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Biomedical subjects

A Kinsella

Publications and source records attributed to A Kinsella.

At least 37 records · Page 2Linked to original sources

Phenotypic characterization of an alpha 4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse.

Neuronal nicotinic acetylcholine receptors (nAChR) are present in high abundance in the nervous system (Decker et al., 1995). There are a large number of subunits expressed in the brain that combine to form multimeric functional receptors. We have generated an alpha(4) nAChR subunit knock-out line and focus on defining the behavioral role of this receptor subunit. Homozygous mutant mice (Mt) are normal in size, fertility, and home-cage behavior. Spontaneous unconditioned motor behavior revealed an ethogram characterized by significant increases in several topographies of exploratory behavior in Mt relative to wild-type mice (Wt) over the course of habituation to a novel environment. Furthermore, the behavior of Mt in the elevated plus-maze assay was consistent with increased basal levels of anxiety. In response to nicotine, Wt exhibited early reductions in a number of behavioral topographies, under both unhabituated and habituated conditions; conversely, heightened levels of behavioral topographies in Mt were reduced by nicotine in the late phase of the unhabituated condition. Ligand autoradiography confirmed the lack of high-affinity binding to radiolabeled nicotine, cytisine, and epibatidine in the thalamus, cortex, and caudate putamen, although binding to a number of discrete nuclei remained. The study confirms the pivotal role played by the alpha(4) nAChR subunit in the modulation of a number of constituents of the normal mouse ethogram and in anxiety as assessed using the plus-maze. Furthermore, the response of Mt to nicotine administration suggests that persistent nicotine binding sites in the habenulo-interpeduncular system are sufficient to modulate motor activity in actively exploring mice.

Aggression↗

Long-term adaptive life functioning in relation to initiation of treatment with antipsychotics over the lifetime trajectory of schizophrenia.

BACKGROUND: There is evidence that the stage of illness at which antipsychotic treatment is initiated in schizophrenia may have consequences for its subsequent course. How this might relate to impaired adaptive life functioning in the long-term is poorly understood. METHODS: Thirty-eight inpatients, many of whom had been admitted in the preneuroleptic era, were assessed using the Social-Adaptive Functioning Evaluation (SAFE); constituent clinical and medication phases of the lifetime trajectory of their illnesses were then analyzed to identify predictors of SAFE score using multiple regression modeling. RESULTS: The primary, independent predictor of SAFE score was duration of initially unmedicated psychosis, which accounted for 22% of variance (p<.001) therein. Conversely, duration of subsequently treated illness, although decades longer, failed to predict SAFE score. CONCLUSIONS: These findings are consistent with some form of "progressive" process, particularly over the first several years following the emergence of psychosis, which is associated with accrual of deficits in adaptive life functioning.

Adaptation, Psychological↗

Topographical evaluation of behavioural phenotype in a line of mice with targeted gene deletion of the D2 dopamine receptor.

The phenotype of spontaneous and dopamine D2-like agonist-induced behaviour was assessed topographically in a line of mice with targeted gene deletion of the D1 receptor. An ethologically-based, rapid time-sampling behavioural check-list technique was used to resolve and quantify all behaviours in the natural repertoire of the mouse. Relative to wildtypes [D2+/+], D2-null [D2-/-] mice evidenced over a 1 h period of initial exploration modest but significant reductions in locomotion, grooming, rearing free and rearing to wall; rearing seated, sniffing, sifting and stillness were not altered. Individual elements of behaviour habituated similarly over a 6 h period for both genotypes. The dose-dependent induction of stereotyped sniffing and ponderous locomotion by the D2-like agonist RU 24213 (0.1-12.5 mg/kg) in wildtypes was essentially absent in D2-null mice. The ethogram of spontaneous behaviour in D2-null mice was characterised by only modest reductions in, and topographical shifts between, certain individual elements of behaviour. Essential abolition of D2-like agonist responsivity in D2-null mice vis-à-vis considerable preservation of spontaneous behavioural topography suggests compensatory processes subsequent to developmental absence of the D2 receptor that are able to sustain function under naturalistic, tonic conditions but not during phasic challenge.

Animals↗

Coagulase-negative staphylococcal contamination of whole blood and its components: the effects of WBC reduction.

