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Biomedical subjects

J Eisman

Publications and source records attributed to J Eisman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Prediction of osteoporotic fractures by postural instability and bone density.

OBJECTIVE: To investigate the utility of risk factors such as bone mineral density, lifestyle, and postural stability in the prediction of osteoporotic fractures. DESIGN: Longitudinal, epidemiological, and population based survey. SETTING: City of Dubbo, New South Wales. SUBJECTS: All residents of Dubbo aged > or = 60 on 1 January 1989. MAIN OUTCOME MEASURE: Incidence of fracture for individual subjects. RESULTS: The overall incidence of atraumatic fractures in men and women was 1.9% and 3.1% per annum respectively. The predominant sites of fracture were hip (18.9%), distal radius (18.5%), ribs and humerus (11.9% in each case), and ankle and foot (9.1% and 6.6% respectively). Major predictors of fractures in men and women were femoral neck bone mineral density, body sway, and quadriceps strength. Age, years since menopause, height, weight, and lifestyle factors were also correlated with bone mineral density and body sway and hence were indirect risk factors for fracture. Discriminant function analysis correctly identified 96% and 93% (sensitivities 88% and 81%) of men and women, respectively, who subsequently developed atraumatic fractures. Predictions based on this model indicated that a woman with a bone mineral density in the lowest quartile in the hip together with high body sway had a 8.4% probability of fracture per annum. This represented an almost 14-fold increase in risk of fracture compared with a woman in the highest bone mineral density quartile with low postural sway. An individual with all three predictors in the "highest risk" quartile had a 13.1% risk of fracture per annum. CONCLUSIONS: Bone mineral density, body sway, and muscle strength are independent and powerful synergistic predictors of fracture incidence.

Aged↗
PubMed1993

Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin.

BACKGROUND: Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroid-induced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25-dihydroxyvitamin D3), and calcitonin. METHODS: One hundred three patients starting long-term corticosteroid therapy were randomly assigned to receive 1000 mg of calcium per day orally and either calcitriol (0.5 to 1.0 microgram per day orally) plus salmon calcitonin (400 IU per day intranasally), calcitriol plus a placebo nasal spray, or double placebo for one year. Data on treatment efficacy were available for 92 of these patients. Bone density was measured every four months for two years by photon absorptiometry. There were no significant differences between groups with respect to age, underlying disease, initial bone density, or corticosteroid dose during the first year. RESULTS: Calcitriol (mean dose, 0.6 microgram per day), with or without calcitonin, prevented more bone loss from the lumbar spine (mean rates of change, -0.2 and -1.3 percent per year, respectively) than calcium alone (-4.3 percent per year, P = 0.0035). Bone loss at the femoral neck and distal radius was not significantly affected by any treatment. In the second year, lumbar bone loss did not occur in the group previously treated with calcitonin plus calcitriol (+0.7 percent per year), but it did occur in the group given calcium alone (-2.3 percent per year). The calcitriol group also lost lumbar bone (-3.6 percent per year) but received more corticosteroid in the second year than the other two groups. CONCLUSIONS: Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroid-induced bone loss in the lumbar spine.

Adolescent↗
PubMed1993

Zipper protein, a newly described tropomyosin-like protein of the intestinal brush border.

We have cloned and sequenced from a chick intestinal library the cDNA for a new tropomyosin-like protein with an extensive leucine zipper motif. The cDNA recognized a 2.5-kilobase transcript with highest levels in the intestine. The open reading frame encoded a protein with 239 residues (28 kDa), the deduced sequence of which forms 27 heptad repeats, 21 of which begin with leucine and the other 6 with conservative substitutions (methionine, valine, threonine). This sequence predicts a coiled coil dimer similar to that of tropomyosin with which it has 34% homology. We have named this newly described protein zipper protein. The protein was expressed in bacteria. Antibodies were made to peptides representing different regions of the deduced sequence and tested for their ability to recognize the recombinant zipper protein on immunoblots. Such antibodies were used to immunolocalize zipper protein to the intestinal brush border. A radioimmunoassay was then established using recombinant zipper protein as standard and tracer and one of the affinity-purified antisera as primary antibody. Extracts from intestine, kidney, and liver displaced tracer zipper protein in parallel with that of the standard curve, and zipper protein levels were readily measured in those tissues to be 2.5 +/- 0.4, 0.34 +/- 0.03, and 0.15 +/- 0.03 micrograms/mg of protein, respectively. Brain contained no detectable zipper protein. We conclude that zipper protein is a tropomyosin-like protein found predominantly in the intestinal brush border; its location and structural similarity to tropomyosin suggest a possible role in regulating the interaction of brush border myosin 1 with the actin core of the microvillus.

