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Biomedical subjects

W B Carter

Publications and source records attributed to W B Carter.

At least 37 records · Page 2Linked to original sources

Community-based surveillance of acute ischemic heart disease: are one-time mailed questionnaires to physicians useful?

A 12-month data collection from medical records in Seattle/King County for acute ischemic heart disease among patients with diabetes mellitus was augmented with mailed questionnaires to personal physicians. The responsible Human Subjects Committee restricted the study to a one-time questionnaire mailing. Only 380 of 1,235 patients required physician contact when information was missing from primary data sources. Questionnaires were highly personalized, and most were limited to one page. Seventy-seven per cent of 330 physicians returned at least one questionnaire, and 62% of all questionnaires were returned with usable data. We conclude that useful data may be collected from physicians by way of mailed questionnaires if researchers use a brief and personal format.

Angina Pectoris↗

Cause and current management of reoperative hyperparathyroidism.

We reviewed 137 cases of hyperparathyroidism followed for 6-72 months to determine the reasons for failure and to outline the successful management of reoperative hyperparathyroidism. Of 127 patients treated initially at Thomas Jefferson University Hospital, three required reoperation (2.4%) and 10 were referred with recurrent or persistent hyperparathyroidism. Reasons for failure were a missed gland in eight cases (62%), an ectopic gland in two cases (15%), supernumerary glands in two cases (15%), and malignant degeneration of an autotransplant in one case (8%). One patient had shortterm hypoparathyroidism requiring vitamin D supplementation (5.6%), but there were no injuries to the recurrent laryngeal nerves. We conclude that adequate knowledge of the location of normal and ectopic glands with meticulous search will reduce most reoperations, and, with identification of all four glands and routine cervical thymectomy in multigland disease, the rate should be less than 5 per cent. Patients requiring reoperation should undergo noninvasive localization studies and, if equivocal, selective venous sampling for parathyroid hormone. The major complication rate should be less than 10 per cent.

Adult↗

Strategies for improving and expanding the application of health status measures in clinical settings. A researcher-developer viewpoint.

Health status instruments may be useful in clinical settings to screen for functional problems, monitor disease progression or therapeutic response, improve doctor-patient communications, assess quality of care, or provide case-mix adjustment for comparing other outcomes between patient groups. However, conceptual, practical, and attitudinal barriers have prevented their wider implementation. Aside from providing more data on how these measures influence the process and outcomes of clinical care, several strategies may help to improve and expand their application. Wider application would be promoted by training health care providers about the methods of health status assessment, their validity, and the available instruments; comparing newer functional measures and older scales with which clinicians are familiar (to make scores more meaningful); providing better data for the selection of instruments; and improving the responsiveness of these questionnaires to clinical changes. If health status measures are used in direct patient care, it is important to determine whether the goal is to screen for functional problems or to monitor patient changes over time. These different purposes may influence the selection of instruments, the types of patients targeted (e.g., based on age or diagnosis), and the frequency of patient assessment. Health status measures must be easily incorporated into the office routine, requiring that they be brief, easy to interpret, and not require complex training or scoring algorithms. In this setting, it may be helpful to provide clinicians not only with functional status scores, but with interpretations and recommendations about management or community resources to consider. The costs of health status measurement and data analysis will probably be borne by third-party payers, who must be persuaded of their utility. When health status measures are used for quality assurance, average scores for groups of patients should be adjusted for disease severity, comorbid conditions, demographic characteristics, socioeconomic status, and baseline health status. Furthermore, the sickest or most vulnerable members of a clinical population may be least able to provide valid health status information because of dementia, frailty, blindness, illiteracy, or inability to speak English. These patients may be of particular interest, and are likely to alter average health status scores for a population, so methods to assure complete ascertainment must be considered.

Attitude of Health Personnel↗

Inhibition by human interleukin-1 alpha of parathyroid hormone-related peptide effects on renal calcium and phosphorus metabolism in the rat.