BACKGROUND: Most bacteria present in blood components are normal skin flora, particularly Staphylococcus epidermidis and other coagulase-negative staphylococci. Growth patterns of these bacteria and the effects of different methods of component preparation may depend on variations in behavior between different isolates of the same species. STUDY DESIGN AND METHODS: Whole-blood units were inoculated with 19 different coagulase-negative staphylococcus (CNS) isolates at 1 to 10 and 10 to 100 CFUs per mL. After overnight holding at 22 degrees C, the units were processed into components. The components were cultured before inoculation and during processing, including before and after WBC reduction. RESULTS: At low inoculum levels, CNS was detected in 15 (79%) of 19 whole-blood units and in 12 (63%) of 19 RBCs after separation; after filtration, bacteria were detected in 3 (16%) of 19 (p = 0.0069). For platelet concentrates, 6 (32%) of 19 grew bacteria before filtration and 1 of 18 after filtration (difference not statistically significant). Three (16%) of 19 plasmas were positive before and after freezing. At high inoculum levels, 16 (89%) of 18 whole-blood samples and RBCs were positive before filtration; 6 (33%) of 18 RBCs were positive after filtration (p = 0.0002); 8 (44%) of 18 platelets were positive before filtration; 3 (17%) of 18 were positive after filtration (difference not statistically significant), and 7 (37%) of 18 plasma samples were positive before and after freezing. CONCLUSION: The growth characteristics of CNS in blood components vary with differences either in the subtype of bacteria or in the donor blood. Filtration reduces but does not eradicate contamination of RBCs and platelets by CNS. Plasma may act as a reservoir for CNS infection.

Blood Component Removal↗

Learning home telehealth: new opportunities.

This article outlines a telehealth training program through East Carolina University. As clinicians and managers learn more about this new way to deliver services, this course provides a needed primer of this emerging field.

Education, Nursing, Continuing↗

Labour and delivery complications at birth and later mania. An Irish case register study.

BACKGROUND: Several reports postulate that manic depression and schizophrenia share environmental risk factors. Although obstetric adversity has been suggested as a risk factor for schizophrenia, few studies have examined its relationship to bipolar affective disorder. AIMS: To assess the rate of obstetric complications incurred by patients with mania compared with controls. METHOD: From the Dublin Psychiatric Case Register we identified individuals with a discharge diagnosis of mania and traced their birth records. Each case was matched with a control of the same gender, born in the same hospital, in the same year, matched for maternal age, parity and social class. Two obstetric complications scales were used to make blind evaluations of labour and delivery data. RESULTS: Patients with mania did not experience a greater frequency or severity of labour and delivery complications than their matched controls. Rates of obstetric adversity were unrelated to the presence or absence of family history of psychiatric disorder. Obstetric adversity was unrelated to the age at first diagnosis. CONCLUSIONS: These findings suggest that obstetric adversity is not a risk factor for later mania.

Bipolar Disorder↗

Labour and delivery complications and schizophrenia. Case-control study using contemporaneous labour ward records.

BACKGROUND: Controversy continues regarding an association between obstetric complications and risk of schizophrenia in early adult life. AIMS: To compare the rate of labour and delivery complications among persons who developed schizophrenia with controls; to establish whether any complication is associated with later schizophrenia. METHOD: We located the labour ward records of 431 individuals with schizophrenia and of same-gender controls from the same hospital birth series. Mothers were matched by age, socio-economic group and parity. Individual complications were evaluated blindly using two obstetric complication scales. RESULTS: Overall, the rate of labour and delivery complications for those who developed schizophrenia did not differ from that of controls. Males who had presented to psychiatric services before the age of 30 had a greater frequency of and more severe labour/delivery complications than their matched controls. CONCLUSIONS: Other than among young-onset males we found no increase in labour and delivery complications among cases.

Case-Control Studies↗

Becoming a virtual caregiver.

The home care community is becoming increasingly familiar with the concept of telehealth services for the home, and perhaps more receptive to using such services. Telehealth services might fit well within the health care continuum as an "adjunct" to conventional services.

Caregivers↗

Geographical variation in rate of schizophrenia in rural Ireland by place at birth vs place at onset.

This study examined geographical variation in rate of occurrence of schizophrenia by place at birth vs place at onset, among a rural Irish catchment area population of unusual stability and socioeconomic homogeneity. Within a catchment area of 21,520 persons, all cases of schizophrenia were sought using current inpatient and outpatient records and key informants active in the community. Suspected cases were interviewed personally and diagnosed using DSM-III-R criteria. Place at birth and place at onset of psychosis were specified among the 32 District Electoral Divisions constituting the study region. For the 72 cases ascertained, an unremarkable overall prevalence rate/morbid risk obscured substantial and significant geographical variations therein between District Electoral Divisions. Particularly after controlling for high-density families, men demonstrated prominent geographical variation both by place at birth and by place at onset, with most men remaining unmarried and becoming ill at their place of birth; conversely, women demonstrated prominent variation by place at birth but more limited variation by place at onset, despite more frequent transitions from the parental home to the marital home before onset. Even when cases changed their location before the onset of psychosis, geographical variation in rate of occurrence of schizophrenia remained associated more strongly with factors related to the place of their birth.

Adult↗

Conservation of behavioural topography to dopamine D1-like receptor agonists in mutant mice lacking the D1A receptor implicates a D1-like receptor not coupled to adenylyl cyclase.

