Functional studies of the protein 4.1 family of junctional proteins in Drosophila.
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Animals↗
Biomedical subjects
R E Ward
Publications and source records attributed to R E Ward.
Evaluation of factors potentially associated with inadequate follow-up of mammographic abnormalities.
BACKGROUND: To increase the proportion of women who receive the recommended follow-up for mammographic abnormalities, factors which inhibit follow-up must be identified. Patient and health care delivery related factors were evaluated, stratified by type of follow-up recommendation, to determine reasons for inadequate follow-up. METHODS: All Caucasian and African American women at the Henry Ford Medical Group, in southeastern Michigan, with an abnormal screening mammogram result between January 1, 1992 and July 31, 1992 were identified. All women with inadequate follow-up, and a random sample of women with adequate follow-up, were invited to participate in a telephone interview that assessed three major dimensions of the Health Belief Model (susceptibility, benefits, and barriers), general health and health behaviors, and related characteristics. The relationship between these factors and inadequate follow-up was evaluated separately for women with immediate and 6-month follow-up recommendations, using univariate and multivariate analyses. RESULTS: A total of 555 women were invited to participate in the study (219 with inadequate follow-up and 336 with adequate follow-up). Interviews were completed for 418 women (75.3%). Women who were not notified of their mammographic abnormality were excluded from this study, leaving 399 women available for analysis. Among the women who had the recommended immediate follow-up, those who reported difficulty in obtaining medical appointments were 4 times more likely to have inadequate follow-up (95% confidence interval [CI] 1.5, 11.3), after adjusting for other variables. Among the women with six-month follow-up recommended, those who received fewer mammograms in the past 5 years were more likely to have inadequate follow-up (odds ratio [OR] = 4.0; 95% CI 1.6, 10.4). In this group, sociodemographic characteristics were not associated with inadequate follow-up, although women with transportation problems were at a higher risk (crude OR = 5.2; 95% CI 1.6, 16.7; adjusted OR = 3. 1; 95% CI 0.5, 18.3). Among women with 6-month follow-up recommended, those who perceived their health as poor or fair (crude OR = 2.4; 95% CI 1.2, 5.1; adjusted OR = 2.3; 95% CI 0.8, 6.8) and those who did not examine their own breasts frequently (crude OR = 2.3; 95% CI 1.0, 5.4; adjusted OR = 2.7; 95% CI 0.5, 18.3) were also more likely to have inadequate follow-up. CONCLUSIONS: Results from this study demonstrate that the relative importance of factors associated with inadequate follow-up of abnormal mammograms differs according to the type of follow-up recommended. For both types of recommendations, the factors identified are noteworthy because they are amenable to intervention. Efforts should be made to facilitate appointment scheduling for follow-up of abnormal mammograms, and information about previous mammography screening should be obtained to identify women who are at a high risk for inadequate follow-up.
Attitude to Health↗
Patient notification and follow-up of abnormal test results. A physician survey.
OBJECTIVE: To investigate physician practices in the handling of patients' test results from the time the test was ordered until the time any required follow-up was completed. METHODS: Survey of 161 attending physicians and 101 residents in family practice and internal medicine practicing at a large urban teaching hospital and 21 suburban primary care practices in Southeastern Michigan. The survey included questions about physician demographics, and whether physicians have methods for ensuring that (1) the results of all tests ordered are received, (2) all patients are notified of results, (3) all patient notification is documented, and (4) all required follow-up is done. Physicians were also asked to self-rate the reliability of their methods and the importance of various steps in the handling of patients' test results. RESULTS: The response rate was 79% for both attending physicians and residents. Approximately 17% to 32% of physicians reported having no reliable method to make sure that the results of all tests ordered are received. One third of physicians do not always notify patients of abnormal results. The most common reasons reported for not notifying patients were that the results were trivial and that the patient was expected to return to the clinic soon. Residents were significantly less likely to document notifying patients of abnormal results (P < .001). Only 23% of physicians reported having a reliable method for identifying patients overdue for follow-up. CONCLUSIONS: Lack of methods to ensure that the results of tests ordered were received, dependence on follow-up visits to inform patients of results, and lack of documentation were relatively common among physicians surveyed. These could lead to an increased risk of malpractice litigation and suboptimal patient care.
Diagnostic Tests, Routine↗
Effect of vaccination of ponies with A4 anti-idiotypic antibody on serum idiotype (1C9) and antilipid A concentration.
