Risk stratification and dental management of the patient with cardiovascular diseases. Part II: Oral disease burden and principles of dental management.

Cardiovascular diseases are the leading cause of death in the United States and most other Western countries. In the United States alone, more than 1 million annual deaths and as many as three times that number of serious consequences can be attributed to these conditions. To provide care to patients with cardiovascular disease, oral health care providers must understand the disease, its treatment, and its impact on the patient's ability to undergo and respond to dental care.     

Chronic modifications of lung and heart development in glucocorticoid-treated newborn rats exposed to hyperoxia or room air

We assessed the mechanics and morphology of the lung in 165 rats treated neonatally with either room air (RA), O₂, RA + steroids, or O₂, + steroids. Newborn Sprague-Dawley male rats were randomly assigned to these groups. O₂,-exposure (0.96-1.0 FiO₂ lasted 5 days, and dexamethasone treatment consisted of eight daily S.C. injections of drug or buffer in successive doses of 0.5,0.4.0.3,0.2,0.1, 0.1. 0.1. and 0.1 mg/kg. At 58 days, right ventricular systolic pressure (RVP) was measured. At 60 days, all rats were sacrificed for obtaining lung weight and DNA, saline pressure-volume (P-V) curves, and morphometry. We weighed right ventricles (RV) and left ventricles + septa (LV). Hyperoxia alone did not, but steroid decreased survival rate to 79.4% (95.3% in RA rats, P < 0.02). Only 21 of 40 (52%) O₂ + steroids rats survived, less than in both RA groups (P < 0.001). RV weight, RVP and muscularization of alveolar duct arteries were significantly increased in O₂ vs. RA rats. In RA + steroids rats, weight of the LV was decreased but RV, RVP, and lung vasculature were not affected. These effects were additive in the O₂ + steroid group. Wet lung weights and DNA were increased for RA + steroid rats over all others. O₂ and steroids shifted the P-V curve to the left and O₂+ steroids still further. Maximal lung volume increased significantly with RA + steroids and still further in O₂ + steroids but not in O₂ alone. O₂ and steroids significantly increased the mean linear intercept and O₂ + steroids even more so. In O₂- and steroid-treated rats, the parenchymal air space increased. In conclusion, both neonatal hyperoxia and steroid administration caused aberrations in the growth of lung and connective tissue. The effects of the two were additive. The vascular system, maximal lung volume, and DNA responded differently, presumably by different modes of action. Pediatr Pulmonol. 1993; 16:81–88. © 1993 Wiley-Liss, Inc.     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

The molecular biology of medullary thyroid carcinoma. A model for cancer development and progression

Medullary thyroid carcinoma (MTC) is an important human cancer for the study of molecular abnormalities that underlie initiation of neoplasia and subsequent cellular changes during tumor progression. This tumor can occur in different inherited forms, each mediated by autosomal dominant genetic events. Germline abnormalities on chromosome 10 are linked to at least one type of genetic MTC, multiple endocrine neoplasia type II. Our studies of chromosome 10 in DNA from MTC tumors failed to detect frequent loss of polymorphic DNA markers, suggesting that the genetic mechanisms involved in MTC development may be different from those for other inherited cancers such as retinoblastoma. During tumor progression of MTC, abnormalities develop in expression of the mature phenotype of the endocrine cell from which the tumor arises. In cell culture, chemical modulation or gene insertion can lead to partial correction of these defects in differentiation capacity by activating cellular signaling processes. These studies offer opportunities to dissect the molecular events that regulate endocrine cell differentiation, to determine the precise abnormalities that may underlie the initiation and tumor progression events in MTC and related cancers, and, thereby, to identify new targets for therapeutic intervention.     

Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity

Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells. Recent results revealed a direct interaction of MIA and epitopes within extracellular matrix proteins including fibronectin. The aim of this study was to analyze functional consequences mediated by this interaction. Here we show that MIA interferes specifically with attachment of melanoma cells to fibronectin, a phenomenon we refer to as active detachment. Antibodies inhibiting binding of alpha4beta1 and alpha5beta1 integrins to fibronectin cross-react specifically with MIA, suggesting that MIA shares significant structural homology with the binding pockets of these integrins and thereby masks the respective epitopes on extracellular matrix molecules. Several peptides derived from fibronectin and from a phage display screening were tested with respect to a potential MIA-inhibitory effect. In vitro tests identified two peptides affecting MIA function; both inhibited growth of melanoma metastases in vivo. In summary, we conclude that MIA may play a role in tumor progression and spread of malignant melanomas via mediating active detachment of cells from extracellular matrix molecules within their local milieu. Further, our results suggest that inhibiting MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease.     

Increased Operative Time Impacts Rates of Short-Term Complications After Unicompartmental Knee Arthroplasty

BackgroundPrevious evidence has demonstrated an exacerbating effect of increased operative time on short-term complications in total joint arthroplasty. While the same relationship may be expected for unicompartmental knee arthroplasty (UKA), supporting evidence remains sparse. The purpose of this study is to determine the impact of operative time on short-term complication rates after UKA and determine a critical threshold in operative times after which complications may increase.MethodsThe American College of Surgeons National Surgical Quality Improvement Project was queried from 2007 to 2018 to identify 11,633 UKA procedures that were included in the final analysis. The effect of operative time on complications within 30 days was evaluated using multivariate logistic regression models. Receiver operating characteristics curves and spline regression models were used to identify critical thresholds in operative time that increase the likelihood of short-term complications.ResultsLonger operative times (in minutes) were associated with higher rates of surgical site infection (90.4 ± 26.7 vs 84.8 ± 25.5, P = .003), blood transfusions (94.9 ± 28.6 vs 84.9 ± 25.5, P = .007), as well as reoperation rates (90.8 ± 27.9 vs 84.9 ± 25.5, P = .01), extended hospital length of stay (93.4 ± 29.8 vs 84.5 ± 25.2, P < .001), and mortality (110.4 ± 35.5 vs 84.9 ± 25.5, P = .008). Following multivariate logistic regression, operative time was found to independently predict increased surgical site infection, blood transfusion, myocardial infarction, extended length of stay, and mortality (odds ratio: 1.09 – 1.45, CI: 1.01 – 1.91, all P values <0.02). Receiver operating characteristics curves found an increase in mortality risk during the 30-day postoperative period after 88.5 minutes of operative time, a finding supported by spline regression plots.ConclusionThe present study found a positive correlation between increased operative times and short-term postoperative complication rates after UKA. Despite a statistically significant association with increasing operative time, odds ratios of reported complications are relatively low.     

Significance of borderline levels of specific IgE obtained by FAST-Plus assay.

The significance of "borderline" levels of allergen-specific IgE as measured by in vitro assays has been questioned. Patients whose specific IgE tests Patients were tested for twelve antigens using the FAST-Plus methodology. All 0/1 results were checked using skin tests at a 1:500 concentration. Positive (histamine) and negative (diluent) controls were used. The antigen-induced wheals were compared with those produced by a control wheal of 2% glycerine (the glycerine concentration in a 1:500 dilution). Positive wheals were arbitrarily considered to be those whose diameter after 10 minutes exceeded that of the glycerine control wheal by 2 mm or more. Using the limits of calibrator fluorescence for the FAST-Plus test in effect before 1990, a significant discordance between skin test results and the class 0/1 in vitro readings was evident. Using the standards in effect since 1990, marked concordance between class 0/1 results and positive skin tests was noted. This was most marked for pollens, less so for molds. Using current standards, FAST-Plus class 0/1 results are best considered positive (pending clinical confirmation), rather than negative.