Biomedical subjects

T Meehan

Publications and source records attributed to T Meehan.

At least 19 recordsLinked to original sources

PubMed2003

Cerebrospinal fluid glucose levels and sensorineural hearing loss in bacterial meningitis.

BACKGROUND: Low cerebrospinal fluid (CSF) glucose levels have been associated with sensorineural hearing loss (SNHL) in bacterial meningitis but systematic investigations are lacking. PATIENTS AND METHODS: A retrospective case control study was conducted comparing CSF glucose levels in 47 cases with and 145 controls without SNHL following bacterial meningitis. RESULTS: The mean CSF glucose level (standard deviation [SD]) was 1.3 mmol/l (1.2) in cases and 2.5 mmol/l (1.6) in controls (p < 0.001). The difference between the groups was significant for Streptococcus pneumoniae and Haemophilus influenzae but not for Neisseria meningitidis infection. It was independent of the delay of treatment if this was greater than 12 h. This delay was significantly longer in cases compared to controls. CONCLUSION: In bacterial meningitis other than that caused by N. meningitidis and independent of the duration of symptoms prior to diagnosis, CSF glucose levels were significantly lower in patients developing a SNHL compared to controls.

Biomarkers↗

PubMed2001

Trans- and cis-DNA adduct concentration in epidermis from mouse and rat skin treated ex vivo with benzo[a]pyrene diol epoxide and its corresponding chlorohydrin.

Benzo[a]pyrene diol epoxide, a metabolite of benzo[a]pyrene (BaP), and chlorohydrin, the reaction product of chloride and the epoxide, form in vitro the same trans- and cis-stereoisomeric DNA adducts, but in different proportions. In this study, we asked whether the DNA adduct concentration can be kept the same by applying the appropriate dose of (+/-)-7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE)and (+/-)-7r,8t,9t-trihydroxy-10c-chloro-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-BPDCH) to rodent skin and whether the DNA adducts formed differ only in their trans- and cis-stereoisomerism. Skin from C57Bl6 mice, spontaneous hypertension rats (SHR) and Sprague-Dawley (SD) rats was treated ex vivo immediately after the death of the animals with anti-BPDE and its corresponding bay region chlorohydrin trans-BPDCH and the epidermis was analyzed for DNA adducts 1h after the application. We found that adduct formation at the exocyclic amino groups of deoxyguanosine and deoxyadenosine in epidermal DNA followed a linear dose-response within 6--100 nmol/cm(2) with both chemicals. In order to achieve the same adduct concentration in mouse, spontaneous hypertension rat (SHR), and Sprague-Dawley (SD) rat skin, respectively, a 37-, 23- and 10-fold lower dose of anti-BPDE than of trans-BPDCH had to be applied. The order of 2'-deoxyguanosine (dGuo) adduct concentration with anti-BPDE was similar to what has been reported, but the order with trans-BPDCH was (+)-cis-BPDE-N(2)-dGuo adduct>(+)-trans-BPDE-N(2)-dGuo=(-)-trans-BPDE-N(2)-dGuo>(-)-cis-BPDE-N(2)-dGuo in mouse skin. Irrespective of species or strain, a significantly higher proportion of cis-adducts was obtained after treatment with trans-BPDCH than after treatment with anti-BPDE. Therefore, DNA adduct concentration can be kept the same by applying the appropriate dose of anti-BPDE and trans-BPDCH to rodent skin and the DNA adducts formed differ only in their trans- and cis-stereoisomerism.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2001

Inhibins, activins and follistatin: actions on the testis.

While the early studies of the inhibins, activins and follistatins concentrated on their role as endocrine regulators of FSH secretion, recent data has emphasized the local actions of the activins and follistatin. Inhibin, through its capacity to suppress FSH secretion can modulate numerous processes within the testis. However, to date, evidence to support a local role for inhibin is limited. In contrast, activin and its binding protein follistatin are produced by a large number of cell-types within the testis raising the possibility of a range of paracrine and autocrine actions. These include the modulation of androgen production, influence on the proliferation of Sertoli cells and germ cells as well as the capacity to influence the structural and functional features of mitochondria within germ cells. Some of these actions are carefully controlled in a temporal relationship during the development of testicular function in the rat in which there is no separation in time between birth and the onset of spermatogenesis. Given the range of actions of activin in different cell-types, recognition of systems that are designed to modulate its actions are crucial in enhancing our understanding of how these many roles can be compartmentalized.

