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Biomedical subjects

B Dean

Publications and source records attributed to B Dean.

At least 19 recordsLinked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

[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↗
PubMed1997

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↗
PubMed1996

Neither protein kinase C nor adenylate cyclase are altered in the striatum from subjects with schizophrenia.

Dopamine (DA) D2 receptors which act by modulating second messenger pathways that include protein kinase C (PKC) and adenylate cyclase (AC) have been repeatedly shown to be increased in striatum from subjects with schizophrenia. Therefore it seemed possible that chronic up-regulation of DA-D2 receptors in the schizophrenic brain could result in a change in either of these two proteins. Hence we measured PKC and AC in striatum from 20 schizophrenic subjects and 20 non-schizophrenic subjects by quantitative autoradiography and could show no difference in the density of either PKC (436 +/- 35 vs. 485 +/- 29 fmol/mg tissue equivalents (TE), mean +/- SEM) or AC (77 +/- 9 vs. 80 +/- 7 fmol/mg TE) in the tissue from schizophrenic compared to the non-schizophrenic subjects. Thus, these data do not support the hypothesis that PKC or AC are changed in the schizophrenic brain.

Adenylyl Cyclases↗
PubMed1996

Decreased frontal cortical serotonin2A receptors in schizophrenia.

5HT2A receptors were measured in the frontal cortex from schizophrenic and non-schizophrenic subjects. There was a decrease in the density of 5HT2A receptors in Brodmann's areas 8, 9 and 10 from the schizophrenic subjects. In addition, there was an age-dependent decrease in the density of 5HT2A receptors in Brodmann's areas 9 from the non-schizophrenic subjects, which was absent in the schizophrenic subjects. Available evidence does not suggest that the change in 5HT2A receptors in the schizophrenic subjects was a result of drug treatment before death. These data may indicate that decreased 5HT2A receptors in the frontal cortex are involved in the pathology of schizophrenia.

Adult↗
PubMed1996

Typical and atypical neuroleptic drugs decrease platelet 3H-dopamine uptake in the rat.

Reports of opposing changes in platelet 3H-dopamine uptake in neuroleptic-free versus neuroleptic-treated schizophrenic subjects have suggested an effect of neuroleptic treatment on this measure. We examined platelet 3H-dopamine uptake in rats treated with haloperidol or clozapine to determine if such treatment did affect platelet 3H-dopamine uptake. Neuroleptic drug treatment reduced platelet 3H-dopamine uptake in a dose- and time-dependent manner. After up to 4 weeks of treatment, these effects were reversed by the discontinuation of neuroleptic drug treatment. These data suggest that the effect of neuroleptic treatment in studies of platelet 3H-dopamine uptake could account for the variable findings in schizophrenia.

Animals↗
PubMed1996

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine.

[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd = 0.50 +/- 0.04 vs. 0.24 +/- 0.02nM; mean +/- S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd = 0.50 +/- 0.07 vs. 0.50 +/- 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.

Adult↗
PubMed1996

Serotonin2 receptors and the serotonin transporter in the schizophrenic brain.

The binding of [3H]paroxetine and [3H]ketanserin to particulate membranes from frontal cortex of subjects who had or did not have schizophrenia was measured as was [3H]paroxetine binding to particulate membranes from the hippocampus and caudate nucleus. There was no change in either the affinity or density of [3H]ketanserin binding to membranes from the frontal cortex of subjects who had schizophrenia. Similarly, there was no difference in the density of [3H]paroxetine binding to membranes from subjects who had or did not have schizophrenia. The affinity of [3H]paroxetine binding in the frontal cortex and putamen did not differ in subjects who had schizophrenia. By contrast, there was a significant decrease in the affinity of [3H]paroxetine binding to the hippocampal membrane from subjects who had schizophrenia (0.40 +/- 0.06 nM vs 0.26 +/- 0.02 nM; p < 0.05). Furthermore, this difference was more apparent in the subjects who had schizophrenia and committed suicide (0.49 +/- 0.09 nM) than it was in those who had schizophrenia but did not commit suicide (0.32 +/- 0.09 nM). As [3H]ketanserin binds to the serotonin2 receptor our data suggest that this receptor is not changed in the Brodmann's area 9 of the frontal cortex. By contrast, [3H]paroxetine binds to the serotonin transporter and therefore our data suggest that the serotonin transporter is altered in the hippocampus of subjects with schizophrenia.

Adolescent↗
PubMed1996

Platelet [3H]dopamine uptake is differentially affected by neuroleptic drug treatment in schizophrenia and schizophreniform disorder.

1. The uptake of [3H] dopamine was measured using platelet-rich plasma (PRP) from neuroleptic-free subjects and again, in some cases, after the subject had been treated with neuroleptic drugs. 2. There were no differences in [3H]dopamine uptake by PRP in subjects who were or were not mentally ill. 3. After treatment with neuroleptic drugs the Km for platelet [3H] dopamine uptake had increased in 76% of subjects with schizophrenia and 87% of subjects with schizophreniform disorder. Similarly, the Vmax for platelet [3H]dopamine uptake had increased in 81% of the subjects with schizophrenia and 86% of the subjects with schizophreniform disorder. 4. By contrast, the Km for platelet [3H]dopamine uptake had decreased in 94% of subjects who had a psychoses associated with an illness other than schizophrenia or schizophreniform-disorder whilst the Vmax for platelet [3H]dopamine uptake also decreased by 94% in these subjects. 5. In subjects with psychoses, platelet [(3)H] dopamine uptake is differentially altered during neuroleptic drug treatment depending on diagnosis.

