Biomedical subjects

J J Anderson

Publications and source records attributed to J J Anderson.

At least 145 records · Page 8Linked to original sources

PubMed1991

Estrogens reduce bone loss in the ovariectomized, lactating rat model.

Estrogen treatment of ovariectomized, lactating rats improved retention of bone mineral mass by 15-25% compared to ovariectomized, lactating rats receiving vehicle only. On the second day postpartum all lactating rats were ovariectomized and were placed along with age-matched non-mated controls on a whole-wheat flour-based diet with 0.1% calcium and 0.4% phosphorus. On day 6 postpartum estrogen treatment was begun with either implantation of a slow-release 17 beta-estradiol pellet or with the first of daily subcutaneous injections in sesame oil (vehicle). Increasing doses of estrogen resulted in decreased food consumption and decreased litter weight gain, both well-known effects of estrogens. Ovariectomized, lactating rats implanted with a slow-release pellet containing 0.35 mg 17 beta-estradiol had mean serum estradiol levels of 113.5 pg/ml. At the end of 21 days of lactation, femurs of dams with placebo pellets showed loss of 54% of bone ash weight compared with the non-mated controls versus only 42% loss by rats receiving estradiol treatment. Rats were also injected with estradiol benzoate in a sesame oil vehicle at 3 dose levels of 1.6, 5, or 16 micrograms/day. Only the 5 and 16 micrograms/day doses significantly improved retention of bone mineral mass during lactation (+17% and +18%, respectively, vs vehicle-injected, lactating rats). Estrone administered by subcutaneous injection also improved retention of bone during lactation; however, injection of 50 micrograms/day of estrone was required to produce an equivalent bone retention compared to 5 micrograms/day of estradiol. Thus, treatment of ovariectomized, lactating rats with estrogens results in a significant reduction of the loss of bone mineral mass associated with lactation.

Animals↗

PubMed1991

Hereditary and environmental influences on blood pressure values of premenopausal women and their college-age daughters.

Blood pressure (BP) and environmental (dietary/lifestyle) variables were measured in 62 healthy normotensive pairs of premenopausal mothers (44.3 years) and their college-age consanguineous daughters (18.7 years) to estimate the relative contributions of genetic vs environmental factors on BP. As expected, the mothers had significantly higher systolic (SBP) and diastolic (DBP) blood pressures than the daughters (p less than 0.004 and 0.012, respectively). Among the dietary/lifestyle variables measured, mothers were found to have significantly higher mean weight and body mass index (BMI) (p less than 0.009 and 0.001, respectively), and significantly lower lean body mass (LBM) and calcium intake than their daughters (p less than 0.003 and 0.037, respectively). Significant correlations were found between mean BP of the mothers and their mean weight and BMI. No significant correlations existed for the daughters. The familial resemblances between BP of the mothers and daughters were relatively low, i.e., 0.14 for SBP and 0.19 for DBP. From these findings we conclude that the higher BP values with increased age among this healthy female population primarily result from an increase in BMI and a shift from lean to fat mass, as measured by midarm circumference. Our results suggest that environmental factors, i.e., excessive energy intake over time, accompanied by decreased physical activity, are primarily responsible for the greater indices of body fat and the higher BPs observed in this sample of healthy premenopausal women.

Adipose Tissue↗

PubMed1991

The predictive value of bone marrow morphologic characteristics and immunostaining in primary (AL) amyloidosis.

The authors previously demonstrated that bone marrow plasmacytosis in primary (AL) amyloidosis may be monoclonal or polyclonal. However, the clinical implications of the degree of plasmacytosis and its clonality have not been studied. The authors evaluated 62 patients with AL amyloidosis, 40 of whom had monoclonal medullary plasma cells. There was complete concordance between the light chain class of the plasma cells in the monoclonal cases and that of the circulating paraprotein in the 22 cases associated with a paraprotein. The remaining 22 patients had polyclonal plasma cells, although a paraprotein was detected in 6. The degree of plasmacytosis was significantly higher among patients with monoclonal plasma cells and correlated inversely with length of survival. The authors' findings indicate that the quantitation of bone marrow plasma cells in AL amyloidosis by immunoperoxidase studies may predict the clinical course.

Adult↗

PubMed1991

Stability of the delta-endotoxin gene from Bacillus thuringiensis subsp. kurstaki in a recombinant strain of Clavibacter xyli subsp. cynodontis.

