Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study

Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4-11.8) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual-energy X-ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 +/- 0.11 vs. 0.26 +/- 0.09%/month), legs (0.76 +/- 0.07 vs. 0.34 +/- 0.08%/month), and total body (0.32 +/- 0.04 vs. 0.17 +/- 0.06%/month) (all p < 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 +/- 0. 32%/month due to a 0.93 +/- 0.33%/month decrease in endocortical (medullary) diameter (both p < 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 +/- 0.33%/month, (p < 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 +/- 2. 35 cm3 in the exercise group, and 3.04 +/- 1.14 cm3 in controls (p < 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption.     

Impetigo in French Guyana. A clinical, bacteriological, toxicological and sensitivity to antibiotics study]

Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p < 0.01), but not at femoral neck level or at Ward's triangle level (0.92 + 0.15 g/cm2 vs 0.97 + 0.11 g/cm2, p = NS; and 0.74 +/- 0.16 g/cm2 vs 0.85 +/- 0.1 g/cm2, p = NS) when compared to controls. Baseline serum levels of TNF-alpha and IL-1 were in the normal range both in patients and controls. After acute octreotide administration, no differences in circulating TNF-alpha and IL-1 levels were found. In conclusion, acromegalic patients present a reduced BMD at lumbar spine but not at femoral neck level and Ward's triangle. Circulating cytokines such as TNF-alpha and IL-1 are in the normal range. These data suggest that cytokines are not involved in the pathogenesis of GH-excess induced osteoporosis. The possibility that the GH excess might affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.     

Investigation of bone mineral distribution in Japanese using dual-energy X-ray absorptiometry

To investigate bone mineral distribution in humans, the authors conducted a cross-sectional survey of, and performed bone-density measurements on, 1,310 healthy Japanese ranging in age 5 to 85 years. Eight hundred fifty-eight of the subjects were female, and 452 were male. Arm, leg, and spine bone mineral content (BMC) and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA), and the subjects were divided into 5-year age groups. BMD showed increases with skeletal growth until reaching a peak at 15 to 19 years in females, and 25 to 29 for males. For both sexes the fastest growth to maturity in terms of bone mass values was in the late 20s. Females, though, had higher arm, leg, and spine remodeling rates than males. In premenopausal women no changes in arm, leg or spine BMC and BMD were observed. Postmenopausal women showed an overall reduction in bone mass, most noticeably in the spine. After menopause, women had about 10 years of accelerated loss (1.46%/year). Vertebral BMD values were similar for men and women (1.10 +/- 0.20g/cm2 for males vs. 1.09 +/- 0.14g/cm2 for females, p > 0.05). BMC values were significantly higher in males, and males at all times had a higher arm and leg BMD. There were no significant value differences in either sex for left and right leg BMC and BMD; however, from the age of 15, right arm values were significantly higher likely due to right handedness. For both sexes the order of BMC and BMD was leg, spine, and arm.     

Type of physical activity, muscle strength, and pubertal stage as determinants of bone mineral density and bone area in adolescent boys

The present study was conducted to evaluate the influence of different types of weight-bearing physical activity, muscle strength, and puberty on bone mineral density (BMD, g/cm2) and bone area in adolescent boys. Three different groups were investigated. The first group consisted of 12 adolescent badminton players (age 17.0 +/- 0.8 years) training for 5.2 +/- 1.9 h/week. The second group consisted of 28 ice hockey players (age 16.9 +/- 0.3 years) training for 8.5 +/- 2.2 h/week. The third group consisted of 24 controls (age 16.8 +/- 0.3 years) training for 1.4 +/- 1.4h/week. The groups were matched for age, height, and pubertal stage. BMD, bone mineral content (BMC, g), and the bone area of the total body, lumbar spine, hip, femur and tibia diaphyses, distal femur, proximal tibia, and humerus were measured using dual-energy X-absorptiometry. When adjusting for the difference in body weight between the groups, the badminton players were found to have significantly higher BMD (p < 0.05) of the trochanter and distal femur compared with the ice hockey players despite a significantly lower weekly average training. The badminton players had higher BMD compared with the control with the control group at all weight-bearing BMD sites, except at the diaphyses of the femur and tibia and lumbar spine. The independent predictors of bone density were estimated by adjusting BMC for the bone area in a multivariate analysis among all subjects (n = 64). Accordingly, the bone density of all sites except the spine was significantly related to muscle strength and height, and the bone density of the total body, neck, trochanter, distal femur, and proximal tibia was significantly related to type of physical activity (beta = 0.09-0.33, p < 0.05). The bone area values at different sites were strongly related to muscle strength and height and less strongly related to the type of physical activity and pubertal stage. In conclusion, it seems that during late puberty in adolescent boys the type of weight-bearing physical activity is an important determinant of bone density, while the bone area is largely determined by parameters related to body size. The higher BMD at weight-bearing sites in badminton players compared with ice hockey players, despite significantly less average weekly training, indicates that physical activity including jumps in unusual directions has a great osteogenic potential.     

