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Biomedical subjects

J J Anderson

Publications and source records attributed to J J Anderson.

At least 55 records · Page 3Linked to original sources

Plant-based diets and bone health: nutritional implications.

Hip fracture incidence rates are predicted to increase dramatically in the first half of the 21st century, especially in Asia, Latin America, Africa, and the Middle East. These increased rates will result primarily from the effects of public health efforts to improve nutrition and infectious-disease control, both of which contribute to improved longevity of populations. An example of a rapid increase in hip fracture incidence rates has been reported in Hong Kong. Findings of studies there suggest that environmental changes, ie, westernization, urbanization, or both, are strongly related with declines in bone mineral density and increases in fractures. Hip fracture incidence rates in Western nations are typically increasing at much more modest rates than those in Hong Kong and other Asian nations. Epidemiologic investigations have identified multiple risk factors, including exposures earlier in life to adverse factors that are considered to contribute to the development of osteoporosis in both Western and Asian nations. The major risk factors are inadequate nutrition, limited physical activity, and low lifetime estrogen exposure. A dietary shift toward a more plant-based diet in Western nations may be beneficial to bone health, but is not likely to counter the adverse effects of limited physical activity and low estrogen exposure.

Aged↗

Functional status outcomes for assessment of quality in long-term care.

OBJECTIVE: Although decline in functional status has been recommended as a quality indicator in long-term care, studies examining its use provide no consensus on which definition of functional status outcome is the most appropriate to use for quality assessment. We examined whether different definitions of decline in functional status affect judgments of quality of care provided in Department of Veterans Affairs (VA) long-term care facilities. METHODS: Six measures of functional status outcome that are prominent in the literature were considered. The sample consisted of 15 409 individuals who resided in VA long-term care facilities at any time from 4/1/95 to 10/1/95. Activities of daily living variables were used to generate measures of functional status. Differences between residents' baseline and semi-annual assessments were considered and facility performance using the various definitions of functional status were described. RESULTS: The percentage of residents seen as declining in functional status ranged from 7.7% to 31.5%, depending upon the definition applied. The definition of functional status also affected rankings, z-scores, and 'outlier' status for facilities. CONCLUSION: Judgments of facility performance are sensitive to how outcome measures are defined. Careful selection of an appropriate definition of functional status outcome is needed when assessing quality in long-term care.

Activities of Daily Living↗

The effect of a teaching skills course on interns' and students' evaluations of their resident--teachers.

PURPOSE: To determine the effect that a six-hour course on resident teaching and leadership skills had on residents' teaching evaluations. METHOD: The authors analyzed six years of teaching evaluations of second- and third-year internal medicine residents at the University of Washington: three years before and three years after a resident teaching skills course was introduced in 1992. Interns and students rated their resident-teachers using a nine-question standardized clinical teaching assessment form (CTAF). Evaluations at baseline (the three years before the course) were compared with evaluations for the three years after the intervention. RESULTS: The authors analyzed 3,946 evaluations of 235 second-year and 211 third-year residents. Despite already high baseline evaluations, mean ratings of the CTAF showed continuous and statistically significant improvement in each year after the introduction of the course (p < .001). There was no significant difference between evaluations from students and those from interns. CONCLUSION: A six-hour teaching skills course significantly improved residents' teacher ratings. Residents are important teachers of interns and medical students and serve as their primary ward supervisors; therefore, sessions on teaching skills should be part of required curricula for all residency programs.

Curriculum↗

ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology.

We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.

Antirheumatic Agents↗

Knowledge of alcohol-related problems in clinical staff in psychiatric community resource centres in Glasgow.

We report on a survey of knowledge of alcohol-related problems in the multi-disciplinary staff in 12 general adult psychiatry community resource centres. In total we obtained data from 111 staff, the majority of whom (63%) were community psychiatric nurses (CPNs). Seventy-three per cent of staff routinely ask clients about their alcohol consumption and 66% felt that they could identify those clients with an alcohol problem. We identified gaps in knowledge that could be seen as significant, for example, the legal driving limit and the number of units of alcohol in bottles of wine and spirits. Less than a third of staff knew the criteria for alcohol dependence. The majority of staff were able to recognise clinical complications of alcohol abuse and to identify alcohol withdrawal symptoms. We consider that it would be useful to provide a simple concise data-sheet, containing basic information about alcohol, for clinical staff.

