Search PubMed⌕ Search

Biomedical subjects

C M Clark

Publications and source records attributed to C M Clark.

At least 55 records · Page 3Linked to original sources
PubMed1998

Clinical trials with glimepiride.

Data from 21 placebo-controlled, active-controlled or noncomparative studies involving more than 6500 patients, more than 4220 of whom were treated with glimepiride, are reviewed. Glimepiride has a rapid onset of action and is effective at a single daily dose. It is equally effective as the other second-generation sulfonylureas at doses of 1-8 mg/day, with doses above 4 mg/day reserved for patients with initial HbA(1c) above 8%. Glimepiride (at doses yielding the same blood-lowering effect as glyburide and glipizide), has a safety profile somewhat superior to that of glyburide, glipizide and gliclazide at a lower mg/day dose. Glimepiride also has been shown to be safe and effective in combination with insulin. Finally, glimepiride has two pharmacologic properties which have theoretical advantages over the other currently available sulfonylureas, but which have not as yet been shown to be clinically significant: it does not activate the cardiovascular K(ATP) channel and it achieves equivalent metabolic control at lower insulin secretion levels than the other sulfonylureas.

Journal Article↗
PubMed1998

Reducing the burden of diabetes. The National Diabetes Education Program.

The National Diabetes Education Program (NDEP) is a joint initiative sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health and the Division of Diabetes Translation of the Centers for Disease Control and Prevention. The program will develop a partnership of public and private organizations and implement educational activities to help reduce the morbidity and mortality associated with diabetes and its complications. Participating public and private organizations include the Indian Health Service, the Department of Veterans Affairs, the American Diabetes Association, the American College of Physicians, the American Dietetic Association, and the American Association of Diabetes Educators. Key program activities will include (1) ongoing public awareness and education (2) and identification and dissemination of existing educational tools and resources for patients and their families, health care providers, and payers and purchasers of health care. The NDEP will also sponsor the development and dissemination of new educational tools and resources, including science-based guidelines, efforts to improve quality and access to diabetes care, and program evaluation.

Centers for Disease Control and Prevention, U.S.↗
PubMed1998

The burden of chronic hyperglycemia.

Diabetic complications constitute the principal clinical and economic burdens of diabetes. Available evidence indicates that sustained reduction in hyperglycemia (as measured by HbA1c) reduces the incidence of diabetic complications, including microvascular and neurological disease, and will likely reduce the risk of macrovascular disease. In the U.S., targeting interventions to aged and ethnic subpopulations, which are currently receiving suboptimal care, and increasing efforts to lower the average HbA1c concentrations one or two percentage points in people with diabetes would be a more cost-effective goal than aiming for a theoretical HbA1c threshold below which the risk of complications is negligible. Other risk factors for diabetic complications, such as obesity, hypertension, cigarette smoking, and hypercholesterolemia, must also be addressed to reduce the burden of diabetes.

Cost of Illness↗
PubMed1997

Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology.

Cerebrospinal fluid tau (CSF-tau) levels were quantified in 8 patients with frontotemporal dementia (FTD), 6 patients with progressive supranuclear palsy (PSP), 3 patients with corticobasal degeneration (CBD), and 6 patients with dementia with Lewy bodies (DLB). The CSF-tau levels were significantly increased in FTD and DLB, but not in PSP and CBD, compared to that previously reported in normal controls. Notably, the CSF-tau level in DLB was as high as that in Alzheimer's disease (AD). Our study suggests that tau may accumulate in the CSF of patients with certain neurodegenerative diseases other than AD and that measurement of CSF-tau may not distinguish AD from DLB.

Aged↗
PubMed1997

Pathological association and dissociation of functional systems in multiple sclerosis and Huntington's disease.

This study examined pathological associations and dissociations of functional cognitive systems in patients with multiple sclerosis and Huntington's disease. Using the subtests of the WAIS-R, two motor tests, and the word fluency test, the interest correlations showed distinct patterns. In comparison to normals, the two clinical groups exhibited a greater degree of association among the tests. Subsequently, word fluency performance was predicted from these tests. For the normals, the overall predictive power was quite low (7%). For the MS group, the predictive power rose to 28%. For the HD group, the predictive power was 50%. These results suggest that pathological association of functional systems may be a marker of brain dysfunction and that the affected systems may be delineated by these methods.

Adult↗
PubMed1997

Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer's Disease Cooperative Study.