Bone mass improves in alcoholics after 2 years of abstinence

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Mineral content in bones of children with symptomless celiac disease and gluten-free diet

Osteoporosis is a complication of adult celiac disease. The gluten-free diet improves but does not normalize bone mineral density. Only few and conflicting data are known about the influence of the disease and diet on bone mineralization in children. The aim of this study was to evaluate the radial bone mineral content (BMC) and density (BMD) in children and adolescents who are asymptomatic on gluten-free diet. The BMD and BMC values of non-dominant radius midshaft in ninety-one children (53 girls and 38 boys, mean age: 11.7 years, mean duration of disease: 8.7 years) were determined by single photon absorptiometry. At the diagnosis and at least three years after gluten-free diet, serum calcium, phosphorous and albumin concentrations and alkaline phosphatase activities were determined in all, and additionally intact parathormone concentrations in 16 patients. The mean BMC Z-score value in the entire study population did not differ from the value of normal age-matched population (mean Z-score: -0.27), but in female adolescent group was significantly lower than the normal value (mean Z-score: -1.04, p < 0.01). In contrast, the mean BMC Z-score value was significantly higher than in normal value in girls (mean Z-score: +1.36, p < 0.001), in boys (mean Z-score: +0.53, p < 0.02) as well as in the total patients group (mean Z-score: +1.01, p < 0.001). The diameter of radius midshaft was significantly smaller in all age group than the normal mean value. Serum laboratory parameters of asymptomatic patients were in the normal range. The serum parathormone value in treated patients was significantly lower than in untreated celiac children (mean +/- SD: 3.77 +/- 1.07 versus 7.89 +/- 2.54, p < 0.01), but significantly higher compared to controls (2.89 +/- 0.9, p < 0.05). The data indicate that the gluten-free diet alone is not able to normalize bone mineralization in children. The significant increase of serum parathormone level in treated asymptomatic patients may be explained by the lower calcium content of gluten-free diet. The authors suppose that low calcium supply in children similarly to adult patients can lead to increased parathormone secretion, which can cause the retardation of bone growth even in treated patients with celiac disease.     

Research fundamentals: I. Getting from hypothesis to manuscript: an overview of the skills required for success in research

Ninety five normal Caucasian subjects (51F, 44M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 +/- 0.007 g/cm2 to 0.365 +/- 0.035 g/cm2 in females and 0.425 +/- 0.040 g/cm2 in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1-5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively (r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age (r > 0.85).     

Effects of immobilization, three forms of remobilization, and subsequent deconditioning on bone mineral content and density in rat femora

