Ki-67 expression in non-tumour epithelium adjacent to oral cancer as risk marker for multiple oral tumours

Objective: The aim of this study was to determine whether the differential assessment of epithelial proliferation is useful to diagnose premalignant fields and assess the risk of multiple tumours. Material and methods: We analysed 83 oral carcinomas with associated non-tumour epithelium classified as distant or close according to its distance (> or < 1 cm) from the invasion point, and as squamous hyperplasia, mild, moderate, severe dysplasia or carcinoma in situ. Twenty-five healthy oral mucosa samples were used as controls. An immunohistochemical technique was applied using Mib-1. Ki-67 in premalignant epithelium was assessed in basal layer, parabasal layer, medium and upper third. Results: Parabasal expression was significantly higher or showed a tendency to be higher in close and distant epithelia with any histological grade than in the controls. Parabasal Ki-67 significantly differed between distant epithelia associated with multiple vs single tumours (P < 0.001) and between distant epithelia associated with multiple tumours vs controls (P < 0.001). This difference was not observed between distant epithelia associated with single tumours and controls (P = 0.175). The cut-off point that differentiated epithelia associated with multiple tumours was > 50% of Ki-67 + parabasal cells in distant epithelia, which yielded 0.88 sensitivity and 0.79 specificity. Conclusions: The concept of a precancerous field may be linked to an increase in the proliferative activity of parabasal cells.

Association between breastfeeding duration and non-nutritive sucking habits

Objective To evaluate the relationship between breastfeeding duration and the prevalence of non-nutritive Sucking habits in children with deciduous dentition. Method A cross-sectional survey was conducted on the mothers of 551 children aged 3 to 6 years, randomly selected from public pre-schools in Sao Paulo, Brazil. Mothers were asked to complete a questionnaire that included items regarding their children`s age, gender, race, method and duration of infant feeding, as well as pacifier use and/or digit-sucking habits. According to the answers pertinent to the method and duration of infant feeding, children were assigned to five groups: 1 - never breastfed, 2 - breastfed for a period shorter than 3 months of life, 3 - breastfed for 3 to 6 months, 4 - breastfed for 6 to 9 months, and 5 - breastfed for 9 months or longer. Data were submitted to the Fisher`s exact test with Bonferroni correction for multiple comparisons to analyse possible associations between breastfeeding duration period categories and non-nutritive sucking behaviours. Results Pacifier use frequency was high in groups 1, 2, 3 and 4 (85%, 87.6%, 78% and 70%, respectively), in comparison with that in group 5 (38.6%). The prevalence of non-nutritive sucking habits was significantly reduced in children who were breastfed for nine months or longer (p=0.000). There were no statistically significant differences in the frequencies of pacifier use and/or digit-sucking habits between genders, regardless of the breastfeeding duration period. Conclusion Children aged 3-6 years who were breastfed for nine months or longer had a lower prevalence of non-nutritive sucking habits.

Metalloproteinase inhibition protects against cardiomyocyte injury during experimental acute pulmonary thromboembolism

Objectives: Up-regulated matrix metalloproteinases may be involved in the development of cardiomyocyte injury and the degradation of troponin associated with acute pulmonary thromboembolism. We examined whether pretreatment with doxycycline (a nonspecific matrix metalloproteinase inhibitor) protects against cardiomyocyte injury associated with acute pulmonary thromboembolism. Design: Controlled animal study. Setting: University research laboratory. Subjects: Mongrel dogs. Interventions: Anesthetized animals received doxycycline (10 mg/kg intravenously) or saline and acute pulmonary thromboembolism was induced with autologous blood clots injected into the right atrium. Control animals received doxycycline (or saline). Measurements and Main Results: Hemodynamic measurements were performed, and acute pulmonary thromboembolism increased baseline mean pulmonary arterial pressure and pulmonary vascular resistance by approximately 160% and 362%, respectively (both p<.05), 120 mins after acute pulmonary thromboembolism. Pretreatment with doxycycline attenuated these increases (to 125% and 232%, respectively; both p<.05). Although acute pulmonary thromboembolism tended to increase the right ventricle maximum rate of isovolumic pressure development and the maximum rate of isovolumic pressure decay, doxycycline produced no effects on these parameters. Gelatin zymograms of right ventricle showed that acute pulmonary thromboembolism marginally increased matrix metalloproteinase-9 (but not matrix metalloproteinase-2) levels in the right ventricle. A fluorometric assay to assess net matrix metalloproteinase activities showed that acute pulmonary thromboembolism increased matrix metalloproteinase activities in the right ventricle by >100% (p<.05), and this finding was confirmed by in situ zymography of the right ventricle. Doxycycline attenuated acute pulmonary thromboembolism-induced increases in right ventricle matrix metalloproteinase activities. Acute pulmonary thromboembolism induced neutrophil accumulation in the right ventricle, as estimated by myeloperoxidase activity, and doxycycline blunted this effect (p<.05). Serum cardiac troponin I concentrations, which reflect cardiomyocyte injury, increased after acute pulmonary thromboembolism, and this increase was attenuated by pretreatment with doxycycline (p<.05). Conclusions: We found evidence supporting the idea that acute pulmonary thromboembolism is associated with increased matrix metalloproteinase activities in the right ventricle, which may lead to degradation of sarcomeric proteins, including cardiac troponin I. Inhibition of matrix metalloproteinases may be an effective therapeutic intervention in the management of acute pulmonary thromboembolism. (Crit Care Med 2011; 39: 349-356)

