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Biomedical subjects

V Matkovic

Publications and source records attributed to V Matkovic.

36 records · Page 2Linked to original sources

Suppression of experimental autoimmune encephalomyelitis by gallium nitrate.

We examined the effect of gallium (Ga) nitrate on the development of the development of experimental autoimmune encephalomyelitis (EAE). Weekly subcutaneous injections of 10-30 mg/kg prevented clinical signs as well as histopathological changes of EAE. The optimal timing of a single injection of Ga was 6 days after induction of EAE, with amelioration also apparent following a single injection on day 3 or 9 but not day 12. Ga administered in vivo suppressed myelin basic protein (MBP) and purified protein derivative-specific lymphocyte proliferative responses in vitro. Addition of Ga to MBP-specific T lymphocyte line cultures at various times after initiation of culture revealed that Ga exerts an effect at an early stage of cellular activation.

Animals↗

Calcium balance during human growth: evidence for threshold behavior.

Calcium balances performed on 519 individuals from birth to 30 years of age, derived from 34 published reports, were pooled by age group and the relationship between intake and balance for each group was compared at both extremes of the intake range. At all ages, from infancy through the young adult years, balance values tended to flatten and become constant at higher intakes, while at lower intakes balance was invariably highly correlated with intake. Threshold intakes and balances were estimated by fitting the data to a two-component, split, linear-regression model. The threshold values at which balance no longer rose with intake exceeded the US recommended dietary allowances for calcium for all the age groups concerned.

Adolescent↗

Hepatic encephalopathy mimicking stroke. A case report.

This case demonstrates focal neurologic deficit mimicking stroke with underlying hepatic encephalopathy. Unilateral weakness in patients with hepatic encephalopathy has not been previously described in the English language literature. A 46-yr-old white woman was admitted to an acute care hospital for left shoulder manipulation, underwent general anesthesia and appeared to have had a right cerebrovascular accident. At transfer to the rehabilitation hospital, in addition to the left hemiparesis, there were inconsistencies in the neurologic examination and signs of cognitive impairment and liver failure. The patient's response to an intensive, multidisciplinary inpatient rehabilitation program along with treatment of the liver dysfunction led to resolution of left-sided weakness and flapping tremor with independence in ambulation and activities of daily living. Relevant literature is reviewed. A thorough history and physical examination with liver function assessment should always be performed in patients with cerebrovascular accident and unusual recovery.

Brain↗

Calcium and peak bone mass.

On the basis of previous epidemiological, clinical and experimental studies, it was demonstrated that adequate calcium intake during growth may influence peak bone mass/density, and may be instrumental in preventing subsequent postmenopausal and senile osteoporosis. Calcium intake during adolescence appears to affect skeletal calcium retention directly, and a calcium intake of up to 1600 mg d-1 may be required. Therefore, adolescent females at the time of puberty probably represent the optimal population for early prevention of osteoporosis with calcium. Young individuals must be in positive calcium balance to provide the calcium necessary for skeletal modelling and consolidation, but the degree of positive balance required to achieve peak bone mass and density is unknown. To assess calcium requirements in young individuals, and also to evaluate the determinants of calcium metabolism during the period of acquisition of peak bone mass, 487 calcium balances from previously published reports have been collected and analysed according to developmental phase and calcium intake. The results of this analysis showed that calcium intake and skeletal modelling/turnover are the most important determinants of calcium balance during growth. The highest requirements for calcium are during infancy and adolescence, and then during childhood and young adulthood. Infants (adequate vitamin D supply) and adolescents have higher calcium absorption than children and young adults to meet their high calcium requirements. Calcium absorption during the periods of rapid bone modelling/turnover is probably mediated by Nicolaysen's endogenous factor. Urinary calcium increases with age, and reaches a maximum by the end of puberty. The results also show that calcium intake has little effect on urinary calcium excretion during the period of most rapid skeletal formation: a weak correlation is present in children and young adults. On the basis of the above studies it was suggested that the RDA for calcium should be higher than currently established for children, adolescents, and young adults, in order to ensure a level of skeletal retention of calcium sufficient for maximal peak bone mass. In addition to nutrition, heredity (both parents) and endocrine factors (sexual development) appear to have profound effects on peak bone mass formation. Most of the skeletal mass will be accumulated by late adolescence, indicating early timing of peak bone mass.

