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M Davidson

Publications and source records attributed to M Davidson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study.

Intrahippocampal injections of N-methyl-D-aspartic acid (NMDA) leads to neurodegeneration in a dose-dependent manner. Chronic administration of ethanol to animals leads to CNS tolerance and dependence. Hyperexcitability following ethanol withdrawal is thought to be related to increased sensitivity of the NMDA receptors. The purpose of this study was to investigate this predisposition to hyperexcitability by intrahippocampal injection of low dose of NMDA. Using control and ethanol-withdrawn male Wistar rats, behavioural indices were determined immediately after injection and morphological damage was assessed after a period of recovery. There was significantly increased hyperactivity in the ethanol-treated rats immediately after injection. Morphological damage resulting from 5 nmol of NMDA was significantly greater in the CA3 region of the hippocampus in these animals. These data support the hypothesis that ethanol dependence and subsequent withdrawal is associated with increased sensitivity to NMDA which may underlie ethanol withdrawal-associated brain damage.

Animals↗
PubMed1995

Analysis of cybrids harboring MELAS mutations in the mitochondrial tRNA(Leu(UUR)) gene.

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), a maternally inherited mitochondrial disorder, has been associated with an A-->G transition at nucleotide 3243 and a T-->C transition at nucleotide 3271, both in the mitochondrial tRNA(Leu(UUR)) gene. We transferred mitochondria harboring these mutations into human cells lacking endogenous mtDNA (rho o cells), and analyzed the resulting transmitochondrial cytoplasmic hybrid (cybrid) cell lines for the relationship of genotype to phenotype. Cybrids containing high levels of mutated genomes showed decreased rates of synthesis of mitochondrial translation products, reduced respiratory chain function, and increased amounts of a novel unprocessed RNA species (RNA 19). Overall effects on mitochondrial functions were more severe for the MELAS 3243 cybrids as compared to the MELAS 3271 cybrids. These data, combined with our previous observations, suggest that RNA 19 may play an important, but as yet uncharacterized, role in the pathogenesis of this mitochondrial disorder.

Genes↗
PubMed1995

Cognitive functioning in chronically hospitalized schizophrenic patients: age-related changes and age disorientation as a predictor of impairment.

Although schizophrenic patients manifest cognitive impairments, there is considerable variability across patients in the severity of this impairment. Very chronic patients with a poor outcome, particularly geriatric patients, manifest the most severe impairments, which have often been characterized as resembling dementia. This study examined age-related changes in cognitive functioning in a sample of schizophrenic patients (n = 393) ranging from 25 to 95 years of age, with a specific focus on identifying aspects of performance that were impaired in the youngest patients and preserved in the oldest patients. Age disorientation was examined in detail because it was previously found to predict global intellectual impairment in chronic patients. All 22 test items changed linearly over time (with age), with aspects of orientation, concentration, and delayed recall most impaired in young patients and naming and sentence repetition most preserved in the oldest patients. Age disoriented patients had more severe cognitive impairments at each age and the age-related changes in global impairment were more severe for these patients. The prevalence of age disorientation was consistent with previous reports and a one-year retest of the sample found that age disorientation was extremely stable over time within patients. The types of functions that are preserved in the oldest patients underscore previous findings of differences between geriatric schizophrenic patients and patients with degenerative diseases and the stability of age disorientation suggests that it is a trait of a subset of schizophrenic patients, those who appear to have the most severely declining course of illness.

Adult↗
PubMed1995

A pen-and-paper human analogue of a monkey prefrontal cortex activation task: spatial working memory in patients with schizophrenia.

In order to pursue the hypothesis that the dorsolateral prefrontal cortex is a source of cognitive deficit in schizophrenia, we developed an easily administered pen-and-paper human analogue of a visuospatial working memory task that in non-human primates activates the neurons of Walker area 46 (Goldman-Rakic, 1987). Compared to normal controls, schizophrenic patients made significantly greater errors in identifying where a visuospatial stimulus had been presented to them 30 and 60 seconds earlier, and these differences were significantly greater than in an immediate recall condition. These data suggest that schizophrenic patients have visuospatial working memory deficits that are sensitive to pen-and-paper versions of the tasks that activate the Walker area 46 in non-human primates. The availability of an easily administered test that may be associated with the functioning of the prefrontal cortex may enable more specific assessment of this brain region in humans.

Adolescent↗
PubMed1995

Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals.