Disuse is associated with bone loss, which may not be recoverable. It is not known whether intensified remobilization is beneficial in restoring disuse-related bone loss nor if any such benefit would depend upon continuing mobilization for its maintenance. After an immobilization period of 3 weeks, the effects of free remobilization (11 weeks), and low-and high-intensity treadmill running (11 weeks) with and without subsequent deconditioning (18 weeks) on the bone mineral content (BMC) and density (BMD) of the hindlimb femora of Sprague-Dawley rats (n = 98) were studied using a dual-energy X-ray absorptiometric (DXA) scanner. Our hypothesis was that intensified remobilization is beneficial in restoring the BMC and BMD from disuse to normal while subsequent deconditioning is deleterious to these parameters. Immobilization for 3 weeks produced a significant BMC and BMD loss in the immobilized left femur (range -4.4 to -12.8%; p < 0.05-0.001). In the groups with free remobilization (free cage activity), the body weight-adjusted BMCs and BMDs always remained below those in the controls (range -2.3 to -12.1%; p values ranging from NS to < 0.01). Both low- and high-intensity running restored BMC and BMD in the immobilized limb, the effect being better in the latter group. In both of these groups, the values of the immobilized left limbs and those of the free right limbs exclusively exceeded the corresponding values of the age-matched control rats (left limb values 3.0-21.1% higher with p values ranging from NS to < 0.01; right limb values 7.9-21.4% higher with p < 0.05-0.01). However, after the deconditioning period of 18 weeks, the above described beneficial effects of low- and high-intensity running were lost, the left and right limb BMC and BMD values being lower than those in the age-matched controls (range -3.8 to -8.7%; p values ranging from NS to < 0.05). In conclusion, this study clearly indicates the need for greater than normal activity to restore the BMC and BMD after disuse to normal levels. However, the benefits of intensified remobilization are lost if the activity is terminated, and therefore, after immobilization and disuse, bone loading activities should be continued, perhaps indefinitely.     

Harmonic/noise ratio and spectrographic analysis in vocal abuse pathology

To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma (MM) we performed a prospective study of 34 patients with newly diagnosed MM. Most patients had advanced disease and all but two patients had osteolytic bone destructions and/or pathological fractures. Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (L1-L4) and hip were measured using a Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis. Data from 289 healthy Danish volunteers aged 21-79 yr were used for calculation of Z-scores. Lumbar spine BMC (Z-score -0.46 +/- 0.23, p = 0.05) and lumbar spine BMD (Z-score -0.56 +/- 0.23, p = 0.02) were significantly reduced in MM patients, whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked reduced BMD (Z-score -1.34 +/- 0.22, p < 0.001), as had non-fractured vertebrae in the same individuals (Z-score -1.42 +/- 0.25, p < 0.001). Lumbar spine BMD correlated with radiologically assessed bone morbidity (r -0.37, p = 0.03) and stronger with the incidence of vertebral fractures (r -0.64, p < 0.001). Thus, osteopenia of the back is common in multiple myeloma and correlates with an increased incidence of fractures. DXA may identify subjects with increased risk of vertebral fractures for more intensive chemotherapeutic or anti-resorptive treatment.     

Beta blockade in congestive heart failure: persistent adverse haemodynamic effects during chronic treatment with subsequent doses

Widespread osteoporosis testing and diagnosis are currently limited due to the high capital cost and reduced portability of many existing bone densitometry techniques. In this study we evaluated an inexpensive, low radiation, X-ray-based technique for assessing bone density of the middle phalanx. The technique, termed computed digital absorptiometry (CDA), is similar to radiographic absorptiometry (RA), using a single-energy X-ray source, an aluminum alloy step-wedge, and a charge-coupled device (CCD) detector system to automatically compute bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2) in the middle phalanx of the third finger. The potential advantage of CDA over current RA techniques is that by using a filmless detector system, no off-site processing of radiographs is required and bone density results are obtained immediately after the test. Using human cadaveric specimens we determined the accuracy and short-term precision of CDA as well as its correlation with other hand and forearm bone densitometry methods. We obtained 26 cadaveric forearms (50% female, mean age 78 years, range 52-96 years). BMC and BMD of the middle phalanx of the third finger were determined using CDA and using RA. We assessed forearm BMC and BMD using single-energy and dualenergy X-ray absorptiometry (SXA and DXA). Precision of CDA was assessed by measuring ten of the specimens five times each with repositioning between measurements. Finally, the middle phalanx was dissected and incinerated to determine ash weight. BMC estimates from CDA and from RA were strongly correlated with ash weight (r = 0.89, p < 0.001 and r = 0.93, p < 0.001, respectively). The mean coefficients of variation using CDA were 1.36% and 0.70% for phalanx BMC and BMD, respectively. BMC and BMD measured by CDA were strongly correlated with hand and forearm bone mineral measurements performed by SXA, DXA and RA (r = 0.74-0.91). These results indicate that CDA accurately and precisely predicts BMC of the middle phalanx. Thus, with further clinical verification, this technique may prove to be a useful tool for the widespread testing and assessment of osteoporotic fracture risk.     

