Search PubMed⌕ Search

Biomedical subjects

K L Davis

Publications and source records attributed to K L Davis.

At least 217 records · Page 12Linked to original sources
PubMed1988

4-Aminopyridine in the treatment of Alzheimer's disease.

The cognitive and behavioral effect of 4-aminopyridine (4-AP) was examined in Alzheimer's disease (AD) using a dose finding/replication study design. Fourteen inpatients, aged 54-89 years (mean 66.1 +/- 10.6 SD), meeting NINCDS criteria for probable AD, were studied. Three doses of 4-AP--2.5 mg b.i.d., 5 mg b.i.d., and 10 mg b.i.d.--or placebo were administered for 4 consecutive days in random order. Symptomatic assessment was performed on the fourth day of each condition using the Alzheimer Disease Assessment Scale (ADAS). Thereafter, the dose on which the best performance occurred was readministered, as was placebo. Of the 13 patients who completed the dose-finding phase, 7 patients had at least one dose of 4-AP that was associated with less severe symptoms than was placebo, and those patients were included in the replication phase. Results indicated no significant difference in total ADAS scores (p greater than 0.05). Examination of the ADAS subscales revealed no significant 4-AP effect on any particular symptom. Possible explanations of the lack of a drug effect in this study include the unselective release of neurotransmitters by 4-AP, poor penetration into the central nervous system (CNS), and the presenile onset of the disease in these patients.

4-Aminopyridine↗
PubMed1988

Purification and characterization of cytochrome P-450-dependent arachidonic acid epoxygenase from human liver.

A novel human liver cytochrome P-450 isozyme (P-450-AA), which catalyzes arachidonic acid epoxidation, has been purified to electrophoretic homogeneity from human liver. As judged spectrally, the newly described isozyme is low spin in the oxidized state, with a soret band at 415 nm and an increased maximum at 451 nm in the CO-difference spectrum. Cytochrome P-450-AA appeared homogeneous as judged by the appearance of a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an estimated molecular weight of 53,100. Although cytochrome P-450-AA had a relatively low specific content of 10.8 nmol/mg, it possessed a high activity of arachidonic acid epoxidation. The P-450-AA oxidized arachidonic acid in a reconstituted system into the four regioisomeric epoxyeicosatrienoic acids (EETs) (5, 6-, 8, 9-, 11, 12-, 14, 15-EETs) at a rate of 2,010 pmol/nmol/min, a rate which is 37-fold higher than that observed with the crude microsomal preparation. Moreover, the purified cytochrome P-450-AA catalyzed the de-ethylation of 7-ethoxyresorufin at the rate of 2970 pmol/nmol/min, whereas other cytochrome P-450-dependent reactions were carried out at 23-2,000-fold lower rates and ranged between 0.3-130 pmol/nmol/min. The amino acid composition is different from that of other cytochrome P-450 isozymes. The NH2-terminal sequence of 20-amino acid residues was compared to that of LM2 and PB2-B2, the phenobarbital-induced forms in rabbit and rats, respectively. Comparison was also made with two forms of human cytochrome P-450, HLc and HLd. There were 7/20 identical residues for P-450-AA and LM2 and 4/20 for P-450-AA and PB2-B2. There were 2/20 identical residues for P-450-AA and HLd, and no identical residues were found for HLc. We conclude that the biologically active EETs, are formed by a distinct and unique P-450 isozyme from human liver and that arachidonic acid can serve as a screen for detection of the novel P-450 isozyme.

Adult↗
PubMed1988

Memory impairment in schizophrenic patients with tardive dyskinesia.

Memory functioning was contrasted in 40 schizophrenic patients with and without tardive dyskinesia (TD). Visual and verbal memory tests were used to investigate specific types of impairments. The presence of TD was ascertained using the Abnormal Involuntary Movement Scale (AIMS). TD patients scored significantly lower than non-TD patients on two measures of visual learning, though no differences were found for verbal learning or immediate recall. These results are consistent with previous reports that schizophrenic patients with TD demonstrate impaired cognitive functioning. They also raise the possibility that the neurochemical and structural changes underlying TD may produce specific deficits in memory for visual materials. In addition, a significant relationship was found between total score on the Brief Psychiatric Rating Scale (BPRS) and performance on all of the test measures included in the cognitive test battery. This demonstrates the importance of attending to the overall level of schizophrenic symptomatology when evaluating results from experimental learning tasks.

Dyskinesia, Drug-Induced↗
PubMed1988

A comparison of plasma homovanillic acid concentrations in schizophrenic patients and normal controls.

Plasma homovanillic acid concentrations, a potential index of central dopamine turnover, were examined in normal control subjects and chronic schizophrenic patients over a 12-hour period, including the period of sleep. Plasma homovanillic acid concentrations were lower in schizophrenic patients compared with normal controls at all times; however, within the group of schizophrenics, the more symptomatic patients had higher plasma homovanillic acid concentrations than the less severely ill patients. These data are consistent with a more complex role of dopamine in schizophrenia than was previously conceptualized.