The safety and immunogenicity of an inactivated hepatitis A vaccine (HM175) were evaluated in 151 seronegative health professionals (age range, 21-65 years; mean, 30). A 720-ELISA unit dose was administered to 78 vaccinees at 0, 1, and 6 months and to 73 vaccinees at 0, 1, and 12 months. Seroconversion rates were 90% in both groups 1 month after the first inoculation and 99% and 100%, respectively, 1 month after the second inoculation. Geometric mean antibody titers (GMTs) 1 month after the third inoculation were highest in the group vaccinated at 0, 1, and 12 months. GMTs were higher in women than in men. The vaccine was well tolerated; the most frequent side effect was transient soreness at the site of inoculation. No serious adverse reactions were observed. Thus, HM175 inactivated hepatitis A vaccine is safe and highly immunogenic.

Adult↗
PubMed1995

Assessment of the central dopaminergic index of plasma HVA in schizophrenia.

Under fasting conditions, the dopamine (DA) metabolite homovanillic acid (HVA) in plasma originates mainly from central DA neurons or from central and peripheral noradrenergic (NA) neurons. The latter source contributes, in addition to HVA, the norepinephrine metabolites, for example, 3-methoxy-4-hydroxyphenylglycol (MHPG). It has been shown in primates that the association between HVA and MHPG in plasma or urine under varying rates of NA metabolism can be used to obtain an estimate of the central DA neuronal contribution of HVA to plasma or urine. This estimate is called the central dopaminergic index (CDI). Two studies presented here examine the applicability of this model in schizophrenia patients. The results were consistent with the proposed model and suggested that only about 30 percent of the total plasma HVA concentrations in our patients were derived from central DA neurons. A convenient modification of this model is proposed for future studies. Since the CDI of plasma HVA is not likely to be confounded by NA activity, this tool may prove useful in disentangling the roles played by the DA and NA systems in schizophrenia.

Brain↗
PubMed1995

The columnar cell variant of thyroid papillary carcinoma. Case report and discussion of an unusually aggressive thyroid papillary carcinoma.

The columnar cell variant of thyroid papillary carcinoma is an aggressive tumor associated with widespread dissemination and a fatal outcome. We report a case of a 29-year-old white woman who presented with a large thyroid mass extending into the mediastinum with local and distant metastases. The histologic features included focal papillary growth with columnar cells and nuclear stratification. However, the histologic picture was dominated by cells with a clear to vacuolated-appearing cytoplasm similar to that seen in association with secretory-type endometrium. In addition, areas of solid growth and organoid or glandular features were also identified. This tumor followed an aggressive course with widespread metastatic disease unresponsive to all therapeutic intervention. The patient died 7 months after diagnosis. We believe this tumor represents the columnar cell variant of thyroid papillary carcinoma. This is only the second reported case of columnar cell carcinoma to occur in a female. Other than the unusual occurrence in a woman, the clinical and pathologic features of this case are similar to those previously reported, including an aggressive behavior followed rapidly by the death of the patient.

Adult↗
PubMed1995

In vitro analysis of mutations causing myoclonus epilepsy with ragged-red fibers in the mitochondrial tRNA(Lys)gene: two genotypes produce similar phenotypes.

Cytoplasts from patients with myoclonus epilepsy with ragged-red fibers harboring a pathogenic point mutation at either nucleotide 8344 or 8356 in the human mitochondrial tRNA(Lys) gene were fused with human cells lacking endogenous mitochondrial DNA (mtDNA). For each mutation, cytoplasmic hybrid (cybrid) cell lines containing 0 or 100% mutated mtDNAs were isolated and their genetic, biochemical, and morphological characteristics were examined. Both mutations resulted in the same biochemical and molecular genetic phenotypes. Specifically, cybrids containing 100% mutated mtDNAs, but not those containing the corresponding wild-type mtDNAs, exhibited severe defects in respiratory chain activity, in the rates of protein synthesis, and in the steady-state levels of mitochondrial translation products. In addition, aberrant mitochondrial translation products were detected with both mutations. No significant alterations were observed in the processing of polycistronic RNA precursor transcripts derived from the region containing the tRNA(Lys) gene. These results demonstrate that two different mtDNA mutations in tRNA(Lys), both associated with the same mitochondrial disorder, result in fundamentally identical defects at the cellular level and strongly suggest that specific protein synthesis abnormalities contribute to the pathogenesis of myoclonus epilepsy with ragged-red fibers.

Cell Line↗
PubMed1995

Severity of symptoms in chronically institutionalized geriatric schizophrenic patients.