Selective incorporation of 111In-labeled PHOTOFRIN by glioma tissue in vivo

BACKGROUND: This study was to evaluate the efficacy, safety and immunogenicity of recombinant human growth hormone (rhGH) in treatment of children with growth hormone deficiency (GHD). METHODS: We selected 15 children with GHD for a 12-month clinical trial and separated them into three groups with each 5 patients receiving one of the 3 tested rhGH (Saizen by Serono, Aubonne, Switzerland; Genotropin by KabiVitrum, Stockholm, Sweden and Humatrope by Eli Lilly, Indianapolis, USA). RESULTS: In Saizen group, 3 boys and 2 girls with a mean chronological age (CA) of 10.6 +/- 1.7 yrs and bone age (BA) of 6.7 +/- 1.2 yrs, at dose of 0.2 IU/kg sc tiw, gained an average BA of 2.1 +/- 1.3 yrs. The mean height velocity (HV) increased from 3.7 +/- 1.2 to 11.1 +/- 3.3 cm/yr. The height standard deviation score (SDS) increased from -4.2 +/- 3.1 to -3.1 +/- 2.9. In Genotropin group, 2 boys and 3 girls with a mean CA of 9.2 +/- 2.3 yrs and BA of 5.6 +/- 2.1 yrs, at dose of 0.1 IU/kg sc qd, gained an average BA of 0.8 +/- 0.2 yr. The mean HV increased from 3.4 +/- 0.7 to 11.3 +/- 2.0 cm/yr. The height SDS increased from -4.0 +/- 0.5 to -2.7 +/- 0.7. In Humatrope group, 4 boys and 1 girl with a mean CA of 10.3 +/- 3.5 yrs and BA of 5.8 +/- 2.9 yrs, at dose of 0.1 IU/kg sc qd, gained at average BA of 0.8 +/- 0.7 yr. The mean HV increased from 4.0 +/- 1.3 to 9.4 +/- 1.9 cm2yr, and the height SDS increased from -2.9 +/- 0.7 to -2.2 +/- 1.0. Very low titers of anti-rhGH antibodies were noted only in two patients, one in Saizen group (titer = 1:10) and the other in Genotropin group (titer = 1:6). Their HV was not affected (Saizen: 13.3 cm/yr, Genotropin: 11.2 cm/yr). One patient evolved subclinical hypothyroidism whereas no side effect at all was noted in the rest of patients. CONCLUSIONS: Three tested GH (Saizen, Genotropin, Humatrope) produced by recombinant DNA technology appear to make no significant difference in this clinical trial, and rhGH therapy is an effective and safe treatment for prepubertal GHD children.     

Laparoscopic cholangiography: a new technique for difficult cannulation

PURPOSE: To test the hypothesis that rejection could affect the contractility and contractile reserve of left ventricle after heart transplantation. METHODS: Echocardiographic parameters and noninvasive blood pressure end-systolic pressure (ESP), heart rate (HR), end diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), end-systolic stress (ESS) and the end-systolic relation (ESS/ESV) were recorded in 68 studies in 11 patients, seven days-12 months after heart transplantation. Accordingly with the endomyocardial biopsies results were divided into two groups: group A-with no rejection (53 studies), and group B-with rejection (15 studies). RESULTS: The nitroprusside infusion changed significantly and in the same way, all the parameters except the ESS/ESV ratio (A = 5.5 +/- 1.7 x B = 4.8 +/- 1.5 g/cm2/mL, p = NS); there was a decrease in ESP (A = 107 +/- 15 and B = 109 +/- 12 mmHg, p = NS), EDV (A = 68 +/- 19 and B = 81 +/- 12 mL, p = NS), ESV (A = 12 +/- 5 and B = 18 +/- 12 mL, p = NS) and ESS (A = 59 +/- 13 and B = 82 +/- 20g/cm2, p = NS); there was an increase in HR (A = 94 +/- 9 and B = 93 +/- 16bpm, p = NS) and EF (A = 83 +/- 5 and B = 79 +/- 8%, p = NS). In the dobutamine study it was observed differences for both groups, except for ESP (A = 156 +/- 26 and B = 149 +/- 26mmHg, p = NS). The increase in HR, EF and ESS/ESV ratio was greater in group A (HR-A = 117 +/- 19 and B = 102 +/- 25bpm, p < 0.05; EF-A = 91 +/- 4 and B = 78 +/- 11%, p < 0.05; ESS/ESV-A = 13.1 +/- 6 and B = 6.1 +/- 3.1 g/cm2/mL, p < 0.05). For group A it was smaller the EDV (57 +/- 18 x 94 +/- 35 mL, p < 0.05), ESV (5 +/- 3 x 24 +/- 20 mL, p < 0.05) and ESS (57 +/- 21 x 102 +/- 40 g/cm2, p < 0.05). CONCLUSION: Rejection may not induce changes in resting left ventricular contractility, however, the contractile reserve is depressed during an episode of moderate to severe rejection.     