OBJECTIVE: To evaluate the humoral response of horses to vaccination, using a murine monoclonal anti-idiotypic antibody (A4) that shares an epitope with lipid A. DESIGN: Serum concentrations of antilipid A antibody and 1C9 (epitope on murine monoclonal antilipid A antibody) were measured serially during the period of vaccination with A4. ANIMALS: 6 clinically normal adult ponies. PROCEDURE: Ponies were inoculated IM 3 times at monthly intervals with A4. Two weeks after each inoculation, serum was obtained and was assayed by ELISA for antilipid A and 1C9 concentrations. Additional vaccinations were given to 2 of the ponies after a several-month rest period. RESULTS: There was significant increase in 1C9 concentration (P < 0.0001) during the period of vaccination and a trend toward increased antilipid A concentration. The latter effect was not significant (P = 0.055). Additional vaccinations produced further increase in serum 1C9 concentration; antilipid A concentration increased in one of these ponies but not the other. Maximal antilipid A concentration recorded in these ponies was approximately 6 times preimmune concentration and was comparable to that found in a commercial antiendotoxin antiserum. 1C9 also was detected in the commercial antiserum. CONCLUSIONS: A4 anti-idiotype vaccination of horses is safe and may be effective in eliciting an antibody response against endotoxin. The finding of 1C9 in a commercial antiendotoxin antiserum indicates that this idiotype may be part of the normal polyclonal antibody response of horses to endotoxin. CLINICAL RELEVANCE: It may be possible to use anti-idiotypic antibody vaccination in horses to induce protection against the effects of endotoxin.
Animals↗
Patient-related risk factors that predict poor outcome after total hip replacement.
OBJECTIVE: To identify factors associated with poor outcome after total hip replacement (THR) surgery. DATA SOURCES: This article is the first to present results from the American Medical Group Association (AMGA) THR consortium. STUDY DESIGN: The outcomes evaluated were pain and physical function. Eight patient risk factors were evaluated. These included the age, sex, race, marital status, and education of the patient; whether the patient had polyarticular disease or other comorbid conditions; and the patient's preoperative pain and physical function score. DATA COLLECTION: Data were collected from patients using AMGA-approved, self-administered questionnaires preoperatively and at six weeks, three months, six months, one year, and two years postoperatively. PRINCIPAL FINDINGS: Of the patient risk factors studied, race, education, number of comorbid conditions, and preoperative Health Status Questionnaire (HSQ) score were found to be associated with poor outcome. These risk factors were found to have an effect on both pain and physical function at six months postoperatively. Patients with higher preoperative scores were found to have higher postoperative scores, but substantially fewer of these patients received any benefit from their surgery. For each 10-point increase in preoperative score, patients could expect at least a 6-point decrease in postoperative improvement. CONCLUSIONS: Our study indicates that preoperative status is an important predictor of outcome for THR.
Activities of Daily Living↗
Development and multi-institutional implementation of coding and transmission standards for health outcomes data.
Health care delivery institutions and providers, employers, and government agencies throughout the U.S. are sharing information and pooling resources in an attempt to produce reliable measurements of health outcomes. The rapid rate of growth in the collection and pooling of health outcomes data has prompted the need for standardization. The work of health care organizations and consortiums pooling data would be greatly facilitated by widely accepted standards for the coding and transmitting of outcomes data. Moreover, standards allow for the inter-operation of data capture products, data analysis tools, and data pooling services developed by a variety of different vendors. The Health Outcomes Institute (HOI) and Henry Ford Health System (HFHS) have developed and maintain a database of health outcomes questions which provides a mechanism for uniquely coding data elements. HFHS and the American Medical Group Association (AMGA) have created a software tool to facilitate the conversion and transmission of health outcomes data elements in an American Society for Testing and Materials (ASTM)/Health Level Seven (HL7) format, which incorporates HOI question standards.
Health Services Research↗
Synthesizing evidence from multiple studies. The role of meta-analysis in pharmacoeconomics.
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Cost Control↗
Economic outcomes of withdrawal of digoxin therapy in adult patients with stable congestive heart failure.
