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Biomedical subjects

J J Anderson

Publications and source records attributed to J J Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Health status response of rheumatoid arthritis to treatment with DAB486IL-2.

OBJECTIVE: To examine and compare health status and disease activity changes in patients with rheumatoid arthritis (RA) in a clinical trial of the biologic agent DAB486IL-2. METHODS: Data on 45 patients with RA who were enrolled in a multicourse, double-blind trial, consisting of a first, placebo-controlled, course followed by open-label treatment with the active agent to a total of 3 active courses, were examined for evidence of improvement in health status (measured using the 5 components of the Arthritis Impact Measurement Scales 2 [AIMS2]) and disease activity (measured using standard clinical measures and erythrocyte sedimentation rate). RESULTS: Over a single course of treatment, DAB486IL-2-treated patients showed significant improvement relative to placebo-treated patients on the symptom and social components of AIMS2 and in patient's assessment of disease activity. With subsequent open-label courses of treatment with DAB486IL-2, all 5 AIMS2 health status components and the disease activity measures of tender and swollen joint counts, grip strength, and the observer and patient assessments showed steady and generally parallel improvement. CONCLUSION: Short-term health status effects of this biologic agent were detected using the AIMS2.

Activities of Daily Living↗
PubMed1996

Reducing work disability associated with rheumatoid arthritis: identification of additional risk factors and persons likely to benefit from intervention.

OBJECTIVE: To study additional risk factors for rheumatoid arthritis (RA)-related work disability and to identify the groups of individuals at high risk and the potentially modifiable factors which place them at risk. METHODS: A cross-sectional mail survey was conducted among 469 adults with RA. Work disability was defined as unemployment due to RA. A broad range of explanatory factors was examined, including sociodemographic, health, work, support given by others, and commuting difficulty. Employed and work-disabled subjects were compared by t-test and chi-square. Attributable fractions were calculated to assess the predictive value of factors. A recursive partitioning procedure identified individuals at varying risks for work disability, and their characteristics were defined. RESULTS: The risk factors joint pain and functional status, commuting difficulty, physical demands of the job, and disease duration were important predictors of work disability in both the attributable fraction and recursive partitioning analytic models. Having a professional or administrative job was protective, provided the salary earned was not low. Younger individuals with RA of shorter duration were placed at high risk by potentially modifiable factors. While older persons with RA of long duration were at high risk, modifiable factors could not be identified. CONCLUSION: Commuting difficulty, a previously overlooked factor, is an important predictor of RA work disability. Younger individuals with RA of relatively short duration can be placed at high risk by potentially modifiable factors including commuting difficulty, physically demanding jobs, greater joint pain and poor functional status, and nonprofessional/non-administrative jobs.

Absenteeism↗
PubMed1996

The effect of smoking at different life stages on bone mineral density in elderly men and women.

To assess the effect of smoking on bone mineral density (BMD) at different life stages, to examine whether the effect of smoking differs between men and women, and to discover whether its effect in women differs according to history of estrogen use, a cohort study was carried out with single cross-section measurement of BMD by single and dual photon absorptiometry. The setting was the Framingham Study, a population-based cohort study with over 40 years prospectively collected data on smoking. Subjects (n = 1164) consisted of cohort members participating in the 20th biennial Framingham examination (1988-1989). The measurements included in the study were BMD measured at the hip, spine and radius, smoking history ascertained at all Framingham Study examinations since 1948, and other factors affecting BMD (age, weight, estrogen use, caffeine use, alcohol use and physical activity). Neither current smoking, recent (last 10 years) smoking, nor early adulthood smoking resulted in significantly lower BMD at any skeletal site among women who had not taken estrogen. Among women who had taken estrogen, BMD at most sites was lower among current or recent smokers, although the small numbers of smokers made it difficult to find significant differences at all skeletal sites. Among men, a consistently lower BMD at all skeletal sites was observed for smokers regardless of when in their life they smoked (4-15.3% lower), although the effect of smoking during early adulthood was of a lesser magnitude (4-8% lower). Former male smokers who had quit < 10 years ago had lower BMD than men who had quit > or = 10 years ago. In conclusion, in women who had used estrogen, BMD was lower in current or recent smokers than it was in non-smokers. In men, smoking at any stage of life had adverse effects on the skeleton that was independent of weight, alcohol or caffeine use, implying other mechanisms for smoking's effect on bone.

Absorptiometry, Photon↗
PubMed1996

Osteoporosis prevention in premenopausal women: using a stage model approach to examine the predictors of behavior.

