Effects of fasting and hypophysectomy on FFA uptake and ketone body production by the isolated, perfused rat liver.
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Biomedical subjects
Publications and source records attributed to C M Clark.
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BACKGROUND: Diabetic retinopathy is a costly and prevalent complication of diabetes mellitus. OBJECTIVE: To assess primary care physicians' self-reported practice patterns for the screening and detection of diabetic retinopathy relative to published guidelines. PARTICIPANTS AND METHODS: All primary care physicians (defined as general internists, family practitioners, and general practitioners) in Indiana were identified and surveyed using a mailed questionnaire. Of 2390 physicians, 1508 (63%) responded and were determined to be eligible. Of these 1508 physicians, 1058 (70%) completed all or some of the eye care-related questions. For each eye care practice, physicians were asked to specify the proportion of patients to which the practice was applied and the frequency (eg, every 3 months) with which the behavior was performed, if appropriate. Physicians were also asked to distinguish between patients with type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus for each practice behavior. RESULTS: Physicians' responses were classified as "high," "moderate," or "low" based on the American Diabetes Association guidelines. Forty-five percent of the physicians' responses were classified as high for referring all of their patients with type I diabetes mellitus to an eye care specialist annually as were 35% of the physicians' responses for referring their patients with type II diabetes mellitus. Fewer physicians reported high levels of routine in-office funduscopic examination. No relationship was found between the extent to which physicians performed an in-office funduscopic examination and patterns of referral to eye care specialists. Logistic regression analysis suggested that recent graduates and general internists are most likely to report behavior that is considered high (P < .05). CONCLUSION: The diabetic retinopathy-related practice patterns of primary care physicians in Indiana differ significantly from published guidelines.
The Diabetes Education Study was a controlled trial of the effects of physician and patient education. This article describes an educational program for internal medicine residents and its effects on ambulatory diabetes management practices. Forty-five of 86 residents practicing in the general medicine clinic of a university-affiliated city/county hospital were assigned randomly to receive a multifaceted program intended to 1) provide specific care recommendations, 2) teach necessary skills, and 3) make the professional and institutional environment more supportive. During the subsequent 11 months, 323 diabetic patients were interviewed and their records audited for evidence of changes in care. Experimental residents utilized fasting blood glucose determinations more often than controls (i.e., during 40% of visits vs. 31%, p = 0.004). Experimental residents also engaged more frequently in a variety of recommended dietary management recommendations. Isolated differences in monitoring/management of chronic complications also were found (e.g., lipid screening: 70% of experimental residents' patients vs. 58%, p = 0.016). Intensive, multifaceted programs of this nature are concluded to result in improvements in diabetes care, over and above that which is attainable through routine methods of clinical training for residents.
Significant losses in the ability to detect the taste of glutamic acid and to recognize odorants were found in demented patients when compared with age-matched controls. These losses were not specific to patients with Alzheimer's disease (AD) but were also found in demented patients without AD. Detection thresholds for bitter-tasting quinine HCl were not higher in demented patients than in age-matched controls but were higher than thresholds in young subjects. These data suggest that losses in taste in demented patients may vary with the chemical structure of the tastant. The degree of loss in the ability to recognize odorants was greater in patients with a family history of senile dementia.
Frontotemporal degeneration (FTD) is a neurodegenerative condition that has been principally associated with frontal lobe dementia. In this study, we compared neuropathological abnormalities in frontal, hippocampal, and calcarine cortices from patients assigned a diagnosis of FTD, normal elderly and Alzheimer's disease (AD). Densities of Nissl-stained neurons and lesions which were immunolabeled for tau, beta-amyloid (Abeta), alpha- and beta-synuclein, ubiquitin, glial fibrillary acidic protein (GFAP) and CD68 antigen were determined using computer-assisted, non-biased quantitative microscopy. We found that FTD frontal and hippocampal regions exhibited marked neuron loss, abundant ubiquitin-immunoreactive (ir) dystrophic neurites, GFAP-ir astrocytes, and CD68-ir microglia, while calcarine cortex was spared. No alpha- or beta-synuclein-ir lesions were observed, and neither the density of tau-ir neurofibrillary tangles nor that of Abeta-ir plaques in FTD exceeded normal controls. In addition, there were no neuropathological differences between FTD subjects who presented clinically with a frontal lobe dementia versus an AD-like dementia. These findings indicate that FTD is a category of neurodegnerative dementias with varying clinical presentations that is characterized by the progressive degeneration of select populations of cortical neurons. The molecular neurodegenerative mechanisms that lead to FTD remain to be elucidated.