Aging↗

Lack of effect of gallium nitrate on bone density in a rat model of simulated microgravity.

The effect of gallium (Ga) nitrate upon bone density was studied in 24 male Sprague-Dawley rats (275-335 g) in an established model of simulated microgravity. Rats, tail-suspended for 14 d from a system of double pulleys, were allowed free mobility with their hind limbs unloaded. Animals were randomized into four groups of six: 1) unsuspended, saline; 2) suspended, saline; 3) unsuspended, Ga; and 4) suspended, Ga. On day 0, 1 d prior to suspension, rats received equal volumes of a single subcutaneous injection of either saline or 30 mg/kg of elemental Ga in the form of Ga nitrate. On day 15, all animals were euthanized under anesthesia, and their hind limbs analyzed in vitro using single-photon absorptiometry. Although we previously demonstrated that Ga inhibits bone resorption in patients with Paget's disease of bone, and although Ga exhibits many apparent similarities in efficacy to diphosphonates, which prevent bone loss in ovariectomized, paralyzed, and single-limb immobilized rats, Ga failed to prevent bone loss in the tail-suspended rats.

Animals↗

Osteoporosis as a pediatric disease: role of calcium and heredity.

Osteoporosis is characterized by a reduction in bone mass. This reduction may be determined during growth or acquired in later life. Since osteoporosis is easier to prevent than to treat, the goal is therefore to identify individuals who might be at high risk. We suggest that the identification of those individuals should start in childhood and adolescence. Calcium intake and skeletal modelling/turnover are the most important determinants of calcium balance during this age period. Adequate calcium supply should contribute to peak bone mass and therefore prevention of osteoporosis later in life. We indicate that genetic information from both parents plays an important role as well.

Aging↗

Calcium metabolism and calcium requirements during skeletal modeling and consolidation of bone mass.

The degree of positive calcium balance in young individuals necessary to achieve peak bone mass and density is unknown. To assess calcium requirements and metabolism during acquisition of peak bone mass, 487 calcium balance studies from published reports were analyzed. The results suggest that 1) calcium intake and skeletal modeling and turnover determine calcium balance during growth, 2) the highest requirements for calcium are during infancy and adolescence and then during childhood and young adulthood, 3) to meet high calcium requirements, infants and adolescents have higher calcium absorption, 4) calcium absorption during rapid bone modeling and turnover is mediated by the Nicolaysen's endogenous factor, 5) urinary calcium reaches its maximum by the end of puberty, 6) calcium intake has little influence on urinary calcium excretion during the period of rapid growth, 7) the recommended dietary allowance for calcium should be higher than the amount currently established for children, adolescents, and young adults to ensure a level of skeletal retention of calcium for maximal peak bone mass, and 8) clinical trials with increased calcium intakes in each age segment of young populations are needed to clarify the above trends.

Absorption↗

Influence of calcium intake and growth indexes on vertebral bone mineral density in young females.

This cross-sectional study examined the relationship between current calcium intake and vertebral bone mineral density (V-BMD) in 49 healthy Caucasian adolescent females aged 8-18 y. The ability of current calcium intake to account for the variance in V-BMD in this population was compared with that seen with weight, height, maturational age (determined by the Tanner Sexual Maturity Rating), chronological age, and total energy expenditure. Calcium intake was determined from the mean of 4-d, food-intake records. Average vertebral bone mineral density from L1-L4 was measured by dual x-ray absorptiometry. A multiple-regression model revealed that 81% of the variance in V-BMD was described by maturational age, chronological age, and calcium intake, with all representing significant predictors of bone mineral density (P less than 0.0001, 0.005, 0.04, respectively). This study supports the hypothesis that better calcium nutrition during adolescence may optimize, within genetic boundaries, peak bone mass.