This article reports the development and psychometric properties of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). At present, a number of unvalidated CGIC scales are used in clinical trials, with various methods for making ratings. The ADCS-CGIC was designed on the basis of a survey of ADCS clinicians and by adapting existing instruments. It includes an organized but unstructured format, with which a clinician can address clinically relevant change. The instrument's reliability and validity were assessed in a prospective trial of Alzheimer's disease (AD) and healthy subjects over a 12-month period. It showed good short-term reliability at 1 and 2 months, with 90 and 94% of AD subjects, respectively, rated as having changed not at all or only minimally. The ADCS-CGIC's face validity was demonstrated by untreated. AD subjects rated as having worsened over time at both 6 months (56% rated as having worsened) and 12 months (81% rated as having worsened), whereas only 2% of control subjects showed minimal worsening. As a measure of predictive validity, ADCS-CGIC ratings at 12 months were significantly associated with change on four severity scales. As with other measures, change ratings were sensitive to dementia severity. Moderately impaired subjects showed greater worsening than other subjects. ADCS-CGIC ratings of greater worsening were made after the informant interview, regardless of whether informants or subjects were interviewed first. The ADCS-CGIC is a valid and reliable instrument for use in clinical trials.

Aged↗
PubMed1997

The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer's disease enrolled in the CERAD Study. Consortium to Establish a Registry for Alzheimer's Disease.

The objective of this study was to determine the relationship between the presence of extrapyramidal signs and the severity of cognitive and functional impairment in patients with Alzheimer's disease (AD). Eleven university medical centers in the United States and France participated in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) study of extrapyramidal signs in AD. Forty-seven patients with probable AD who had extrapyramidal signs were matched by sex, race, education, and age with 132 probable AD patients without extrapyramidal signs. The main outcome measures were the Clinical Dementia Rating, Blessed Dementia Scale, and the CERAD Neuropsychology Battery (verbal fluency, naming, Mini-Mental State Examination, word list learning, word list recall, savings ratio, word list recognition, and constructional praxis). AD patients with extrapyramidal signs performed more poorly than AD patients without parkinsonism on various neuropsychological tests, even after controlling for the Clinical Dementia Rating and reported duration of cognitive impairment. The severity of the extrapyramidal manifestations was related to the degree of cognitive and functional impairment. Muscular rigidity and bradykinesia were the most frequent extrapyramidal signs associated with AD. Patients with AD associated with extrapyramidal signs have greater cognitive and functional impairment than AD patients without clinical evidence of parkinsonism.

Aged↗
PubMed1997

Gestational diabetes: should it be added to the syndrome of insulin resistance?

OBJECTIVE: The significance of gestational diabetes mellitus (GDM) results from its short-term detrimental effects on the fetus and its long-term prediction of NIDDM in the mother. We compared several variables associated with insulin resistance between GDM and non-GDM pregnant women to show the similarities between GDM and NIDDM (and thus insulin resistance). RESEARCH DESIGN AND METHODS: On the basis of a 3-h oral glucose tolerance test (OGTT), 52 GDM patients and 127 non-GDM patients were recruited from pregnant, non-diabetic women who had a nonfasting 1-h-50-g glucose screening test > or = 7.2 mmol/l (130 mg/dl) performed between 16 and 33 weeks of gestation (a total of 518 of 3,041 women drawn from six community health care prenatal clinics were screened positive). During the OGTT, several potential markers of insulin resistance were measured at fasting and 2-h time points, in addition to the standard glucose measurements. The relationship of these variables with the diagnosis of GDM was studied. RESULTS: GDM patients, compared with non-GDM patients, had 1) higher prepregnancy weight (P = 0.011), prepregnancy BMI (P = 0.006), C-peptide at fasting (P = 0.002) and at 2 h (P < 0.001), insulin at fasting (P = 0.001) and at 2 h (P < 0.001), triglycerides at fasting (P = 0.005) and at 2 h (P = 0.003), free fatty acids at fasting (P = 0.017), beta-hydroxybutyrate at fasting (P = 0.007); and 2) lower HDL cholesterol at fasting (P = 0.029). These variables were all predictive of GDM (P < 0.036) individually. Using stepwise logistic regression with all of these variables available, fasting (P = 0.019) and 2-h (P < 0.001) insulin levels, fasting free fatty acids (P = 0.031), and fasting beta-hydroxybutyrate (P = 0.036) were statistically significant as jointly predictive of GDM. Comparisons between GDM patients and non-GDM patients matched by BMI confirmed that the metabolic abnormalities persisted when difference in BMI was taken into account. Concomitant blood pressure measurements in women with GDM did not differ significantly from those without GDM. CONCLUSIONS: Our results show that many of the known metabolic components of the syndrome of insulin resistance (syndrome X) are predictive of GDM. These results are in keeping with the argument that GDM is one phase of the syndrome of insulin resistance. We suggest that GDM be looked upon as a component of the syndrome of insulin resistance that provides an excellent model for the study and prevention of NIDDM in a relatively young age-group.