Average length of spontaneous labor in Chinese primigravidas

The effect of long-term L-thyroxine (LT4) replacement therapy on bone mineral density and on biochemical markers of bone turnover were studied in children with congenital hypothyroidism (CH). Forty-four children and adolescents (mean age 8.5 +/- 3.5 years) with primary CH who began LT4 replacement therapy within the first month of life were studied. Bone mineral density (BMD) of the lumbar vertebrae and the upper femoral bone was measured by dual energy X-ray absorptiometry. Serum osteocalcin (OC) and bone alkaline phosphatase were measured as markers of bone formation and urinary deoxypyridinoline was taken as a marker of bone resorption. Bone mineral densities of CH children were not different from those in age-matched controls. The biochemical markers of bone turnover were normal except for the serum OC levels which were found to be higher than in controls and positively correlated with the free thyroid hormone levels (for FT4 r = 0.42, p = 0.02). Eight CH children demonstrated low BMD values (below -1 SDS) at -2 +/- 0.7 SDS for the lumbar spine and -1.6 +/- 0.5 SDS for the femoral site. These eight children showed lower mean weight (p < 0.05) and their dietary calcium intake tended to be less (p <0.06) than that seen in the normal BMD group. In conclusion, our results show that LT4 replacement therapy for 8 years is not detrimental to the skeletal mineralization of CH children. As in a healthy population, weight and current intake of calcium seem to be major determinants of bone density. Dietary recommendations, especially when calcium intake is below the recommended dietary allowance, may have to be reconsidered.     

Maintenance of bone mass in patients receiving dialytic therapy

To determine what factors contribute to and change bone mineral density (BMD) in dialysis patients, serial lumbar spine dual x-ray absorptiometry studies were analyzed by stepwise regression analysis in 67 black dialysis patients. The patients were 50.5 +/- 2.0 years of age (mean +/- SE) and 49% were men; the patients had received dialytic therapy for 3.7 +/- 0.5 years. The mean initial BMD z-score was 0.147 +/- 0.182. By cross-sectional analysis, the BMD increased in the male and premenopausal female patients but decreased in the postmenopausal female patients by 2.5% g/cm2/decade of life, less than that observed in black patients with normal renal function. Univariate analysis and stepwise regression analysis demonstrated radiographic evidence of osteopenia (beta-coefficient = -0.180 +/- 0.050; P = 0.001) and prior parathyroidectomy (beta-coefficient = 0.133 +/- 0.070; P = 0.054) as the only variables significantly correlated to the BMD. The effects of biochemical variables and different treatments on the delta BMD, calculated as the difference between each patient's first and second BMDs divided by the interval in years, were evaluated by stepwise regression analysis in 41 patients. The mean interval between the two BMDs was 18.4 +/- 1.02 months (range, 5 to 34 months) and the delta BMD was 0.025 +/- 0.018 g/cm2/yr, increasing in 65% of the patients. By univariate and stepwise regression analysis, the mean monthly serum total alkaline phosphatase concentration was the only variable that correlated with the delta BMD (beta-coefficient = 0.0001; P = 0.030).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transesophageal echocardiographic assessment of the contribution of intrinsic tissue thickness to the appearance of a thick mitral valve in patients with mitral valve prolapse

