Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. INTRODUCTION: Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. MATERIALS AND METHODS: BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. RESULTS: Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to fracture risk. CONCLUSIONS: Girls with fractures have decreased bone mass gain in the axial and appendicular skeleton and reduced vertebral bone size when reaching pubertal maturity. Taken together with the evidence of tracking and heritability for BMC, these observations indicate that childhood fractures may be markers for low peak bone mass and persistent bone fragility.     

Pulmonary embolism.

Pulmonary embolism (PE) is an important health problem and often a major clinical challenge, not only because of the low specificity of its clinical manifestations but also because of the increasing number of medical circumstances that are risk factors for this illness and the importance of early identification, since prompt and appropriate treatment can decrease mortality from this disease by about 25%. In recent years research on PE has been extensive, directed mainly at trying to determine and characterize its risk factors, establish new clinical probability algorithms, develop new diagnostic methods and put existing ones into perspective, seek new therapeutic approaches (pharmacological and non-pharmacological), and above all establish protocols that can guide the clinician from the stage of clinical suspicion to measures to prevent recurrence. It was the authors' aim to review the most significant literature on this subject, in order to produce a text that reflects the state of the art concerning PE and that can be used as a guide in the clinical approach to this pathology.     

Preliminary evaluation of a fuzzy logic-based automatic quantitative analysis in myocardial SPECT.

This study validates a new quantitative myocardial perfusion SPECT software. METHODS: The processing starts with the extraction of the morphologic skeleton of the left ventricular myocardium from reconstructed transverse sections. Fuzzy logic is used to decide whether a pixel belongs to the myocardium and any perfusion defect is filled according to a truncated bullet model. The resulting image is partitioned in 18 isovolumetric sectors. Sex-matched normal limits, criteria of abnormality for rest (201)Tl and (99m)Tc-labeled perfusion tracers, reproducibility studies, and detection of coronary artery disease were developed and validated in an overall population of 343 patients. The sex- and tracer-matched means and SDs of a normal response were calculated in 93 male and 93 female patients with a <5% likelihood of coronary artery disease. Reproducibility measurements and assignment of different sectors of the myocardium to a specific coronary were performed from data collected in 49 and 60 patients, respectively. The accuracy of the detection of a coronary artery occlusion was assessed in 48 patients who also underwent coronary angiography. RESULTS: The intra- and interoperator reproducibility of the sectorial activity was high with a linear regression coefficient of 0.97 and a SD of the difference measurement at 4.4% and 3.8%, respectively. Overall sensitivity and specificity for the detection of occluded coronary artery were 90% and 80%, respectively. For the detection of left anterior descending, left circumflex, and right artery coronary occlusion, sensitivity was 92%, 75%, and 92.5%, respectively, and specificity was 75%, 78%, and 90%, respectively. CONCLUSION: The new quantitative myocardial perfusion SPECT software appears to be a very helpful program for the objective analysis of perfusion tracer distribution in myocardial SPECT and a very accurate tool in the detection and localization of coronary artery occlusion.     

Reconstruction of upper digestive tract: reducing morbidity by laparoscopic pull-up.

BACKGROUND: Gastric pull-up is a useful method for reconstruction of the upper digestive tract, with considerable morbidity/mortality, especially in esophageal cancers (EC). OBJECTIVE: To analyze the experience of a multidisciplinary team with a laparoscopic gastric pull-up (LGPU) method, with or without thoracoscopy, in a series of 120 patients with EC. STUDY DESIGN: Retrospective. PATIENTS AND METHODS: From 1992 to 2004, 120 EC [cervical/cervicothoracic (3.0%), middle third (15.0%), and inferior third (82.0%)]. Most were squamous cell carcinomas (47.0%) and adenocarcinomas (34.0%). Stomach was dissected and mobilized exclusively by laparoscopy. Occasionally, laparoscopic approach was extended cranially, until connecting with cervical dissection. In other cases, dissection of thoracic esophagus was accomplished through a thoracoscopic approach. RESULTS: Eighty-one patients (68.0%) had LGPU; 39 (32.0%) needed thoracoscopy. Mortality was 5.9%. Complications were fistula (10.0%) and pneumonia (10.0%). All fistulae closed spontaneously; 89.2% of patients could swallow a normal oral diet. CONCLUSION: Low morbidity/mortality of LGPU for EC compared favorably with conventional techniques.     

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

Evidence that peroxynitrite affects human osteoblast proliferation and differentiation.

Peroxynitrite (PN), a nitric oxide (NO*)-derived anion, has been associated with NO* damage in various cell types. We examined the effects of adding PN to cultured human osteoblast-like (hOB) cells obtained after hip arthroplasty. Exposure to PN (0.1-0.4 mM) decreased both hOB proliferation and differentiation, measured by [3H]thymidine uptake and alkaline phosphatase production, respectively. Incubation with 3-morpholinosydnonimine (SIN-1; 0.25-1 mM), an NO* and O2- donor that leads to PN release, also reduced both hOB proliferation and differentiation. Coincubation with both superoxide dismutase (SOD; 100 U/ml) and catalase (CAT; 50 U/ml), rendering SIN-1 a pure NO* donor, reversed its effects on hOB proliferation and differentiation. However, SIN-1-induced NO* production, measured by nitrite release to the hOB medium, was not altered by cotreatment with SOD and CAT. Expression of nitrotyrosine by hOB, a marker of PN action, was significantly increased after SIN-1 addition, as compared with untreated cells, as revealed by Western blot analysis. Interleukin-1alpha (IL-1alpha) and interferon gamma (IFN-gamma) but not tumor necrosis factor alpha (TNF-alpha) also significantly increased nitrotyrosine expression in these cells. These data show that PN is at least partially responsible for osteoblast derangement by NO* and that cytokines released during inflammatory arthropathies can induce PN production in hOB cells.     

Heparin effect on ionised calcium concentration

The effect of heparin on plasma ionised calcium was studied by adding it in increasing amounts to whole blood from 10 normal subjects. There was no significant change in ionised calcium from the addition of 1 U/ml but a significant fall of 0.02 mmol/1 when 2 U/ml were added and a progressive further fall with increasing concentrations. Heparin from three different manufacturers produced similar results. The effect of heparinisation in vivo was studied during regular haemodialysis on 10 patients with chronic renal failure. Following intravenous injection of 10000 U of heparin there was a consistent and significant fall averaging 0.03 mmol/l.