Humoral hypercalcemia of malignancy (HHM) is at least partly caused by tumor secretion of PTH-related peptide (PTHrP), but there is growing evidence for cosecretion with PTHrP of other bone-resorbing peptides, such as the cytokine interleukin-1 alpha (IL-1 alpha). Administration of PTHrP in vivo and in vitro generally mimics the actions of PTH itself, with increases in both resorption and formation of bone. However, bone in HHM is characterized by uncoupling of bone turnover, with increased resorption and decreased formation. We performed experiments to determine whether IL-1 alpha might alter the effects of PTHrP and produce uncoupling. Thus, we administered to 100-g male rats by sc osmotic minipumps synthetic PTHrP-(1-34) alone (2 micrograms/100 g/day), recombinant IL-1 alpha alone (1.5 micrograms/100 g/day), both peptides together at the previous doses, or vehicle only. We infused 5 groups of 12 rats each (PTHrP, IL-1 alpha, PTHrP plus IL-1 alpha, ad libitum fed control, and controls pair-fed to the PTHrP plus IL-1 alpha group) for 14 days. At the end of the study, blood and urine were taken for chemical measurements, and tibias and femurs were harvested for histomorphometry and extraction of RNA from periosteal cells. As expected, PTHrP induced hypercalcemia, relative hypophosphatemia, phosphaturia, and reduced bone mass. Osteoblast number was increased, but osteoclast number was not. Indices of bone formation were unchanged or reduced. The dose of IL-1 alpha chosen had no statistically significant effect, except for reduced longitudinal bone growth, but when combined with PTHrP, IL-1 alpha reduced hypercalcemia, hypophosphatemia, and phosphaturia. In contrast to the blood and urine effects, IL-1 alpha did not interact significantly with PTHrP's effect on bone measurements. Northern analysis of periosteal cell mRNA showed that PTHrP reduced expression of osteocalcin, but not glyceraldehyde-3-phosphate dehydrogenase; IL-1 alpha had no additional effect. These data suggest that 1) continuously administered PTHrP alone may induce uncoupled bone turnover with decreased cortical bone formation; 2) IL-1 alpha appears to inhibit strongly the renal effects of PTHrP and weakly (if at all) its actions on bone and, thus, to decrease its hypercalcemic, phosphaturic, and hypophosphatemic actions; and 3) cosecretion of IL-1 alpha, and possibly other peptide cytokines, with PTHrP may modify the clinical expression of HHM.

Animals↗

Psychology and decision making: modelling health behavior with multiattribute utility theory.

The success of much of dental practice is linked to patient behavior. Understanding the issues that influence patients' decisions when they choose to not follow preventive or therapeutic dental recommendations is instrumental to improving adherence, and ultimately, to improving dental health outcomes. Multiattribute Utility Theory (MAU) provides a methodology for systematically exploring these issues. It is based on a well-established body of knowledge in the psychological literature, and currently represents a state-of-the-art model for predicting behavior and delineating potentially modifiable behavioral determinants. Two examples are presented to illustrate how MAU can be used in clinical settings. In the first example, MAU is used to identify key reasons why nearly 70 percent high-risk patients did not obtain flu shots, a behavioral problem comparable to many confronted in dentistry. MAU correctly predicted the vaccination behavior of 82 percent of patients, and an intervention based on MAU findings nearly doubled vaccination rates. The second example used MAU to identify physician behaviors that influenced patients' satisfaction with an ambulatory care visit. MAU findings from this study identified specific behaviors in a provider's style that if modified may improve patient satisfaction. These MAU applications also emphasize the importance of soliciting the patient's perspective in clinical interactions since some of the most important determinants of patient behavior are not represented in traditional clinical decision models.

Decision Making↗

Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion.