Adult↗

Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent?

OBJECTIVE: To determine whether improvement of more than 20% in core set parameters should be required before patients are characterized as improved in rheumatoid arthritis (RA) clinical trials. METHODS: Data from 6 RA trials were reanalyzed to evaluate the discriminant validity (ability to differentiate active treatment from control) of 4 proposed definitions of improvement: the current American College of Rheumatology (ACR) definition (a 20% threshold for core set parameters [ACR 201), a 50% threshold (ACR 50), a 70% threshold (ACR 70), and an ordinal definition in which a patient could be classified in any of 3 categories (unimproved, ACR 20, or ACR 50). To evaluate the discriminant validity of these 4 definitions of improvement, we characterized each patient in each trial as improved or not, based on each definition, and computed a chi-square value differentiating the active treatment group from the control group, with the corresponding P value. RESULTS: With an increase in the threshold for improvement, the percentage of placebo-treated patients who were classified as experiencing response dropped dramatically in all trials, as did the percentage of patients receiving active therapy (second-line drug, combination therapy, tumor necrosis factor p75-Fc fusion protein) who were classified as experiencing response. Generally, the drop in active treatment response rates was greater than the drop in placebo response rates, leaving the difference between the 2 groups less at the higher thresholds. Therefore, chi-square values fell as the threshold for response was raised. The ordinal definition of improvement yielded chi-square values similar to those obtained using ACR 20 alone. CONCLUSION: Adopting a definition of efficacy in RA trials that requires 50% or 70% improvement in core set parameters would likely compromise statistical power and make it more difficult to distinguish between 2 treatments with different efficacy. ACR 20 should continue to be the primary measure of efficacy in RA trials, with higher thresholds for improvement being determined and reported as secondary efficacy measures.

Antirheumatic Agents↗

Using a short food frequency questionnaire to estimate dietary calcium consumption: a tool for patient education.

OBJECTIVE: To develop a short food frequency questionnaire (FFQ) assessing calcium intake and a prediction equation for estimating total calcium intake from the short FFQ. METHODS: Data were collected from 536 women via mailed questionnaires at 3 time points. Stepwise regression analyses were used to identify those foods and beverages included in the Black Health Habits and History Questionnaire (HHHQ) that explained the most variance in participants' dietary calcium intake. A prediction equation was developed to estimate total calcium intake based only on information from the foods/beverages identified. RESULTS: Calcium obtained from 15 foods/beverages explained 97.2% of the variance in total calcium intake. The mean absolute difference between total calcium intake estimated from the 15 foods/beverages and the full HHHQ was less than 50 mg at each time point. CONCLUSION: Findings suggest that a short FFQ can provide estimates of total dietary calcium consumption comparable to the full Block HHHQ.

Adult↗

Phytoestrogens and bone.

Practically all plant foods contain small amounts of the diverse phytoestrogen molecules that have the potential to improve health. Phytoestrogens, especially the soy-derived isoflavones, are receiving great scrutiny as food supplements for the purposes of both enhancing the health of tissues and preventing several common diseases, such as cardiovascular diseases, cancers of reproductive tissues and osteoporosis. Investigations of isoflavones, in particular, have recently become more prominent because of their oestrogenic activities. These actions may be as either partial oestrogen agonists or anti-oestrogens (inhibitors of natural oestrogen activity). For example, the isoflavones of soy, mainly genistein and daidzein, have been shown by at least three different laboratories to conserve bone in ovariectomized rodent models, and they probably have similar conservatory effects in higher mammalian species. Nevertheless, the only positive effects of phytoestrogens on bone observed so far in post-menopausal women have been small and limited to the lumbar vertebrae. Additional information on human studies currently in progress is needed before the efficacy of these preparations in human subjects is known.

Animals↗

Reducing random variation in reported rates of pressure ulcer development.