Deletion of chromosomally inserted gene sequences from Clavibacter xyli subsp. cynodontis, a xylem-inhabiting endophyte, was studied in vitro and in planta. We found that nonreplicating plasmid pCG610, which conferred resistance to kanamycin and tetracycline and contained segments of C. xyli subsp. cynodontis genomic DNA, integrated into a homologous sequence in the bacterial chromosome. In addition, pCG610 contains two copies of the gene encoding the CryIA(c) insecticidal protein of Bacillus thuringiensis subsp. kurstaki HD73. Using drug resistance phenotypes and specific DNA probes, we found that the loss of all three genes arose both in vitro under nonselective conditions and in planta. The resulting segregants are probably formed by recombination between the repeated DNA sequences flanking pCG610 that resulted from the integration event into the chromosome. Eventually, segregants predominated in the bacterial population. The loss of the integrated plasmid from C. xyli subsp. cynodontis revealed a possible approach for decreasing the environmental consequences of recombinant bacteria for agricultural use.

Bacillus thuringiensis↗

PubMed1990

Time for changes in the design, analysis, and reporting of rheumatoid arthritis clinical trials.

We have proposed a set of changes in the design, analysis, and reporting of RA clinical trials which emphasizes the standardization of trials. We have suggested limiting the number of outcome measures used to those most sensitive to change and using uniform measurements of the same outcome measures in all clinical trials. We have also suggested that investigators focus on enumerating which patients improve in a trial, rather than on the mean level of improvement in treated patients versus the control patients. Finally, we have suggested the reporting of confidence intervals rather than simply stating P values. With the inauguration of these changes and more attention to other issues relevant to the quality of clinical trials, we hope that drug treatments of rheumatoid arthritis can be more easily compared with respect to effectiveness.

Arthritis, Rheumatoid↗

PubMed1990

Estrogen use and radiographic osteoarthritis of the knee in women. The Framingham Osteoarthritis Study.

Female participants of the Framingham Osteoarthritis Study (n = 831, mean age 73, age range 63-93) were evaluated for osteoarthritis with weight-bearing radiographs of the knee during 1983-1985. At each biennial examination (1963-1981), the women were asked about their use of estrogen during the previous 2 years. We categorized estrogen use as no use reported, use reported at 1 examination, or use reported at 2 or more examinations. We found no positive association of estrogen use with radiographic knee osteoarthritis after controlling for age, body mass index, age at menopause, physical activity, history of knee injury, and smoking. In fact, a modest but nonsignificant protective effect for both radiographic osteoarthritis (odds ratio 0.71, 95% confidence interval 0.42, 1.20) and severe radiographic osteoarthritis (odds ratio 0.66, 95% confidence interval 0.33, 1.32) was seen in women who reported estrogen use at 2 or more examinations. Subgroup analyses also showed no association between estrogen use and radiographic knee osteoarthritis. We conclude that estrogen use in women is not associated with an increased risk of radiographic knee osteoarthritis.

Aged↗

PubMed1990

The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses.

We performed 2 metaanalyses of placebo-controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second-line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P less than 0.0001), DP (P less than 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second-line drugs. None of the reported interdrug comparative trials we reviewed were this large. For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P less than 0.05) and higher total dropout rates (P less than 0.01) than any other drug; 30% of gold-treated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second-line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimalarials↗

PubMed1990

Update on the use of distal radial bone density measurements in prediction of hip and Colles' fracture risk.

A controversy has developed around the question as to whether bone density values from the distal radius can be used to accurately predict risk of future fractures. To address this question, two separate studies were undertaken: (a) Bone density was measured in 460 healthy ambulatory women living in retirement centers in the state of North Carolina; 83% of these women were followed for up to 60 months for occurrence of minimal trauma hip and wrist fractures. Thirty-one minimal trauma fractures were reported in our study population, representing 8% of those followed. The fracture incidence density rate showed a close inverse relationship with incremental changes in bone density at the distal site. Twenty-eight of the 31 fractures were reported in women with bone density values below the 325-mg/cm2 "at risk" value. (b) Bone density values of the distal radius and the lumbar spine from 360 women (aged 18-85 years) from the Chapel Hill area were used to analyze the error in predicting individual spinal density from the distal radial density. Although the overall correlation was high (r = 0.67) and the confidence intervals were narrow, the prediction intervals were quite wide. Thus, prediction of an individual value of spine density from the distal radius density would result in a value with a range too wide to be clinically useful. We conclude that single-photon absorptiometry appears to be a useful tool for screening normal populations of asymptomatic women for prediction of hip or Colles' fracture risk even though it has limited usefulness in prediction of spinal fracture risk or individual values for spinal density.