The precaution adoption process model was used to examine the predictors of 2 behaviors recommended to reduce the risk of developing osteoporosis: calcium consumption and weight-bearing exercise. A total of 452 premenopausal women completed a mailed questionnaire assessing stage in the precaution adoption process and 12 knowledge and attitudinal variables. Participants were also given an opportunity to request information about osteoporosis. In all, 11 of the 12 knowledge and attitudinal variables were associated with calcium stage; 8 were associated with exercise stage. Information requests were associated with both calcium and exercise stage. Findings provide substantial support for the precaution adoption process model and suggest that the model can be usefully applied in this area to increase understanding of why many women do not practice behaviors that could reduce their risk of developing osteoporosis.

Adult↗
PubMed1996

p53 protein as a prognostic indicator in breast carcinoma: a comparison of four antibodies for immunohistochemistry.

We examined the reactivity of four p53-specific monoclonal antibodies--PAb 1801, p53-BP-12, D07 and CM1--on sections of formalin-fixed tissue collected from 245 breast carcinomas. Immunodetection of p53 varied between 37.6% and 46.6%. The greatest variation was observed among lobular carcinomas and low-grade tumors in which immunodetection varied between 8.3% and 27.3%. In contrast, immunodetection of p53 in invasive ductal carcinomas was subject to a lower degree of variability with between 40.6% and 49.7% of these tumours proving to be positive. In general, we found antibodies PAb 1801 and DO7 to be the most effective in immunolocalising p53. Immunodetection of p53 with each of the four antibodies was found to correlate strongly with tumour grade. In survival analysis, the results gained using antibody PAb 1801 proved to be of greatest statistical significance and to provide the strongest index of prognosis. A significant relationship was observed between immunodetection of p53 with each of the four antibodies and poor responsiveness to endocrine therapy. In addition, relationships were also observed between p53 immunostaining and tumour oestrogen receptor (ER) status as well as c-jun expression. We observed no correlation between abnormalities of the p53 and the Rb gene products or between elevated c-erbB-2 or epidermal growth factor receptor (EGFR) expression and immunodetection of p53.

Adult↗
PubMed1996

Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer.

The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.

3T3 Cells↗
PubMed1996

Peak bone mass development of females: can young adult women improve their peak bone mass?

The purpose of this review is to summarize the effects of calcium intake on peak bone mass (PBM) accrual by premenopausal females during their 20s and possibly 30s. Prospective studies are highlighted because of the value of investigating the same subjects for one or more years. Results of cross-sectional studies are also summarized. Findings from both prospective and cross-sectional investigations suggest a positive benefit of adequate or supplemented calcium intakes on bone mineral content (BMC) in females during the third (20s) and fourth (30s) decades of life. PBM of subjects was found to be increased or maintained in comparison to PBM of controls in the five intervention studies that used calcium supplementation or the addition of calcium-rich foods. The results of cross-sectional studies, including a meta-analysis of approximately 20 such studies, also support the benefit to PBM of adequate calcium intakes. In summary, sufficient consumption of calcium during the various stages of the early life cycle, when combined with overall sound nutrition, regular physical activity, and possibly pregnancy, lactation, and child-rearing, may contribute to PBM accrual of women during the early adult decades.

Adult↗
PubMed1996

Calcium, phosphorus and human bone development.

Calcium intakes by girls and adult females should approximate or exceed the Recommended Dietary Allowances so that peak bone mass can be achieved during early adulthood and bone mass can be maintained thereafter until the menopause. Investigations of the relationship between dietary calcium consumption and measurements of bone mass or density strongly support the contention that adequate intakes of calcium by females contribute to greater values of bone mass through adolescence and into adulthood. Prospective studies have especially been robust in support of this relationship. Inadequate calcium intakes early in life may lead to low bone mass because of several possibilities. Three potential mechanisms for the development of low bone mass are proposed, and in all a role for elevated parathyroid hormone is emphasized. A likely mechanism contributing to low bone mass in the United States involves a low calcium:high phosphorus intake ratio, but this possibility has not been adequately tested with a prospective design. Future investigations are needed to address the etiologic risk factors influencing less than optimal development of bone mass in females living in affluent nations.

Adult↗
PubMed1996

Regaining functional independence in the acute care setting following hip fracture.

