Transesophageal echocardiography-guided cardioversion of atrial fibrillation. Selection of a low-risk group for immediate cardioversion.

INTRODUCTION: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec. METHODS AND RESULTS: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01). CONCLUSION: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.     

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.     

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.     

p53 and skin carcinomas with skull base invasion: a case-control study.

BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b.     

Stability of risk factors for cardiovascular diseases in Portuguese children and adolescents from the Porto area.

An important aspect of preventive medicine is to identify subjects at risk as soon as possible, so preventive strategies can be introduced at early ages. The justification for this strategy is twofold: firstly, the assumption that children maintain a particular high value of a risk factor for disease throughout life; and secondly, the assumption that lowering the level of the risk factor in early life will have a greater impact on the disease than will risk factor changes in later life. In epidemiology the analysis of such factors over time is referred to as tracking. Tracking analysis has been applied to risk factors for cardiovascular diseases (CVD) in pediatric years. The aims of this study were: I) to analyze the stability of biological risk factors [high blood pressure (BP), high percentage of fat mass (%FM) and high total cholesterol (TC)] and lifestyle risk factors [low physical activity index (PAI)] in isolation; and II) to analyze the stability of zero, one, two or three biological risk factors. There were two evaluations in 692 children and adolescents (325 boys and 367 girls), aged between 8 and 15 years. The quartiles, adjusted for age and gender, were the criterion used to identify subjects with biological risk factors (fourth quartile) and with lifestyle risk factors (first quartile) for CVD. The stability was calculated through the relative frequency of subjects who maintained or changed quartile between the two evaluations. There is stability for biological risk factors as well as for behavioral and/or lifestyle risk factors. However, the highest stability is seen in biological risk factors.