Denis Mariano-Goulart

Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state.

OBJECTIVE: To compare insulin sensitivity indexes derived from plasma insulin (I) and glucose (G) in the basal state (Sib) and at the second hour (I2h and G2h) of an oral glucose tolerance test (OGTT, Si2h) (i) with measurements of insulin sensitivity using the insulin modified frequently sampled intravenous glucose tolerance test (FSIVGTT) [Si(IVGTT)] and (ii) with modelling of fasting glucose and insulin by the homeostasis model assessment (HOMA).SUBJECTS: 47 subjects entered the study. 31 subjects were classified as having normal glucose tolerance (NGT), 10 as having impaired tolerance to glucose (IGT) and six as type 2 diabetes mellitus according to the World Health Organisation (WHO) criteria.MEASUREMENTS: Sib and Si2h were calculated as follows. Sib=108/(I×G×VD), Si2h=108/(I2hr×G2hr×VD) where VD is an estimate of the apparent glucose distribution volume. A third insulin sensitivity index (SiM) was calculated by averaging Sib and Si2h. HOMA was calculated as follows: I/(22.5×e−lnG)RESULTS: Si(IVGTT), Sib, SI2h and SiM were all significantly higher in subjects with NGT than in those with IGT or type 2 diabetes. Si(IVGTT) was highly correlated (P≤0.0001) with the three insulin sensitivity indexes found in the total population, in subjects with NGT and in those with IGT. In type 2 diabetic patients, a significant correlation was only noted when SiM was tested against Si(IVGTT) (P≤0.05). In most circumstances, the associations of Si(IVGTT) with Sib, SI2h and SiM were stronger than the corresponding associations with Ib, I2h or HOMA. SiM was the index that correlated best with Si(IVGTT) in the whole group (r=0.92, P<0.0001) as well as in NGT (r=0.86, P<0.0001), IGT (r=0.96; P<0.0001) and type 2 diabetes (r=0.83, P≤0.05) subgroups.CONCLUSIONS: Calculations of sensitivity indexes from G and I concentrations in the basal state and during a conventional 2 h OGTT appear to be useful for coupling in the same simple and single test both a determination of glucose tolerance and an estimate of insulin sensitivity.

Changes in Osteoprotegerin/RANKL System, Bone Mineral Density, and Bone Biochemicals Markers in Patients with Recent Spinal Cord Injury

This study analyzed the temporal and regional variations in bone loss and explored bone cell activities via biochemical markers during an extended follow-up in patients with spinal cord injury (SCI). In parallel, the possible role of the osteoprotegerin (OPG)/RANKL system in disuse osteoporosis was investigated. Seven male patients with acute and complete SCI (31.3 ± 9.5 years) and 12 able-bodied (AB) men (26.9 ± 4.2 years) participated in the study. Measurements were performed 16, 24, 36, 48, and 71 weeks after injury. At week 16, marked calcium homeostasis disturbance and a concomitant increase in bone resorption markers were observed, reflecting an intense bone degradation process. Resorption activity decreased continuously with time. Contrasting with the great rise in the resorption markers, the bone formation markers showed little variation. During the period of investigation, a loss in bone mineral density (BMD) was demonstrated for the total body (−4.3%), pelvis (−15.7%) and lower limbs (−15.2%), whereas BMD did not change at the lumbar spine, upper limbs, or skull. At all stages, SCI patients had lower serum RANKL levels and higher serum OPG levels than did AB controls, but no significant variation with time was observed for either cytokine. These findings suggest that bone resorption persisted long after SCI and specifically affected BMD at sublesional sites. The marked modification of serum OPG/RANKL levels in SCI patients suggests that this system is affected, in disuse osteoporosis. However, the precise biologic role of the OPG/RANKL system in the bone tissue of SCI patients has yet to be determined.