Amino Acid Sequence↗
PubMed1993

Changes in axial bone density with age: a twin study.

Bone mineral density in adult life, which is an important determinant of fracture risk, is determined by peak adult bone density, achieved in early adulthood and subsequent rates of change during adult life. Cross-sectional twin and family studies indicate that the majority of population variation in bone density may be explained by genetic factors. Although there is evidence for a genetic effect on peak bone mass, it is unknown whether there is a genetic effect on rates of changes in bone density with age. Changes in lumbar spine and femoral neck bone density determined by dual-photon absorptiometry (Lunar DP3) were examined in a cohort of monozygotic (MZ, n = 21, 3 male and 18 female pairs, median age, range, 46; 24-75 years) and dizygotic twins (DZ, n = 19; 43, 25-65 years). The median follow-up was 3 years (range 1.1-5.5 years), with each subject having at least two and up to four bone density assessments. In these twins, genetic factors determine variation in rates of change (% change/year) in lumbar spine bone density, rMZ = 0.93 and rDZ = 0.51, p < 0.02 (one tailed), and Ward's triangle, rMZ = 0.60, rDZ = 0.11, p < 0.05 (one tailed). Model-fitting analysis was also consistent with a genetic effect on rates of change in bone density at the trochanteric site, although such an effect was not shown at the femoral neck. These data demonstrate, for the first time, the possible existence of genetic determinants of rates of change in bone mineral density in adults.

Absorptiometry, Photon↗
PubMed1993

Role of the negative glucocorticoid regulatory element in glucocorticoid repression of the human osteocalcin promoter.

In osteoblast-like cells in culture, the human osteocalcin gene promoter basal activity is repressed by glucocorticoids, reflecting the repression of serum osteocalcin concentrations noted in syndromes of glucocorticoid excess. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the active hormonal form of vitamin D, induces the osteocalcin promoter through a vitamin D response element (VDRE), and glucocorticoids also repress the vitamin D-induced promoter. This study addresses the role of a glucocorticoid receptor (GR) binding site overlapping the TATA box of the osteocalcin promoter, which had been proposed as a negative glucocorticoid response element (nGRE), invoking a steric interference mechanism of glucocorticoid repression. Confirmation of the role of the nGRE in regulating basal activity was obtained using promoter constructs containing a TATA box swap. However, a minor component of repression of 1,25-(OH)2D3 induced activity remained in the absence of the nGRE. In addition, glucocorticoid repression of the human osteocalcin promotor was shown to be cell line specific. This result is not compatible with a simple model of repression and suggests the existence of unidentified cell-specific factors that are involved in the repression event. Repression of the osteocalcin promoter was compatible with a composite model involving both the nGRE site and glucocorticoid regulation of factors that bind the vitamin D response element.

Base Sequence↗
PubMed1993

Prevention of corticosteroid bone loss.

Prolonged corticosteroid therapy is known to result in an increased risk of osteoporotic fracture, probably as a consequence of enhanced bone resorption and depressed bone formation. We examined the effects of prophylactic treatment with 1,25-dihydroxyvitamin D3 (calcitonin) and nasal salmon calcitonin on corticosteroid-induced bone loss in 103 patients being treated with long-term corticosteroids for the first time in a randomized, double-masked prospective study. Patients were randomly allocated to one of three groups receiving either calcium supplementation alone, calcium plus calcitriol, or calcium plus calcitriol and nasal salmon calcitonin. Treatment was given for 12 months. Bone mineral density (BMD) was measured every 4 months by dual-photon absorptiometry in the lumbar spine and femoral neck. Calcium supplementation alone did not prevent bone loss at either site. In the lumbar spine calcitriol, with or without nasal calcitonin, significantly reduced bone loss (p < 0.0001). Neither calcitriol alone nor calcitriol with calcitonin prevented bone loss at the femoral neck. These data suggest that treatment with calcium and calcitriol, or with calcium and intranasal calcitonin, greatly reduced or prevented corticosteroid-induced bone loss in the lumbar spine.

Adrenal Cortex Hormones↗
PubMed1993

Bone mass and ageing.

Bone can be divided into two kinds of tissue, cortical and trabecular bone. The skeleton comprises approximately 80% cortical bone, mainly in peripheral bones, and 20% trabecular bone, mainly in the axial skeleton. Bone density increases with skeletal growth to a peak in late adolescence or early adulthood. Bone loss subsequently occurs with ageing in both sexes, and in females accelerated loss occurs at the menopause. The risk of osteoporotic fracture in later life is the result of peak bone mass achieved at skeletal maturity and subsequent age-related and postmenopausal bone loss. Peak bone mass is largely genetically determined but is also influenced by environmental factors such as dietary calcium and physical activity. Bone loss with ageing occurs at different rates and different times in different skeletal sites. Femoral neck bone loss probably occurs in a linear fashion throughout life from early adulthood but may be accelerated at the menopause. Spinal bone loss may commence before the menopause but is rapidly increased in the immediate postmenopausal years. Bone strength is directly related to bone density, but the loading force is also relevant to risk of fracture.