Developmental changes of gene expression after spinal cord injury in neonatal opossums

Changes in gene expression have been measured 24 h after injury to mammalian spinal cords that can and cannot regenerate In opossums there is a critical period of development when regeneration stops being possible at 9 days postnatal cervical spinal cords regenerate, at 12 days they do not By the use of marsupial cDNA microarrays we detected 158 genes that respond differentially to injury at the two ages critical for regeneration For selected candidates additional measurements were made by real time PCR and sites of their expression were shown by immunostaining Candidate genes have been classified so as to select those that promote or prevent regeneration Up regulated by injury at 8 days and/or down regulated by injury at 13 days were genes known to promote growth, such as Mitogen activated protein kinase kinase 1 or transcripton factor TCF7L2 By contrast, at 13 days up regulation occurred of Inhibitory molecules including annexins ephrins and genes related to apoptosis and neurodegeneranve diseases Certain genes such as calmodulin 1 and NOGO changed expression similarly in animals that could and could not regenerate without any additional changes in response to injury These findings confirmed and extended changes of gene expression found in earlier screens on 9 and 12 day preparations without lesions and provide a comprehensive list of genes that serve as a basis for testing how identified molecules singly or in combination, promote and prevent central nervous system regeneration (C) 2010 Elsevier B V All rights reserved

A simple, inexpensive and easily reproducible model of spinal cord injury in mice: Morphological and functional assessment

Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance, and significantly impacts life expectancy and quality. Animal models provide a good opportunity to test therapeutic strategies in vivo. C57BL/6 mice were subjected to laminectomy at T9 and compression with a vascular clip (30 g force, 1 min). Two groups were analyzed: injured group (SCI, n = 33) and laminectomy only (Sham, n = 15). Locomotor behavior (Basso mouse scale-BMS and global mobility) was assessed weekly. Morphological analyses were performed by LM and EM. The Sham group did not show any morphofunctional alteration. All SCI animals showed flaccid paralysis 24 h after injury. with subsequent improvement. The BMS score of the SCI group improved until the intermediate phase (2.037 +/- 1.198): the Sham animals maintained the highest BMS score (8.981 +/- 0.056). p < 0.001 during the entire time. The locomotor speed was slower in the SCI animals (5.581 +/- 0.871) than in the Sham animals (15.80 +/- 1.166), p < 0.001. Morphological analysis of the SCI group showed, in the acute phase, edema, hemorrhage, multiple cavities, fiber degeneration, cell death and demyelination. In the chronic phase we observed glial scarring, neuron death, and remyelination of spared axons by oligodendrocytes and Schwann cells. In conclusion, we established a simple, reliable, and inexpensive clip compression model in mice, with functional and morphological reproducibility and good validity. The availability of producing reliable injuries with appropriate outcome measures represents great potential for studies involving cellular mechanisms of primary injury and repair after traumatic SCI. (C) 2008 Elsevier B.V. All rights reserved.