OBJECTIVES: This study sought to analyze the health and economic outcomes of withdrawal of digoxin therapy among U.S. adult patients with stable congestive heart failure. BACKGROUND: New information regarding the outcomes of digoxin withdrawal has been provided by the Prospective Randomized Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trials. We interpreted and extrapolated the results of these trials to describe implications on a national level. METHODS: We used a decision-analytic model to estimate the outcomes of two alternative strategies to 1) continue and 2) withdraw digoxin in patients with congestive heart failure with normal sinus rhythm, New York Heart Association functional class II or III and left ventricular ejection fraction < or = 35%. Epidemiologic assumptions were derived from published reports and expert opinion. Assumptions regarding the effectiveness of digoxin therapy were derived from the RADIANCE and PROVED digoxin withdrawal trials. Hospital and Medicare data were used for economic assumptions. Calculated outcomes included treatment failures, cases of digoxin toxicity and health care costs. RESULTS: The continuation of digoxin therapy in these patients with congestive heart failure nationally would avoid an estimated 185,000 clinic visits, 27,000 emergency visits and 137,000 hospital admissions for congestive heart failure. After accounting for an estimated 12,500 cases of digoxin toxicity, the net annual savings would be $406 million, with a 90% range of uncertainty of $106 to $822 million. One-way sensitivity analysis indicated that digoxin therapy is cost-saving when the assumed annual incidence of digoxin toxicity is < or = 33%. CONCLUSIONS: The continuation of digoxin therapy in patients with stable congestive heart failure should be strongly considered, because this strategy is likely to lead to both lower costs and greater health benefits on the basis of available information.
Adult↗
Familial crossed polysyndactyly.
We have observed a distinct form of "crossed" polysyndactyly in 6 generations of a family with 5 affected persons, all males. The polydactyly is postaxial in the hands and preaxial in the feet. Syndactyly in the hands is observed in some relatives, while syndactyly in the feet is present bilaterally in all affected relatives. This seems to be an autosomal dominant trait with male to male transmission over 3 generations by examination and an additional 3 generations by history. This form of polysyndactyly could not be readily categorized by the existing classification by Temtamy and McKusick [1978: BD OAS XIV 6:363-392]. We review and expand the present classification of polydactyly and syndactyly syndromes.
Abnormalities, Multiple↗
Cephalometric evidence for a dominantly inherited predisposition to cleft lip-cleft palate in a single large kindred.
Several studies have demonstrated an association between facial shape in parents and the presence of oral clefts in their offspring. However, these observations have been of little practical value because it has been assumed that facial shape was just one predisposing component among many in a multifactorial model of inheritance. Cephalometric analysis of a large family with 5 generations of affected individuals suggests that facial shape can be used to identify presumed carriers of a major gene associated with an increased risk for oral clefts. Discriminant function analysis indicates that such at risk individuals can be recognized effectively through a combination of increased midfacial and nasal cavity widths, reduced facial height, and a flat facial profile. The ability to identify minimally affected gene carriers within families would provide critical information needed in the search for molecular markers that segregate with the genetic risk for clefting.
Cephalometry↗
Dr Deming and primary care internal medicine.
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Clinical Competence↗
The secondary B cell lineage for phosphorylcholine is conserved in CBA/CaHN-xid/J mice.
In order to determine the mechanism of generation of immunological memory, we used the splenic focus assay to analyze primary and in vitro generated secondary phosphorylcholine (PC)-specific B cell precursors in CBA/CaHN-xid/J mice (CBA/N) expressing an X-linked immune defect (xid). A quantitative analysis of the kinetics of the appearance of these precursors over the time of the culture period was performed. The precursors were analyzed for TEPC15 idiotype expression and epitope specificity. We found that there was a significantly reduced total frequency of PC-specific precursors in CBA/N female and (CBA/CaHN-xid/J female x BALB/cRos male)F1 (NBF1) male mice (xid phenotype), relative to BALB/c and NBF1 female mice (normal phenotype). Memory precursors representing a distinct lineage of B cells, however, were present at normal levels in CBA/N female and NBF1 male mice. These results help explain the reported characteristics of the serum antibody responses induced in these mice and also better our understanding of the mechanism of B cell memory generation.
Animals↗
Ig repertoire expression of BALB/c primary and secondary B cell precursors specific for phosphorylcholine.
To better understand the regulation of Ig repertoire expression and the generation of memory B cells, we have used the splenic focus assay to analyze primary and in vitro generated secondary phosphorylcholine (PC)-specific BALB/c B cell precursors. A quantitative analysis of the kinetics of appearance of these precursors over the time of the culture period was performed. The precursors were analyzed for TEPC15 Id expression, H chain isotype, relative affinity, and epitope specificity (PC vs p-nitrophenyl PC). In addition, we tested the hypothesis that primary and secondary precursors could be distinguished on the basis of the expression of the cell-surface Ag defined by the mAb JIId. We found that secondary in vitro PC-hemocyanin stimulation resulted in an increase in the anti-PC precursor frequency, relative to primary stimulation, of 37%. This increase was caused almost entirely by the secondary stimulation of non-TEPC15 expressing precursors. Relative to the primary precursors, the secondary precursors also: 1) expressed a lower percentage of IgM and a higher percentage of IgG, 2) had a higher relative affinity, and 3) expressed a lower level of JIId-defined Ag. Very little difference was observed in the epitope specificity of the primary vs secondary precursor repertoire. Based on an analysis of the kinetics of the response, together with JIId cell sorting and transfer experiments, our results support a model whereby a portion of the secondary anti-PC response is derived from secondary precursors arising from primary precursors, and the other portion is derived from distinct secondary precursors expressing a relatively low amount of the JIId Ag.