Activins↗

PubMed2001

Developmental regulation of the bcl-2 family during spermatogenesis: insights into the sterility of bcl-w-/- male mice.

Expression of bcl-w, a close relative of bcl-2 is essential for male fertility in mice. Although the initial wave of spermatogenesis in bcl-w -/- mice proceeds normally until 3-4 weeks of age, adults fail to produce sperm. To clarify why bcl-w is essential for adult but not juvenile spermatogenesis, we investigated the expression pattern of eight bcl-2 family members. We found that both the level and pattern of expression varied in different cell types during juvenile and adult spermatogenesis. Anti-apoptotic genes bcl-w, bcl-2 and bcl-xL were all expressed in spermatogonia during juvenile spermatogenesis, but only bcl-w was detected in spermatogonia of adult mice. A similar shift was evident in Sertoli cells. This developmental regulation may co-ordinate physiological germ cell apoptosis in wild type mice and account for the time of onset for pathological germ cell apoptosis in bcl-w -/- animals.

Animals↗

PubMed2001

The impact of relocation on elderly patients with mental illness.

Twenty-three elderly patients with long-term mental illness were relocated from a large tertiary mental health facility to two extended care units (ECUs) in their district of origin. The patients were assessed on measures of functioning, aggression and agitation at 6 weeks pre-relocation, and again at 6 weeks and 6 months post-relocation. The impact of relocation on the group proved to be less dramatic than findings reported in the literature. The adverse affects of relocation were likely to have been offset by the preparation and planning undertaken prior to relocation, and the support provided to staff and patients in the period following relocation. The findings have implications for nursing staff involved in the relocation of people with mental illness between wards within a hospital or from one hospital to another.

Adaptation, Psychological↗

PubMed2001

Support for condom availability and needle exchange programs among Massachusetts adults, 1997.

This study was conducted to determine whether demographic factors, variables related to HIV risk status, or personal attitudes predicted public support for condom availability programs in high schools and needle exchange programs. Data for these analyses were collected from the 1997 Massachusetts Behavioral Risk Factor Surveillance System (BRFSS) among adults aged 18-64. Overall, 79% of Massachusetts adults aged 18-64 supported condom availability programs, and 60% supported needle exchange programs. Younger age was the strongest demographic predictor of support for condom availability, and higher socioeconomic status was the strongest predictor of support for needle exchange programs. Support for both programs was weakly associated with personal HIV risk status but strongly associated with positive attitudes toward teaching about HIV in schools and advising sexually active teens to use condoms. Our data suggest that there is broad-based public support for implementation of condom availability and needle exchange programs as tools for HIV prevention.

Adolescent↗

PubMed2000

Cloning and characterization of a 72-kDa inositol-polyphosphate 5-phosphatase localized to the Golgi network.

The inositol-polyphosphate 5-phosphatase enzyme family removes the 5-position phosphate from both inositol phosphate and phosphoinositide signaling molecules. We have cloned and characterized a novel 5-phosphatase, which demonstrates a restricted substrate specificity and tissue expression. The 3.9-kb cDNA predicts for a 72-kDa protein with an N-terminal proline rich domain, a central 5-phosphatase domain, and a C-terminal CAAX motif. The 3. 9-kilobase mRNA showed a restricted expression but was abundant in testis and brain. Antibodies against the sequence detected a 72-kDa protein in the testis in the detergent-insoluble fraction. Indirect immunofluorescence of the Tera-1 cell line using anti-peptide antibodies to the 72-kDa 5-phosphatase demonstrated that the enzyme is predominantly located to the Golgi. Expression of green fluorescent protein-tagged 72-kDa 5-phosphatase in COS-7 cells revealed that the enzyme localized predominantly to the Golgi, mediated by the N-terminal proline-rich domain, but not the C-terminal CAAX motif. In vitro, the protein inserted into microsomal membranes on the cytoplasmic face of the membrane. Immunoprecipitated recombinant 72-kDa 5-phosphatase hydrolyzed phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3, 5-bisphosphate, forming phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3-phosphate, respectively. We propose that the novel 5-phosphatase hydrolyzes phosphatidylinositol 3,4, 5-trisphosphate and phosphatidylinositol 3,5-bisphosphate on the cytoplasmic Golgi membrane and thereby may regulate Golgi-vesicular trafficking.

