Vulvar intraepithelial neoplasia in a young woman with systemic lupus erythematosus: a case report.

Diagnosing vulvar intraepithelial neoplasia in a young woman presenting mainly with skin manifestations of lupus and with no other risk factors is a major challenge. The case of a 27-year-old woman with systemic lupus erythematosus and vulvar intraepithelial neoplasia is described. Although progression of vulvar intraepithelial neoplasia to invasive planocellular carcinoma is rare, prompt and adequate diagnosis and treatment will help ensure the best possible quality of life.

Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model.

To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result of continuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized.

Leptin is inversely related to age at menarche in human females.

Over the last century there has been a trend toward an earlier onset of menarche attributed to better nutrition and body fatness. With the discovery of the obesity gene and its product, leptin, we reexamined this hypothesis from a new perspective. As delayed menarche and leanness are considered risk factors for osteoporosis, we also evaluated the relation between leptin and bone mass. Body composition and serum leptin levels were measured, and the timing of menarche was recorded in 343 pubertal females over 4 yr. Body composition was measured by dual x-ray absorptiometry, and leptin by a new RIA. All participants were premenarcheal at baseline (aged 8.3-13.1 yr). Leptin was strongly associated with body fat (r = 0.81; P < 0.0001) and change in body fat (r = 0.58; P < 0.0001). The rise in serum leptin concentration up to the level of 12.2 ng/mL (95% confidence interval, 7.2-16.7) was associated with the decline in age at menarche. An increase of 1 ng/mL in serum leptin lowered the age at menarche by 1 month. A serum leptin level of 12.2 ng/mL corresponded to a relative percent body fat of 29.7%, a body mass index of 22.3, and-body fat of 16.0 kg. A gain in body fat of 1 kg lowered the timing of menarche by 13 days. Leptin was positively related to bone area (r = 0.307; P < 0.0001) and change in bone area (r = 0.274; P < 0.0001). A critical blood leptin level is necessary to trigger reproductive ability in women, suggesting a threshold effect. Leptin is a mediator between adipose tissue and the gonads. Leptin may also mediate the effect of obesity on bone mass by influencing the periosteal envelope. This may have implications for the development of osteoporosis and osteoarthritis.

Gain in body fat is inversely related to the nocturnal rise in serum leptin level in young females.

Both genetic and environmental factors contribute to adolescent obesity. Evidence of a genetic basis for obesity development is substantial, although the exact mechanism of action has yet to be identified. The purpose of this study was to document the circadian rhythmicity of the serum leptin level in young females and to assess the impact of the change in body fat stores during growth on the nocturnal rise in the serum leptin level with implications for obesity traits. There was a significant rise in serum leptin at midnight and 0400 h, suggesting a diurnal variation in serum leptin concentrations (ANOVA F ratio = 6.2; P < 0.0001). There was also a strong association between relative total body fat and the average daytime serum leptin level (r = 0.78; P < 0.0001). The percent increase in the nocturnal leptin concentration was inversely related to the percent gain in total body fat (r = 0.45; P < 0.024). Forward stepwise regression analysis selected the change in total body fat over a 6-month interval as the most powerful determinant of the percent increase in the nocturnal leptin concentration (partial R2 = 0.203; beta = -0.450; SE of beta = 0.186; t = -2.418; P < 0.024). If the lack of a nocturnal rise in serum leptin persists over a longer period of time, it may have implications for the development of obesity, presumably by inadequate suppression of nighttime appetite.

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.

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.

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.

Magnesium balance in adolescent females consuming a low- or high-calcium diet.