OBJECTIVES: The authors evaluated methods of reporting on rates of pressure ulcer development in long-term care to identify approaches that lead to more stable estimates of actual performance. METHODS: Performance measures for facilities that adequately adjust for both random variation and casemix should be relatively stable from one time period to the next. The authors calculated facility rates of pressure ulcer development over eight consecutive time periods and correlated measures over time using different reporting methods including z-scores, combining rates from several time periods, and limiting analyses to large facilities. Results were compared with a Monte Carlo simulation. RESULTS: Observed facility rates of pressure ulcer development varied considerably over time. The average correlation coefficient across seven time comparisons for observed rates was 0.17. Reporting performance as a z-score or limiting the analyses to large facilities increased the correlation. Combining two time periods was effective only when used with one of these other approaches. The correlation coefficient based on a simulation using only large facilities was 0.51. CONCLUSIONS: Random variation affects reported rates of pressure ulcer development. Using only large facilities and combining two time periods limits the effects of random variation and results in more stable estimates of performance. When describing performance, management must consider tradeoffs between having more accurate data, the frequency with which data are provided, and whether it is given to all providers.

Bias↗

Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model.

The ovariectomized (OVX), lactating rat model has been used to investigate the skeletal effects of the plant estrogen, genistein, over a 14-day period. The OVX, lactating rat on a low-calcium diet loses slightly more than 50% of its bone mineral mass during the first 2 weeks of lactation, and we have demonstrated that estrogen treatment can significantly reduce the loss of femoral mass (ash weight). Following OVX, the rats were assigned to treatment or control groups (both placebo and positive control with estrogen replacement). The treatment groups received one of three doses of a genistein-rich preparation each day via the feed for 2 weeks, after which time the pups began to have an interest in solid feed. A positive control group received conjugated estrogen in the feed. The genistein doses were: low (0.5 mg/d); intermediate (1.6 mg/d); and high (5.0 mg/d). Measurements included ash weights of the femur, scanning electron microscopy (SEM) of the proximal tibia, and uterine weights. SEM results were as follows: (1) at the low dose genistein was approximately equally effective to estrogen in the retention of cancellous bone tissue, as reflected in the number and density of trabeculae in hemisections of the tibial subepiphyseal region, but at high doses genistein was less effective; and (2) rats treated with low-dose genistein, like estradiol, had rougher endosteal surfaces and smaller pores on these surfaces than untreated control rats. Mean ash weights of the entire femur were highest in the rats treated with the low dose compared to control rats (P < 0.05), and they were higher than ash weights of rats administered the intermediate or high doses of genistein. The mean ash weights of the femurs were consistent with the genistein effects on the tibias observed by SEM. In summary, a biphasic response to the genistein preparation was found in this OVX rat model. Interpretation of the results suggests that, at the low dose, genistein appears to be an agonist at the estrogen receptor locus, whereas at higher doses the genistein is less effective and may even have adverse effects on bone cells. These findings of a biphasic effect of genistein (i.e., an inverted U effect) are consistent with those of other recent reports in the literature on isolated bone cells and on reproductive tissues. In summary, lower doses of genistein from soy foods would be expected to act similarly to estrogens with a beneficial effect on bone tissue, but at high doses that are unlikely to be consumed in human diets, this soy derivative may have potentially adverse effects on bone cell functions and thereby on bone tissue.

Animals↗

Transmyocardial laser revascularization: old theory, new technology.

Transmyocardial laser revascularization provides a promising alternative for patients with intractable angina. The concept of blood flow directly from the left ventricular chamber into the myocardium is not a new one, and recent studies have found the potential for this application in human hearts. Laser technology has provided an avenue for exploring the possibility of revascularization through channels created in the left ventricle. Early studies have demonstrated improved relief of angina symptoms in patients who are not candidates for traditional medical and surgical revascularization modalities.

Angina Pectoris↗

Statistical and study design issues in assessing the quality and outcomes of care in rheumatic diseases.

As we have pointed out in this article, a health care study should have a well-defined intent that is matched to the study type, population of interest, and outcome. Care must be taken to collect samples in a meaningful way, so that results can be generalized to larger populations. Outcomes must be selected carefully to ensure that they will be sensitive to the types of care being considered, and only a few main outcomes should be selected so as to preserve the level of statistical significance of the research results. Sample sizes should be sufficient to detect an effect of reasonable size, after accounting for attrition in longitudinal studies and rates of occurrence with dichotomous outcomes. If the study purpose is to compare multiple institutions or health care providers, statistical adjustments for case mix will generally be required. Outcome research is an expanding area of development for rheumatology care and for medical care in general. It offers the promise of the use of administrative data bases to answer questions that are important both to arthritis researchers and to consumers of rheumatology care. As with all areas of clinical research, we must maintain appropriate levels of statistical rigor to protect the integrity of the results. Inadequate attention to the design and analysis of data can compromise research results before a study even gets started, and health care research studies have as many potential statistical pitfalls as other types of clinical research.

