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Biomedical subjects

M Davidson

Publications and source records attributed to M Davidson.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1994

Effects of ipsapirone in healthy subjects: a dose-response study.

A dose-response study of ipsapirone (IPS), a 5HT1a partial agonist, was conducted in healthy male subjects. IPS was administered in doses of 5, 10 and 20 mg PO in a placebo-controlled, double-blind design to 15 subjects on 4 test days separated by at least 3 days. Oral temperature, ACTH, cortisol, prolactin, blood pressure, pulse rate and behavioral variables were assessed every 30 min for 3 h after administration of tablets (at 10:00 A.M.). IPS at 20 mg significantly decreased temperature and increased cortisol levels. Although IPS increased ACTH levels at 20 mg, this effect was variable and not significant. IPS did not affect prolactin levels nor did it have any behavioral effects. Although 20 mg IPS decreased blood pressure and pulse rate in one subject, overall it had no significant effect on these parameters. IPS at 20 mg PO appears a useful probe to test 5HT1a function when temperature and cortisol are used as response variables. These results replicate earlier studies on the effect of IPS in healthy human subjects.

Adrenocorticotropic Hormone↗
PubMed1994

Neuropsychological correlates of central monoamine function in chronic schizophrenia: relationship between CSF metabolites and cognitive function.

Schizophrenia is associated with multiple cognitive deficits which in turn may be related to abnormal dopamine (DA) function. To examine possible associations between cognitive dysfunction and central DA activity in schizophrenia, neuropsychological measures (visuospatial and verbal recall; performance on the Wisconsin Card Sort Test (WCST); visuospatial perception) were examined in 17 drug-free male schizophrenic patients and related to cerebrospinal fluid concentrations of the metabolites of dopamine (homovanillic acid (HVA)), serotonin, and norepinephrine. CSF HVA concentrations were correlated with the ability to recall visuospatial information, with attention to verbal tasks, and with WCST performance (low CSF HVA concentrations predicting poor performance on these tests) but not with the ability to recall verbally presented material and visuospatial perception. These data are consistent with earlier results suggesting that (cortical) DA function is associated with recall and retrieval of visuospatial information and with WCST performance.

Adult↗
PubMed1994

Attentional predictors of clinical change during neuroleptic treatment in schizophrenia.

Improvement in auditory selective attention performance was examined in acute schizophrenic inpatients (n = 13) both off and on medication using the digit span distraction task. Subjects were tested at drug-free baseline and weekly for three weeks during treatment with haloperidol. Improvements in distractability preceded and predicted clinical improvements. A control group of stable schizophrenic outpatients (n = 12) medicated at all testing intervals were examined during the same time period. No significant clinical or attentional changes were found in the control group over the four testing intervals. These results suggest that specific types of attentional functions are intrinsically related to the biological processes affected by neuroleptic treatment and lend preliminary support to the contention that schizophrenic symptoms are mediated by attentional impairment.

Adult↗
PubMed1994

Cortical cholinergic markers in schizophrenia.

Cortical cholinergic deficits have been implicated in the cognitive deficits produced by a variety of neurodegenerative diseases including Alzheimer's disease (AD). Recent studies have suggested that many of the chronically institutionalized geriatric schizophrenic patients are also cognitively impaired. In this postmortem study we compared cholinergic marker activity in six different cortical regions derived from elderly controls, chronically institutionalized geriatric schizophrenic patients, and AD patients. All of the Alzheimer's disease cases met neuropathological criteria for AD, while none of the schizophrenic cases met criteria for AD. Cholinergic marker activity (choline acetyltransferase and acetylcholinesterase) was significantly diminished in the AD cohort but not in the schizophrenic cohort. Additionally, cortical choline acetyltransferase activity was significantly and negatively correlated with Clinical Dementia Rating scores (CDR), whereas no such correlations were evident in the schizophrenic cohort. These results suggest that cognitive deficits in geriatric schizophrenics are not due to diminished cortical cholinergic activity.

Acetylcholine↗
PubMed1994

Plasma homovanillic acid and performance on motor and cognitive tasks in community-dwelling elderly: MacArthur studies of successful aging.

To investigate the dopaminergic correlates of the aging-related motor and cognitive deficits, the dopamine metabolite homovanillic acid (HVA) in plasma was studied in a community-dwelling elderly cohort (n = 141). The results showed that hand-signature time (HST), a measure of bradykinesia, correlated negatively with plasma HVA (r = -0.24, p < .007). Similarities task performance showed a trend-level positive correlation with plasma HVA (r = 0.15, p = .08). Because plasma HVA is derived from several sources including central dopaminergic neurons and both central and peripheral noradrenergic neurons, the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma was also measured to indirectly estimate the relationships, with HVA originating from noradrenergic metabolism. Plasma MHPG significantly correlated with similarities scores (r = 0.34, p < .001) but not with HST. The results suggested that the association of HVA with prolonged HST may be related to central dopamine metabolism, but its association with similarities scores may be due to noradrenergic metabolism. The results raise the possibility that prolonged HST may be an indicator of preclinical brain dopamine loss in the elderly.