Adult↗
PubMed1988

Platelet alpha 2-adrenergic receptor function in psychiatric disorders.

The inhibitory effects of norepinephrine (NE) on the cyclic adenosine-3',5'-monophosphate (cAMP) response to prostaglandin E1 (PGE1), a measure of alpha 2-adrenergic receptor function, have been compared in platelets from drug-free schizophrenic patients, depressive patients, and normal controls. The absolute value of the inhibition by NE of the cAMP response to PGE1 was smaller in platelets from schizophrenic and depressive patients than in controls. However, this result was secondary to the smaller baseline platelet cAMP response to PGE1 in patients with these disorders. Effects of NE on cAMP production did not discriminate between actively ill and remitted patients with either schizophrenia or depression. Platelet alpha 2-receptor sensitivity, as measured by the effects of NE on cAMP production, does not appear to be altered in these psychiatric disorders.

Adult↗
PubMed1988

Age-dependent expression of familial risk in Alzheimer's disease.

There is growing evidence for genetic causes of Alzheimer's disease; therefore, consideration of its age at onset among genetically predisposed individuals is timely. The authors studied the onset of Alzheimer-like dementia in families of 79 probands ascertained clinically for the Bronx Veterans Administration/Mt. Sinai School of Medicine longitudinal studies of Alzheimer's disease. Analyses among their 379 first-degree relatives, living and decreased, suggested that 1) early onsets form a distribution that is distinct from that of later onsets, and thus, different causes or mechanisms may operate in early- and late-appearing disease; 2) age at onset varies as a familial characteristic; 3) with present population survival, only one third of the theoretical predisposition to Alzheimer's disease will become manifest during the lifetime of relatives at risk; and 4) a stable annual incidence of 1.5 per cent in the early ninth decade, reported by others, can be explained by the operation of a dominant gene with a population allele frequency of 0.13. The authors conclude that different (possibly genetic) causes of Alzheimer's disease may operate in different families or individuals, although much of its predisposition remains latent during the lifetime of those at risk.

Age Factors↗
PubMed1988

Central serotoninergic stimulation by fenfluramine challenge does not affect plasma thyrotropin-stimulating hormone levels in man.

Thyrotropin-stimulating hormone (TSH) and prolactin (PRL) responses to an acute oral challenge of fenfluramine (60 mg), a central serotoninergic (5-hydroxytryptamine) releasing/uptake inhibiting agent, were examined in 8 healthy males in order to assess the role of central serotoninergic stimulation in the release of TSH. Plasma PRL, but not TSH, was significantly elevated by fenfluramine. These data suggest that central serotoninergic activity does not play an important role in the physiologic release of plasma TSH in man. Further, thyrotropin-releasing hormone is unlikely to be the PRL-releasing factor involved in the fenfluramine-induced stimulation of PRL.

Administration, Oral↗
PubMed1988

Familial aggregation in Alzheimer's disease: comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations.

Although the morbid risk of Alzheimer's disease (AD) is increased among relatives of AD index cases, it is not yet clear whether the extent of familial aggregation is similar for probands of all ages, or for male and female relatives. The present study investigated the incidence of AD-like illness among 379 first-degree relatives of 79 probands in a continuing longitudinal study of AD. Cumulative incidence among relatives increased strikingly with age to 49% by age 87, and the risks observed did not differ appreciably among relatives of presenile-onset versus senile-onset probands. Risks were also similar among parents and sibs. Female relatives appeared to develop the disease earlier than males, but the age-specific risk curves for the two sexes did not differ significantly. These results should not be viewed as direct evidence for dominant genetic transmission of late-onset AD, but they suggest a rationale for formal genetic studies in late-onset (often apparently "sporadic") disease as well as earlier-onset ("familial") cases.

Adult↗
PubMed1988

Endocrine changes in Alzheimer's disease.

In conclusion, at present, no consistent endocrine abnormalities can be detected in patients suffering from Alzheimer's disease. However, assessment of neuroendocrine function might help identify subpopulations of patients with particular neurotransmission abnormalities who are likely to benefit from a specific pharmacologic strategy. For example, patients in whom cholinomimetic drugs produce the greatest elevation in plasma cortisol concentration appear to derive the most symptomatic benefit from these drugs.

Alzheimer Disease↗
PubMed1988

Endocrine changes in Alzheimer's disease.

In conclusion, at present, no consistent endocrine abnormalities can be detected in patients suffering from Alzheimer's disease. However, assessment of neuroendocrine function might help identify subpopulations of patients with particular neurotransmission abnormalities who are likely to benefit from a specific pharmacologic strategy. For example, patients in whom cholinomimetic drugs produce the greatest elevation in plasma cortisol concentration appear to derive the most symptomatic benefit from these drugs.

Alzheimer Disease↗