Epidemiologic Studies↗

Defining radiographic osteoarthritis for the whole knee.

OBJECTIVE: To determine in the knee which individual radiographic feature or combination of features in the patellofemoral and tibiofemoral joints correlate best with a nonradiographic definition of clinical osteoarthritis in order to recommend a definition of radiographic osteoarthritis for use in studies. METHODS: Using data from the Framingham Osteoarthritis Study, we tested the correlation of clinical OA, defined as frequent knee pain plus crepitus, with a variety of definitions of radiographic OA including those based on individual radiographic features, e.g. > or = grade 2 osteophyte 0-3 scale, and new definitions that included alternative combinations of features, [e.g. either > or = grade 2 osteophyte or joint space narrowing > or = grade 2 (0-3 scale) with a bone feature (such as cyst, sclerosis, or grade 1 osteophyte)]. We performed analyses looking at participants who had obtained both weight-bearing anteroposterior (AP) and lateral radiographs of both knees. RESULTS: In 519 participants, we found that the definitions of radiographic osteoarthritis best correlated with clinical OA were definite osteophyte > or = grade 2' (efficiency 62.4-67.1%) and an 'alternate definition' of either osteophytes > or = grade 2 or joint space narrowing > or = grade 2 with a bony feature of OA (efficiency 62.8-68.1%). A recursive partitioning analysis selected the 'alternate definition' as best. Also, we found that adding lateral views to the AP view improved the diagnostic test performance of the best performing radiographic definitions. CONCLUSION: We suggest that a knee should be characterized as having radiographic OA if there is either an osteophyte of grade 2 or greater severity (0-3 scale) present or the presence of moderate to severe joint space narrowing (> or = 2 on a 0.3 scale) with co-occurrence of a bony feature in the compartment affected.

Aged↗

A novel quantitative immunoassay system for p53 using antibodies selected for optimum designation of p53 status.

AIM: To develop a highly sensitive and specific enzyme linked immunosorbent assay (ELISA) system for analysis of p53 protein in cancer lysates. METHODS: The anti-p53 monoclonal antibodies DO7, 1801, BP53.12, and 421, and anti-p53 polyclonal antiserum CM1 were assessed by immunohistochemistry and western blot analysis to identify those most suitable for determining p53 status of cancer cells. Antibodies with desired characteristics were used to develop a non-competitive sandwich type ELISA system for analysis of p53 expression in cancer cytosols. Using the ELISA, p53 protein concentrations were measured in a small series of breast cancers, and the quantitative values compared with p53 immunohistochemical data of the same cancers. RESULTS: DO7 and 1801 gave the most specific and reliable results on immunohistochemistry and western blot analysis. Using these two antibodies, a non-competitive sandwich type ELISA system was developed to analyse p53 quantitatively. Analysis of the breast cancer series showed a good correlation between immunohistochemistry and the ELISA-tumours were generally positive using both techniques. Discrepancies were noted however: some cancers were immunohistochemically negative but ELISA positive. One explanation for this may be that the ELISA is more sensitive than immunohistochemistry. CONCLUSION: The p53 ELISA system is a non-competitive double monoclonal antibody sandwich method, using DO7 and 1801 which have been shown to be highly specific for p53 protein by immunohistochemistry and western blot analysis. The lower threshold of the assay is 0.1 ng/ml analyte in an enriched recombinant p53 preparation. As p53 is now regarded as a protein associated with prognosis in breast and other cancers, the assay may have clinical applications.

Antibodies, Monoclonal↗

Effects of high-intensity resistance exercise on bone mineral density and muscle strength of 40-50-year-old women.