Amino Acid Sequence↗

PubMed2000

Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH.

We have demonstrated a role for activin A, follistatin, and FSH in male germ cell differentiation at the time when spermatogonial stem cells and committed spermatogonia first appear in the developing testis. Testis fragments from 3-day-old rats were cultured for 1 or 3 days with various combinations of these factors, incubated with bromodeoxyuridine (BrdU) to label proliferating cells, and then processed for stereological analysis and detection of BrdU incorporation. Gonocyte numbers were significantly elevated in cultures treated with activin, while the combination of FSH and the activin antagonist, follistatin, increased the proportion of spermatogonia in the germ cell population after 3 days. All fragment groups treated with FSH contained a significantly higher proportion of proliferating Sertoli cells, while activin and follistatin each reduced Sertoli cell division. In situ hybridization and immunohistochemistry on normal rat testes demonstrated that gonocytes, but not spermatogonia, contain the activin beta(A) subunit mRNA and protein. In contrast, gonocytes first expressed follistatin mRNA and protein at 3 days after birth, concordant with the transition of gonocytes to spermatogonia. Collectively, these data demonstrate that germ cells have the potential to regulate their own maturation through production of endogenous activin A and follistatin. Sertoli cells were observed to produce the activin/inhibin beta(A) subunit, the inhibin alpha subunit, and follistatin, demonstrating that these cells have the potential to regulate germ cell maturation as well as their own development. These findings indicate that local regulation of activin bioactivity may underpin the coordinated development of germ cells and somatic cells at the onset of spermatogenesis.

Activins↗

PubMed2000

The roles of inhibin and related peptides in gonadal function.

Inhibin A and B are dimeric proteins capable of suppressing FSH both in vitro and in vivo. The principal form in the male is inhibin B which is produced in the testis and circulates to inhibit pituitary FSH secretion. Activin A, B and AB are dimeric proteins that share the same beta subunits with the inhibins but, in contrast, stimulate FSH secretion. Although activin A circulates, castration does not lead to a decrease in serum concentrations, indicating that the testis is not the major source of activin A. In the circulation, the activins are bound to a structurally unrelated binding protein, follistatin, that neutralizes the biological actions of these proteins. The subunits of the inhibins/activins as well as follistatin are also produced locally within the pituitary and their levels can be modulated by testosterone and gonadotrophin releasing hormone as well as by autocrine mechanisms. Consequently, the output of FSH is dependent of the balance between local processes and the circulating feedback exerted by testosterone and inhibin. There is increasing data to support the local gonadal production of not only inhibin but also activin and follistatin by both germ cells and somatic cells such as the Sertoli cells. Evidence is accumulating to support the concept that these proteins exert local regulatory mechanisms in the testis.

Activins↗

PubMed2000

Patients' perceptions of seclusion: a qualitative investigation.

Twelve patients receiving acute in-patient psychiatric care in Queensland, Australia, participated in semi-structured interviews to elicit their perceptions of seclusion. All respondents had experienced time in seclusion within the 7 days prior to interview. Interviews were audiotaped, transcribed and analysed using content analysis. Five major themes emerged: use of seclusion, emotional impact, sensory deprivation, maintaining control and staff-patient interaction. The prevailing negativity towards seclusion underscores the need for ongoing critical review of its use. In particular, the relationship between patient responses to seclusion and the circumstances in which seclusion takes place requires greater consideration. Interventions such as providing information to patients about seclusion, increased interaction with patients during seclusion, attention to privacy and effective debriefing following seclusion may help to reduce the emotional impact of the practice.