Animals↗
Brief communication: measurement size, precision, and reliability in craniofacial anthropometry: bigger is better.
In this paper we examine the results of an intraobserver measurement error study involving 49 craniofacial variables that ranged in size from less than 1 cm to approximately 20 cm. Repeat measurements were taken on 10 male and 10 female adult subjects (19-59 years old). Our focus is on the relationship between measurement size and measurement error across the 49 variables. We found that the size of the variable showed no relationship with the magnitude of the error as measured by the technical error of measurement. When the error was expressed as a coefficient of relative variation (Malina et al.: Vital and Health Statistics, Series 11, No. 23. Washington, DC: US Department of Health and Human Services, 1973), this quantity was negatively associated with the size of the measurement. Conversely, reliability (Fleiss: The Design and Analysis of Experiments. New York: John Wiley & Sons, 1986) was positively correlated with measurement size. We did not find effects of scale (Marks et al.: Am. J. Epidemiol. 130:578-587, 1989) within the individual measurements. Thus, for the range of size of the craniofacial measurements in this study, measurement size must be added to the list of factors such as ease of locating landmarks, measurement technique, and systematic bias in the application of the technique that can affect precision and reliability in anthropometry.
Adult↗
A nontoxic, idiotope vaccine against gram-negative bacterial infections.
Experiments were performed to test the ability of mouse antiidiotopic mAb, specific for an antilipid A mAb, to act as a vaccine against gram-negative bacterial infections. Lipid A is a conserved region of bacterial LPS. Immunization with the antiidiotopic antibodies, coupled to an immunogenic carrier protein (hemocyanin), specifically induced anti-LPS antibody responses in animals from different species. In a mouse model, this immunization resulted in protection against both lethal gram-negative bacteremia and endotoxemia. The antiidiotopic antibodies, however, did not stimulate endotoxin-associated bioactivities, such as induction of TNF and IL-1. These results support the hypothesis that an idiotope vaccine can stimulate beneficial protective immunity against gram-negative infections without the toxicity inherent in LPS.
Animals↗
The primary B cell response to the O/core region of bacterial lipopolysaccharide is restricted to the Ly-1 lineage.
Experiments were performed to test the hypothesis that Ly-1 B cells respond to antigenic challenge with LPS from gram-negative bacteria. To perform these experiments, the splenic fragment culture system for the study of B cell precursors was used. We found that a significant number of anti-O/core, but not anti-lipid A, precursors expressed the lambda L chain. A restriction of the anti-LPS response to Ly-1 B cells was tested using a Ly-1 depletion protocol. We found that the anti-O/core antibody response was restricted to the Ly-1 B cell lineage. In contrast, conventional B cells, not Ly-1 B cells, respond to an antigenic challenge with lipid A. Our results further support the idea that the Ly-1 B cell lineage serves a direct role in protecting against certain bacterial infections.
Animals↗
Design considerations of CareWindows, a Windows 3.0-based graphical front end to a Medical Information Management System using a pass-through-requester architecture.
The Care Windows development project demonstrated the feasibility of an approach designed to add the benefits of an event-driven, graphically-oriented user interface to an existing Medical Information Management System (MIMS) without overstepping economic and logistic constraints. The design solution selected for the Care Windows project incorporates three important design features: (1) the effective de-coupling of severs from requesters, permitting the use of an extensive pre-existing library of MIMS servers, (2) the off-loading of program control functions of the requesters to the workstation processor, reducing the load per transaction on central resources and permitting the use of object-oriented development environments available for microcomputers, (3) the selection of a low end, GUI-capable workstation consisting of a PC-compatible personal computer running Microsoft Windows 3.0, and (4) the development of a highly layered, modular workstation application, permitting the development of interchangeable modules to insure portability and adaptability.
Academic Medical Centers↗
Analysis of the immune response to lipopolysaccharide. Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies.
LPS is the major surface glycolipid on gram-negative bacteria. In this work, we have idiotypically characterized the antibody response against LPS in different species. To do this, we have produced mAb against LPS. Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule. One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models. We generated anti-idiotypic antibodies against IC9. The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A. We used these anti-Id to characterize the anti-LPS response, and the results revealed that the IC9 Id is conserved in different species. The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed.
Animals↗