An in vitro study of non-axial forces upon the retention of an O-ring attachment

Objective The purpose of this study was to evaluate the retention force of an O-ring attachment system in different inclinations to the ideal path of insertion, using devices to compensate angulations. Material and methods Two implants were inserted into an aluminum base, and ball attachments were screwed to implants. Cylinders with O-rings were placed on ball attachments and connected to the test device using positioners to compensate implant angulations (0 degrees, 7 degrees, and 14 degrees). Plexiglass bases were used to simulate implant angulations. The base and the test device were positioned in a testing apparatus, which simulated insertion/removal of an overdenture. A total of 2900 cycles, simulating 2 years of overdenture use, were performed and 36 O-rings were tested. The force required for each cycle was recorded with computer software. Longitudinal sections of ball attachment-positioner-cylinder with O-rings of each angulation were obtained to analyze the relationship among them, and O-ring sections tested in each angulation were compared with an unused counterpart. A mixed linear model was used to analyze the data, and the comparison was performed by orthogonal contrasts (alpha=0.05). Results At 0 degrees, the retention force decreased significantly over time, and the retention force was significantly different in all comparisons, except from 12 to 18 months. When the implants were positioned at 7 degrees, the retention force was statistically different at 0 and 24 months. At 14 degrees, significant differences were found from 6 and 12 to 24 months. Conclusions Within the limitations of this study, it was concluded that O-rings for implant/attachments perpendicular to the occlusal plane were adequately retentive over the first year and that the retentive capacity of O-ring was affected by implant inclinations despite the proposed positioners. To cite this article:Rodrigues RCS, Faria ACL, Macedo AP, Sartori IAM, de Mattos MGC, Ribeiro RF. An in vitro study of non-axial forces upon the retention of an O-ring attachment.Clin. Oral Impl. Res. 20, 2009; 1314-1319.doi: 10.1111/j.1600-0501.2009.01742.x.

Injury and alcohol: a hospital emergency department study

A pilot survey was undertaken of injury presentations to a public hospital emergency department to determine patterns of alcohol use in this population. Of the 402 injury presentations in the study period, a total of 236 injury cases were interviewed, of whom 45% (n=107) and 29% (n=69) had consumed alcohol 24 and 6 hours prior to injury. Mean age for all injury presentations was 35.1 years, and 32.6 years for alcohol injury cases. For both injury groups, males were significantly younger than females. Recent alcohol ingestion was three times more common among male than female injury presentations, but with females drinking at significantly lower levels. Of males who had consumed alcohol 6 hours prior to injury, nearly 70% were drinking at NHMRC harmful levels and 61% had drunk more than eight standard drinks. Overall, alcohol-involved injury cases commonly occurred among low-income, single males around 30 years of age who were regular heavy drinkers who were drinking heavily in licensed premises prior to their injury, and who sustained injury through intentional harm. In addition, one in five of the alcohol-involved injury cases were aged 15-18 years, i.e. below the legal age of purchase. The high proportion of hazardous and harmful drinkers among those who had consumed alcohol within the last 6 hours, and the injury sample overall, highlights the need for further research to explore the relationship between the occurrence of injury and the drinking patterns and environments associated with injury. Further research is also required to assess the efficacy of early and brief interventions for alcohol and drug use within the emergency ward setting. This information would enable appropriate public health interventions to be initiated.

Resting energy expenditure of children attending a rehabilitation programme following head injury

Statement of purpose: Increased resting energy expenditure following head injury is well documented, but whether this increase extends into rehabilitation and whether this is affected by changes in body composition have not been studied. The aim of this study was to determine whether children attending a rehabilitation program following head injury had altered energy expenditure and body composition. Methods: Measurements of resting energy expenditure by indirect calorimetry were performed in 21 head injured children (mean age 10.2±3.8 years). Measurement of body composition was performed using total body potassium. Results: Measured resting energy expenditure values were widely distributed, ranging from 52.3-156.4% of predicted values, yet the mean percentage predicted using Schofield weight, Schofield weight and height and World Health Organization predictive equations were 97.5%, 97.4% and 98.6%, respectively. Mean percentage of expected total body potassium for weight, height and age for head injured children were 85.1 ± 15.5%, 89.1 ± 14.1% and 86.9 ± 15.9%, thus all showed significant depletion. Conclusions: During rehabilitation, using predictive equations to estimate resting energy expenditure in this group revealed a small bias on average but very large bias at the individual level. Head injured children had altered resting energy expenditure and body composition.