OBJECTIVE: The goal of this study was to characterize the symptoms of geriatric, chronically ill, institutionalized schizophrenic patients and investigate age-related differences in schizophrenic symptoms and cognitive performance from early adulthood to late senescence. METHOD: The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitive performance, respectively, of 393 institutionalized schizophrenic patients stratified into seven groups designated by 10-year age intervals from 25 years to over 85 years. RESULTS: In the comparisons of the seven age groups, significant differences between groups in positive and negative subscale scores on the Positive and Negative Syndrome Scale and in Mini-Mental State scores were revealed. Significant correlations between Mini-Mental State scores and Positive and Negative Syndrome Scale negative symptom scores, but not positive symptom scores, were found for all age groups, except for the youngest patients studied. Current treatment with neuroleptics and prior treatment with ECT, insulin coma, or leukotomy could not account for the poor cognitive performance of the older schizophrenic patients. CONCLUSIONS: The older schizophrenic patients continued to experience psychotic and nonpsychotic symptoms in senescence. Their positive symptoms were moderately less severe and their negative symptoms and cognitive impairment were significantly more severe than those of the younger patients. Somatic treatment appeared not to be responsible for the severe cognitive impairment and negative symptoms of the older patients. These data are relevant to chronically hospitalized geriatric schizophrenic patients but not necessarily to all geriatric schizophrenic patients.

Adult↗
PubMed1995

Validity and utility of the ADAS-L for measurement of cognitive and functional impairment in geriatric schizophrenic inpatients.

This study examined the usefulness of the Alzheimer's Disease Assessment Scale-Late Version (ADAS-L) for assessing cognitive and behavioral impairment in geriatric schizophrenic patients. Subjects were 339 geriatric schizophrenic inpatients. Discriminant function analyses compared the Mini-Mental State Examination (MMSE) with the ADAS-L as independent variables predicting the level of impairment on the criterion measure, the Clinical Dementia Rating. The ADAS-L surpassed the MMSE at correctly distinguishing severe to profound impairment; the MMSE was superior for identifying absent or questionable impairment. Findings provide evidence for the concurrent validity of the ADAS-L as an instrument for measuring impairment in geriatric schizophrenic inpatients.

Aged↗
PubMed1995

Memory functions in geriatric chronic schizophrenic patients: a neuropsychological study.

This study characterized memory functions in geriatric schizophrenic inpatients with a battery of memory tests sensitive to neuropsychological impairments in either temporal or frontal brain regions. In patients clinically rated as cognitively impaired (n = 24), nearly all of these measures showed deficits relative to less impaired patients (n = 25). Factor analysis found consistent correlations between the tests and their putative cortical localization. Discriminant analysis suggested the pattern of impairments was not consistent with a generalized deficit. These results introduce the possibility, to be directly tested with neuropathological study, that the severe cognitive deficits in elderly schizophrenic patients are due to dysfunctions in either the temporal or frontal regions of the cerebral cortex, with the specific type of dysfunction varying across cases.

Aged↗
PubMed1995

The longitudinal stability of cognitive impairment in schizophrenia. Mini-mental state scores at one- and two-year follow-ups in geriatric in-patients.

BACKGROUND: Severe cognitive impairment affects many patients with schizophrenia, especially geriatric in-patients. Little is known about the course of this impairment, however. METHOD: Two hundred and twenty-four geriatric schizophrenic in-patients were examined for changes in cognitive functioning over a one-year follow-up period, and 45 of them were assessed over a two-year period. In addition, the subset of 45 patients participated in a one-week and one-month test-retest reliability study of the instrument used to assess cognitive impairment, the Mini-Mental State Examination (MMSE). RESULTS: The average MMSE scores did not change over a one- or two-year follow-up period. The test-retest reliability of the scale was extremely good at both retest intervals. CONCLUSION: Among the implications of these data are that cognitive changes in geriatric schizophrenic patients are very slow and are more consistent with a neurodevelopmental process than a neurodegenerative course.

Aged↗
PubMed1995

Prevalence of psychiatric morbidity among remand prisoners in Scotland.

BACKGROUND: Determining the prevalence of psychiatric disorders among remand populations has been made a priority in England and Wales. Differences in legal process and psychiatric services in Scotland make similar research there important. METHOD: Demographic data were collected on 389 prisoners, the clinical Interview Schedule was completed and cognitive function assessed. RESULTS: The prevalence of major psychiatric disorders was low. Less severe symptoms were more common. The sample was of average IQ, but low educational attainment. Reported drug abuse was high. CONCLUSIONS: Few of those interviewed required hospital care, but other symptoms and drug-related problems may place heavy demands on prison medical and psychiatric services.