BACKGROUND AND PURPOSE: Factors that predict functional recovery in the first few days following hip fracture and that may facilitate discharge to the home directly from the acute care setting have not been identified. This study investigated the attainment of key functional milestones by patients and discharge status from an acute care hospital following hip fracture. SUBJECTS: Subjects were 162 community-based individuals (59 men, 103 women) aged 60 years or older who were admitted to an acute care hospital following unilateral hip fracture. METHODS: Data on personal, medical surgical, hospital course, and acute rehabilitation factors as well as functional status and placement at the time of discharge were collected. Adjusted odds ratios were calculated to determine predictors of independence in seven types of transfers and ambulation activities and discharge directly to the home. RESULTS: Subjects who ambulated independently prior to fracture, stayed longer in the acute care setting, and received physical therapy on average more than once a day had improved odds of regaining independence in bed mobility, transfers, and ambulation. Subjects who regained independence and received physical therapy on average more than once a day had improved odds of discharge directly to the home from the acute care setting. Increasing age and postoperative complications reduced the odds of discharge directly home. CONCLUSION AND DISCUSSION: A substantial proportion of patients with hip fracture achieve independence in bed mobility and transfers and in ambulation with a walker during the early postoperative phase, although few progress to a higher level during a short-term stay in the acute care setting. Frequency of physical therapy, among other factors, appears to improve the odds of regaining functional independence and discharge directly to the home from the acute care setting.

Aged↗
PubMed1996

Roles of diet and physical activity in the prevention of osteoporosis.

In recent years, much attention has been directed toward the prevention of osteoporosis, since this disease has become a leading cause of morbidity and mortality in elderly women. Research has demonstrated that the prevention of osteoporosis and osteoporosis-related fractures may best be achieved by initiating sound health behaviors early in life and continuing them throughout life. Evidence suggests that osteoporosis is easier to prevent than to treat. In fact, healthy early life practices, including the adequate consumption of most nutrients, regular physical activity, and other health behaviors, contribute to greater bone mineral measurements and optimal peak bone mass by the fourth decade of life of females, and, perhaps, also of males. Several reports have shown that the adequate consumption of nutrients, calcium in particular, during the pre-pubertal and early post-pubertal years of females contribute to increased peak bone mass. Indeed, skeletal benefits from long-term calcium supplementation have been reported for females at practically every period of the life cycle. Vitamin D, which may be either consumed or produced endogenously through the action of sunlight, promotes calcium absorption and thereby enhances bone mineralization. Thus, the adequate consumption of calcium, in conjunction with vitamin D, in early life will likely optimize peak bone mass, and adequate intakes of these two nutrients should continue through the remainder of life to help maintain bone mass. On the other hand, excess phosphorus consumption may deter bone mineral accrual because of the resultant elevation of serum parathyroid hormone levels. Additionally, high intakes of protein, sodium, and caffeine may decrease bone mineral mass through increased urinary excretion of calcium. Vitamin K may also have an important positive effect on the development and maintenance of bone through its role in promoting carboxylations of the matrix protein, osteocalcin. In conclusion, the prevention of osteoporosis needs to begin during the pre-pubertal years and it should be continued throughout life. Bone mass can better be maintained later in life through adequate consumption of several nutrients with specific roles in calcium and bone metabolism, regular physical activity, and the practice of a healthy lifestyle. Mechanisms through which the nutrients and exercise affect bone mass will be explored.

Bone Development↗
PubMed1996

Fast Track recovery after aortocoronary bypass surgery: early extubation and intensive care unit transfer.

Fast Track is a practical method of delivering care to aortocoronary bypass (ACB) patients with minimal risks to the patients or their care providers. A prospective study designed by an interdisciplinary practice team will evaluate the effects of an accelerated recovery program on clinical and financial outcomes of ACB patients. Essential components of the accelerated recovery program include early extubation, accelerated activity, and appropriate patient selection. Preliminary results on early extubation are discussed.

Coronary Artery Bypass↗
PubMed1995

The cannabinoid agonists WIN 55,212-2 and CP 55,940 attenuate rotational behavior induced by a dopamine D1 but not a D2 agonist in rats with unilateral lesions of the nigrostriatal pathway.

The effect of cannabinoid receptor stimulation on rotational behavior induced by a dopamine D1 and a D2 agonist was studied in rats with unilateral 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal pathway. The cannabinoid agonists WIN 55,212-2 (2.5 mg/kg) and CP 55,940 (0.1 mg/kg) both markedly attenuated contralateral rotation induced by the D1 agonist SKF 38393 (1.5 mg/kg). In contrast, WIN 55,212-2 and CP 55,940 did not alter rotation elicited by the D2 agonist quinpirole (0.1 mg/kg). Doses of WIN 55,212-2 and CP 55,940 that attenuated D1-mediated rotation did not produce catalepsy in intact rats or in rats with 6-hydroxydopamine-induced lesions, indicating that the reduction in rotation produced by the cannabinoids was not due to a generalized motor impairment. In addition, the effective dose of WIN 55,212-2, but not CP 55,940, produced only a slight increase in ipsilateral rotation when administered alone, making it improbable that this ipsilateral tendency accounts for the reduction in D1-mediated contralateral rotation. These results suggest a preferential interaction between cannabinoid receptor stimulation and dopamine D1 receptor-mediated behavior.

