Patterns of cell death and cell cycle profiles of cultured WEHI 13 var fibroblasts exposed to eluates of composite resins used for direct and indirect restorations

Previous studies have shown that in vitro exposure to single compounds released from composite resins may induce cell death. In the present study the effects of eluates from commercially available composite resins used for direct or indirect restorations were evaluated on the cell cycle progression and type of cell death of cultured WEHI 13 var fibroblasts. Cells exposed to eluates of the materials were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell death, for cell cycle profiles by flow cytometry, for caspase-3 biochemically and by immunocytochemistry, and for morphological changes by fluorescence microscopy with acridine orange. The direct composite resin eluates induced extensive apoptosis, followed by secondary necrosis. This was accompanied by cell enlargement, micromultinucleation, chromatin disintegration, cell cycle arrest at different phases, and caspase-3 activation. The composites for indirect restorations were much less cytotoxic at all biological end-points investigated. The findings suggest that composite resins used for direct and indirect dental restorations differ in their cytotoxic potential and their ability to affect basic cellular functions. This underlines the impact of improved polymerization with respect to their biologic behavior.     

Comparison of skeletal and dental morphology in asymptomatic volunteers and symptomatic patients with unilateral disk displacement with reduction

The purpose of this study was to evaluate the effect of unilateral disk displacement with reduction (UDDR) on the skeletal and dental pattern of affected individuals. There were 18 symptomatic female patients and 46 asymptomatic normal female volunteers. All study participants had bilateral high-resolution magnetic resonance scans in the sagittal (closed and open) and coronal (closed) planes to evaluate the temporomandibular joints. Linear and angular cephalometric measurements were taken to evaluate the skeletal, denture base, and dental characteristics of the two groups. Analysis of variance was used to compare the symptomatic with the control subjects. A few skeletal differences were found. There was an overall reduction in length of the anterior (S-Na) and posterior (S-Ba) cranial base measurements in the UDDR group. The cranial base angle was also increased. Both upper and lower dentures bases were retropositioned. The posterior ramal height (Ar-Go) was shorter in the symptomatic group. This study showed that alterations in skeletal morphology may be associated with UDDR. The mechanisms that produce DD or the mechanisms that cause this skeletal alteration are yet to be clarified. This study suggests that subjects with UDDR may manifest altered craniofacial morphology. The clinician should be aware of this possibility, especially for growing patients.     

Comparison of skeletal and dental morphology in asymptomatic volunteers and symptomatic patients with bilateral disk displacement without reduction

The purpose of this study was to evaluate the effect of bilateral disk displacement without reduction (BDDN) on the skeletal and dental pattern of affected individuals. There were 59 symptomatic female patients and 46 asymptomatic normal female volunteers. All study participants had bilateral high-resolution magnetic resonance imaging scans in the sagittal (closed and open) and coronal (closed) planes to evaluate the temporomandibular joints. Linear and angular cephalometric measurements were taken to evaluate the skeletal, denture base, and dental characteristics of the two groups. A smaller cranial base length (Ba-Na) was found in the symptomatic group. The facial plane angle was smaller, and the angle of convexity was larger because of the retropositioned mandible. The lower denture base was also retruded as shown by the smaller SNB angle. The BDDN group exhibited a larger overjet. The mandibular plane angle was steeper, the Y-axis was more vertical (S-Gn to FH), the posterior ramal height (Ar-Go) was shorter, and the angle between the mandibular and the palatal plane (PP to MP angle) was increased in the symptomatic group. No significant dental differences were found. This study showed that alterations in skeletal morphology might be associated with BDDN. This study suggests that subjects with BDDN may manifest altered craniofacial morphology. The clinician should be aware of that possibility, especially for the growing patients and the surgical candidates.     

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators

OBJECTIVE: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro. DESIGN: Prospective clinical study followed by cell culture studies. SETTING: General intensive care unit and research laboratory of a university hospital. SUBJECTS: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). INTERVENTIONS: Cells were exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6. MEASUREMENTS AND MAIN RESULTS: Patients' serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-alpha (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-alpha and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels. CONCLUSIONS: First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.     

Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels

OBJECTIVE: To investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Forty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 +/- 16 yrs) were studied the day after termination of mechanical ventilation (7-60 days after trauma). INTERVENTIONS: First, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 microg of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels <18 microg/dL were defined as nonresponders to the low-dose stimulation test. Thirty-one patients underwent also a human corticotropin releasing hormone test. MEASUREMENTS AND MAIN RESULTS: In traumatic brain injury patients, mean baseline and low-dose stimulation test-stimulated cortisol levels were 17.2 +/- 5.4 microg/dL and 24.0 +/- 6.6 microg/dL, respectively. The median increment in cortisol was 5.9 microg/dL. Basal corticotropin levels ranged from 3.9 to 118.5 pg/mL. Six of the 40 patients (15%) failed the low-dose stimulation test. The human corticotropin releasing hormone test (performed in 26 responders and five nonresponders) revealed diminished cortisol release only in the low-dose stimulation test nonresponder patients. Corticotropin responses to corticotropin releasing hormone were consistent with both primary (three patients) and/or secondary (two patients) adrenal dysfunction. In retrospect, nonresponders to the low-dose stimulation test more frequently required vasopressors (6/6 [100%] vs. 16/34 [47%]; p =.02) and for a longer time interval (median, 0 vs. 293 hrs; p =.006) compared with responders. Furthermore, nonresponders had higher interleukin-6 levels compared with responders (56.03 vs. 28.04 pg/mL; p =.01), whereas tumor necrosis factor alpha concentrations were similar in the two groups (2.42 vs. 1.55 pg/mL; p =.53). CONCLUSIONS: Adrenal cortisol secretion after dynamic stimulation is deficient in a subset of critically ill patients with moderate to severe head injury. This disorder is associated with prior vasopressor dependency and higher interleukin-6 levels.     

Multidisciplinary lymphedema treatment program

Lymphedema is an underrecognized and undertreated condition that requires a multidisciplinary approach in an individualized program that will address the special needs of each patient. In an ideal setting of an outpatient management program the team should be composed of a vascular surgeon, a dermatologist, a physiotherapist, a dietician, a psychologist, a social worker, and an office employee, working together in the assessment and management of all aspects of lymphedema. All treatment strategies and actions taken should ultimately focus on the improvement of the quality of life of patients suffering from lymphedema and on the prevention of lymphedema in high-risk patients.