Vasoactive neuropeptides, present in unmyelinated C-fibers, can be released from perivascular sensory axons by antidromic stimulation, to mediate vasodilation and extravasation of plasma protein (neurogenic inflammation). In this report, the effects of antidromic trigeminal stimulation on levels of calcitonin gene-related peptide (CGRP) in plasma were examined in the superior sagittal sinus and the effects of drugs that have been shown previously to block extravasation of neurogenic plasma determined. The levels of immunoreactive CGRP in plasma were measured both before and during electrical stimulation of the trigeminal ganglion (0.1-1.0 mA, 5 msec, 5 Hz, 3-5 min), using a highly specific and sensitive immunochemiluminometric assay. Levels of CGRP increased and became maximal within the first minute of stimulation. The increases were detectable at intensities of current as small as 0.1 mA. Peak levels related to the intensity of the stimulus. Samples from femoral arterial blood did not show concomitant increases at 1 min. Pretreatment with dihydroergotamine (DHE) (50 micrograms/kg i.v.) did not change the baseline levels but decreased levels of CGRP during stimulation (0.3 mA), by 55% at 1 min and 50% at 3 min. Sumatriptan (GR43175) (300 micrograms/kg) attenuated the increase by 57% at 3 min (0.1 mA, 5 msec, 5 Hz) but not after 1 min of stimulation, although decreases were observed at the latter time during an individual experiment. Drug-induced attenuation of levels of CGRP in plasma may reflect inhibition of release, to thereby provide evidence to explain blockade of neurogenic extravasation of plasma.

Animals↗

Participation of older adults in health programs and research: a critical review of the literature.

This collection of five papers evaluates the participation of older adults in clinical trials, health promotion/disease prevention initiatives, and health programs designed to maintain or improve the functioning of chronically ill older adults. Understanding the willingness or unwillingness of older adults to participate in these programs is critical to the development and implementation of health programs and policies for this population. In this introductory paper we briefly review illustrative literature to provide both an overview of the participation of older adults in health programs as well as background information relevant to the symposium papers.

Aged↗

Parathyroid hormone (PTH)-induced intracellular Ca2+ signalling in naive and PTH-desensitized osteoblast-like cells (ROS 17/2.8): pharmacological characterization and evidence for synchronous oscillation of intracellular Ca2+.

We showed recently that the initial peak cytosolic ionized calcium ([Ca2+]i) response to PTH (2-min exposure) is preserved relative to the cAMP response in osteoblast-like rat osteosarcoma cells (ROS 17/2.8) desensitized by 72-h exposure to PTH. We attempted in the present studies to determine the mechanisms for preservation of the [Ca2+]i response and to explore the effects of longer PTH rechallenges. The [Ca2+]i response to a 20-min perifusion with rat PTH [rPTH-(1-34)] was monitored by aequorin luminescence in both naive and PTH-desensitized ROS 17/2.8 cells. The responses of both naive and desensitized cells consisted of two phases: an initial peak, followed by an intermediate plateau that was sustained in the presence of PTH. We observed in the naive cell populations synchronous oscillations in [Ca2+]i concentration during this second phase (amplitude, 10-60 nM; frequency, 1-3/100 sec). These oscillations were maintained through extracellular calcium (EC Ca2+) entry; the initial peak was the result of Ca2+ release from intracellular stores. In desensitized cells, these two phases could not be clearly separated with respect to Ca2+ source, but, as we showed before, exhibited an enhanced dependence on EC Ca2+ entry for the response to PTH. Nevertheless, in the desensitized cells, the sustained [Ca2+]i response was diminished in magnitude and showed little oscillatory behavior. Brief exposure to neomycin sulfate, an inhibitor of phosphoinositide turnover, attenuated the PTH-induced [Ca2+]i rise in both naive and desensitized cells. Protein kinase-C activity did not appear to be required for either phase of the PTH-induced [Ca2+]i response. Exposure to cholera toxin attenuated the [Ca2+]i response to hormone in both naive and desensitized cells, more markedly in the latter. Cholera toxin treatment dramatically increased basal cAMP levels in both cell preparations; PTH-stimulated cAMP production was unchanged in naive cells, but increased nearly 4-fold in desensitized cells. We propose that the preserved PTH-induced peak [Ca2+]i rise in desensitized cells results primarily from the diminished regulation of EC Ca2+ entry by the cAMP response limb. The attenuated sustained oscillatory behavior observed in desensitized cells upon rechallenge with hormone may be the result of reduced phosphoinositide turnover and reduced Ca2+-stimulated Ca2+ release. Thus, the [Ca2+]i response to PTH in osteoblast-like cells is complex and modulable and seems to provide a number of ways to regulate intracellular metabolism under various conditions. We speculate that this plasticity of the [Ca2+]i response to PTH is related to the pleiotropic actions of the hormone on cells of the osteoblast lineage.