Aging↗
PubMed1993

Diagnosis and treatment of osteoporosis.

Risk of osteoporotic fracture is dependent on peak bone mass achieved at skeletal maturity and subsequent bone loss. Accordingly, reduction in this risk can be achieved by maximizing the peak bone mass, preventing subsequent bone loss, or increasing bone density in patients with established osteoporosis. Recent studies in twins have shown that although peak bone mass is strongly genetically determined, it can be influenced by dietary calcium intake and physical activity. Bone mass gain is rapid during puberty, and delayed puberty may alter peak bone mass. Estrogen therapy can prevent bone loss in postmenopausal women. Bone densitometry can be used to select patients who are suitable for therapy and enhance compliance; however, screening is not justified. Treatment of established bone loss remains a problem, although recent studies of estrogen, vitamin D, and bisphosphonates are encouraging.

Bone Development↗
PubMed1992

Treatment of the murine, retrovirus-induced lymphoproliferative immunodeficiency disease (LP-BM5) in C57BL/10 mice with the immunomodulator Imexon.

Imexon (4-imino-1, 3-diazabicyclo-(3.1.0)-hexan-2-one) a cyanoaziridine compound was studied in the treatment of the murine retrovirus-induced immunodeficiency disease model of AIDS (LP-BM5, MAIDS). Imexon, in dose-dependent fashion, partially prevented the development of hypergammaglobulinemia and splenomegaly, and partially prevented the decline in the phytohemagglutinin-induced proliferative response of spleen lymphocytes when started 1 or 15 days after virus inoculation. There was a statistically significant reduction in these disease-associated manifestations. When animals were treated starting 78 or 92 days after virus inoculation, lymphadenopathy was completely abrogated and survival was significantly prolonged in a dose-responsive manner. Since Imexon and other cyanoaziridine compounds have been safely administered to humans, we suggest that this class of compounds be further investigated in both large animal models of HIV infection and in patients with HIV-induced disease.

Animals↗
PubMed1992

Postmenopausal bone loss in rheumatoid arthritis: effect of estrogens and androgens.

Osteoporosis is a frequent complication of rheumatoid arthritis (RA), especially in postmenopausal women, and may involve both juxtaarticular and generalized bone loss. To examine the effect of exogenous estrogens and endogenous androgens on bone loss in RA we determined rates of bone loss by serial bone density measurement for up to 4 years in 38 postmenopausal women with RA. Serum dehydroepiandosterone sulfate concentrations correlated significantly with the change in femoral neck bone but not in lumbar spine bone. Estrogen therapy prevented lumbar spine bone loss, but did not affect bone loss from the hip. These data suggest adrenal androgen status may influence bone loss in RA and that, although estrogen therapy can prevent bone loss from the spine, it may not prevent bone loss at sites near involved joints.

Androgens↗
PubMed1992

Update on osteoporosis.

Osteoporosis is an increasing and major public health problem as our population ages. Advances in our understanding of osteoporosis have been facilitated by the advent of accurate and precise methods of bone density measurement. Developments in therapy include transdermal oestrogens, nasal calcitonin and bisphosphonates. The most important principles of management involve maximising bone mass in early adult years and preventing postmenopausal bone loss by oestrogen therapy.

Absorptiometry, Photon↗
PubMed1991

Close linkage of bipolar disorder to chromosome 11 markers is excluded in two large Australian pedigrees.

The relationship between bipolar disorder and chromosome 11 markers remains uncertain. Whilst re-analysis of the Amish pedigree weakened previous evidence for close linkage (but could not exclude the possibility of genetic heterogeneity), a recent French study has found a significant association between this condition and tyrosine hydroxylase polymorphisms. We aimed to determine if bipolar disorder in two large Australian pedigrees (of Irish and English extraction respectively) was linked to these markers. Of the 84 family members available for testing, nine were diagnosed as bipolar I, one as bipolar II and six had recurrent unipolar depression. Linkage of bipolar disorder and recurrent depression to the chromosome 11p15 markers c-Harvey ras, insulin and tyrosine hydroxylase was tested using a series of genetic models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective status (ranging from bipolar I alone to all affective illnesses). Close linkage to these markers was strongly excluded using each model and definition. The findings also persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis. These results are consistent with other recent studies indicating that bipolar disorder is not linked to chromosomal region 11p15.

Adolescent↗
PubMed1990

Corticosteroid effects on proximal femur bone loss.