OBJECTIVES: This prospective, blinded transesophageal echocardiographic study was performed to determine the relative contributions of leaflet redundancy and overlap versus intrinsic tissue thickening as mechanisms for the apparent increase in diastolic thickness of the mitral valve. BACKGROUND: Increased diastolic thickness of the mitral valve has been identified as an echocardiographic feature that predicts subsequent adverse sequelae in patients with mitral valve prolapse (MVP). METHODS: Eleven patients with clinical and transthoracic echocardiographic evidence of MVP and 11 age-matched control subjects underwent protocol transesophageal echocardiography to image the mitral valve in two orthogonal planes and to measure its thickness in systole and diastole. RESULTS: Maximal diastolic width of the slack, unloaded anterior leaflet was significantly greater in patients with MVP than in control subjects (mean +/- SD: 0.64 +/- 0.20 cm vs. 0.30 +/- 0.04 cm, p < 0.001). Similarly, diastolic posterior leaflet width was greater in patients with MVP (0.67 +/- 0.39 cm vs. 0.31 +/- 0.06 cm, p < 0.01). In contrast, minimal systolic width of the distended pressure-loaded mitral valve was not significantly different between patients with MVP and control subjects for either the anterior (0.22 +/- 0.05 cm vs. 0.20 +/- 0.04 cm, p = NS) or the posterior (0.25 +/- 0.07 cm vs. 0.24 +/- 0.05 cm, p = NS) leaflets. The percent change in leaflet width from diastole to systole (% delta W), an index of the contribution of dynamic factors (e.g., leaflet redundancy and overlap) to the apparent increase in diastolic leaflet thickness, was significantly greater in patients with MVP than in control subjects for both the anterior (% delta W 62 +/- 13% vs. 34 +/- 16%, p < 0.001) and the posterior (% delta W 54 +/- 19% vs. 22 +/- 21%, p < 0.005) leaflets. CONCLUSIONS: The apparent increase in diastolic mitral leaflet thickness in patients with MVP versus control subjects is largely attributable to dynamic factors such as leaflet redundancy, overlap and deformation. During diastole, when the mitral leaflets are slack and unstressed, the leaflets appear markedly thickened in patients with MVP. In contrast, during systole, when developed intraventricular pressure distends the leaflets, causing them to stretch and balloon into the left atrium, the intrinsic tissue thickness is much less than that measured in diastole. These findings have important implications for the morphologic criteria used to diagnose MVP and the potential pathophysiologic mechanisms for adverse sequelae in this syndrome.     

Influence of spontaneous calcium intake and physical exercise on the vertebral and femoral bone mineral density of children and adolescents

Peak bone mass is determined mainly by genetic-ethnic factors, but environmental factors such as calcium intake and physical activity during childhood and adolescence could play a role. We have measured the bone mineral density (BMD) of 151 healthy children and adolescents, ages 7-15.3 years. Density was measured by dual X-ray absorptiometry (DXA) at two sites (lumbar verterbrae L1-L4 and the upper femur), and the data were analyzed in terms of the height, weight, sexual maturation, spontaneous calcium intake, and physical activity. Of the children, 57-71% had calcium intakes below 1000 mg/day. BMD increased with pubertal maturation from 0.68 +/- 0.08 to 0.92 +/- 0.09 g/cm2 (vertebral bone density, VBD) and from 0.87 +/- 0.10 to 1.03 +/- 0.09 g/cm2 (femoral bone density, FBD) between Tanner stage 1 and 5. Multiple regression analysis showed that body weight and Tanner stage were main determinants of bone density when expressed as g/cm2. The weekly duration of sports activity also influenced both the vertebral (p < 0.001) and femoral (p = 0.01) sites, especially in girls and during puberty. Dietary calcium appeared to be another independent determinant of BMD, especially before puberty, at the vertebral (p = 0.02) site. Most important, dietary calcium was found to be the main determinant of vertebral mineral density, when expressed as z score, in both sexes. Moreover, 93% of the 28 children with low vertebral z score values (below -1) and 84% of the 31 children with low femoral z score values (below -1) had dietary calcium intakes below 1000 mg/day.     