Animals↗

Determination of plasma calcitonin gene-related peptide concentrations by a new immunochemiluminometric assay in normal persons and patients with medullary thyroid carcinoma and other neuroendocrine tumors.

There is doubt about concentrations of circulating calcitonin gene-related peptide (CGRP) and the value of plasma CGRP measurements in the detection and follow-up of medullary thyroid carcinoma (MTC). Thus, we developed an immunochemiluminometric sandwich assay for CGRP using antibodies purified from a polyclonal antiserum against human CGRP. The assay was sensitive (limit of detection, 0.4 pmol/L; multiply by 3.7892 to derive nanograms per L) and highly specific [no cross-reaction with human calcitonin (CT)]. Normal plasma CGRP values ranged from less than 0.4 to 4.5 pmol/L (median, 0.8; n = 31), with 61% having detectable levels. Values in samples from patients with MTC were elevated: unoperated patients (n = 10), 4.7-137 pmol/L (median, 7.1); and operated patients with gross persistent or recurrent tumor (n = 14), 4.7-171 pmol/L (median, 23.2). In contrast, CGRP values were normal in 78% of nine postoperative patients with elevated CT, but no detectable tumor (range, less than 0.4 to 6.3 pmol/L; median, 1.6). CGRP levels increased after pentagastrin injection in MTC patients, but less than did CT values. Cultured MTC cells in vitro secreted large amounts of CGRP, and rat nerve root ganglia, human osteoblasts, and microvessel endothelial cells secreted lesser amounts. We conclude that CGRP circulates in normal plasma, but at very low levels. Plasma CGRP concentrations are frequently high in patients with MTC, but primarily in those with gross tumor or metastases. Plasma CT assay is the preferable test for MTC, but CGRP assay deserves prospective study for a possible role in predicting gross metastasis.

Animals↗

Cyclic adenosine 3',5'-monophosphate responses to parathyroid hormone, prostaglandin E2, and isoproterenol in dermal fibroblasts from patients with familial benign hypercalcemia.

Plasma concentrations of PTH are much lower for a given calcium or phosphorus level in patients with familial benign hypercalcemia (FBH, or familial hypocalciuric hypercalcemia) than in those with primary hyperparathyroidism; these and other data suggest that there might be tissue hypersensitivity to PTH in FBH. To test this hypothesis, we have used cultured dermal fibroblasts from abdominal skin biopsies of six patients with FBH and six age- and sex-matched controls as surrogate PTH-responsive tissues. Cells in 24-well plastic plates were exposed to vehicle, human PTH-(1-34) (10(-10)-10(-7) M), prostaglandin E2 (10(-6) M), or isoproterenol (10(-4) M) for 10 min in the presence of isobutylmethylxanthine, and cellular cAMP was determined by RIA. All cells responded to PTH with dose-dependent increases in cAMP, and all responded strongly to prostaglandin E2 and isoproterenol. There were no consistent or significant differences between control and FBH fibroblasts in maximal responses to the three agonists, and half-maximal stimulation was achieved with about 10(-9) M PTH in both normal and FBH cells. These data are not consistent with increased tissue sensitivity to PTH in FBH.

1-Methyl-3-isobutylxanthine↗

Improving follow-up after an abnormal Pap smear: a randomized controlled trial.