Aged↗

PubMed1990

Age and anthropometric determinants of radial bone mass in premenopausal Caucasian women: a cross-sectional study.

A sample of 181 healthy premenopausal Caucasian women, 20 to 50 years of age, was part of a cross-sectional study on the determinants of radial bone mineral content (BMC), bone width (BW) and areal bone mineral density (BMD) at two sites, the distal (Dis) or 5 mm-site (about 50% cancellous tissue) and the mid-radial (Mid) site (over 90% cortical tissue), as measured by single photon-absorptiometry. Women in their 20s (n = 45) had significantly lower DisBMC and DisBW values than women in their 30s (n = 65) or 40s (n = 71). No such trends were noted for any of the mid-radial measurements with increasing age. With age, height and weight included in the same regression equation, age remained the only significant positive predictor of all three distal variables, while height was the only significant positive predictor of the mid-radial variables. Body weight was not associated with any of the bone variables in this model. A low lean body mass (LBM) or low body mass index (BMI) was consistently correlated with significantly lower bone values at both radial sites. These data suggest that peak bone mass (PBM), for the distal and largely cancellous portion of the radius, was achieved later in adulthood (30s) than the mid-radial or mostly cortical portion of the radius in which PBM was achieved much earlier, probably in late adolescence.

Adult↗

PubMed1990

Relationship of dietary fat content to food preferences in young rats.

Weanling rats were fed either a high-fat (30% of calories) or a low-fat (10% of calories) diet for four weeks, after which fat preference was assessed using a choice paradigm. Fat preference was measured during 2-hour intake tests in which three peanut butter/peanut oil mixtures containing 0.50, 0.61, and 0.71 grams fat/gram were offered to each animal. Rats fed the high-fat (HF) diet preferred the highest-fat mixture and consumed more total fat during intake tests than animals fed the low-fat (LF) diet. Intake of NaCl and sucrose solutions was measured during separate intake tests. LF-fed rats drank more NaCl solution than HF-fed rats. Following these tests a subgroup of the LF-fed animals was fed the HF diet, and a subgroup of the HF-fed group was fed the LF diet for a further four weeks. Upon repetition of the intake tests, rats that had been fed the HF diet during the initial four weeks still preferred the highest-fat mixture.

Animals↗

PubMed1990

The ovariectomized, lactating rat as an experimental model for osteopenia: calcium metabolism and bone changes.

The ovariectomized, lactating rat (Sprague-Dawley) is proposed as an experimental model for the rapid development of osteopenia which may be used to test the effectiveness of bone-retentive drugs potentially useful in treating osteoporotic women. Rats were ovariectomized (OVX) on day 2 postpartum and were kept on a low-calcium diet (0.1%). Measurements of serum total calcium, ionic calcium, albumin and parathyroid hormone were conducted between days 4 and 21 of lactation. Serum total and ionic calcium and albumin were significantly lower and serum parathyroid hormone was significantly higher in all lactating rats at 16 days postpartum compared to nonlactating controls. Mean bone mass of the femurs of OVX lactating rats measured at day 21 was approximately 50% of that of non-lactating intact controls. The enhanced duodenal calcium absorption (in everted gut sacs) associated with lactation was not affected by OVX and neither was the average litter weight gain between 2 and 14 days of lactation. In conclusion, lactation coupled with a low-calcium diet resulted in marked osteopenia, depressed serum calcium (both total and ionic) and significantly elevated serum parathyroid hormone concentration. The rapid and extensive bone loss of this model makes it appropriate for the study of therapeutic agents designed to retain bone mass.

Animals↗

PubMed1990

Obesity and mortality in the Lipid Research Clinics Program Follow-up Study.

