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Biomedical subjects

C M Clark

Publications and source records attributed to C M Clark.

At least 73 records · Page 4Linked to original sources
PubMed1996

Performance of the dementia severity rating scale: a caregiver questionnaire for rating severity in Alzheimer disease.

The Dementia Severity Rating Scale (DSRS) is an informant-based, multiple-choice questionnaire that assesses severity from the mildest to the most severe stages in the major functional and cognitive domains affected in Alzheimer disease (AD). The DSRS has good reliability as measured by making repeated observations over short time periods and by comparing caregiver responses to information collected by a physician or an experienced nonphysician research associate. The measure correlates favorably with the Washington University Clinical Dementia Rating scale and with standard cognitive testing measures. The DSRS provides a simple, valid, and sensitive measure of impairment associated with AD. It is ideally suited for multisite collaborative studies and can be implemented with a minimum of staff time and training.

Activities of Daily Living↗
PubMed1995

H1 histone sub-type distribution and DNA topoisomerase activity in skeletal muscle of tumour-bearing rats.

In an investigation of possible causes of the transcriptional defect which has been observed in muscles atrophying in response to tumour growth, the amounts of histone H1 subtypes and the activities of DNA topoisomerase I and II, factors which can affect the structural organisation of chromatin, were studied in nuclei of skeletal muscle of rats bearing a Walker 256 carcinoma. The H1 histones were separated by SDS/PAGE into three fractions, H1.1, H1.2 and H1(0). The level of H1.2 but not that of H1.1 or H1(0) was increased in the tumour-bearing animal. Tumour growth did not affect the activity of either DNA topoisomerase I or II.

Animals↗
PubMed1995

Prolactin response to buspirone challenge in the presence of dopaminergic blockade.

Buspirone-stimulated prolactin release has been employed as an indirect measure of central serotonin activity; however, it is not clear whether serotonergic or dopaminergic systems are responsible for this response. In an attempt to further elucidate the mechanism, we studied the prolactin response to buspirone in eight subjects in the presence of maximal dopaminergic receptor blockade with metoclopramide under placebo-controlled, double-blind conditions. The prolactin response to buspirone in the presence of metoclopramide was not statistically different from that to placebo under the same conditions. The demonstration of further prolactin release by a bolus of thyrotropin-releasing hormone under maximal dopaminergic receptor blockade provided evidence against potential pituitary prolactin depletion by metoclopramide. These results lend further support to a dopaminergic mechanism in buspirone-induced prolactin secretion; therefore, further caution is warranted in interpreting the results of this challenge test as a measure of serotonergic activity in the brain.

Adult↗
PubMed1995

Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease.

Cerebrospinal fluid from 70 patients with Alzheimer's disease (AD) and 96 patients with non-AD neurological diseases as well as 19 normal control subjects was surveyed by sandwich enzyme-linked immunosorbent assay to quantitate levels of the microtubule-associated protein tau in cerebrospinal fluid. The tau level was significantly increased in AD patients as compared with that in patients with non-AD neurological diseases and control subjects. Increased tau levels were found irrespective of age at onset, apolipoprotein E genotype, and clinical stage. Western blots of AD cerebrospinal fluid proteins revealed two to three tau-immunoreactive bands with an apparent molecular mass between 50 and 65 kd consistent with phosphorylated cerebrospinal fluid tau. Taken together, our results suggest that cerebrospinal fluid tau might reflect the progressive accumulation of altered tau due to the progressive death of neurons in the AD brain, and that the enzyme-linked immunosorbent assay of cerebrospinal fluid tau may prove to be a reliable and early diagnostic test for AD.

Adult↗
PubMed1995

Glucocorticoid-induced changes in liver: inhibition of nuclear Ca2+, Mg(2+)-dependent endonuclease activity in response to dexamethasone administration.

The endogenous Ca2+, Mg(2+)-dependent endonuclease activity in nuclei from livers of rats receiving daily injections of the synthetic glucocorticoid dexamethasone was examined with respect to the production of both single and double strand breaks in chromatin DNA. The ability to form single strand breaks was measured by means of a nick translation assay and double strand breaks by following the appearance of nucleosomal ladders. A fall in the activity causing double strand breaks to approximately 50 per cent of the control value was apparent at 12 h after the first injection of the steroid. A fall of 25-30 per cent was also observed in the nicking activity but this was not apparent until 24 h after the first steroid injection. Both endonuclease activities remained at these lower levels for the remainder of the period of treatment. Nuclear extracts from dexamethasone-treated rats also showed a reduced ability to produce nucleosomal ladders when incubated with rat muscle nuclei, indicating that the inhibition observed in intact nuclei from treated animals was independent of any changes in chromatin structure. On the other hand the nick translation activity of the two extracts was the same when calf thymus DNA was used as the substrate suggesting that steroid-induced alterations in chromatin structure may be a critical factor in the reduced level of this activity observed in intact nuclei.

Animals↗
PubMed1995

Enhanced cardiac metabolism of plasma glucose in high-altitude natives: adaptation against chronic hypoxia.