Less than 60% of women diagnosed with cervical abnormalities on Pap smears return for proper surveillance and timely treatment. Previous tactics used to motivate these women to return have mainly relied on costly intensive recall efforts. Using a framework based on psychological value expectancy theory, a pamphlet was designed to motivate women with abnormal Pap smears to return for a repeat Pap smear. The effect of this pamphlet was tested in a randomized controlled trial. A total of 161 women with abnormal Pap smears were randomized and received either the pamphlet plus a notification letter or the letter only. The compliance rate was 64.2% in the intervention group and 51.3% in the comparison group (P = 0.10; two-tailed). In addition, subgroups of women who do not practice health-related behaviors were identified as groups where more intensive interventions may be needed. These results have implications for future strategies used to recall women with abnormal Pap smears.

Adult↗

Compliance behavior in women with abnormal Pap smears. Developing and testing a decision model.

This study investigated the reasons why women choose whether or not to seek treatment after being notified about an abnormal Pap smear in a women's clinic in Seattle. A hierarchic weighted utility model was developed from in-depth open-ended interviews with women who had an abnormal Pap smear and was used to identify beliefs and values related to the decision to seek treatment, i.e., a repeat Pap smear, for an abnormal Pap smear. Interviews with 18 women who had an abnormal Pap smear produced 12 issues pertinent to the behavior in question. These issues were grouped to form the hierarchy, and the decision model was then administered to 44 additional women. The model accurately classified the compliance behavior of 68% of study subjects. Moreover, the model differentiated persons who sought treatment for an abnormal Pap smear along several important dimensions: 1) doctor's opinion; 2) the accuracy or seriousness of the Pap smear result; 3) the importance of early detection; 4) familiarity with the treatment procedure; 5) time hassles (i.e., difficulties) involved in getting further treatment; 6) femininity concerns; 7) fear of cancer; and 8) perceived risk of cancer. These dimensions suggest specific content areas that may be used to develop low-cost compliance intervention strategies for use in clinical settings.

Adult↗

Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans.

Recent interest has focused on the potential role of amylin in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). This 37-amino acid peptide is found in extracellular amyloid deposits in approximately 50% of pancreatic islets of patients with NIDDM and has been shown to inhibit skeletal muscle glycogen synthesis in vitro. Immunocytochemical studies have colocalized amylin and insulin within beta-cell secretory granules in nondiabetic humans, provoking the following questions. Is amylin cosecreted with insulin? Are circulating amylin concentrations higher in patients with NIDDM either before or after food ingestion? To answer these questions, we developed a sensitive and specific immunoassay to measure plasma concentrations of amylin in humans. Use of this assay indicated that, in lean nondiabetic subjects, glucose ingestion resulted in an increase (P less than 0.001) in the plasma concentration of amylin (from 2.03 +/- 0.22 to 3.78 +/- 0.39 pM) and insulin (from 48.3 +/- 3.1 to 265 +/- 44 pM). There was a significant correlation between the concentrations of insulin and amylin (r = 0.74, P less than 0.001) and the increase in insulin and amylin concentration (r = 0.65, P less than 0.005). Fasting concentrations of amylin did not differ in diabetic and weight-matched nondiabetic subjects and showed a similar pattern of change after ingestion of a mixed meal. We conclude that amylin is secreted in response to ingestion of either glucose or a mixed meal and circulates at concentrations that do not differ in patients with NIDDM and nondiabetic subjects. It remains to be determined whether amylin at physiological concentrations influences carbohydrate metabolism and if so whether its effects differ in diabetic and nondiabetic humans.

Adult↗

Health education: special issues for older adults.

The older adult population in the United States has grown substantially since the turn of the century. With extended longevity and the relatively good functional status of most older adults, prevention programs that identify and intervene on risk factors in older adults may be an effective means to dealy ill health. The availability of data to guide both the selection and evaluation of prevention services for older adults, however, is strikingly limited in virtually all areas. Until recently, all persons over the age of 65 were treated as a single category of older adults although the older population is very heterogeneous. Most agree that prevention and education for this age group should focus on the prevention of disease, maintenance of existing abilities, and on prevention of deterioration of impairments that result in dysfunction or handicap. The most effective methods for developing behavioral intervention strategies may result from an integration of the behavioral diagnostic framework and current value expectancy and social learning theories. Health education interventions based on these strategies can be very effective in older age groups in terms of both improving adherence behavior with therapeutic and prevention intervention, and potentially in reducing morbidity and excess mortality.