Adolescent↗
PubMed1997

The severe impairment battery: concurrent validity and the assessment of longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Measurement of cognitive dysfunction in the early stages of Alzheimer's disease (AD) has been well studied and there are many objective tests in use for this purpose. However, with the exception of clinical rating scales, such as the Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional Assessment Staging, there are few objective measures of cognition in the more advanced stages of AD. Given a renewed interest in potential AD therapies, objective measures of mental functioning are needed to adequately assess change in more advanced AD patients. As part of an effort by the NIA-Alzheimer's Disease Cooperative Study to evaluate new measures of efficacy for their utility in treatment studies, the Severe Impairment Battery (SIB) was examined in a 1-year evaluation of change across a wide range of AD severity. The data suggest that the SIB is a reliable and valid measure of progression, particularly in persons with moderate to severe AD. The SIB may therefore be a useful outcome measure in clinical trials that include patients with more advanced stages of AD.

Aged↗
PubMed1996

31P magnetic resonance spectroscopy of the Sherpa heart: a phosphocreatine/adenosine triphosphate signature of metabolic defense against hypobaric hypoxia.

Of all humans thus far studied, Sherpas are considered by many high-altitude biomedical scientists as most exquisitely adapted for life under continuous hypobaric hypoxia. However, little is known about how the heart is protected in hypoxia. Hypoxia defense mechanisms in the Sherpa heart were explored by in vivo, noninvasive 31P magnetic resonance spectroscopy. Six Sherpas were examined under two experimental conditions [normoxic (21% FiO2) and hypoxic (11% FiO2) and in two adaptational states--the acclimated state (on arrival at low-altitude study sites) and the deacclimating state (4 weeks of ongoing exposure to low altitude). Four lowland subjects were used for comparison. We found that the concentration ratios of phosphocreatine (PCr)/adenosine triphosphate (ATP) were maintained at steady-state normoxic values (0.96, SEM = 0.22) that were about half those found in normoxic lowlanders (1.76, SEM = 0.03) monitored the same way at the same time. These differences in heart energetic status between Sherpas and lowlanders compared under normoxic conditions remained highly significant (P < 0.02) even after 4 weeks of deacclimation at low altitudes. In Sherpas under acute hypoxia, the heart rate increased by 20 beats per min from resting values of about 70 beats per min, and the percent saturation of hemoglobin decreased to about 75%. However, these perturbations did not alter the PCr/ATP concentration ratios, which remained at about 50% of the values expected in healthy lowlanders. Because the creatine phosphokinase reaction functions close to equilibrium, these steady-state PCr/ATP ratios presumably coincided with about 3-fold higher free adenosine diphosphate (ADP) concentrations. Higher ADP concentrations (i.e., lower [PCr]/[ATP] ratios) were interpreted to correlate with the Km values for ADP-requiring kinases of glycolysis and to reflect elevated carbohydrate contributions to heart energy needs. This metabolic organization is postulated as advantageous in hypobaria because the ATP yield per O2 molecule is 25-60% higher with glucose than with free fatty acids (the usual fuels utilized in the human heart in postfasting conditions).

Acclimatization↗
PubMed1996

Forum Two: Unanswered research questions about metabolic control in non-insulin-dependent diabetes mellitus.

The participants of Forum Two addressed the unanswered research questions about metabolic control and non-insulin-dependent diabetes mellitus (NIDDM). The most compelling issue was the effect of metabolic control on both the development and progression of macrovascular disease in patients with NIDDM. Associated questions that could be answered by a well-controlled clinical trial related to the goal of blood glucose control in NIDDM in the elderly and in persons with clinical vascular disease. The specific suggestion was a trial similar to the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM. Another important research issue that was discussed was the benefit of treating other risk factors such as hypertension and hyperlipidemia in diabetic patients. Yet another area discussed was the study of health services delivery to examine the best care-delivery methods for diabetes and other chronic diseases. Other areas of discussion centered on basic research, that is, the fundamental cause of insulin resistance and the genetics of NIDDM and the loss of protection against atherosclerosis in postmenopausal women with diabetes.