Despite recognition that Alzheimer's disease (AD) is a polygenic and heterogeneous dementing neurodegenerative disorder, there is continued merit in defining the AD phenotype by the presence of progressive cognitive impairments and the pathological brain lesions (senile plaques, neurofibrillary tangles) as originally formulated by Alois Alzheimer. This position paper discusses the rationale for emphasizing the detection of both beta amyloid-rich plaques and tau-rich tangles in the next iteration of the neuropathological criteria for the postmortem diagnosis of AD that has been recommended by the Working Group on Consensus Criteria for the Postmortem Diagnosis of AD. Further, it also underlines the need to exploit continuing advances in understanding the pathobiology of plaques and tangles in subsequent iterations of these criteria. It is expected that such efforts, now and in the future, will hasten the development of strategies for the early and accurate antemortem diagnosis of AD as well as the discovery of effective treatments for this common dementing illness of the elderly.
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During the past 10 years, there has been a rapidly growing number of pharmaceutical industry-sponsored drug trials for treatment of Alzheimer disease (AD) and other neurodegenerative diseases. As public awareness and concerns about AD have grown, so has interest in developing drug therapies for retarding symptom progression, delaying onset, and ultimately curing the disease. Ethical debate on the use of placebo control trials in AD research has come of age in the United States with the availability of treatments approved by the Food and Drug Administration. The experts and the public agree that more effective therapies are necessary, and new therapeutic options are being developed as rapidly as possible. The arguments on each side of the debate are provocative and important but do not provide unequivocal justification for either the abandonment or the maintenance of placebo-controlled trials in all AD research. Clinical trials differ with respect to scientific and practical goals, and these factors inherently affect the ethical priorities of each study. We present these contrasting points of view to delineate some of the issues rather than to make specific recommendations other than to urge that all clinical trials in AD should be designed with careful consideration of the ethical issues surrounding the use of placebo controls. As new and more effective treatments emerge, the ethical framework for placebo use in AD studies will require frequent re-examination. To make wise choices, patients, caregivers, physicians, and ethicists (among others) must have a voice in this continuing discussion.
Substance abuse among nursing students is a significant problem requiring careful and prudent consideration. Studies reveal that many impaired professional nurses were addicted as students. This article provides a step-by-step guideline for developing comprehensive procedures for faculty who must deal with chemically-impaired.
OBJECTIVE: To compare rates of cognitive decline between probable Alzheimer's disease (AD) patients treated with long-duration cholinesterase inhibitors (ChE-Is) and those who remained untreated. BACKGROUND: ChE-Is, including donepezil and tracrine, have shown beneficial effects on cognition and global functioning in patients with AD. The duration of these benefits is unknown because the longest double-blind placebo-controlled studies reported were only approximately 6 months long. Ethical concerns regarding randomization of patients to placebo for long periods make it difficult to undertake trials of longer duration. METHODS: We identified patients in 4 AD centers who were or were not consistently treated with ChE-Is and who had demographic, psychometric and follow-up data. We compared 205 ChE-I-treated and 218 untreated AD patients on baseline variables hypothesized to differ between these groups, on baseline Mini Mental Status Examination (MMSE) scores and on rates of MMSE change at 1 year. The analysis was performed initially with all ChE-I-treated patients as a single group versus untreated subjects, and then with donepezil versus untreated subjects and tacrine versus untreated subjects. RESULTS: As expected, treated and untreated patients differed with respect to age, education, ethnicity, percentage of community dwelling and exact days of follow-up (ANOVA and chi2) in several comparisons, but did not differ on baseline MMSE score. These baseline variables were highly intercorrelated. MMSE scores declined significantly more slowly after 1 year of ChE-I treatment compared to untreated patients (p = 0.05) after controlling for baseline differences in age, education, ethnicity and percentage of community dwelling. Slowing of decline was significant in the donepezil-treated patients (p = 0.007) but not in the tacrine-treated group (p = 0.33). CONCLUSIONS: This study, utilizing concurrent, nonrandomized controls, suggests that donepezil continues to have efficacy over at least the first year of therapy. Other studies are needed to determine whether the benefits are maintained beyond 1 year.