The metabolism of glucose in mammalian heart is 25-50% more O2 efficient than the metabolism of free fatty acids. To assess the role of substrate preference in adaptations to chronic hypoxia, positron emission tomographic measurements of heart regional glucose uptake rates after an overnight fast were made in volunteer Quechua subjects and in Sherpa subjects, both indigenous to altitudes of over 3,000 m, and in a group of lowlander volunteers. Highest uptake rates were found in the Quechuas on arrival and in the Sherpas after a 3-wk period at low altitude, intermediate rates in Quechuas after a 3-wk period at low altitude and in the lowlanders, and lowest rates in Sherpas on arrival. These low values were probably related to the stress of travel to the site of the experiments. Measured plasma catecholamines, hormones, and substrates indicated that glucose concentrations correlated best with observed variations in glucose uptake, with a negative correlation for the control subjects and a positive correlation for the Quechuas and Sherpas. Uptake values in Quechuas declined significantly after a 3-wk period at low altitude, but the positive correlation with glucose levels persisted. We conclude that an elevated glucose preference in heart is a true metabolic adaptation in humans adapted over generations to chronic hypoxia.

Adaptation, Physiological↗
PubMed1995

Patterns of referral and examination for retinopathy in pregnant women with diabetes by primary care physicians.

PURPOSE: Family practice (FP), General Practice (GP) and obstetrics-gynecology (OB/GYN) physicians were surveyed to determine whether they routinely referred pregnant patients with diabetes to an ophthalmologist, looked into the patient's eyes to screen for retinopathy, and dilated the eyes for fundi examination. METHODS: Hospitals providing obstetrical services were contacted to identify primary-care physicians. Physicians identified as having obstetrical privileges were surveyed by mail to determine if they were actively providing obstetrical care. Physicians who provided both obstetrical and diabetes care were mailed a survey. RESULTS: Of 668 physicians surveyed, 429 responded: 224 FPS, 184 OB/GYNS and 21 GPS. A relatively small percentage (27%) of physicians in both groups routinely refer all of their pregnant patients with pre-existing diabetes to an ophthalmologist. Family practice physicians were more likely to perform an eye exam to screen for retinopathy in patients with both pre-existing and gestational diabetes than OB/GYNS (p < .0005). Only 11% of FPS and no OB/GYNS reported that they dilated the eyes when performing a fundus examination (p = .04). CONCLUSION: The physicians surveyed under-utilize recommended strategies for eye care of pregnant women with pre-existing diabetes. Based upon these results, we call for a recommitment to partnership of primary-care physicians and ophthalmologists in the detection and treatment of diabetic retinopathy during pregnancy.

Adult↗
PubMed1994

Glucocorticoid-induced changes in liver: effect of dexamethasone administration on DNA topoisomerase I and II activities and distribution of histone H1 subtypes.

The activities of DNA topoisomerase I and II and the relative proportions of the histone H1 subtypes were investigated in rat liver which was undergoing hypertrophy and exhibiting increased transcriptional activity following the administration of dexamethasone. There was a rise in the level of activity of DNA topoisomerase I and a slight fall in that of DNA topoisomerase II. The relative proportions of the H1 subtypes were altered due to a preferential increase in H1.1. The results are discussed in relation to the effect of glucocorticoids on the transcription and replication of hepatic DNA.

Animals↗
PubMed1994

The brain at high altitude: hypometabolism as a defense against chronic hypoxia?

The brain of hypoxia-tolerant vertebrates is known to survive extreme limitations of oxygen in part because of very low rates of energy production and utilization. To assess if similar adaptations may be involved in humans during hypoxia adaptation over generational time, volunteer Quechua natives, indigenous to the high Andes between about 3,700 and 4,900 m altitude, served as subjects in positron emission tomographic measurements of brain regional glucose metabolic rates. Two metabolic states were analyzed: (a) the presumed normal (high altitude-adapted) state monitored as soon as possible after leaving the Andes and (b) the deacclimated state monitored after 3 weeks at low altitudes. Proton nuclear magnetic resonance spectroscopy studies of the Quechua brain found normal spectra, with no indication of any unusual lactate accumulation; in contrast, in hypoxia-tolerant species, a relatively large fraction of the glucose taken up by the brain is released as lactate. Positron emission tomographic measurements of [18F]2-deoxy-2-fluoro-D-glucose (FDG) uptake rates, quantified in 26 regions of the brain, indicated systematically lower region-by-region glucose metabolic rates in Quechuas than in lowlanders. The metabolic reductions were least pronounced in primitive brain structures (e.g., cerebellum) and most pronounced in regions classically associated with higher cortical functions (e.g., frontal cortex). These differences between Quechuas with lifetime exposure to hypobaric hypoxia and lowlanders, which seem to be expressed to some degree in most brain regions examined, may be the result of a defense adaptation against chronic hypoxia.

Adaptation, Physiological↗
PubMed1994

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part VI. Family history assessment: a multicenter study of first-degree relatives of Alzheimer's disease probands and nondemented spouse controls.