OBJECTIVE: The purpose of the study was to determine the effect of six months of heavy resistance training (weightlifting) on the bone density of premenopausal women. EXPERIMENTAL DESIGN: A 6-month prospective design with random assignment to groups. SETTING: Measurements of bone mineral density (BMD) were obtained from the Radiology Clinic at North Carolina Memorial Hospital. Exercise sessions were completed in the Physical Education Department facilities at the University of North Carolina, Chapel Hill, NC. PARTICIPANTS: Thirty-five premenopausal women, 40-50 years of age, were randomly assigned to either a resistance training (RT) and sedentary control (CON) group. The study finished with 12 women exercising and 14 in the control group. INTERVENTION: The resistance training consisted of three days per week of high-intensity weightlifting specifically designed to place strain on the spine and hips. MEASURES: Bone density of the lumbar vertebrae, femoral neck, and distal radius, were determined prior to and at the end of the exercise program using dual energy X-ray absorptiometry (DEXA). RESULTS: Resistance-training produced strength gains: overhead press = 125%, leg press = 86%, and calf raises = 91% (p < 0.001). RT tended to increased lumbar BMD 1.03%, while the CON decreased 0.36% (p = 0.072). Both groups lost radial BMD (CON = -0.45%; RT = -1.04%). Both groups gained femoral neck BMD (CON = 1.26%; RT = 1.22%). CONCLUSIONS: These results suggest that even a short-term weight training program can either maintain or improve the BMD of the femoral neck and lumbar vertebrae in premenopausal women.

Absorptiometry, Photon↗

Multiple-outcome meta-analysis of clinical trials.

When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.

Antirheumatic Agents↗

Effects of cannabinoid receptor stimulation and blockade on catalepsy produced by dopamine receptor antagonists.

The ability of cannabinoid receptor stimulation or blockade to alter catalepsy produced by dopamine D1 and D2 receptor antagonists was studied in rats. The cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H- pyrazole-3-carboxamidehydrochloride) (0.5 and 2.5 mg/kg) reduced catalepsy elicited by the cannabinoid receptor agonist CP 55,940 (1 alpha,2-(R)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl ) cyclohexyl-phenol) (0.5 mg/kg). However, SR 141716A (0.5 and 2.5 mg/kg) did not decrease catalepsy produced by the dopamine D1 receptor antagonist SCH 23390 (R-(+)-7chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1-H-3-benzazepine) (0.5 mg/kg) or the dopamine D2 receptor antagonist raclopride (S(-)-3,5-dichloro-N-(1-ethyl-2-pyrrolidinyl)-methyl-6-methoxysalicylami de) (2.5 mg/kg), suggesting that, under these conditions, endogenous cannabinoid ligands do not modulate the cataleptic effects of dopamine D1 or D2 receptor antagonists. In contrast, CP 55,940 (0.025 and 0.1 mg/kg), at doses which do not produce catalepsy when administered alone, enhanced catalepsy produced by SCH 23390 and raclopride. These results suggest that stimulation, but not blockade, of brain cannabinoid receptors modifies catalepsy behavior produced by selective dopamine D1 and D2 receptor blockade.

Animals↗

Retinoblastoma protein in human breast carcinoma: immunohistochemical study using a new monoclonal antibody effective on routinely processed tissues.

Cyclic phosphorylation/dephosphorylation of the retinoblastoma gene product (pRB) has been found to play a central role in the progression of the normal cell cycle, through modulation of the activity of the E2F family of transcription factors. Mutations of the retinoblastoma gene have been described in a wide variety of human malignancies including carcinomas of the breast. The present investigation reports the production and application of a new monoclonal antibody in an immunohistochemical study of pRB expression in 233 primary breast carcinomas, allowing an assessment of the contribution made by this tumour suppressor gene to tumour development and progression. Overall, there was loss of pRB expression in 21 per cent of breast tumours. Although high-grade tumours were found to lack detectable pRB more frequently than low-grade tumours, the difference did not prove statistically significant. In addition, pRB immunostaining was not related significantly to relapse or survival. No significant correlations were observed between apparent loss of pRB and tumour size, parity, patient lymph-node status, p53, c-erbB-2, c-jun, EGFR or steroid hormone receptor expression. Preliminary findings, however, did suggest a relationship between pRB expression and response to endocrine therapy.

Adult↗