Increasing emphasis is being placed on optimizing calcium intake during growth as a way to enhance peak bone mass. Although some studies in adults have shown that high calcium intake may negatively affect magnesium utilization, few data are available regarding the interaction of calcium and magnesium in healthy children. The purpose of our study was to measure the effect of calcium intake on magnesium balance in 26 adolescent girls (mean age 11.3 y) during a 14-d period. Subjects ate a controlled basal diet containing 667 mg Ca and 176 mg Mg. In addition to the basal diet, subjects were randomly assigned in a double-blind fashion to consume 1000 mg elemental Ca/d as calcium citrate malate or a placebo. Magnesium use did not differ between the low-calcium and high-calcium groups as measured by absorption (50% compared with 55%), urinary excretion (70 compared with 74 mg/d), and fecal excretion (88 compared with 79 mg/d). Accordingly, magnesium balance was not different in subjects consuming 667 or 1667 mg Ca/d and averaged 21 mg Mg/d for the whole study group. Magnesium balance was significantly correlated with magnesium intake (r = 0.511, P = 0.008) and magnesium absorption (r = 0.723, P < 0.001). Prediction intervals from the regression of magnesium balance on intake indicated that the current recommended dietary allowance of magnesium would result in magnesium balance > or = 8.5 mg/d in 95% of the girls. This value appears consistent with long-term accretion rates needed to account for the expansion of the total-body magnesium pool during growth. In summary, our observations support the adequacy of the current recommended dietary allowance for magnesium and indicate that alterations in magnesium utilization should not be anticipated in adolescent females consuming a high-calcium diet.

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.

Zinc balance in adolescent females consuming a low- or high-calcium diet.

There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.

Bone status and fracture rates in two regions of Yugoslavia.

Bone status and fracture rates were evaluated in two Yugoslav populations with very different dietary habits. In district A (Podravina) the daily calcium intake was about twice that in district B (Istra). There were similar but smaller differences in the intakes of other nutrients. In district B metacarpal cortical width was reduced in all age groups of both sexes but the difference tended to decrease with age. The proximal femur fracture rate was higher in district B than district A but there was no difference between the forearm fracture rates in the two districts. Our results confirm that bone mass at any age is clearly the result of age and sex and most probably other genetically determined factors but also show that this expression is nutrition related. The data suggest that nutrition (in particular the calcium intake) is an important determinant of bone mass in young adults but seems to have little effect on age-related bone loss in either males or females. The main determinant of cortical bone mass in the elderly seems to be the cortical bone mass in middle life. The proximal femur fractures of old people reflect declining cortical bone mass but the distal forearm fractures of middle-aged women are unrelated to cortical bone mass or nutritional status.

Urinary calcium, sodium, and bone mass of young females.

Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron status, menarche, and calcium supplementation in adolescent girls.

The effects of growth, menstrual status, and calcium supplementation on iron status were studied over 4 y in 354 girls in pubertal stage 2 who were premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate. Anthropometric characteristics, bone mass, and nutritional status were measured biannually; ferritin was measured annually; and red blood cell indexes were determined at 4 y. The simultaneous effects of iron intake and menstrual status on serum ferritin, after change in lean body mass (LBM) was controlled for, were evaluated in subjects in the upper and lower quartiles of cumulative iron intake. The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5 y before the onset of menarche. Change in LBM was a significant predictor of serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=-4.12). The 2 fitted mathematical models representing ferritin concentrations of subjects in the upper and lower quartiles of cumulative iron intake were significantly different (P < 0.018). The regression line of the ferritin concentration in menstruating girls with high iron intakes had a less negative slope than the line fit to serum ferritin concentrations in girls with low iron intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not significantly different between groups. In addition, there was no significant difference between groups in any of the red blood cell indexes. In summary, growth spurt and menstrual status had adverse effects on iron stores in adolescent girls with low iron intakes (<9 mg/d), whereas long-term supplementation with calcium (total intake: approximately 1500 mg/d) did not affect iron status.

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)

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.

Calcium requirements for growth: are current recommendations adequate?

Peak adult bone mass is determined in each individual by a combination of endogenous and environmental factors. Insufficient accumulation of skeletal mass by the time young adulthood is reached appears to enhance the likelihood of fractures later in life. It is speculated that environment (nutrition and exercise) contributes to about 20% of the variance in bone mass. Although much is yet to be learned about how diet contributes to skeletal growth and development, it now appears that calcium intake may be an important factor in the attainment of peak bone mass. A review of the scientific literature suggests that the current recommended dietary allowance (RDA) for calcium may not be high enough to optimize the genetically programmed peak bone mass in a substantial number of growing individuals. New standards for dietary calcium intakes during growth may be indicated.