Using data from the Lipid Research Clinics Program for 1972-1983, the study presented here examined weight history and two indices of obesity: the body mass index (BMI) and the triceps skinfold (TSF) thickness. Cox regression analyses with and without adjustment for cardiovascular disease risk factors revealed a significant (p less than 0.05) quadratic association between BMI and all-causes mortality among men, but not women, after an average 8.4 years of follow-up; mortality was relatively high at both extremes of the BMI distribution. The association was stronger among smokers compared with nonsmokers, and it was apparent among male normotensives, but not hypertensives. All TSF-mortality associations and BMI associations with cancer and coronary heart disease mortality were weak and nonsignificant. Among men, per cent weight change in adulthood showed a significant inverse association with all-causes and cancer mortality. Because BMI and weight history were significantly associated with mortality after adjustment for other risk factors, they appear to be independent predictors of mortality among men.

Adult↗

PubMed1990

Caffeine and the risk of hip fracture: the Framingham Study.

Caffeine increases urinary calcium output and has been implicated as a risk factor for osteoporosis. The authors examined the effect of caffeine on hip fracture risk in 3,170 individuals attending the 12th (1971-1973) Framingham Study examination. Coffee and tea consumption, age, Framingham examination number, weight, smoking, alcohol consumption, and estrogen use were used to evaluate hip fracture risk according to caffeine intake. Hip fractures occurred in 135 subjects during 12 years of follow-up. Fracture risk over each 2-year period increased with increasing caffeine intake (one cup of coffee = one unit of caffeine, one cup of tea = 1/2 unit of caffeine). For intake of 1.5-2.0 units per day, the adjusted relative risk (RR) of fracture was not significantly elevated compared with intake of one or less units per day. Consumption of greater than or equal to 2.5 units per day significantly increased the risk of fracture. Overall, intake of greater than two cups of coffee per day (four cups of tea) increased the risk of fracture. In summary, hip fracture risk was modestly increased with heavy caffeine use, but not for intake equivalent to one cup of coffee per day. Since caffeine use may be associated with other behaviors that are, themselves, risk factors for fracture, the association may be indirect. Further studies should be performed to confirm these findings.

Age Factors↗

PubMed1990

Analysis of the local and systemic immune responses induced in BALB/c mice by experimental respiratory syncytial virus infection.

Pulmonary A2 strain respiratory syncytial virus infection of BALB/c laboratory mice persisted for up to 7 days after initial infection with peak virus titres being recovered on day 4. Virus antigen within the lungs was found to be restricted essentially to the alveolar regions. Similarly, pulmonary histopathological changes remained confined to the peri-alveolar regions being consistent with mild pneumonia. Infection was found to elicit a pulmonary major histocompatibility complex-restricted cytotoxic T lymphocyte (CTL) response which was first detectable 6 days after infection and optimal 7 to 9 days after infection. This local CTL response was preceded by a rapid transient virus-specific lymphocyte transformation response which was detectable only 3 days after intranasal infection. In addition, infection induced rapid interferon production within the lungs which was accompanied by an equally rapid rise in pulmonary natural killer (NK) cell cytotoxic activity. Enhanced NK cell cytotoxicity could be detected after only 1 day post-infection and continued to rise to maximum levels on day 3. This response like the acute CTL response was found to be restricted to the lower respiratory tract. IgG was the first class of virus-specific immunoglobulin to be detected in the lungs of infected animals after experimental infection. However, IgG was not detected until day 10 post-infection, 5 days after the initial decline of virus shedding. Virus-specific IgA although detectable did not appear in the lung until day 24.

Animals↗

PubMed1990

Defining arthritis and measuring functional status in elders: methodological issues in the study of disease and physical disability.

This study explores the degree to which the association of knee osteoarthritis with physical disability changes with different definitions of osteoarthritis in 1,416 Framingham Study elders. When all categories of radiographic osteoarthritis were aggregated into a single "arthritis" variable and dependence upon human assistance in one or more functional activities combined into a single variable, elders with osteoarthritis had only moderately increased odds for dependence after controlling for age or sex (OR = 1.25). A definition of osteoarthritis based only upon symptoms produced larger odds for dependency (OR = 1.85). Elders with mild osteoarthritis and infrequent knee pain had no significantly elevated risk for dependence in any of the seven functional activities. Elders with infrequently symptomatic, moderate to marked radiographic osteoarthritis were at increased risk for dependence in stair climbing, walking a mile, housekeeping, and carrying bundles. Elder with radiographic osteoarthritis accompanied by frequent pain had an increased odds of dependence in stair climbing, walking a mile, and housekeeping. Using a generic definition of "arthritis" and aggregating functional activities may underestimate the impact of osteoarthritis on physical disability in the elderly and obscure the task-specific nature of that relationship.

