The improvement of care for paediatric and congenital cardiac disease across the World: a challenge for the World Society for Pediatric and Congenital Heart Surgery

The diagnosis and treatment for paediatric and congenital cardiac disease has undergone remarkable progress over the last 60 years. Unfortunately, this progress has been largely limited to the developed world. Yet every year approximately 90% of the more than 1,000,000 children who are born with congenital cardiac disease across the world receive either suboptimal care or are totally denied care. While in the developed world the focus has changed from an effort to decrease post-operative mortality to now improving quality of life and decreasing morbidity, which the focus of this Supplement, the rest of the world still needs to develop basic access to congenital cardiac care. The World Society for Pediatric and Congenital Heart Surgery [http://www.wspchs.org/] was established in 2006. The Vision of the World Society is that every child born anywhere in the world with a congenital heart defect should have access to appropriate medical and surgical care. The Mission of the World Society is to promote the highest quality comprehensive care to all patients with pediatric and/or congenital heart disease, from the fetus to the adult, regardless of the patient`s economic means, with emphasis on excellence in education, research and community service. We present in this article an overview of the epidemiology of congenital cardiac disease, the current and future challenges to improve care in the developed and developing world, the impact of the globalization of cardiac surgery, and the role that the World Society should play. The World Society for Pediatric and Congenital Heart Surgery is in a unique position to influence and truly improve the global care of children and adults with congenital cardiac disease throughout the world [http://www.wspchs.org/].

Comparison of MB fraction of creatine kinase mass and troponin I serum levels with necropsy findings in acute myocardial infarction

Serum levels of troponin and heart-related fraction of creatine kinase (CK-MB) mass are used as diagnostic and prognostic criteria in myocardial infarction, but the relation between those levels and-the necropsy-determined size of necrosis has not been tested in human beings. In this retrospective study, 1-cm-thick transverse sections of the ventricles were cut from the base to the apex in the necropsy hearts of 27 patients aged 47 to 86 years (mean 66, median 69; 19 men). Total and necrotic areas were measured using a computer-linked image analysis system. The weights of the necrotic areas were also calculated. The correlations of the areas and weights of necrotic myocardium with the highest serum values of CK-MB mass and troponin 1, which had been quantified during life by chemiluminescence immunoassays, were verified by Pearson`s test; results were considered significant at p <= 50.05. Significant correlations were detected between CK-MB mass peak and infarct size (r = 0.63, p < 0.01) and weight (r = 0.69, p < 0.01) and between CK-MB mass and highest troponin level (r = 0.73, p < 0.01); however, the correlations between highest troponin level and myocardial infarct size (r = 0.31, p = 0.11) and weight (r = 0.35, p = 0.07) were small and nonsignificant. In conclusion, despite the well-established role of serum levels of troponin as a diagnostic tool for myocardial infarction, their highest values showed poor correlations with the extent of infarct. In contrast, the highest serum level of CK-MB mass was well correlated with myocardial infarct size. (c) 2008 Elsevier Inc. All rights reserved.

Low-intensity Treadmill Exercise-related Changes in the Rat Stellate Ganglion Neurons

Stellate ganglion (SG) represents the main sympathetic input to the heart. This study aimed at investigating physical exercise-related changes in the quantitative aspects of SG neurons in treadmill-exercised Wistar rats. By applying state-of-the-art design-based stereology, the SG volume, total number of SG neurons, mean perikaryal volume of SG neurons, and the total volume of neurons in the whole SG have been examined. Arterial pressure and heart rate were also measured at the end of the exercise period. The present study showed that a low-intensity exercise training program caused a 12% decrease in the heart rate of trained rats. In contrast, there were no effects on systolic pressure, diastolic pressure, or mean arterial pressure. As to quantitative changes related to physical exercise, the main findings were a 21% increase in the fractional volume occupied by neurons in the SG, and an 83% increase in the mean perikaryal volume of SG neurons in treadmill-trained rats, which shows a remarkable neuron hypertrophy. It seems reasonable to infer that neuron hypertrophy may have been the result of a functional overload imposed on the SG neurons by initial posttraining sympathetic activation. From the novel stereological data we provide, further investigations are needed to shed light on the mechanistic aspect of neuron hypertrophy: what role does neuron hypertrophy play? Could neuron hypertrophy be assigned to the functional overload induced by physical exercise? (C) 2008 Wiley-Liss, Inc.

Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan

Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, long-lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in larger-bodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16(Ink4a) and p21(Cip1/Waf1) cycline-dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro. Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms.

Healing of critical-size cranial defects in guinea pigs using a bovine bone-derived resorbable membrane

Purpose: To investigate the healing of critical-size cranial bone defects (9-mm-diameter) in guinea pigs treated with a bovine bone-derived resorbable membrane. Materials and Methods: A sample of 42 guinea pigs was divided into test (n = 20), control (n = 20), and standard (n = 2) groups. A full-thickness trephine defect was made in the fronto-parietal bone of each animal. In the test group, the internal and external openings of the defect were each closed with a separate membrane, and the space between them was filled with blood clot and a central spacer. In the control group, the defect was filled only with the blood clot and spacer. At 1, 3, 6, and 9 months later, the calvarias (5 per period) for both the test and control groups were collected, fixed, radiographed, and histologically processed. The Standard-group animals were sacrificed immediately after surgery and used to determine the initial size of defect radiographically. The areas of defects in the radiographs were measured with image-analysis software and were compared between groups and periods by multiple regression analysis with the Bonferroni correction. Results: At 1 and 3 months, newly formed woven bone was histologically observed in both test and control groups. Radiographically, this new bone occupied an average of 32% of the defect area at 1 month and 60% at 3 months in the test group. In the control group, 21% of the defect was filled at 1 month and 39% at 3 months. However, the differences between treatments were not statistically significant (P > .05). At 6 and 9 months, a significant increase in newly formed lamellar bone was seen histologically in both groups. Radiographically, for the test group, the new bone occupied an average of 82% of the defect area at 6 months and 96% at 9 months. For the control group, new bone composed an average of 45% of the defect area at 6 months and 40% at 9 months. The differences between the test and control groups were statistically significant at 6 and 9 months (P < .05). Complete or almost complete filling of the defect was observed in several cases. Conclusion: It was concluded that the bovine bone-derived membrane is highly biocompatible and is able to promote good healing of critical-size defects in calvaria of guinea pig.

Biological monitoring of a xenomaterial for grafting: an evaluation in critical-size calvarial defects

Our purpose was to evaluate the osteoconduction potential of mixed bovine bone (MBB) xenografts as an alternative for bone grafting of critical-size defects in the calvaria of rats. After surgery, in the time intervals of 1, 3, 6, and 9 months, rats were killed and their skulls collected, radiographed and histologically prepared for analysis. The data obtained from histological analysis reported that the particles of MBB did not promote an intense immunological response, evidencing its biocompatibility in rats. Our results clearly showed the interesting evidence that MBB was not completely reabsorbed at 9 months while a small amount of newly formed bone was deposited by osteoprogenitor cells bordering the defect. However, this discrete bone-forming stimulation was unable to regenerate the bone defect. Overall, our results suggest that the properties of MBB are not suitable for stimulating intense bone regeneration in critical bone defects in rats.

Morphometric evaluation of the repair of critical-size defects using demineralized bovine bone and autogenous bone grafts in rat calvaria

Objective: To evaluate the repair of critical-size bone defects in rats treated with demineralized bovine bone (DBB) compared with autogenous bone (AB). Material and method: A bone defect of 8 mm in diameter was created in the calvaria of 50 Rattus norvegicus, treated either with DBB or AB. Sub-groups of five rats of each group were killed at 7, 14, 21, 30 and 90 days post-operatively, and the skulls were removed and processed histologically. Histological sections were stained with hematoxylin and eosin. Result: Histological analysis showed complete closure of the defects with new bone at 90 days in group AB, and substitution of the biomaterial by fibrotic connective tissue in the DBB group at 21 days. Morphometric analysis showed that DBB was rapidly absorbed at 14 days, with its volume density decreasing from 47%+/- 0.8% at 7 days to 1.2%+/- 0.41% at 14 days. Subsequently, volume densities of the connective tissue and neoformed bone increased from 51.1%+/- 11.17% to 86.8%+/- 7.92% and from 1.9%+/- 1.13% to 12%+/- 8.02%, respectively, for the same time interval. The volume density of AB particles did not change throughout the experimental periods, but the amount of new bone increased markedly between 7 and 90 days, from 4.5%+/- 1.57% to 53.5%+/- 6.42% (P < 0.05). Conclusion: DBB did not provide complete repair of the defects, with significantly less new bone formation than in the AB group.