Adult↗
PubMed1996

Treatment with haloperidol or clozapine causes changes in dopamine receptors but not adenylate cyclase or protein kinase C in the rat forebrain.

The effect of treating rats with daily injections of haloperidol (1 mg/kg/day) or clozapine (20 mg/kg/day) for four weeks on second messengers and dopamine receptors was studied. The binding of [3H]forskolin to adenylate cyclase (AC), [3H]phorbol 12,13-dibutyrate (PDBu) to protein kinase C (PKC), [3H]SCH23390 binding to the dopamine D1 (DA-D1) receptor and [3H]spiperone binding to the dopamine D2 (DA-D2) receptor were measured using quantitative autoradiography. The density of AC was greatest in the caudate-putamen, nucleus accumbens and olfactory tubercle, a distribution resembling that of DA-D1 receptor. The distribution of PKC was relatively homogeneous in the forebrain. Neither haloperidol nor clozapine administration significantly altered the levels of AC or PKC in the caudate-putamen. By contrast treatment with haloperidol, but not clozapine, significantly increased the density of DA-D2 receptors in the caudate-putamen without affecting the density of DA-D1 receptors. By contrast, both haloperidol and clozapine increased the density of DA-D1 receptors in the olfactory tubercle.

Adenylyl Cyclases↗
PubMed1996

Problem of diagnosis in postmortem brain studies of schizophrenia.

OBJECTIVE: The purpose of this study was to determine 1) the reliability of diagnoses of schizophrenia at coronal autopsy and 2) the degree to which the use of different diagnostic instruments for schizophrenia would affect postmortem brain research. METHOD: Eighty-three subjects, recorded at coronal autopsy as having had schizophrenia, were referred for neurochemistry studies. The diagnoses reported to the state coroner's office were reevaluated by a review of psychiatric case histories by clinicians using semistructured assessment and diagnostic criteria. RESULTS: The application of DSM-III-R, Research Diagnostic Criteria (RDC), ICD-10, Schneiderian, and Feighner criteria to the diagnosis of the 83 subjects revealed that 63.9%, 48.2%, 48,2%, 43.4%, and 42.2%, respectively, met the criteria for schizophrenia. Highest concordance was between the RDC and ICD-10 systems, while lowest concordance was between the RDC and Schneider systems. CONCLUSIONS: These data suggest that unless carefully reviewed, diagnosis may be a major confounding factor in postmortem studies of brain tissue from subjects with schizophrenia.

Adult↗
PubMed1996

The density of muscarinic M1 receptors is decreased in the caudate-putamen of subjects with schizophrenia.

Changes in cholinergic neurons have been implicated in the pathology of schizophrenia. Clozapine, an atypical anti-psychotic drug, has been shown to bind with high affinity to the muscarinic1 (M1) receptor suggesting this receptor could be involved in the therapeutic efficacy of the drug. Because of this we measured the density of M1 receptors in the caudate-putamen, obtained at autopsy, from 19 schizophrenic subjects and 19 non-schizophrenic subjects. The density of M1 receptors was decreased in the caudate-putamen from the schizophrenic subjects (181 +/- 20 vs 287 +/- 10 fmol mg-1 TE; mean +/- s.e.m.; P < 0.001). Furthermore, preliminary studies would not suggest that the change in the density of M1 receptors in the tissue from the schizophrenic subjects had resulted from drug treatment prior to death. These data raise the possibility that changes in muscarinic receptors may be involved in the pathology of schizophrenia.

Adult↗
PubMed1995

Effect of pyridoxal 5'-phosphate on the function of the purified mitochondrial tricarboxylate transport protein.

The effect of pyridoxal 5'-phosphate (PLP), a lysine-selective reagent, on the function of the purified and reconstituted mitochondrial tricarboxylate transport protein has been studied. PLP caused a concentration-dependent inhibition of citrate transport with an IC50 value of 0.09 mM. At 10 mM PLP virtually complete inhibition of transport was observed (i.e. 97%), thereby indicating that modification of a residue(s) whose participation is essential to the translocation mechanism had occurred. Substrate protection studies demonstrated that substrates for the tricarboxylate transporter (i.e., citrate, isocitrate, phosphoenolpyruvate, and malate) effectively protected against PLP inhibition, whereas other organic anions which are not transported by the tricarboxylate carrier (i.e., malonate, alpha-ketoglutarate, phosphate, and succinate) afforded considerably less protection. Kinetic studies in which the transport rate was measured at varying citrate and PLP concentrations indicated that PLP caused an increase in the apparent Km of transport with little change in the Vmax, thereby resulting in a primarily competitive inhibition pattern. In combination, the above findings indicate that PLP interacts with the tricarboxylate transporter at a site(s) (i.e., a lysine residue(s) and/or the amino-terminal alanine residue) that is important in the translocation mechanism and may reside within or near the substrate binding site.

Animals↗