Adaptation, Psychological↗

PubMed2000

Development and validation of clinical indicators for mental health nursing practice.

A national study was undertaken in Australia to develop and validate a set of clinical indicators for mental health nursing. Using survey and action research procedures, the indicators were developed in two stages. During stage one, focus group interviews involving 39 nurses were conducted at national conferences in Australia and New Zealand in order to provide a pool of indicator statements. A Delphi survey of an Australian sample of mental health nurses (n = 33) was then conducted to refine the indicators. In stage two, the refined indicators were tested and validated in selected clinical settings. A total of 1751 mental health nurses employed at 14 sites were involved in the second stage of the study. The resulting data were used to establish the set of national indicators that the Australian and New Zealand College of Mental Health Nurses will use in practice accreditation and benchmarking.

Australia↗

PubMed2000

The use of the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) in clinical practice.

Forty-four mental health clients completed the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS)--a self-rating scale to assess the prevalence and intensity of neuroleptic side-effects. In the month prior to the study, 50% of the clients surveyed had experienced more than half of the side-effects outlined on the 41-item scale. A prevalence profile allowed us to rank the frequency of individual side-effects across the sample. Some side-effects such as 'difficulty concentrating', 'difficulty remembering', 'tiredness' and 'restlessness' were experienced by most of the clients in the study while 'unusual skin marks', 'difficulty passing water', 'rashes' were experienced by a few. A prevalence profile may be a useful guide in developing strategies for managing side-effects more effectively in small groups of clients. In addition, the use of the LUNSERS in clinical practice would enable case managers to establish baseline measures for individual clients and evaluate changes in medication and other non-medical strategies for reducing unwanted side-effects. The identification and assessment of antipsychotic side-effects is an important area for client and professional carer education.

Adolescent↗

PubMed2000

Enhancing case managers' skills in the assessment and management of antipsychotic medication side-effects.

OBJECTIVE: Our goal was to reduce the prevalence of antipsychotic medication side-effects by providing a short-term training program on the assessment and management of side-effects to case managers. METHOD: Forty-four patients in receipt of community-based mental health services were allocated to comparison (n = 20) and intervention (n = 24) groups based on the health service district in which they resided. While case managers working with the intervention group attended a short-term training program to improve their assessment and management of neuroleptic side-effects, case managers providing services to the comparison group received no additional training. Side-effects were assessed pre- and postintervention using the Liverpool University Neuroleptic Side-effect Rating Scale (LUNSERS). RESULTS: A reduction in the overall prevalence of side-effects in both groups was observed, however, only those patients in the intervention group reported a statistically significant reduction in mean side-effect scores between the pre- and postmeasures (Wilcoxon Matched Pairs Signed-ranks Test, z = -2.8411, two-tailed, p < 0.01). In addition, qualitative data collected during the second survey revealed that patients in the intervention group had acquired some positive management strategies for dealing with unwanted side-effects. The strategies were elicited from eight different patients distributed across six of the 12 case managers who took part in the training program. CONCLUSIONS: Training cases managers in the assessment and management of side-effects may help to reduce their impact on the lives of people prescribed neuroleptic medication.

Adolescent↗

PubMed1999

Application of morphometric techniques to postnatal rat testes in organ culture: insights into testis growth.