Adolescent↗

Use of gallium to treat Paget's disease of bone: a pilot study.

The effects of gallium nitrate on bone turnover were evaluated in four patients with active Paget's disease. Treatment with gallium nitrate (100 mg/m2 daily for 5 days, intravenously in 5% glucose) significantly reduced serum calcium, serum phosphate, urinary calcium, and the ratio of maximum tubular reabsorption of phosphate to glomerular filtration rate in each patient. Serum parathyroid hormone levels rose. The findings suggest that the fall in serum calcium caused secondary hyperparathyroidism, resulting in a fall in serum phosphate. Serum alkaline phosphatase and urinary hydroxyproline levels fell substantially, showing that gallium effectively suppressed bone turnover. The fall in hydroxyproline excretion preceded that in serum alkaline phosphatase, suggesting that suppression of bone resorption by osteoclasts preceded that of bone formation by osteoblasts. Alkaline phosphatase levels remained low throughout follow-up (85-141 days), so the effect of gallium seems to be long-lasting.

Aged↗

Factors that influence peak bone mass formation: a study of calcium balance and the inheritance of bone mass in adolescent females.

We suggested that calcium may be an important determinant of peak bone mass. For further elucidation, calcium balances in adolescent females with different calcium intakes (270-1637 mg/d), and a 2-y intervention study of calcium supplementation were performed. Hereditary influences on bone status were also evaluated by comparing subjects' and parents' bone mass. The main determinant of calcium balance was calcium intake; net calcium absorption increased with intake and urinary calcium did not change. Adolescent females retained 200-500 mg Ca/d, suggesting that inadequate calcium intake may translate into inadequate calcium retention and a reduction in peak bone mass. There was a more pronounced increase in bone mass over time in the calcium-supplemented group (1640 mg Ca/d) than in the control group (750 mg Ca/d), but the differences between bone mass measurements were not statistically significant, possibly because of a type II error. By the age of 16 y daughters had accumulated 90-97% of the bone mass of their premenopausal mothers.

Adolescent↗

A comparison of single photon and dual X-ray absorptiometry of the forearm in children and adults.

We compared single photon absorptiometry (SPA) to dual x-ray absorptiometry (DXA) for determination of bone mineral content (BMC), bone mineral density (BMD), and bone width (BW) of the forearm. The SPA and DXA measurements were done on the same subjects, using Lunar densitometers. The measurements were performed over the proximal radius (1/3 shaft) of the nondominant arm in 285 healthy, Caucasian females and males, ages 9-53. Correlation, linear, and split regression analyses for all subjects, and for subgroups (adults and children), were performed to compare SPA and DXA measurements. Corresponding measurements performed on two densitometers were highly correlated: r = 0.987, 0.975, and 0.943 for BMC, BMD, and BW, respectively. The corresponding measurements were also very similar in value, ranging from 0.9% to 4.1% difference, although they were different statistically. Correlations dropped slightly when subjects were separated into adult and children subgroups, and therefore, split regression analysis was performed resulting in R2 (adjusted) values of 97.6%, 95.5%, and 89.0% for BMC, BMD, and BW, respectively. Because the group indicator was statistically significant (p < 0.001) only for the BMC measurements but not for BMD and BW, linear regression of the whole sample was done as well. The difference in fitted values between the two regression methods was insignificant; therefore, we concluded that linear regression was sufficient for description of the relationship between SPA and DXA measurements. The precision study showed that the DXA had better reproducibility than SPA. The DXA precision in vivo (CV%) for BMC, BMD, and BW was 1.06, 0.83, and 0.95, respectively; and the SPA precision for same variables was 2.08, 2.12, and 0.95, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