Effects of physical activities that induce moderate external loading on bone metabolism in male athletes

Sports characterized by little or moderate weight bearing or impact have a low osteogenic effect. However, the action of such sports on bone turnover remains unclear. The objective of this study was to determine the effect on bone remodelling of physical activities that induce moderate external loading on the skeleton. Thirty-eight male athletes aged 18–39 years (cyclists, n = 11; swimmers, n = 13; triathletes, n = 14) and 10 age-matched sedentary controls aged 22–35 years participated in the study. The study combined measurement of bone mineral density by dual-energy X-ray absorptiometry and bone turnover assessment from specific biochemical markers: serum bone-specific alkaline phosphatase, osteocalcin, urinary type I collagen C-telopeptide and calcium. Compared with the controls and swimmers, adjusted bone mineral density was higher (P < 0.05) in triathletes at the total proximal femur and lower limbs. No differences in bone mineral density were found between cyclists, swimmers and controls. Compared with controls, osteocalcin was higher (P < 0.05) in triathletes and swimmers and urinary type I collagen C-telopeptide was higher in swimmers only. Serum bone-specific alkaline phosphatase was lower (P < 0.05) in cyclists than in all other groups. In conclusion, an osteogenic effect was found only in triathletes, mainly at bone sites under high mechanical stress. Bone turnover differed in athletes compared with controls, suggesting that bone turnover may be sport-practice dependent. Despite some encouraging observations, it was not possible to show that changes in the bone remodelling process were sport-discipline dependent.

Major increase in brain natriuretic peptide indicates right ventricular systolic dysfunction in patients with heart failure.

This study sought to investigate whether the presence of right ventricular systolic dysfunction with pre‐existing left ventricular systolic dysfunction is associated with higher plasma brain natriuretic peptide (BNP) levels, compared with patients with isolated left ventricular dysfunction. Eighty‐five patients referred for evaluation of isotopic ventricular function were prospectively included in the study. Left (LVEF) and right (RVEF) ventricular ejection fractions were evaluated by gated blood pool scintigraphy and compared with plasma BNP levels. BNP correlated negatively with LVEF, except in patients with ischaemic heart disease (P=0.09) and in patients with LVEF<40% (P=0.11). In contrast, BNP levels correlated negatively with RVEF for all subgroups. Among patients with RVEF<40%, no significant BNP difference was found between patients with or without additional left ventricular systolic dysfunction (P=0.51). Among patients with LVEF<40%, plasma BNP levels were significantly higher in patients with RVEF<40% than in patients with RVEF≥40% (P=0.004) whereas age, renal function, clinical findings, ventricular volumes, LVEF or medication were not significantly different. In conclusion, an important increase in BNP levels in patients with left ventricular systolic dysfunction should be considered by cardiologists as an indication of high risk of right ventricular dysfunction and should justify further investigation.

Response of bone metabolism related hormones to a single session of strenuous exercise in active elderly subjects

Objective: To evaluate the effect of strenuous exercise on bone metabolism and related hormones in elderly subjects. Methods: Twenty one active elderly subjects (11 men and 10 women; mean age 73.3 years) showing a mean theoretical Vo2max of 151.4% participated. Concentrations of plasma ionised calcium (iCa), serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and 1.25-dihydroxy-vitamin D3 (1.25(OH)2D3), as well as the bone biochemical markers type I collagen C-telopeptide for bone resorption and osteocalcin and bone alkaline phosphatase for bone formation, were analysed before and after a maximal incremental exercise test. Results: At basal level, iPTH was positively correlated with age (r = 0.56, p<0.01) and negatively correlated with 25(OH)D (r = −0.50; p<0.01) and 1.25(OH)2D3 (r = −0.47; p<0.05). Moreover, 25(OH)D and 1.25(OH)2D3 levels were negatively correlated with age (r = −0.50, p<0.01 and r = −0.53, p<0.01, respectively). After exercise, iCa and 25(OH)D decreased (p<0.001 and p = 0.01, respectively) while iPTH increased (p<0.001). The levels of 1.25(OH)2D3, bone biochemical markers, haematocrit, and haemoglobin were unchanged. The variations in iCa and 25(OH)D were not related to age and/or sex. The iPTH variation was directly related to basal iPTH levels (p<0.01) and indirectly related to age. Conclusions: In active elderly subjects, strenuous exercise disturbed calcium homeostasis and bone related hormones without immediate measurable effect on bone turnover. Although an increase in iPTH could have an anabolic action on bone tissue, our findings from our short term study did not allow us to conclude that such action occurred.