The extent of Sertoli cell proliferation during fetal and neonatal development determines the final adult testis size and potential for sperm output. To gain further knowledge of the factors that regulate Sertoli cell proliferation, the present study used a new approach to analyse changes in morphology and proliferation in the postnatal testis by combining organ culture with morphometric analysis. Fragments of rat testes from days 0 to 10 postpartum were cultured in contact with DMEM for 6 h or 72 h and fixed. The effects of ovine follicle-stimulating hormone (FSH) and activin were studied in an additional 72-h organ culture experiment using day 9 testes. Bromodeoxyuridine (BrdU) was added for the last 6 h of culture to mark proliferating cells. Two-microm sections of the fragments were analysed for morphological changes of the seminiferous cords, and the proportion of BrdU-labelled Sertoli and germ cells was determined. Assessment of 6-h samples revealed growth characteristics consistent with those observed in vivo during days 1-10 of postnatal development. From day 2 onwards, the volume fraction of seminiferous cords began to increase, while significant growth in cross-sectional area of the cords occurred only after day 6. In these culture conditions, germ cell proliferation and testicular architecture was consistent with that expected for the age of the tissue at time of explant. The proportion of dividing Sertoli cells declined from 15-20% at days 0-4 postpartum to below % at day 10 postpartum in the 6-h culture, and it was low or abolished in the 3-day culture at all time points. Activin and FSH together, but not singly, stimulated Sertoli cell proliferation in the 72-h culture. This paper presents a new approach to analysis of in vitro testis development. The combination of fragment culture and stereological analysis permits rigorous and detailed assessment of developmental changes in the postnatal testis.

Activins↗

PubMed1999

Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa.

The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11-13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology.

Amino Acid Sequence↗

PubMed1999

Factors influencing nurse-patient interaction in the acute psychiatric setting: an exploratory investigation.

Nurse-patient interaction in acute psychiatric in-patient facilities has been the subject of much discussion in the literature and remains a contentious issue. How and why nurses interact with patients in the acute care setting requires definition within the current dynamic environment of mental health service provision. Factors which impact on the manner in which nurses care for patients also require investigation. This article presents the findings of a collaborative research study that investigates factors that influence nurse-patient interaction in the acute psychiatric setting. Ten nurses on the study ward were given opportunity, through semi-structured interviews, to outline and describe the factors perceived to influence nurse-patient interaction. Factors identified as influencing interaction included the ward environment, something always comes up, nurses' attributes, patient factors, instrumental support and focus of nursing. Issues which emerged from the study provide managers and clinical nurses with an opportunity for generating new possibilities for nurse-patient interaction. However, these issues must be addressed in a sensitive way that takes into account the complex and dynamic nature of acute care settings.

Acute Disease↗

PubMed1999

Absconding behaviour: an exploratory investigation in an acute inpatient unit.

OBJECTIVE: The aim of this study is to identify patient and environmental characteristics associated with absconding behaviour, and to gain an understanding of the behaviour from the patients' perspective. METHOD: A prospective analysis of 77 consecutive incidents of absent-without-leave (AWOL) behaviour (n = 51 patients) was undertaken to develop a profile of patient and environmental characteristics associated with absconding behaviour. In addition, semi-structured interviews were carried out with a subsample of 14 patients within 24 h of returning to hospital from being AWOL. RESULTS: Those who absconded were male (58%), under 40 years of age (74%), admitted involuntarily (78%), and had a diagnosis of schizophrenia (42%). One-third of all AWOL incidents resulted from repeated absconding by the same individuals. The first 7 days post admission was a high-risk period for absconding behaviour. Issues raised in the interviews with patients identified a number of situational and environmental factors which are likely to increase the risk of absconding. CONCLUSIONS: Situational and environmental factors are more likely than patient characteristics to be predictive of absconding behaviour.

Adult↗

PubMed1998

Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise redundant.

Proteins of the Bcl-2 family are important regulators of apoptosis in many tissues of the embryo and adult. The recently isolated bcl-w gene encodes a pro-survival member of the Bcl-2 family, which is widely expressed. To explore its physiological role, we have inactivated the bcl-w gene in the mouse by homologous recombination. Mice that lack Bcl-w were viable, healthy, and normal in appearance. Most tissues exhibited typical histology, and hematopoiesis was unaffected, presumably due to redundant function with other pro-survival family members. Although female reproductive function was normal, the males were infertile. The testes developed normally, and the initial, prepubertal wave of spermatogenesis was largely unaffected. The seminiferous tubules of adult males, however, were disorganized, contained numerous apoptotic cells, and produced no mature sperm. Both Sertoli cells and germ cells of all types were reduced in number, the most mature germ cells being the most severely depleted. The bcl-w-/- mouse provides a unique model of failed spermatogenesis in the adult that may be relevant to some cases of human male sterility.

Animals↗