The short-term effects of a weight-maintenance diet high in fiber and carbohydrate (HFHC) was studied in seven very obese individuals with type II diabetes mellitus. Such diets contained 68% of kcal as carbohydrate and total fiber content of 81 g (in contrast to 42% and 28 g during baseline). Fasting glucose concentrations, summed glucose concentrations, and 24-h glucosuria were unaffected in six of seven individuals. Fasting insulin levels decreased (-6.0 +/- 2.0 microU/ml, P less than 0.05), but meal-stimulated insulin concentrations were not altered. Triglyceride and HDL cholesterol concentrations were also unaffected. Total cholesterol concentrations fell in four individuals whose initial values exceeded 200 mg/dl. Basal glucose production rates were similar in the obese diabetic subjects, in five nonobese normal subjects, and in one obese normal individual (2.05 +/- 0.19 versus 2.63 +/- 0.30 and 1.85 mg/kg/min for the obese normal individual) while on baseline diets, and did not change with HFHC. During isoglycemic hyperinsulinemic glucose clamp procedures (maintenance of basal glucose concentrations), 40 mU/m2/min was infused intravenously for 2 h. Glucose disappearance rates increased significantly in the normal-weight control subjects, but did not increase during baseline diets in the obese type II diabetic subjects (4.65 +/- 0.80 versus 0.68 +/- 0.40 mg/kg/min). HFHC diet had no effect on glucose disappearance rates. Plasma insulin levels were 131.0 +/- 11.0, 120.0 +/- 11.0, and 120.0 +/- 5.0 microU/ml during these studies. These studies indicate that short-term HFHC diets without caloric restriction were ineffective in improving glycemic control or lessening insulin resistance in very obese patients with type II diabetes.
The prevalence of carotid artery occlusive disease (CAOD) in a population of adults with diabetes mellitus was determined, and factors associated with its presence were identified. By oculoplethysmography and phonoangiography, 20% of the population studied had detectable CAOD. Univariate analyses revealed that patients with CAOD had a higher prevalence of retinopathy proteinuria, a slower mean conduction velocity in two of three nerves tested, and more atherosclerosis in the leg arteries. Furthermore, increased age, higher cholesterol, lower fasting insulin, higher systolic blood pressure, and less adiposity were associated with the presence of CAOD. Sex, race, type of diabetes (type I or II), duration of diabetes, and measures of glycemia were not related to CAOD. When 10 variables were analyzed by multivariate methods, higher systolic blood pressure, higher cholesterol, and reduced adiposity were found to be the combination most significantly related to CAOD.
The Diabetes Education Study (DIABEDS) was a randomized, controlled trial of the effects of patient and physician education. This article describes a systematic education program for diabetes patients and its effects on patient knowledge, skills, self-care behaviors, and relevant physiologic outcomes. The original sample consisted of 532 diabetes patients from the general medicine clinic at an urban medical center. Patients were predominantly elderly, black women with non-insulin-dependent diabetes mellitus of long duration. Patients randomly assigned to experimental groups (N = 263) were offered up to seven modules of patient education. Each content area module contained didactic instruction (lecture, discussion, audio-visual presentation), skill exercises (demonstration, practice, feedback), and behavioral modification techniques (goal setting, contracting, regular follow-up). Two hundred seventy-five patients remained in the study throughout baseline, intervention, and postintervention periods (August 1978 to July 1982). Despite the requirement that patients demonstrate mastery of educational objectives for each module, postintervention assessment 11-14 mo after instruction showed only rare differences between experimental and control patients in diabetes knowledge. However, statistically significant group differences in self-care skills and compliance behaviors were relatively more numerous. Experimental group patients experienced significantly greater reductions in fasting blood glucose (-27.5 mg/dl versus -2.8 mg/dl, P less than 0.05) and glycosylated hemoglobin (-0.43% versus + 0.35%, P less than 0.05) as compared with control subjects. Patient education also had similar effects on body weight, blood pressure, and serum creatinine. Continued follow-up is planned for DIABEDS patients to determine the longevity of effects and subsequent impact on emergency room visits and hospitalization.
This article describes a team case management model using a group therapy approach developed and implemented for chronically mentally ill veterans. The model was developed to address inadequacies in the system and to provide mentally ill veterans with more frequent interventions and an organized support system to maintain them in the community. Two hundred seventy-five patients enrolled in the case management system attend weekly groups led by two or three interdisciplinary staff. In addition to serving as primary therapists and case managers, the interdisciplinary staff broker services, linking patients with needed services within the Veterans Affairs system and the community. The results indicate that the case management model has improved the lives of those enrolled by improving quality of life, medication and treatment compliance, social relationships, and general well-being. Use of emergency room services has decreased, as well as psychiatric symptomatology. For some diagnostic categories, the number of hospital readmissions and days hospitalized also decreased.