Decreased hippocampal (CA3) NMDA receptors in schizophrenia.
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Adult↗
Biomedical subjects
B Dean
Publications and source records attributed to B Dean.
No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia.
Changes in serotonin receptors and the serotonin transporter have been reported in the dorsolateral prefrontal cortex from subjects with schizophrenia, an area of the brain thought to be important in the pathology of the illness. To further our understanding on how such changes could play a role in the pathology of the illness, in situ radioligand binding with autoradiography was used to measure the density of the serotonin1A receptor, the serotonin4 receptor and the serotonin transporter in the dorsolateral prefrontal cortex, obtained at autopsy, from 10 schizophrenic and 10 control subjects. The binding of [3H]8-OH-DPAT to serotonin1A receptor, [3H]GR113808 to the 5HT4 receptor and [3H]citalopram to serotonin transporter was not altered in subjects with schizophrenia. significantly, only in tissue from the control subjects was there a relationship between age and the density of the serotonin4 receptor in Brodmann's areas 8 (r = 0.71, P = 0.02) and 10 (r = -0.67, P = 0.03). Importantly, this confounding factor did not influence the comparison of the density of serotonin4 receptor in the tissue from the schizophrenic and control subjects. This study has failed to show a difference in the density of serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9 and 10) from subjects with schizophrenia. These data suggest that not all serotonergic markers are altered in the dorsolateral prefrontal cortex from schizophrenic subjects.
Carrier Proteins↗
Hospital drug distribution systems in the UK and Germany--a study of medication errors.
The aim of this study was to compare the incidence of medication errors and the stages of the drug distribution system at which they occur in a United Kingdom (UK) hospital using the ward pharmacy system, a German hospital using the unit dose system and a German hospital using their traditional system. Medication errors were identified by observing the preparation and administration of regularly scheduled solid oral medication. In the UK hospital using the ward pharmacy system, the medication error rate was 8.0% (95% confidence interval 6.2-9.8%). The majority of these errors occurred at the stage of medication administration. In the hospital using the traditional German system, the error rate was 5.1% (4.4-5.8%). With the German unit dose system, the error rate was 2.4% (2.0-2.8%). In both German systems the errors were mainly attributable to the stage of transcription. It was noted that patient turnover was much higher in the wards using the ward pharmacy system and therefore the study sites may not be comparable. However, recommendations can be made in order to reduce the error rate associated with each system. Errors associated with the ward pharmacy system may be reduced if medication is stored in individual patient medicine cabinets and patients' own drugs used. Errors occurring with the traditional system and the unit dose system may be reduced if the original prescription is used for medication administration.
Data Collection↗
A comparative proteome analysis of hippocampal tissue from schizophrenic and Alzheimer's disease individuals.
The proteins expressed by a genome have been termed the proteome. Comparative proteome analysis of brain tissue offers a novel means to identify biologically significant gene products that underlie psychopathology. In this study we collected post mortem hippocampal tissue from the brains of seven schizophrenic, seven Alzheimer's disease (AD) and seven control individuals. Hippocampal proteomes were visualised by two-dimensional gel electrophoresis of homogenised tissue. A mean of 549 (s.d. 35) proteins were successfully matched between each disease group and the control group. In comparison with the control hippocampal proteome, eight proteins in the schizophrenic hippocampal proteome were found to be decreased and eight increased in concentration, whereas, in the AD hippocampal proteome, 35 proteins were decreased and 73 were increased in concentration (P<0.05). One protein, which was decreased in concentration in both diseases, was characterised as diazepam binding inhibitor (DBI) by N-terminal sequence analysis. DBI can regulate the action of the GABA(A) receptor. Protein changes involved 6% of the assessed AD hippocampal proteome, whereas, in schizophrenia protein changes involved less than 1% of the assessed hippocampal proteome. We conclude that schizophrenia has a subtle neuropathological presentation and comparative proteome analysis is a viable means by which to investigate diseases of the brain at the molecular level.
Adult↗
Growth failure in cystic fibrosis.
