Performance of complex tests and response time to simple brief tests can be disrupted by toluene inhalation at 100 ppm. Differences in performance between air and toluene conditions were greatest after exercise, indicating that physical activity may enhance the response to volatile organic solvents.

Adult↗
PubMed1995

No association between the c2 allele at the cytochrome P450IIE1 gene and alcohol induced liver disease, alcohol Korsakoff's syndrome or alcohol dependence syndrome.

Cytochrome P450IIE1 metabolises, and is induced by ethanol. The 5' regulatory sequence of the gene is polymorphic; that identified by the c2 allele has been shown by transfection studies to confer an increased rate of transcription. A recent report indicating an association between this allele and alcohol induced cirrhosis suggests that it may contribute to the genetic vulnerability to this disease. We have examined this polymorphism in patients of western European origin with alcohol induced cirrhosis, alcohol Korsakoff's syndrome and alcohol dependence syndrome. We were unable to detect any association between this allele and any of these diseases.

Alcohol Amnestic Disorder↗
PubMed1995

Drunkenness among police detainees.

All detainees at seven police stations within the Metropolitan Police Area were observed by the authors. Continuous 24-hour cover was provided at each station for periods of 3 weeks. The number of people arrested for offences of drunkenness was noted, as was the apparent degree of drunkenness of all detainees, irrespective of arrest offence. Arrest for drunkenness in London was strongly associated with being white and with having been born in Scotland or Ireland. Within the confines of the station, being drunk was associated with aggressiveness, with the need for medical examination and with delays in implementing interview procedures. The physical condition of many chronically drunk people was very poor and evidence of long-term self neglect was common. Formal cautioning of drunkenness offenders has effectively removed such people from the courts; in the present study only 5% of those arrested for drunkenness alone were subsequently charged. Despite this the police in London must continue to arrest and detain the drunk and incapable for want of suitable alternatives.

Adolescent↗
PubMed1994

Neonatal frontal cortical lesions in rats alter cortical structure and connectivity.

Rats were given frontal cortical lesions at day 1 or 10 of life. Later, as adults, they were either: (1) processed with Golgi-Cox in order to analyze cortical dendritic arborization; (2) given injections of True Blue into the parietal or visual cortex, or (3) given injections of [3H]leucine into the substantia nigra. An additional group of normal rats were given injections of fluorescent dyes into the cortex on day 4 or 10 of life. The main findings were that (1) adult hemispheres with day 10 lesions had greater dendritic arbor than normal hemispheres, (2) adult hemispheres with day 1 lesions had reduced dendritic branching relative to normal hemispheres, (3) adult rats with day 10 lesions had no obvious abnormalities in cortical connections, (4) adult rats with day 1 lesions had abnormal thalamo-cortical, amygdalo-cortical, and nigro-cortical connections, and (5) many of these abnormal connections were present in the brains of 4-day-old normal rats. Since the 'abnormal' connections in the very early frontal operates were present in day 4 animals, it appears that they result from the failure of exuberant connections to retract after the lesions. The increased dendritic growth in day 10 operates does not appear related to qualitative changes in cortical afferents or efferents and may related to increased intrinsic cortical connectivity. Since rats with day 10 lesions have previously been shown to exhibit significant recovery of function, it is possible that the increased dendritic arborization is supporting the functional restitution.

Aging↗