Blood Glucose↗
PubMed1996

Effect of stimulus intensity on prolactin and cortisol release induced by unilateral electroconvulsive therapy.

Prolactin (PRL) plasma levels rise several fold in response to electroconvulsive therapy (ECT). There is evidence that the magnitude of ECT-induced PRL release varies as a function of electrode placement with bilateral (BL) ECT, producing a larger PRL increase than does unilateral (UL) ECT. Although there is some evidence that the amount of PRL released by ECT may also vary as a function of stimulus intensity, the effect of stimulus intensity on the amount of PRL released by UL ECT has not been studied. This is an important question because it is with UL electrode placement that large differences in clinical efficacy as a function of stimulus intensity have been documented. We studied patients undergoing a course of UL ECT as the clinically indicated treatment for their illness. Subjects received low-dose (threshold) and high-dose (three times the threshold) ECT on two consecutive treatments. The order of low- and high-dose treatments was counterbalanced. Blood samples were drawn at 15-minute intervals before and for 1 hour after the administration of ECT and assayed for PRL and cortisol levels. Our results clearly indicate that the PRL and cortisol response to UL ECT-induced PRL release varies as a function of stimulus intensity. In fact, the amount of PRL released by high-dose UL ECT was nearly three times greater than that released by threshold stimulation. These results are consistent with the hypothesis advocating that the therapeutic advantage of high-intensity over low-intensity UL ECT is the result of greater seizure generalization and spread to subcortical regions and suggest that ECT-induced PRL release has the potential to distinguish a seizure induced by a therapeutic stimulus from a seizure induced by a stimulus known to have little therapeutic effect.

Adult↗
PubMed1996

Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

OBJECTIVES: To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS: Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS: Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. CONCLUSIONS: Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.

Aged↗
PubMed1996

Sherpa brain glucose metabolism and defense adaptations against chronic hypoxia.

The brain of hypoxia-tolerant vertebrates is known to survive extreme oxygen limitation at least in part because of very low rats of ATP utilization and ATP production. To asses whether similar adaptations are involved in healthy humans during hypoxia adaptation over generational time, we initially used positron-emission tomography measurements of glucose metabolic rates in the brain of Quechuas, whose ancestors have been indigenous to the Andes at altitudes between approximately 3,300 and 4,500 m for several hundred years. Workers in this field generally believe that the lineage of Sherpas has been indigenous to the Himalayas for even longer and that Sherpas and other peoples indigenous to the Tibetan plateau are perhaps the most exquisitely hypoxia adapted of all humans. For this reason, in this study we extended our database to include Sherpas. With the use of the same protocol as before, two metabolic states were analyzed: 1) the presumed normal (hypoxia-adapted) state, monitored as soon as possible after subjects left the Himalayas and 2) the deacclimated state, monitored after 3 wk at low altitudes. Positron-emission tomography measurements of 2-[18F]deoxy-2-fluoro-D-glucose metabolic rates, quantified in 26 regions of the brain, indicated that the Sherpas' brain metabolism differed significantly from that of Quechuas but was essentially identical to that of lowlanders. Region-by-region patterns were similar in all three groups, indicating that the regional organization of glucose metabolism in the brain is a conservative, relatively constant characteristic.

Adaptation, Physiological↗
PubMed1996

Clinical evaluation of global change in Alzheimer's disease: identifying consensus.

It is important that clinicians who rate global change as part of Alzheimer's disease (AD) clinical drug trials agree on a relevant set of behaviors and information to be considered in formulating their rating. Yet, consensus among raters has been difficult to establish, and inter-rater reliability of clinical global impression of change (CGIC) ratings has been low. In preparation for the development of a new CGIC scale to be used in AD clinical trials, the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), we surveyed clinicians at sites comprising the National Institute on Aging-sponsored ADCS participating centers to identify whether or not consensus regarding CGICs exists. Overall, respondents reported that a CGIC should include an assessment of the patient's function and mental status, a care giver interview, and a standardized set of questions, and it should take approximately 20 minutes per interview. Depending on a patient's level of impairment, raters consider different areas of behavior in formulating a CGIC rating. These findings demonstrate the considerable consensus regarding the CGIC rating process, and were integrated into the design of the ADCS-CGIC, currently in use.

Alzheimer Disease↗