OBJECTIVE: The aim of this study was to describe and compare the nutritional status of children aged 0-18 years attending the cystic fibrosis (CF) clinic at the Royal Children's Hospital, Brisbane, Australia, as outpatients in 1986 and 1996. METHODOLOGY: The heights, weights and pulmonary function of children attending the CF clinic as outpatients in 1986 (n = 97) and 1996 (n = 227) were retrospectively analysed using a computerized database maintained by the CF clinic. The heights and weights were analysed in terms of z scores for height for age (HAZ), weight for age (WAZ) and weight for height (WHZ). Pulmonary function data is not available for all children. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced mid expiratory flows (FEF) were expressed as a percentage of predicted and are presented here. RESULTS: The 1986 sample consisted of 41 males (age range 0.18-14.59 years, mean age 6.52 (4.33)) and 56 females (age range 0.15-14.97 years, mean age 7.75 (3.70)). The 1996 sample consisted of 111 males (age range 0.09-17.97 years, mean age 8.80 (5.49)) and 114 females (age range 0.12-17.98 years, mean age 8.49 (5.26)). In 1986, males were shorter than females (P = 0.0096) and females had a lower mean FVC than males (P = 0.0438). In 1996, males were shorter, lighter and more wasted than females (P = 0.0357, P = 0.0034 and P = 0.0273, respectively) and females had a lower mean FEV1 and mean FVC than males (P = 0.0176 and P = 0.0079, respectively). Males in 1996 were lighter and more wasted than males in 1986 (P = 0.0023 and P = 0.0139, respectively) and had a lower mean FEV1, mean FVC and mean FEF (P < 0.0001, P = 0.0012 and P = 0.0069, respectively). Females in 1996 were shorter and lighter than females in 1986 (P = 0.0273 and P = 0.0405, respectively) and had a lower mean FEV1, mean FVC and mean FEF (P < 0.0001, P < 0.0001 and P < 0.0001, respectively). When subjects were classified according to FEV1 (FEV1 > or = 75% or FEV1 < 75%), there were no significant differences in z scores between the 1986 group and 1996 group. Similarly, when the 1986 group were matched for gender and FEV1 with the 1996 group, there were no significant differences in z scores for males or females. CONCLUSIONS: It is suggested that the apparent worsening of nutritional status among the 1996 group of CF patients is in fact due to an effect of increased survival of patients with more severe clinical symptoms. The findings from this study highlight the continuing, and in fact, worsening problem of growth failure in children with CF.
Adolescent↗
Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex.
Having shown a decrease in serotonin2A receptors in the dorsolateral prefrontal cortex (DLPFC) from schizophrenic subjects, we have now determined if this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA) 9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [3H]ketanserin binding to serotonin2A receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents (ETE); p < 0.005]. In addition, the density of [3H]muscimol binding to GABA(A) receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02). [3H]YM-09151-2, N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine, [3H]SCH 23390, [3H]mazindol, and N(G)-nitro-L-[3H]arginine binding to BA 9 did not differ between groups, and there was no specific binding of [3H]raclopride or 7-hydroxy-2-(di-n-[3H]propylamino)tetralin to BA 9 from either cohort of subjects. This suggests the density of dopamine D1-like and NMDA receptors, the dopamine transporter, and nitric oxide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin2A and GABA(A) receptors in DLPFC could indicate that these changes are involved in the pathology of schizophrenia.
Adult↗
No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia.
The A(-1438)G promoter polymorphism of the 5-hydroxytryptamine 2a receptor (5-HT2AR) gene and its influence on the cortical density of 5-HT2AR was studied using brain tissue donated at autopsy from 58 schizophrenic and 64 non-schizophrenic subjects. A linkage between genotypes for the A(-1438)G and a T102C polymorphic site identified in a previous study was observed. Our data suggest no association of the A(-1438)G polymorphism with schizophrenia and no effect of the promoter genotype upon 5-HT2AR densities in either the schizophrenic or non-schizophrenic groups.
Alleles↗
Clozapine and olanzapine treatment decreases rat cortical and limbic GABA(A) receptors.
The density of GABA(A) receptors in the hippocampus and the temporal cortex from rats treated for 28 days with either haloperidol, chlorpromazine, clozapine or olanzapine was measured. Compared to haloperidol (0.01 and 0.1 mg kg(-1) day(-1)) and chlorpromazine (0.1 and 1 mg kg(-1) day(-1)), clozapine and olanzapine (0.1 and 1 mg kg(-1) day(-1)) markedly decreased the density of GABA(A) receptors in these two brain regions. These data suggest that modulation of GABAergic transmission could be an important action of some antipsychotic drugs.
Animals↗
Reflections on technology: increasing the science but diminishing the art of nursing?
Technology has had a huge impact on the delivery of health care over the last 10-20 years and although this has been, in general, in the Intensive Care (ICU) environment, the Accident and Emergency (A & E) department has not been immune from technical developments and innovations, a trend that looks destined to continue. The impact of technological developments has given rise to much nursing literature relating to the effects technology has had in 'dehumanizing' the patients in their care, as critical care nurses in all fields endeavour to balance the need for technical competence with the traditional and still important traditional arts of nursing. This paper explores some of the definitions and terminology surrounding technology, nursing, art and science in an attempt to illustrate that technical proficiency, scientific knowledge and nursing artistry can be combined by skilled nurses to achieve a balance of care which preserves the humanity and dignity of patients and their relatives in a critical care environment.