Elderly patients with adult-onset growth hormone deficiency are not osteopenic

The age-related decline in GH secretion has been implicated in the development of osteoporosis. GH-deficient adults show a significant reduction in bone mineral density (BMD), which is greater in those with childhood-onset GH deficiency than in those with GH deficiency occurring in adult life. To determine whether GH deficiency in late adult life causes a reduction in BMD beyond the decline observed with increasing age, we studied 21 patients over the age of 60 yr with GH deficiency caused by organic pituitary disease and 23 controls of similar age and sex distribution and BMI. Dual energy x-ray absorptiometry was used to determine total bone mass and BMD at the hip and in the lumbar spine. Serum osteocalcin was determined in all subjects and urinary deoxypyridinoline/creatinine ratio in 19 patients and 21 controls. The median (range) known duration of GH deficiency in the patients was 8 yr (range, 4-41 yr). The median (range) total bone mass was 2774 g (range, 1534-3734) in the patients and 2717 g (range, 1235-3549) in the controls (P = 0.42). Specific measurements of BMD made at L2-L4, the right femoral neck, the right femoral trochanter, and Ward's triangle were 1.234 (range, 0.778-1.507) vs. 1.144 g/cm2 (range, 0.809-1.466; P = 0.48), 0.921 (range, 0.605-1.372) vs. 0.96 g/cm2 (range, 0.534-1.315; P = 0.62), 0.92 (range, 0.523-1.229) vs. 0.915 g/cm2 (range, 0.353-1.313; P = 0.68), and 0.773 (range, 0.408-1.289) vs. 0.806 g/cm2 (range, 0.353-1.154; P = 0.81) in the patients and controls, respectively. The median (range) serum osteocalcin was 11.5 (range, 3.6-23.0) vs. 15.1 ng/mL (range, 0.7-40.5; P = 0.019) in the patients and controls, respectively. The median (range) deoxypyridinoline cross-links/creatinine ratio was 3.5 micromol/mol (range, 0.8-8.3) in the patients and 4.9 micromol/mol (range, 3.0-9.7) in the controls (P 0.038). There was a significant correlation between serum insulin-like growth factor I and total bone mass in the controls, but not in the patients. These data demonstrate that BMD is not significantly altered in GH-deficient adults over the age of 60 yr. Markers of bone formation and resorption are decreased, however, suggesting that bone turnover is reduced. Further studies are required to determine whether the reduction in bone turnover in these patients is of benefit.     

Normal growth hormone secretory reserve in men with idiopathic osteoporosis and reduced circulating levels of insulin-like growth factor-I

Many men with idiopathic osteoporosis have reduced circulating insulin-like growth factor-I (IGF-I) levels. The major source of circulating IGF-I is GH-mediated production by the liver. The known anabolic effects of GH on the skeleton raised the possibility of GH deficiency in these men. We sought to test this hypothesis in this study. Fourteen men (mean age, 52.1 +/- 3.2 yr, range 31-68) with idiopathic osteoporosis were studied. Mean lumbar spine bone mineral density (BMD) was 0.723 g/cm2, T score -3.5; femoral neck BMD was 0.642 g/cm2, T score, -3.07; distal (1/3) radius BMD was 0.708 g/cm2, T score, -2.05. Eleven of 14 (79%) had frank reductions in serum IGF-I levels compared with age and sex-matched values (158.5 +/- 50 SD vs. 180 +/- 45 SD). GH secretion was stimulated by iv arginine infusion (30 g) over 30 min followed 1 h later by oral L-dopa (500 mg). Serum GH was measured at time (t) = -15, 0, 30, 45, 60, 90, 120, 150, and 180 min. All patients responded to at least one stimulus with the majority (n = 9) responding to both. Five patients responded either to arginine or to L-dopa but not to both. Baseline GH for the entire group was 0.77 + 0.08 ng/mL (SEM). Peak GH following arginine (t = 45-60 min) was 14.0 +/- 2.8 ng/mL, a 17.7 +/- 2.8-fold rise. Peak GH following L-dopa (t = 120-180 min) was 5.7 +/- 1.0 ng/mL, a 9.2 +/- 2.2-fold rise. No difference in maximal secretion was observed between those with low or normal IGF-I levels. Neither IGF-I nor IGF binding protein-3 concentrations changed significantly during the short period of GH stimulation. These data suggest that men with osteoporosis and reduced IGF-I levels do not appear to have a deficiency in the GH axis. Other hormonal or local factors may be important in regulating IGF-I expression. Deficiencies of IGF-I production at skeletal sites may be important in the pathogenesis of this syndrome.