Activities of Daily Living↗

PubMed1990

Effect of local inhibition of gamma-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of gamma-aminobutyric acid and on stress-induced tachycardia: a study using microdialysis.

Previous studies involving local microinjection of drugs that interfere with gamma-aminobutyric acid (GABA)A receptor-mediated synaptic inhibition have led to the suggestion that endogenous GABA suppresses the activity of a sympatho-excitatory mechanism in the dorsomedial hypothalamus in rats. In this study, microdialysis was used to assess and to alter pharmacologically extracellular-levels of GABA within this region while simultaneously monitoring heart rate and blood pressure. In anesthetized rats, local microdialysis for 15 min with 2.5, 10 and 40 mM nipecotic acid, an inhibitor of GABA uptake, caused concentration-related increases in GABA and taurine in the extracellular space, but no significant change in heart rate or arterial pressure. Similar perfusion with 37.5, 75 and 150 mM KCl caused concentration-related increases in GABA as well as aspartate, glutamate, taurine, glycine and alanine. Only modest, variable increases in heart rate and no effect on arterial pressure were observed during the perfusions with high potassium. In conscious rats, unilateral microdialysis of the dorsomedial hypothalamus with 0.5 mM nipecotic acid for 2 to 2.5 hr before stress coupled with contralateral microinjection of muscimol (88 pmol/250 nl) 5 min before stress significantly reduced air stress-induced tachycardia; this reduction in tachycardia was associated with markedly elevated levels of GABA in dialysates collected from the dorsomedial hypothalamus. Neither treatment alone significantly influenced stress-induced increases in heart rate, although perfusion with nipecotic acid alone evoked similar elevations in extracellular GABA. These results suggest that extracellular levels of endogenous GABA in the dorsomedial hypothalamus may regulate the cardiovascular response to stress.

Amino Acids↗

PubMed1990

Health status as a predictor of mortality in rheumatoid arthritis: a five-year study.

We examined the utility of health status scores as predictors of mortality in a 5-year study of patients with rheumatoid arthritis (RA). Of 279 patients with a known outcome after an average of 5 years of followup, 37 had died. Scores derived from the Arthritis Impact Measurement Scales indicated that mobility and general health perception were significant predictors of mortality with odds ratios (95% confidence interval) of: 1.19 (1.05, 1.33) and 1.27 (1.04, 1.55), respectively. These measures were particularly predictive of dying at worse levels of health status with a significant linear trend for mobility (p less than 0.05) and general health perception (p less than 0.01). Even after controlling for physical function, poorer levels of general health perception were significantly associated with mortality, (p less than 0.01 for linear trend). Our results confirm that certain health status measures are related to subsequent mortality in patients with RA.

Adult↗

PubMed1989

Does smoking protect against osteoarthritis?

While studying knee osteoarthritis (OA) in the first Health and Nutrition Examination Survey, we unexpectedly found a protective association between smoking and OA. After adjustment for age, sex, and weight, smokers had a significantly lower rate of OA than did nonsmokers, and heavier smokers were less likely to have the disease than were light smokers. To test this association in a separate study and see if it was due to confounding factors, we looked at the Framingham Osteoarthritis Study, a study of elderly members of the Framingham Heart Study cohort. We evaluated whether the presence of knee OA in 1983-1985 was related to smoking status at the first Framingham examination, 36 years earlier. Subjects who had been smokers at examination 1 had a lower rate of OA (190 of 679, 28%) than did nonsmokers (276 of 736, 37.5%). In an analysis adjusted for age, sex, and weight, heavy smokers had a modestly lower risk of developing knee OA than did nonsmokers (relative risk 0.81). Also, the adjusted risk of severe OA was less in heavy smokers than in nonsmokers (relative risk 0.73). The negative association with OA persisted when we examined the average cigarette consumption over the first 10 years of the Framingham study. Furthermore, after controlling for age, sex, weight, knee injury history, sports activity history, physical activity level, coffee and alcohol consumption, and weight change after examination 1, and after modeling weight and age in a nonlinear manner, smoking remained a significant protector against later knee OA. It appears that smoking or some unidentified factor correlated with smoking modestly protects against the development of knee OA.

Adult↗