Adolescent↗
PubMed1995

Protocadherin Pcdh2 shows properties similar to, but distinct from, those of classical cadherins.

Cell adhesion and several other properties of a recently identified cadherin-related protein, protocadherin Pcdh2, were characterized. A chimeric Pcdh2 in which the original cytoplasmic domain was replaced with the cytoplasmic domain of E-cadherin was expressed in mouse L cells. The expressed protein had a molecular mass of about 150 kDa and was localized predominantly at the cell periphery, as was the wild-type Pcdh2. In a conventional cell aggregation assay, the transfectants showed cell aggregation activity comparable to that of classical cadherins. This activity was Ca(2+)-dependent and was inhibited by the addition of anti-Pcdh2 antibody, indicating that the chimeric Pcdh2, and probably the wild-type Pcdh2, has Ca(2+)-dependent cell aggregation activity. Mixed cell aggregation assay using L cells and different types of transfectants showed that the activity of Pcdh2 was homophilic and molecular type specific and that Pcdh2 was transfectants did not aggregate with other types of transfectants or with L cells. In immunoprecipitation, the chimeric Pcdh2 co-precipitated with a 105 kDa and a 95 kDa protein, whereas wild-type Pcdh2 co-precipitated with no major protein. Pcdh2 was easily solubilized with non-ionic detergent, in contrast to the case of classical cadherins. On immunofluorescence microscopy, the somas of Purkinje cells were diffusely stained with anti-human Pcdh2 antibody. Mouse Pcdh1 and Pcdh2 were mapped to a small segment of chromosome 18, suggesting that various protocadherins form a gene cluster at this region. The present results suggest that Pcdh2, and possibly other protocadherins as well as protocadherin-related proteins such as Drosophila fat, mediate Ca(2+)-dependent and specific homophilic cell-cell interaction in vivo and play an important role in cell adhesion, cell recognition, and/or some other basic cell processes.

Animals↗
PubMed1995

A phase II trial of prednisone, oral etoposide, and novantrone (PEN) as initial treatment of non-Hodgkin's lymphoma in elderly patients.

This phase II study was designed to improve the outcome of elderly patients with advanced aggressive non-Hodgkin's lymphomas (NHL's) by employing a novel chemotherapy regimen PEN (prednisone, oral etoposide and mitoxantrone), as initial treatment. Between July 1991 and September 1993, 43 patients (14 male, 29 female) aged 66-82 years (median 74) received 1-8 (median 4) courses of PEN (total 192) q28 days (prednisone 50 mg od x 14 days, oral etoposide 50 mg od x 14 days and mitoxantrone 8 mg/m2 i.v. day 1) in the ambulatory setting. Pathologies of patients' tumors classified by the Working Formulation (WF) included C = 4, D = 2, E = 1, F = 7, G = 25, H = 4. Eighteen patients (42%) had stage IV, 15 (35%) stage III, 9 (21%) stage II and 1 (2%) stage I disease. Nineteen patients (44%) had B symptoms, 7 (16%) primarily extranodal disease and 15 (35%) bone marrow involvement. Patients with congestive heart failure, current anti-failure medication or pretreatment Muga left ventricular ejection fraction (LVEF) of < 45% (median pretreatment 60%) were excluded from PEN. After a median follow-up of 8.5 months (range 1-30), 14 of 33 evaluable patients (42%) have achieved CR of their disease for 8+ months (range 4-19) and 6 (18%) PR for 6+ months (range 5-10), giving an overall response rate of 61%. Ten (30%) patients did not respond to PEN and 10 were not evaluable for response. Response to PEN was not predicted by any pretreatment characteristic.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Transverse vaginal septum. A case report.

A case occurred of imperforate, complete transverse vaginal septum in the lower third of the vagina. The patient presented at 16 years of age with primary amenorrhea and was found to have hematocolpos. The clinical impression was an imperforate hymen because of the very low position of the septum in the vagina. After excision the diagnosis of transverse vaginal septum was made histologically because of the presence of müllerian duct (mesodermal origin) tissue in the septum. The patient also had syndactyly of the second and third toes on her right foot. The association of these two congenital abnormalities has not been reported previously.

Adolescent↗