Aged↗
PubMed1994

Galanin-like immunoreactivity is increased in the postmortem cerebral cortex from patients with Alzheimer's disease.

Galanin is a peptide that is associated with cholinergic neurons of the basal forebrain, and, thus, of interest for the neuropathology of Alzheimer's disease. In the present study, human galanin-like immunoreactivity was measured in postmortem human cerebral cortical tissues by using a homologous radioimmunoassay. In an initial study, six cerebral cortical regions were evaluated from nine elderly controls, 13 neuropathologically verified Alzheimer's disease patients, and 19 elderly schizophrenics. A significant 65% increase in galanin was found in frontal cortex Brodmann area 8 of Alzheimer's disease patients compared with controls. In contrast, cerebral cortical tissues from elderly schizophrenics were not different from those from elderly controls in any region. In a second study, 10 cerebral cortical regions were evaluated from 50 neuropathologically verified Alzheimer's disease patients and nine elderly controls. Concentrations of galanin were increased significantly 26-61% in six of 10 cerebral cortical regions examined (Brodmann areas F8, F44, T20, T21, T36, and P22). Purification of brain extracts by size-exclusion Sephadex G-50 chromatography revealed that human galanin-like immunoreactivity eluted in two peaks of different molecular weights. These studies reveal increased concentrations of galanin in the cerebral cortex of Alzheimer's disease, similar to previous findings in basal forebrain tissue. Because galanin inhibits cholinergic neurotransmission, these findings may have important implications in the understanding of Alzheimer's disease neuropathology and associated cognitive deficits.

Alzheimer Disease↗
PubMed1994

Incidence of invasive cervical cancer preceded by negative screening in high-risk Alaska Native women.

BACKGROUND: Alaska Native women experience higher invasive cervical cancer incidence and mortality rates than US whites despite a long-standing cancer screening programme including recommendations for annual Pap smears. METHODS: To determine the frequency and results of cytological screening preceding their diagnoses, a histological and medical record review was completed for 44 of 46 Alaska Native cases of invasive cervical cancer from a defined population. An interval cancer (no prior dysplasia and a negative screening report within 3 years of diagnosis) was determined for 23 women. Mean number of negative reports during the 3- and 5-year intervals before diagnosis was 1.7 and 2.6 respectively. The age-adjusted incidence rate for all cervical cancer was 24.0/100,000 women/year and for interval cancer with single and multiple negative reports during the 3-year interval before diagnosis it was 11.6, and 9.6 respectively. Sensitivity of a Pap smear to demonstrate dysplasia during the year before diagnosis was 51%. CONCLUSIONS: Annual cytological screening of all Alaska Native women with current methods would provide earlier diagnoses for only an additional 15% of cervical cancer cases. Plausible but unproven explanations include rapid progression through precursor stages of neoplasia or random screening errors. Improved or ancillary screening methods appear necessary.

Adolescent↗
PubMed1994

The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women.

Alaska Native women historically have high rates of sexually transmitted diseases (STDs) and invasive cervical cancer. Their prevalence of cervical infections with human papillomavirus (HPV) in relation to cervical dysplasia was determined with a commercial dot hybridization test for seven HPV genotypes. Type-specific HPV DNA, similarly distributed between genotype groups 16/18 and 31/33/35, was detected in 234 cervical specimens (21%) from 1126 Alaska Native women seeking routine care and colposcopy or from population-based lists. The prevalence of HPV DNA declined with age and increased with sexual activity and cigarette smoking. It was unrelated to use of oral contraceptives or condoms or to STDs. Relative risks associating HPV with increasing severe grades of cervical dysplasia increased markedly with HPV infection, up to 7.1 for high-risk genotypes 16/18 and 14.4 for coinfection with 31/33/35. These genotypes were detected in 8% of women without dysplasia seeking routine care. Screening for strain-specific HPV DNA may identify women at highest risk for cervical neoplasia.

Adolescent↗
PubMed1994

The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990--ethnic differences and opportunities for prevention.

To assess prevention strategies for pneumococcal disease in Alaska, prospective surveillance during 1986-1990 identified 672 invasive pneumococcal infections, including 315 among Alaska Natives. Age-adjusted annual incidence was 74 per 100,000 for Alaska Natives and 16 per 100,000 for nonnatives. The annual incidence in Alaska Native children < 2 years old was 624 per 100,000; rates of 84 per 100,000 for meningitis and 290 per 100,000 for bacteremic pneumonia were 8-10 times higher than for other US groups. By age 75, cumulative incidence (7%) and mortality (1%) in Alaska Natives were almost 4 times higher than for nonnatives. Only 17% of Alaska Native adults with predisposing conditions and invasive infections previously received pneumococcal vaccine. For Alaska Natives, a proposed heptavalent conjugate pneumococcal vaccine will include serotypes responsible for 85% of invasive isolates from children < 2 years but only 32% of those from adults. The 23-valent polysaccharide pneumococcal vaccine, which contains > 94% of serotypes identified in Alaska Native toddlers and adults, should be used more widely.

