Biomedical subjects

M Davidson

Publications and source records attributed to M Davidson.

At least 19 recordsLinked to original sources

PubMed1996

Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.

BACKGROUND: Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. METHODS: We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin (75 mg per square meter of body-surface area) with either cyclophosphamide (750 mg per square meter) or paclitaxel (135 mg per square meter over 24 hours). RESULTS: Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin-paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin-paclitaxel group responded to therapy, as compared with 60 percent in the cisplatin-cyclophosphamide group (P = 0.01). The frequency of surgically verified complete response was similar in the two groups. Progression-free survival was significantly longer (P < 0.001) in the cisplatin-paclitaxel group than in the cisplatin-cyclophosphamide group (median, 18 vs. 13 months). Survival was also significantly longer (P < 0.001) in the cisplatin-paclitaxel group (median, 38 vs. 24 months). CONCLUSIONS: Incorporating paclitaxel into first-line therapy improves the duration of progression-free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer.

Adult↗

PubMed1995

In vivo pharmacological study of spermine-induced neurotoxicity.

Spermine-induced neurotoxicity and its pharmacological manipulation was studied in the rat striatum in vivo. Spermine (50, 100, 250 nmol) was injected into the striatum and the volume of damage quantified by computer-based image analysis. Spermine produced a dose-dependent increase in the volume of damage. Co-administration of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate; dizocilpine, 60 nmol), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (25, 40 nmol) and pretreatment with pentobarbital (40 mg/kg, i.p.) significantly reduced the volume of damage induced by 100 nmol spermine. MK-801 (30 nmol) was also effective in reducing the damage induced by 50 nmol spermine. Treatment with a specific inhibitor of nitric oxide synthase, N omega-nitro-L-arginine methyl ester (50 mg/kg, i.p., twice daily for 10 days) was ineffective. These results suggest an involvement of both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the cascade of spermine-induced neurotoxicity.

Animals↗

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

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

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↗

PubMed1994

Immunogenicity of pneumococcal revaccination in patients with chronic disease.

BACKGROUND: To prevent serious pneumococcal infections, 23-valent pneumococcal polysaccharide vaccine is recommended for individuals over 24 months of age with chronic predisposing diseases and for healthy older adults. This nonrandomized controlled study in rural Alaska assessed the immunogenicity of revaccination in adults. METHODS: Twenty-six adults, 33 to 88 years of age, vaccinated a mean of 7.4 years before this study, were matched to 26 previously unvaccinated subjects by age, number of chronic diseases, sex, and ethnicity. One or more chronic diseases were validated in 62% of subjects (32 of 52). All received a first or second intramuscular dose of pneumococcal vaccine. Antibody levels were determined by radioimmunoassay for 12 pneumococcal capsular serotypes immediately before and 20 to 84 days after vaccination. RESULTS: Six to 9 years after primary vaccination, over one third of serotype-specific antibody levels were below 500 ng of antibody nitrogen per milliliter, equal to the percentage in unvaccinated subjects of similar age. Antibody levels against all pneumococcal serotypes rose to similar levels after primary vaccination and revaccination, and 54% and 55%, respectively, of subjects who received primary vaccination and revaccination had at least a 1.4-fold increase in antibody levels. Only the antibody level for serotype 4 remained low. Neither gender nor age affected peak response. For those with chronic diseases, there was a trend toward fewer low antibody levels against three or more serotypes after revaccination (two subjects [13%]) than after primary vaccination (five subjects [31%]). CONCLUSIONS: Following the initial immunization of high-risk and elderly patients with pneumococcal polysaccharide, pneumococcal antibody levels appear to wane with time. Primary vaccination and revaccination 6 or more years after a first dose of pneumococcal vaccine stimulate comparable mean antibody levels.

Adult↗

PubMed1994

Adverse reactions in cattle to a capripox vaccine.

Capripox vaccine (strain 0240) caused severe generalised skin reactions in vaccinated dairy cattle in two herds, whereas beef cattle did not develop reactions. All the reacting animals developed lumpy skin disease-like lesions. The incidence of skin lesions in first-lactation cows in herd A was 22.9 per cent and in herd B 29.3 per cent, mainly in the post-calving period. In older cows, the incidence was 10 per cent in herd A and 12.4 per cent in herd B. In herd B the high-yielding lactating cows were the most severely affected. There was a decrease of 3.5 per cent in milk production in each herd over a period of 12 days, and six first calving animals (3.5 per cent) and six cows (1.5 per cent) were slaughtered. A capripox virus was isolated from the animals with severe lesions, and was also demonstrated by electron microscopy. The histopathological lesions were similar to those of lumpy skin disease. The extent of the lesions appeared to be stress-related and, to a lesser degree, correlated with age and breed.

Animals↗

PubMed1994

Clozapine treatment and its effect on neuroendocrine responses induced by the serotonin agonist, m-chlorophenylpiperazine.

The effects of clozapine treatment on neuroendocrine responses induced by the serotonin agonist, m-chlorophenylpiperazine (mCPP) were examined. mCPP and placebo were administered after a 2-week drug-free period and again after 5 weeks of clozapine treatment in nine schizophrenic inpatients. Adrenocorticotropic hormone (ACTH), prolactin, and mCPP levels were measured. Clozapine treatment completely blocked mCPP-induced ACTH and prolactin release suggesting that clozapine blocks serotonin receptors that mediate these hormone responses.

Adrenocorticotropic Hormone↗

PubMed1994

Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction.

Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction have a high but variable annual mortality and some may benefit from myocardial revascularization. This study aimed to evaluate the prognostic value of positron emission tomography (PET), and its interrelation with the choice of medical therapy or revascularization for predicting survival and improvement in symptoms of heart failure in patients with CAD and LV dysfunction. Ninety-three consecutive patients with angiographic CAD and a mean LV ejection fraction of 0.25 who underwent cardiac PET studies for assessment of hypoperfused yet viable myocardium ("mismatch pattern") using N-13 ammonia and 18-F deoxyglucose were followed up for an average of 13.6 months. Fifty patients underwent medical treatment and 43 underwent revascularization. The Cox model analysis showed that the extent of mismatch had a negative effect (p = 0.02), whereas revascularization had a positive effect on survival (p = 0.04). The annual survival probability of patients with mismatch receiving medical therapy was lower than of those without mismatch (50 vs 92%, p = 0.007). Patients with mismatch who underwent revascularization had a higher survival rate than those treated medically (88 vs 50%, P = 0.03). The presence of mismatch also predicted improvement in heart failure symptoms after revascularization (p < 0.001). These results suggest that the presence of mismatch in patients with CAD and severe LV dysfunction is associated with poor annual survival with medical therapy. Revascularization in patients with PET mismatch appears to be associated with improved survival and heart failure symptoms.

Aged↗

PubMed1994

Myocardial viability in asynergic regions subtended by occluded coronary arteries: relation to the status of collateral flow in patients with chronic coronary artery disease.

OBJECTIVES: This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries. BACKGROUND: Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying severely asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients. METHODS: We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose for assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyglucose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake). RESULTS: There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI] 46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angiographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability. CONCLUSIONS: In patients with chronic coronary artery disease, angiographically visualized collateral vessels to asynergic myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.

Adult↗