Art↗
Confirmation of the diagnosis of schizophrenia after death using DSM-IV: a Victorian experience.
OBJECTIVE: This study examines the reliability of antemortem diagnoses of schizophrenia using DSM-IV criteria. METHOD: The case histories of 83 subjects with a provisional diagnosis of schizophrenia at autopsy were retrospectively reviewed using a semi-structured chart review and application of DSM-IV criteria. Agreement between antemortem and postmortem diagnoses of schizophrenia was examined, as well as the concordance between DSM-IV diagnoses and previously obtained diagnoses using DSM-III-R and ICD-10 criteria for schizophrenia. RESULTS: According to DSM-IV, 30.1% of cases did not have schizophrenia, compared to 36.1% using DSM-III-R criteria and 51.8% of cases using ICD-10 criteria. Concordance between DSM-IV and DSM-III-R diagnoses of schizophrenia was excellent (kappa = 0.81), but only fair between DSM-IV and ICD-10 (kappa = 0.57). Of the cases that did not meet the formal criteria for schizophrenia, the majority were reassigned diagnoses of schizoaffective disorder and affective disorder. CONCLUSIONS: The use of human brain tissue in postmortem studies of schizophrenia must be linked to standardised diagnostic assessment procedures. Diagnoses can be upgraded with the development of new criteria, providing sufficient clinical data is available in case histories.
Adult↗
Magnetic resonance image of postcraniotomy retained cotton or rayon. Case illustration.
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Adult↗
Qualifying the cytologic diagnosis of "atypical squamous cells of undetermined significance" affects the predictive value of a squamous intraepithelial lesion on subsequent biopsy.
OBJECTIVE: To evaluate whether different qualifications of a cytologic diagnosis of "atypical squamous cells of undetermined significance" predict a greater or lesser likelihood of cervical pathology. DESIGN: Comparison of different cytologic qualifications of atypical squamous cells of undetermined significance with the frequency of significant cervical disease as documented by tissue biopsy. PARTICIPANTS AND SETTING: Four hundred, fifty-two consecutive Papanicolaou smears showing atypical squamous cells of undetermined significance (diagnosed by nine cytopathologists) in women who had undergone cervical biopsy within the previous 90 days at Brigham and Women's Hospital, Boston, Mass (January-June 1995). MAIN OUTCOME MEASURE: The histopathologic diagnosis of squamous intraepithelial lesion of the cervix. RESULTS: The 452 smears were qualified as "favor reactive" (22%), "not otherwise specified" (42%), "favor squamous intraepithelial lesion" (29%), and "favor high-grade squamous intraepithelial lesion" (6%). High-grade squamous intraepithelial lesions and total squamous intraepithelial lesions were pathologically confirmed by cervical biopsy in 3.6% and 6% of the favor reactive smears, in 11% and 21% of the not otherwise specified smears, in 12% and 30% of the favor squamous intraepithelial lesion smears, and in 53% and 59% of the favor high-grade squamous intraepithelial lesion smears. Significant associations were seen between a favor reactive smear and a benign finding on cervical biopsy (94%, P = .04) and between a favor high-grade squamous intraepithelial lesion smear and a biopsy that showed a high-grade squamous intraepithelial lesion (53%, P = .00001). CONCLUSIONS: Qualifying atypical squamous cells of undetermined significance stratifies women into different risk groups for squamous intraepithelial lesion. It is reasonable for physicians to make patient management decisions based, at least in part, on such qualifications.
Biopsy↗
No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus.
BACKGROUND: Allelic association case-control analysis of a deletion/insertion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has suggested associations with unipolar disorder, bipolar disorder, depression, and Alzheimer's disease. Moreover, the heterozygous long form of the 5-HTTLPR has been associated with increased levels of mRNA for the serotonin transporter (5-HTT) and increased serotonin uptake in lymphoblastic cell lines. This study attempts to determine whether there is an association between 5-HTTLPR genotype and schizophrenia or the binding of [3H]paroxetine to the human hippocampal 5-HTT. MATERIALS AND METHODS: DNA from the cerebellum from 58 schizophrenic and 62 control subjects was used to genotype the 5-HTTLPR. In addition, the relationship between 5-HTTLPR genotype and the affinity and density of [3H]paroxetine binding to the hippocampal 5-HTT was assessed. RESULTS: There were no associations between 5-HTTLPR allotype or genotype and/or the parameters of [3H]paroxetine binding to the hippocampal 5-HTT. CONCLUSIONS: Our data suggest that 5-HTTLPR genotype neither confers an increased susceptibility for schizophrenia nor dictates the expression of the 5-HTT in the human hippocampus.