Adolescent↗
PubMed1994

Serotype distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska 1986-1990.

From January 1986 through December 1990, 672 cases of invasive pneumococcal disease were identified. From these, 574 pneumococcal isolates were recovered from normally sterile sites (blood, cerebrospinal and pleural fluid); 92% were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. The most common serotypes from children < 2 years old were 4, 6B, 9V, 14, 18C, 19F, and 23F, recovered from 83% of Alaska Native and 75.1% of nonnative children with invasive disease. Moderate penicillin resistance (MIC, 0.1-1.0 micrograms/mL) was found in 3.8% of isolates. All were sensitive to chloramphenicol, vancomycin, rifampin, ceftriaxone, cefotaxime, cephalothin, and cefaclor. However, in the Yukon-Kuskokwim Delta region, 16.9% of isolates were moderately resistant to penicillin, and 10.8% were resistant to erythromycin and 6.2% to trimethoprim-sulfamethoxazole; the number resistant to two or more antibiotics increased significantly during surveillance. All multiply resistant isolates were serotype 6B, and all were from Alaska Native patients < 2 years old.

Adolescent↗
PubMed1994

Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens.

A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.

Adult↗
PubMed1994

Early response to clozapine in schizophrenia.

Forty schizophrenic patients were treated with clozapine for 5 weeks. Patients were then classified as treatment responders or nonresponders according to a priori established criteria. After only 1 week of treatment, the responders showed a significant decrease on the Brief Psychiatric Rating Scale (BPRS) total score and the psychosis and tension subscale scores. Higher BPRS scores at baseline and larger improvements in BPRS scores after the first week predicted a more favorable outcome in this trial and yielded good classification accuracy.

Clozapine↗
PubMed1994

A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration.

OBJECTIVE: This study measured the annual rate of cognitive change in patients with Alzheimer's disease and determined the effects of clinical variables on that rate. It also compared the ability of two cognitive scales to measure change over the entire range of dementia severity. METHOD: The cognitive subscale of the Alzheimer's Disease Assessment Scale and the Blessed test for information memory and concentration were given to 111 patients with Alzheimer's disease and 72 nondemented elderly comparison subjects at 6-month intervals for up to 90 months. Longitudinal changes in scores on the cognitive subscale were measured with several different methods of data analysis. RESULTS: For the patients with Alzheimer's disease, the annual rate of change in cognitive subscale scores showed a quadratic relationship with dementia severity in which deterioration was slower for mildly and severely demented patients than for patients with moderate dementia. Gender, age at onset, and family history of dementia had no effect on the rate of cognitive deterioration. The comparison group showed a slight improvement in cognitive performance over time. All data analytic methods gave similar results. The cognitive subscale of the Alzheimer's Disease Assessment Scale was more sensitive to change in both mild and severe dementia than was the Blessed test. CONCLUSIONS: These results suggest that cognitive deterioration is slow during the early and very late stages of Alzheimer's disease and more rapid during the middle stages. No clinical variables other than degree of cognitive impairment and previous rate of cognitive decline predicted rate of deterioration. These results have implications for treatment trials and attempts to identify subgroups.

Adult↗
PubMed1994

Characterization of cadherin-4 and cadherin-5 reveals new aspects of cadherins.

Several properties of cadherin-4 and cadherin-5 were characterized by using the cDNA transfection approach. The proteins of both cadherins had a relative molecular mass of about 130 kDa and were present at the cell periphery, especially at cell-cell contact sites. These cadherins were easily digested with trypsin, and Ca2+ protected cadherin-4, but not cadherin-5, from the digestion. In immunoprecipitation, cadherin-4 co-precipitated with two major proteins of 105 kDa and 95 kDa, respectively. The 105 kDa and the 95 kDa proteins are likely to correspond to alpha- and beta-catenins. Cadherin-5 co-precipitated with only one major protein of 95 kDa, but seems to associate with the 105 kDa protein. On the other hand, plakoglobin or gamma-catenin did not co-precipitate well with either cadherin-4 or cadherin-5 in immunoprecipitation, but plakoglobin also appears to associated weakly with these cadherins. Cadherin-4 transfectants aggregated within 30 minutes in a cell aggregation assay, but cadherin-5 transfectants did not aggregate under the same conditions. Furthermore, the transfectants of chimeric cadherin-4 with cadherin-5 cytoplasmic domain showed cell aggregation activity comparable to that of wild-type cadherin-4 transfectants, whereas the transfectants of chimeric cadherin-5 with cadherin-4 cytoplasmic domain did not show appreciable cell aggregation, suggesting that the extracellular domains of cadherins, in conjunction with their cytoplasmic domains, play an important role in cell aggregation activity. These results show that cadherin-4 is very similar to the classical cadherins, whereas cadherin-5 is functionally as well as structurally distinct from classical cadherins.

Animals↗