Animals↗
PubMed1995

Determination of the prognostic value of cyclin D1 overexpression in breast cancer.

Cyclin D1 plays a critical role in the timing of the initiation of DNA synthesis in the normal cell cycle of mammalian cells. Deregulated expression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in breast cancer and B cell malignancies respectively. In order to determine the role this putative oncoprotein plays in breast cancer, we have applied a new monoclonal antibody, recently produced in our laboratory, in an immunohistochemical study of 93 primary breast carcinomas. We show that approximately 28% of the cases displayed enhanced expression of the cyclin D1 protein. Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression of any one member of this family may relieve cancer cells of their mitogenic stimulatory requirement. In addition, we show that those patients whose breast cancers co-express cyclin D1 with either epidermal growth factor receptor (EGFR) or the retinoblastoma protein (pRB) have a significantly poorer prognosis in comparison to those expressing cyclin D1 alone. Our observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy.

Animals↗
PubMed1995

American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis.

OBJECTIVE: Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. METHODS: Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. RESULTS: The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. CONCLUSION: We present a definition of improvement which we hope will be used widely in RA trials.

Adult↗
PubMed1995

The effects of analytic software and scan analysis technique on the comparison of dual X-ray absorptiometry with dual photon absorptiometry of the hip in the elderly.

As part of a longitudinal comparison of bone mineral density (BMD) results originally obtained using a Lunar dual photon absorptiometry (DPA) scanner and later, using a Lunar dual X-ray absorptiometry (DXA) scanner, we compared femur results between DPA and DXA according to DXA analytic software (versions 1.3y and 1.4), and according to the method of placement of the femoral neck box (software algorithm or operator placement according to the appearance of the pair of images) in 58 elderly men and women. The mean BMD at each of three femoral sites was higher using DXA version 1.3y than DPA, but the use of software version 1.4 brought the BMD value closer to that of DPA at all sites. Of 58 scans, 12 (21%) were changed by the operator, resulting in an overall reduction in mean percent BMD difference between scan pairs of 79% (from 1.24% to 0.29%). Although the differences between the DPA/DXA software-driven analysis and the DPA/DXA operator-driven analysis appeared small (high r2 values and intra-class correlation coefficients), the increase in sample size that would be required for the same power to detect 2-year changes in BMD if the software-driven analysis was used instead of taking the time to perform the operator-driven analysis was 18%. The findings of this study highlight the need to account for upgrades in analytic software. Furthermore, we present a rational approach for the analysis of serial scans that has face validity and that results in smaller differences between pairs of scans performed on the same individual. The decision to adapt these methods must be based on the relative costs of reducing unwanted scan variability.

Absorptiometry, Photon↗
PubMed1995

Problems and suggested solutions in creating an archive of clinical trials data to permit later meta-analysis: an example of methotrexate trials in rheumatoid arthritis.

Because data archives contain patient-based rather than study-based data, they can address meta-analytic questions on uncommon outcomes and on predefined patient subsets, questions that are difficult to address using the traditional meta-analytic approach based on grouped data. We report the tasks involved in establishing the first data archive of rheumatoid arthritis trials. In general, problems stem from the heterogeneity of trials in the archive and we suggest some solutions. In the initial phases, difficulties include recruitment and incomplete participation of trial investigators, whereas later on, other issues arise, such as quality control, coping with different dataset designs, and incomplete documentation. Other issues include heterogeneous measures, missing variables, and comparing data across different visit intervals and trial lengths. Suggested solutions include requesting trial data in predefined archive-wide structures and asking for all possible documentation for each dataset. Data cleaning is necessary, as is rescaling of variables or developing unit-free outcomes, and estimating data for missing variables. Archive design should allow for referencing a patient's data among various datasets. Although one goal is to reduce the quantity of data in the archive while retaining information content, data from early stages of archive building must be accessible for developing new analysis datasets. Documentation of archive building and software choices are discussed. Our experience suggests data archiving for meta-analysis is time consuming and expensive, yet it provides a useful method for analyzing data from multiple trials.

Archives↗
PubMed1995

Methodological and statistical approaches to criteria development in rheumatic diseases.

We have discussed methodological and statistical considerations in developing disease classification and assessment criteria. In choosing cases with disease and nondisease controls, classification criteria should be developed with an eye toward face, content and construct validity, and toward their ultimate applicability. The validity of disease criteria should be tested in a patient sample different from the one used to develop the criteria. Several analytic approaches are available to reduce the candidate diagnostic elements to those that will define the presence of disease. Methodological issues in the assessment of disease severity, activity or damage are similar to those faced in criteria development studies, although the analytic concerns are different and the options more varied.

Humans↗