Aged↗

Use and misuse of metered-dose inhalers by patients with chronic lung disease. A controlled, randomized trial of two instruction methods.

Metered-dose inhalers are often used incorrectly by patients with chronic airflow obstruction, and there is a lack of controlled studies designed to evaluate methods to teach the correct use of these devices. Therefore, we screened 100 consecutive stable outpatients for correct or incorrect inhaler use and then conducted a randomized trial of two methods to teach correct use. Patients were classified as correct or incorrect users with a modified metered-dose inhaler containing a thermistor that detected inspiration, inhaler activation, and the duration of breath-holding. Patients were classified as incorrect users if they failed to: (1) activate the inhaler once during inspiration, and/or (2) hold their breath at the end of inspiration. There were 38 correct users and 62 incorrect users. Incorrect users were randomized to one of two teaching protocols: (1) standardized verbal instruction alone, or (2) standardized verbal instruction plus an automatic visual signal during inspiration. Incorrect users were restudied 6 to 10 wk later to reassess technique. Both treatment protocols were equally effective in converting incorrect user. However, the verbal instruction alone required significantly less time than the instruction with the mechanical aid. For all subjects, the proportion using correct technique declined over time, particularly for incorrect users. We also examined a series of patient characteristics, obtained by questionnaire and spirometry, to determine whether they could be used in the clinical setting to identify incorrect users. By discriminant analysis, a group of four variables predicted correct metered-dose inhaler use: bronchodilator responsiveness, a history of additional about proper technique, verbal knowledge of the correct inhaler maneuvers, and the patient's perception of whether it is important to use an inhaler.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The short-term impact of Army smoking policies.

A cross-sectional study was performed among soldiers of an infantry battalion to determine smoking prevalence and to assess the short-term impact of Army smoking policies instituted within the preceding 6 months. Data were collected using a structured pretested questionnaire. The response was 91.5%. Smoking prevalence was 45%. This study yielded conflicting data on the effectiveness of the new policies. The importance of educating the smoker on health risks was corroborated. Army health care providers had questioned the majority of the soldiers regarding their smoking status, but failed to suggest they quit or provide suggestions on how to quit.

Adult↗

Diagnosis of alcoholism in a simulated patient encounter by primary care physicians.

Although early detection and treatment of alcoholism have been shown to be efficacious, it is widely accepted that primary care physicians often fail to diagnose alcoholism. In this study, a computerized, simulated encounter with an alcoholic patient was used to assess the performance of a randomly selected sample of primary care physicians in diagnosing alcoholism. Of 95 physicians in this study, only 32 percent diagnosed alcoholism with maximal certainty. There was great variability among physicians in the threshold of information needed to diagnose alcoholism. One third of subjects misinterpreted symptoms of alcoholism and erroneously made other psychiatric diagnoses, chiefly anxiety or depression. Results of this pilot study were not associated with the physicians' age, sex, specialty, duration of training, or reported personal impact of alcoholism. This study provides further evidence of the need for additional education of primary care physicians if such physicians are to succeed in reducing the dramatic impact of alcoholism and alcohol abuse on public health.

Alcoholism↗

The flu shot study: using multiattribute utility theory to design a vaccination intervention.

Differences between the multiattribute utility (MAU) profiles of participants who had previously gotten flu shots and those who had not done so were used to design an informational brochure urging influenza vaccination. The effectiveness of the MAU brochure was evaluated in a VA ambulatory care clinic with a long-standing influenza vaccination program. The target population for the intervention was high-risk clinic patients who had not gotten a shot the previous year. Participants received either a letter urging them to get a flu shot, or a letter plus the informational brochure. A significantly larger proportion of the patients who received the brochure got shots; 36% versus 23% for the letter only. While a 13 percentage point increase is modest, influenza and related complications (preventable through vaccination) are the fourth-leading killers of older persons. Adding a MAU-based brochure to an ongoing vaccination program is inexpensive and may save additional lives.

Aged↗