Osteoporosis in Persons With Spinal Cord Injury: The Need for a Targeted Therapeutic Education

OBJECTIVES To identify circumstances surrounding the onset of fracture and common risk factors in persons with spinal cord injury (SCI) and to suggest an alternative or complement to the pharmacologic approach by evaluating the need for a prospective study based on the impact of a targeted therapeutic education on risk management of fractures in this population. DESIGN Retrospective study. SETTING Hospital and Rehabilitation Center Setting. PARTICIPANTS Women (n=7) and men (n=25; N=32; with ≥1 fracture after the initial SCI that occurred at home or in a hospital setting; mean ± SD age, 53±12y at the time of clinical review) with bone mineral density (BMD) measurements. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Demographics, main circumstances of onset, and complications of fractures, as well as transversal bone mineral density evaluation. RESULTS Nine patients had more than 1 fracture and 23 patients had only 1 fracture (total, 43 fractures; mean age at onset of fracture, 49±12y; median time since injury, 13.9y; mean delay in diagnosis, 6.5±15d). Fractures occurred mostly in the lower limbs. The circumstances of onset of these fractures were different and very stereotyped. In 3 cases, no trauma was reported. The most frequent mechanisms identified were forced maneuvers by the patient or a third party and falls. In 10 cases, the fracture occurred during a wheelchair transfer with forced maneuver or a fall from the wheelchair. Twenty-five patients were confined to bed after the fracture (mean duration of bed confinement, 18±28d; range, 0-120d). Postfracture follow-up showed that for 43 cases of fractures, 19 had at least 1 orthopedic complication, 15 had local complications, and 23 had general complications. Patients (23 of 32) benefited from dual-energy X-ray absorptiometry to assess BMD a few months or years after the fracture (mean femoral neck BMD, 0.574±0.197g/cm²; mean femoral neck T score, -3.8±1.5). CONCLUSION With this retrospective analysis of common risk factors and circumstances of onset of secondary fractures, there is a clear future for a prospective study to evaluate the impact of targeted therapeutic education on risk factors for secondary fractures in patients with SCI.

Appendicular skeletal muscle mass is the strongest independent factor associated with femoral neck bone mineral density in adult and older men.

The relationship between bone mass and muscle mass may be due to the site-specific effects of loading on bone in adults and to lifestyle, nutritional, and hormonal factors. Another hypothesis is that the maintenance with aging of both appendicular muscle and bone mass may be determined by factors independent of all these previous factors, including genetic factors. In 160 healthy men aged 20 to 72years, we recorded femoral neck bone mineral density (FN BMD), relative appendicular skeletal muscle mass [RASM; appendicular skeletal muscle mass (kg)/height (cm)], age, body mass, maximum grip and knee extension strength, lifetime physical activities, calcium intake, tobacco smoking, and serum parathyroid hormone (PTH), estradiol (E2), free testosterone, dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor (IGF-I), sex hormone-binding globulin (SHBG), calcium, 25(OH) vitamin D, albumin, and creatinine clearance. The correlation between FN BMD and RASM (that includes upper and lower limb muscle mass) was of slightly greater magnitude than that between FN BMD and the relative upper limb muscle mass and between FN BMD and the relative leg muscle mass (r=0.39; p< or =0.001 versus r=0.36; p< or =0.001 and r=0.34; p< or =0.001, respectively). The stepwise multiple linear regression model showed that FN BMD was significantly associated with RASM (15% of FN BMD variance, p<0.0001), age (10% of FN BMD variance, p<0.0001), physical activities from age 11-20years (5% of FN BMD variance, p<0.01), and blood PTH, IGF-I, and creatinine clearance, (2%, 2%, and 1% of FN BMD variance, respectively, p<0.05). These results show that RASM, with ASM measured by DXA, is the strongest factor associated with FN BMD in men. It remains to be determined whether assessing RASM by anthropometric methods would help screening adult men at risk of low FN BMD. Furthermore, since RASM is associated with FN BMD independently of appendicular skeletal loads and other lifestyle, nutritional, and hormonal factors, this suggests that common factors, possibly genetic factors, might also influence the coupled maintenance of appendicular muscle mass and FN BMD in adult men.

Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.

OBJECTIVE Intensive physical training may have a sport-dependent effect on bone mass acquisition. This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone. MATERIALS/METHODS Eighty girls from 10.7 to 18.0 years old (mean 13.83 ± 1.97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity <3h/wk). Areal bone mineral density (aBMD) was determined using DEXA. Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm(2)), section modulus (Z, cm(3)), and buckling ratio. Bone turnover markers and OPG/RANKL levels were analyzed. RESULTS AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius. RG had higher aBMD than SW and CON only in the femoral region. CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON. In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON. Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status. All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW. CONCLUSION High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche.

A comparative study of Powell's and Downhill simplex algorithms for a fast multimodal surface matching in brain imaging

Multimodal images registration can be very helpful for diagnostic applications. However, even if a lot of registration algorithms exist, only a few really work in clinical routines. We developed a method based on surface matching and compared two minimization algorithms: Powells and Downhill Simplex. We studied the influence of some factors (chamfer map computation, number and order of parameters to determine, minimization criteria) on the final accuracy of the algorithm. Using this comparison, we improved some processing steps to allow a clinical use, and selected the simplex algorithm which presented the best results.

SPECT Myocardial Perfusion Reserve in Patients with Multivessel Coronary Disease: Correlation with Angiographic Findings and Invasive Fractional Flow Reserve Measurements

Quantification of myocardial perfusion reserve (MPR) is an emerging topic in nuclear cardiology with an expected diagnostic and prognostic incremental value, especially for patients with severe coronary artery disease. The advent of new dedicated solid-state cameras has opened new perspectives for perfusion quantitation in SPECT. We appraised the feasibility of perfusion reserve estimation using a cadmium zinc telluride camera in a cohort of multivessel patients and its pertinence with respect to angiographic data. Methods: Twenty-three patients with known multivessel coronary artery disease were prospectively enrolled. Dynamic SPECT acquisitions using 99mTc-tetrofosmin at rest and after vasodilator stress were performed using a dedicated cadmium zinc telluride camera. Reconstructed frames were automatically segmented to extract the vascular input function and the myocardial uptake curve. One-compartment kinetic modeling was used to estimate global and regional uptake values, and then myocardial blood flow was derived using the Renkin–Crone equation. Global and regional MPR was assessed using flow difference (stress − rest) and flow ratio (stress/rest). All patients underwent control coronary angiography within 4 wk, which served as the reference for MPR index assessment. Relevant angiographic findings included maximal stenosis and (for a subgroup of 26 vessels) invasive measurement of fractional flow reserve (FFR). A stenosis was considered obstructive if greater than 50% and an FFR abnormal if lower than 0.8. Results: Global MPR correlated well with number of obstructed vessels (P < 0.001). After multivariate analysis, both regional flow ratio and flow difference were significantly associated with maximal stenosis (P < 0.001) and FFR (P < 0.001). Regional MPR indices were significantly different in obstructed and nonobstructed vessels (P < 0.001) and in vessels with normal and abnormal FFR (P < 0.001). With a cutoff of 2, the sensitivity, specificity, and accuracy of regional flow ratio were, respectively, 80%, 85%, and 81% for the detection of obstructed vessels and 89%, 82%, and 85% for the detection of abnormal FFR. Conclusion: Scintigraphic estimations of global and regional MPR in multivessel patients using a cadmium zinc telluride camera appear to correlate well with invasive angiographic findings, including maximal stenosis and FFR measurements.