Though D1-like dopamine receptors [D1A/B] are defined in terms of linkage to the stimulation of adenylyl cyclase, with D1A assumed to be the functionally prepotent subtype, evidence suggests the existence of another, novel D1-like receptor without such coupling. To investigate these issues we challenged mutant mice having targeted gene deletion of the D1A receptor with selective agonists and used an ethologically-based assessment technique to resolve resultant behavioural topography. D1-like-dependent behaviour was substantially conserved in D1A-null mice relative to wild-types following challenge with each of two selective D1-like agents: A 68930 (0.068-2.0 mg/kg s.c.) which exhibits full efficacy to stimulate adenylyl cyclase, and SKF 83959 (0.016-2.0 mg/kg s.c.) which fails to stimulate adenylyl cyclase, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine. Furthermore, responsivity to the selective D2-like agonist RU 24213 (0.1-12.5 mg/kg s.c.) was conserved in D1A-null mice, indicating the integrity of D1-like:D2-like interactions at the level of behaviour. These data are consistent with behavioural primacy of a D1-like receptor other than D1A [or D1B] that is coupled to a transduction system other than/additional to adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Seasonal influences on admissions for affective disorder and schizophrenia in Ireland: a comparison of first and readmissions.

Although genetic and environmental factors operating before or around the time of birth have been demonstrated to be relevant to the aetiology of the major psychoses, a seasonal variation in the rates of admission of such patients has long been recognised. Few studies have compared first and readmissions. This study examined for seasonal variation of admission in the major psychoses, and compared diagnostic categories by admission status. Patients admitted to Irish psychiatric inpatient facilities between 1989 and 1994 with an ICD-9/10 diagnosis of schizophrenia or affective disorder were identified from the National Psychiatric Inpatient Reporting System (NPIRS). The data were analysed using a hierarchical log linear model, the chi-square test, a Kolmogorov-Smirnov (KS) type statistic, and the method of Walter and Elwood. The hierarchical log linear model demonstrated significant interactions between the month of admission and admission order (change in scaled deviance 28.77, df = 11, P < 0.003). Both first admissions with mania, and readmissions with bipolar affective disorder exhibited significant seasonality. In contrast, only first admissions with schizophrenia showed significant seasonal effects. Although first admissions with mania and readmissions with bipolar disorder both show seasonality, seasonal influences appear to be more relevant to onset of schizophrenia than subsequent relapse.

Hospitalization↗

Aspects of human factors engineering in home telemedicine and telerehabilitation systems.

Human factors engineering and system design are critical elements in the newly developing field of telerehabilitation. Telerehabilitation is the remote delivery of rehabilitative services such as monitoring, training, and long-term care of persons with disabilities using telecommunications technology. This paper describes projects at the Rehabilitation Engineering Research Center (RERC) on Telerehabilitation in the context of three conceptual models: telecounseling and training, telemonitoring and assessment, and teletherapy. Issues pertaining to human factors engineering design are identified, and ongoing challenges are discussed.

Biomedical Engineering↗

Seasonal influences on admissions in schizophrenia and affective disorder in Ireland.

Although the seasonal patterns of admissions of affective disorder have been extensively studied, less attention has been given to the seasonal admission patterns of schizophrenia. The traditional method of aggregating the data over a study period, rather than analysing by year of admission may obscure potentially relevant fluctuations in the seasonal pattern. We examined the year-to-year variation in the admission patterns of schizophrenia and affective disorder in Ireland. Using the National Psychiatric Inpatient Reporting System (NPIRS), individuals admitted with an ICD-9/10 diagnosis of a first episode of schizophrenia or affective disorder during the 6-year period 1989-1994 were identified. Seasonal variations in their admission patterns were examined statistically and graphically. There was a significant seasonal variation in the monthly admission patterns of both schizophrenia and affective disorder. This pattern was more marked for individuals with affective disorder. However, the seasonal pattern was not constant from year to year, particularly for schizophrenia.

Humans↗

p53 expression and p53 gene mutation in oral cancer and dysplasia.

BACKGROUND: The aim of the current study was to examine the possible association of the p53 tumor suppressor gene with the development of oral cancer. We examined biopsy material from patients with oral squamous cell carcinoma for p53 protein expression and p53 mutations. METHODS: Eighteen samples were analyzed. These comprised oral squamous cell carcinoma biopsy samples and oral dysplastic biopsy material taken from nine patients. An immunohistochemical technique was used to determine p53 protein expression. A direct sequencing technique was used to detect mutations in the p53 gene itself. RESULTS: Overall seven of nine (77%) oral squamous cell carcinomas and seven of nine (77%) oral dysplastic lesions analyzed showed evidence of p53 protein over-expression. Mutations in exons 5 and 6 of the p53 gene were detected in five of nine (55%) oral squamous cell carcinomas and four of nine (44%) dysplastic lesions analyzed. CONCLUSIONS: Both p53 protein over-expression and p53 mutations were noted in dysplastic oral lesions. Over-expression of the p53 protein and p53 gene mutations were not always coexistent, however, suggesting that gene mutation may be only one of the mechanisms responsible for stabilization of the p53 protein.

Carcinoma, Squamous Cell↗