Comparison of absorptiometric evaluations from total-body and local-regional skeletal scans.

The most common measurement sites for dual-energy absorptiometry (DXA) in clinical practice are posteroanterior (PA) spine and femur. However, other skeletal regions may provide different bone density information. The purpose of this study was to establish the least number of DXA measurements needed to obtain complete information about bone. A total of 262 normal female subjects, 8-50, were measured on a Lunar DPX-L scanner under total body, PA spine, lateral spine, and femur protocol. Forearm measurements were performed with a Lunar SP2 single-photon absorptiometry scanner. The various measurements were compared based on a linear regression model. The correlation coefficients for bone mineral density (BMD) between adjacent vertebrae were 0.92-0.95, and the associated standard errors of the estimate (SEE) were 4.5-5.5%. Total-body BMD can best predict BMD of the trunk, arms, and legs (SEE<4.3%), but least that of the lateral view of the spine (SEE>13.9%). BMD values of the leg from total-body scans predict those from the femoral neck with an error of 9.0%, and those of the trochanteric region with 11.1%. The error between adjacent vertebrae (6%) is considered acceptable, then a total-body measurement combined with a lateral view of the spine and a femur scan are adequate.

Simultaneous reduction of radioactive strontium, caesium and iodine retention by single treatment in rats.

The effect of a mixture of calcium alginate, iron (III) ferrocyanide and potassium iodide added to rat diet on 85Sr, 137Cs and 131I metabolism and health was investigated in female rats after four weeks of treatment. The retention of these radioisotopes was determined in the whole body and critical organs six days after 85 Sr and 137CS and one day after 131I oral administration. The health effect of the mixture was evaluated by measuring body weights, haematological parameters, concentrations of iron, zinc and manganese in the kidneys, liver and femur, bone parameters (femur composition and morphometry) and by a histopathological examination. The mixture reduced 85Sr retention in the femur 11 times, 137Cs retention in the thigh muscle 102 times and 131I retention in the thyroid 134 times. Treated animals were in good health and the only differences found between the control and experimental rats were slightly lower haemoglobin values in the blood and a slightly lower iron concentration in the liver. It is concluded that the mixture was very efficient for decreasing body retention of three important fission products and that it can be used over long periods without causing adverse health effects.

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.

Holistic approach to analysis of medical data: cancer of the corpus uteri.

Besides the information regarding his/her disease, each hospitalized cancer patient also provides the variety of data regarding his/her psychological, cultural, social, economical, genetic, constitutional and medical background. The aim of this study was to introduce a holistic approach to analysis of medical data, in this case clinical data regarding cancer of the corpus uteri. Such approach requires the collection of data regarding different aspects of the cancer patient, and after the satisfactory sample size is obtained (which should be at least five times greater than the number of examined patient characteristics), the performance of factor analysis. In this study, the authors have processed the data regarding 25 characteristics of 928 corpus uteri cancer patients treated between 1980 and 1990 at the Department for Gynecological Oncology of the University Hospital for Gynecology and Obstetrics, Zagreb, Croatia. In factor analysis, the principal components were rotated after the initial extraction (the authors recommended the use of oblimin rotation) in order to obtain better ground for interpretation of the obtained results. The next step in this approach was the stepwise exclusion of characteristics with smallest communalities according to Kaiser-Meyer-Olkin criteria, and retaining the characteristics and components with the most significant impact on the explained system variance. When the number of principal components and initial analyzed characteristics was reduced to 3-4 and 7-10, respectively, the ultimate interpretations and conclusions were made. This approach outlined some clusters of correlations between medical data which are difficult to identify using other statistical procedures, primarily the impacts of various socioeconomic and hereditary-constitutional variables on overall survival.