Carrier Proteins↗
Repeated antidepressant drug treatment, time of death and frequency of handling do not affect [3H]paroxetine binding in rat cortex.
[3H]Paroxetine binding to the serotonin transporter has been shown to be altered in brain tissue from schizophrenic subjects. Some schizophrenic subjects are treated with antidepressant drugs, some of which bind to the serotonin transporter and their time of death is variable. To determine if these confounding factors could affect [3H]paroxetine binding, [3H]paroxetine binding to cortical membrane from rats treated with the antidepressant drugs for 10 or 28 days and in non-treated rats that were killed at different times of the day was measured. Drug treatment, when compared to injection with 0.9% saline and time of death, did not affect [3H]paroxetine binding. Treatment with imipramine [10 days: mean +/- S.D.: 590 +/- 59 fmol/mg protein (P < 0.05); 28 days: 653 +/- 59 fmol/mg protein (P < 0.01)] or mianserin [10 days: 600 +/- 43 (P < 0.05)] caused a significant decrease in the density of [3H]paroxetine binding compared to that in fluoxetine-treated rats (10 days: 820 +/- 211 fmol/mg protein; 28 days: 764 +/- 100 fmol/mg protein). Thus, overall, these data do not suggest changes in [3H]paroxetine binding reported in the human brain tissue would be due to antidepressant drug treatment or time of death.
Animals↗
5-HT2A receptor polymorphism and steady state receptor expression in schizophrenia.
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Alleles↗
Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia.
Changes in G-protein linked neurotransmitter receptors have been reported in a number of regions of the brain of schizophrenic subjects. These changes, if functional, could cause a change in proteins such as protein kinase C (PKC) and adenylate cyclase (AC) which are important components of the G-protein linked second messenger cascades. We therefore used autoradiography to measure the distribution and density of [3H]phorbol ester binding to PKC and [3H]forskolin binding to AC in tissue obtained at autopsy from schizophrenic and non-schizophrenic subjects (Controls). There were significant decreases in the density of PKC in the parahippocampal gyrus (687 +/- 60 vs. 885 +/- 51 fmol/mg TE; mean +/- SEM; p < 0.01) and in AC in the dentate gyrus (75 +/- 4.9 vs. 92 +/- 6.5, p < 0.05) from the schizophrenic subjects. These data could indicate that changes in neurotransmitter receptors in the hippocampus from subjects with schizophrenia could have resulted in a change in their associated second messenger systems.
Adenylyl Cyclases↗
[3H]raclopride binding to brain tissue from subjects with schizophrenia: methodological aspects.
The binding of [3H]raclopride to particulate membrane and frozen sections (with quantitative autoradiography) from the caudate-putamen, obtained at autopsy from schizophrenic and non-schizophrenic subjects, was measured. The affinity of [3H]raclopride to particulate membrane was significantly decreased in the schizophrenic compared to non-schizophrenic subjects. The density of [3H]raclopride binding to tissue from subjects with schizophrenia was increased, unchanged or decreased depending on the methodology used. Finally, there was an age-dependent decrease in [3H]raclopride binding in the frozen sections from the caudate-putamen of the non-schizophrenic subjects. This age-dependent decrease was not apparent using particulate membrane from schizophrenic or non-schizophrenic subjects or tissue sections from the schizophrenic subjects. We conclude that the binding of [3H]raclopride is dependent on methodology and therefore data from in vitro and in vivo studies using this drug should be interpreted with caution.
Adult↗
Evidence-based suction management in accident and emergency: a vital component of airway care.
Effective airway management aims to establish and maintain a patent airway to ensure adequate alveolar ventilation and patient survival. Suction therapy must be regarded as a vital component of airway care, with all staff who are required to perform this procedure being aware of the principles of safe, effective suctioning. This paper provides an outline of the types of suction catheters available for use in the emergency care setting, and describes the safe procedures to be followed for both endotracheal and oro-pharyngeal suctioning. Potential complications are discussed other headings of respiratory, cardiovascular, immunological and traumatic, all of which are relevant to safe patient care whatever the setting, and all of which should be recognizable by any staff undertaking this procedure. The final section looks at the ways in which some of the complications can be minimized or detected by relating some of the more important theoretical points discussed throughout the paper to the practical situation. Suction therapy is not without risk for the patient and, although the frequency of suction therapy is far less in Accident and Emergency (A & E) than in the Intensive Care Unit, the potential dangers remain the same. In order to minimize some of the dangers and reduce confusion amongst staff, this paper concludes with a recommendation for a degree of standardization in suction catheter use.
Airway Obstruction↗