Prolonged high-dose corticosteroid therapy is known to result in an increased risk of osteoporotic fracture. Reductions in bone density have been demonstrated at the distal radius and lumbar spine in patients receiving corticosteroids; however there have been few studies of bone density in the hip (the most important site of osteoporotic fracture) in this context. To examine the effect of corticosteroids on the hip we measured bone mineral density (BMD) by dual-photon absorptiometry at three sites in the proximal femur as well as the lumbar spine in 32 patients aged 18-77 years who had been treated with corticosteroids (mean daily prednisone dose 12.7 mg) for up to 23 years. BMD was compared with the expected values using age regressions in normal subjects. BMD was significantly reduced in the femoral neck, Ward's triangle, and the trochanteric region (p less than 0.001 all sites). In the lumbar spine BMD was also significantly reduced (p less than 0.001). We also measured BMD serially in 29 patients receiving corticosteroids. BMD measurements were made in 12 patients who had already been treated with long-term corticosteroids at the time of first BMD measurement (chronic group) and from the commencement of corticosteroid therapy in 17 patients (acute group). The mean (+/- SEM) change in BMD (g/cm2 per year) in the lumbar spine and femoral neck were 0.006 +/- 0.006 and -0.021 +/- 0.007, respectively, for the chronic group and -0.02 +/- 0.005 and -0.039 +/- 0.006 for the acute group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Muscle strength, physical fitness, and weight but not age predict femoral neck bone mass.

Hip fractures are the most serious complication of osteoporosis. Although low proximal femoral bone mineral density (BMD) does not cause hip fractures directly, it is clearly a prerequisite for the increased risk associated with aging. To investigate the mechanism of the age-related decline in proximal femoral bone mineral density, we have examined the relative importance of muscle strength, physical fitness, and body mass index (BMI) in addition to age in the determination of proximal femoral BMD in 73 healthy female volunteers age 20-75 years. Muscle strength was an independent predictor of BMD at all three sites in the proximal femur as well as in the lumbar spine and forearm; proximal femur BMD was also predicted by physical fitness. BMI was a positive predictor of bone mass at all sites. In the proximal femur, age was not an independent predictor of BMD at any site. In postmenopausal women muscle strength was a significant predictor of bone mass in the femur and forearm, but not in the spine. However, BMI remained predictive of bone mineral at all sites. Muscle strength, physical fitness, and weight appear to exert independent effects upon bone mass. Age effects may be mediated indirectly through associated changes in these factors. The integrated physical load on the skeleton may be a final common pathway.

Adult↗
PubMed1979

Juxta-articular adiposis dolorosa: what is it? Report of 2 cases.

Juxta-articular adiposis dolorosa may be defined as the localised accumulation of painful fat near joints, most commonly the knee. It exists as a separate entity that must be distinguished from other causes of knee pain. We present 2 patients with this condition and review the literature. Various approaches to therapy are discussed. A classification of painful fat near joints is proposed.

Adiposis Dolorosa↗
PubMed1979

Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium.

Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)(2)D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P < 0.01) and with serum 1,25(OH)(2)D (r = -0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)(2)D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 mug/d) of synthetic 1,25(OH)(2)D(3). In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH(2)-terminal assay) relative to age-matched controls, and mean serum phosphate was increased. The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)(2)D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)(2)D, analagous to that seen in aging rats, cannot be excluded.

Adult↗
PubMed1978

Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone.

In spite of the increasing use of single and multiple pharmacologic intravenous pulses of MPS for immunosuppression in various diseases, their immunosuppressive effects have not been documented. We treated two groups of six patients with classic RA unresponsive to conventional therapy with either one or three daily 1 gm intravenous doses of MPS and measured the immune response and clinical activity over 16 weeks. Lymphocytopenia with selective T lymphocyte suppression was noted 2 hr following each infusion, which was maximal at 6 hr with complete recovery 24 hr after each dose beyond which no lymphocytopenia or T lymphocyte depletion was seen. Preservation of skin test positivity to recall antigens such as PPD and histoplasmin, rise in antibody titers to the secondary antigens tetanus and typhoid, and primary antibody response to KLH were found in both groups after treatment. Serum gamma globulin concentrations were unchanged. Five of six patients receiving 3 doses and three of six receiving 1 dose had satisfactory improvement in clinical parameters, with maximal benefit seen within the first 4 days. Six patients still felt better at 4 weeks, and one patient in each group entered a clinical remission greater than 16 weeks. We conclude that higher and repeated doses of MPS caused neither greater lymphocytopenia nor more prolonged suppression of recirculating lymphocytes than the conventional oral doses. The clinical benefits stem from reduction of inflammation, and it is doubtful that pulse therapy by itself induced significant generalized immunosuppression.

Aged↗