Patterns of community integration 2-5 years post-discharge from brain injury rehabilitation

Outcome after traumatic brain injury (TBI) is characterized by a high degree of variability which has often been difficult to capture in traditional outcome studies. The purpose of this study was to describe patterns of community integration 2-5 years after TBI. Participants were 208 patients admitted to a Brain Injury Rehabilitation Unit between 1991-1995 in Brisbane, Australia. The design comprised retrospective data collection and questionnaire follow-up by mail. Mean follow-up was 3.5 years. Demographic, injury severity and functional status variables were retrieved from hospital records. Community integration was assessed using the Community Integration Questionnaire (CIQ), and vocational status measured by a self administered questionnaire. Data was analysed using cluster analysis which divided the data into meaningful subsets. Based on the CIQ subscale scores of home, social and productive integration, a three cluster solution was selected, with groups labelled as working (n = 78), balanced (n = 46) and poorly integrated (n = 84). Although 38% of the sample returned to a high level of productive activity and 22% achieved a balanced lifestyle, overall community integration was poor for the remainder. This poorly integrated group had more severe injury characterized by longer periods of acute care and post-traumatic amnesia (PTA) and greater functional disability on discharge. These findings have implications for service delivery prior to and during the process of reintegration after brain injury.

New perspectives on the role of aldosterone excess in cardiovascular disease

1. Evidence from recent experimental and clinical studies suggests that excessive circulating levels of aldosterone can bring about adverse cardiovascular sequelae independent of the effects on blood pressure. Examples of these sequelae are the development of myocardial and vascular fibrosis in uninephrectomized, salt-loaded rats infused with mineralocorticoids and, in humans, an association of aldosterone with left ventricular hypertrophy, impaired diastolic and systolic function, salt and water retention causing aggravation of congestion in patients with established congestive cardiac failure (CCF), reduced vascular compliance and an increased risk of arrhythmias (resulting from intracardiac fibrosis, hypokalaemia, hypomagnesaemia, reduced baroreceptor sensitivity and potentiation of catecholamine effects). 2. These sequelae of aldosterone excess may contribute to the pathogenesis and worsen the prognosis of CCF and hypertension. 3. The heart and blood vessels may be capable of extra-adrenal aldosterone biosynthesis, raising the possibility that aldosterone may have paracrine or autocrine (and not just endocrine) effects on cardiovascular tissues. 4. The high prevalence of CCF, which is associated with secondary aldosteronism, and primary aldosteronism (PAL; recently recognized to be a much more common cause of hypertension than was previously thought) argue for an important role for aldosterone excess as a cause of cardiovascular injury. 5. The recognition of non-blood pressure-dependent adverse sequelae of aldosterone excess raises the question as to whether normotensive individuals with PAL, who have been detected as a result of genetic or biochemical screening among families with inherited forms of PAL, are at excess risk of cardiovascular events. 6. Provided that patients are carefully investigated in order to permit the appropriate selection of specific surgical (laparoscopic adrenalectomy for PAL that lateralizes on adrenal venous sampling) or medical (treatment with aldosterone antagonist medications) management and safety considerations for the use of aldosterone antagonists are kept in mind, the appreciation of a widening role for aldosterone in cardiovascular disease should provide a substantially better outlook for many patients with CCF and hypertension.

Analysis of thermodynamic non-ideality in terms of protein solvation

The effects of thermodynamic non-ideality on the forms of sedimentation equilibrium distributions for several isoelectric proteins have been analysed on the statistical-mechanical basis of excluded volume to obtain an estimate of the extent of protein solvation. Values of the effective solvation. parameter delta are reported for ellipsoidal as well as spherical models of the proteins, taken to be rigid, impenetrable macromolecular structures. The dependence of the effective solvated radius upon protein molecular mass exhibits reasonable agreement with the relationship calculated for a model in which the unsolvated protein molecule is surrounded by a 0.52-nm solvation shell. Although the observation that this shell thickness corresponds to a double layer of water molecules may be of questionable relevance to mechanistic interpretation of protein hydration, it augurs well for the assignment of magnitudes to the second virial coefficients of putative complexes in the quantitative characterization of protein-protein interactions under conditions where effects of thermodynamic non-ideality cannot justifiably be neglected. (C) 2001 Elsevier Science B.V. All rights reserved.