Although familial factors in Alzheimer's disease (AD) are well established, uniform family-history assessment in genetic and epidemiologic studies of AD is needed to reconcile the divergent estimates of the cumulative risk of this illness among relatives of AD probands. To answer the need, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a standardized Family History Assessment of AD to identify the presence of AD, Parkinson's disease (PD), and Down's syndrome (DS) in family members. This paper describes the use of this new assessment instrument in 118 patients with AD (estimated mean age at onset [+/- SD] = 64.5 +/- 7.7 years) and their nondemented spouses who were enrolled in 11 different CERAD sites in the U.S. The first-degree relatives of the probands with AD had a significantly greater cumulative risk (p < 0.005) of AD or primary progressive dementia (24.8%) than did the relatives of spouse controls (15.2%). Furthermore, the cumulative risk for this disorder among female relatives of probands was significantly greater than that among male relatives. There were no differences between the families of probands and controls for the numbers of affected first-degree relatives with PD or DS. This is the first reported multicenter family-history study of AD, and it supports earlier reports of familial factors in AD and indicates a higher risk to female relatives of AD probands. The CERAD Family History Assessment instrument may be useful for further multicenter and epidemiologic studies designed to delineate familial factors associated with AD.

Age of Onset↗
PubMed1994

Clinical assessment of adolescents involved in Satanism.

Satanism is a destructive religion that promises power, dominance, and gratification to its practitioners. Unfortunately, some adolescents are seduced by these promises, often because they feel alienated, alone, angry, and desperate. This article explores the psychosocial needs of adolescents that are often met by participation in Satanic worship. Gratification of these needs, when met, may make leaving the cult a difficult and lengthy process. Included is a method for determining the adolescents' level of involvement and an assessment strategy for the therapeutic evaluation process. A brief overview of clinical intervention is also discussed.

Adolescent↗
PubMed1993

Actin and actin-binding proteins in plasma membranes derived from Walker 256 ascites or solid tumour cells.

Plasma membranes from Walker 256 carcinoma cells grown ascitically or as a solid tumour were examined with respect to actin content, [3H]cytochalasin B-binding and the binding of 125I-labelled G-actin to membrane proteins separated by SDS-PAGE. Differences were observed both in cytochalasin B-binding to membrane actin and affinity of 125I-labelled G-actin for specific membrane proteins.

Actins↗
PubMed1993

Metabolic subtypes in patients with schizophrenia.

Patterns of regional cerebral glucose metabolism were examined in a group of patients with schizophrenia (n = 17) and normal controls (n = 16) to determine if different metabolic profiles were present. For the patients with schizophrenia, two profiles were found. The first was characterized by a normal "shape" but overall reductions in cerebral metabolism. The second had focal reductions in frontal metabolism. This latter group also had significantly larger frontal horns than the other schizophrenic group. The two groups with schizophrenia did not differ on other attributes or clinical variables. These results are discussed in terms of our understanding of heterogeneity in schizophrenia and etiology.

Adult↗
PubMed1993

Operational and policy considerations of data monitoring in clinical trials: the Diabetes Control and Complications Trial experience.

Many clinical trials incorporate a system for monitoring emerging data that utilizes a committee composed of individuals who are independent of the investigators conducting the study. Although this is a common practice, there is a paucity of publications examining the operating methods of these groups. This paper describes the composition, functions, and procedures of the Data, Safety and Quality Review Group (DSQ) of the Diabetes Control and Complications Trial (DCCT). The DSQ is not masked to emerging data and the voting membership is made up of individuals with a wide diversity of expertise that reflects the needs of the trial. There are also nonvoting exofficio members who represent other components of the study organization. In addition to data monitoring, the DSQ provides external review of coordinating center operations. A distinctive aspect of the DCCT's DSQ is the creation of a free-standing operations manual for the DSQ's use during the trial and the involvement of the study investigators in developing certain sections of this document. Utilizing a process that allowed participation of the investigators was considered critical to achieving a mutual understanding regarding the planned uses and interpretations of the study data prior to the study's completion so as to minimize the chances of major disagreements regarding the conclusions drawn. Equally important, the existence of such a manual provides documentable reassurance to all interested parties that both scientific integrity and patient safety are being closely watched and gives the study investigators confidence that the results of the study will be scientifically credible and clinically important.

Clinical Trials as Topic↗
PubMed1993

Protein and enzyme content of plasma membranes derived from Walker 256 carcinoma cells grown as ascitic or solid tumours.

A preliminary investigation of enzymes functioning at the cell surface indicates that when Walker 256 carcinoma cells growing ascitically are induced to grow as a solid tumour there is a marked increase in the activities of Na+, K(+)-ATPase, Mg(2+)-ATPase, 5'-nucleotidase, alkaline phosphatase and phosphodiesterase I; 5'-nucleotidase and alkaline phosphatase being particularly affected. These enzyme changes occur in the absence of any major alteration in the protein composition of the plasma membrane.

Alkaline Phosphatase↗