An electronic database for outcome studies that includes digital radiographs.

We report on acquisition of key data from the clinical medical record, surgical data, radiologic studies, and patient surveys for a novel digital total hip arthroplasty (THA) registry that includes electronic capture of digital radiographic images into a database on an internet platform for query. We now have the ability to collect demographic and operative data, including the operative note, discharge summary, surgery data, and Digital Imaging Communications in Medicine (DICOM) radiology images. Steps are being completed to assemble office encounters, hospital procedural codes, and implant bar codes. Two examples include a THA surgery record and a THA outcome study with plain radiograph set. Analysis of such data could suggest ways to improve clinical practice.

Biomechanical evaluation of dual-energy X-ray absorptiometry for predicting fracture loads of the infant femur for injury investigation: an in vitro porcine model.

OBJECTIVE: The purpose of this study was to determine the ability of bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) and geometry measured by biplanar x-ray to predict fracture mechanics in vitro in an immature femur model. DESIGN: Prospective analysis of radiographic and biomechanical data was performed. SETTING: In vitro experimentation. INTERVENTIONS: Bone geometry and DXA data were obtained before mechanical testing. Twenty-two porcine femora from males and females (age 3 to 12 months; body weight 3.6 to 7.0 kilograms) were fractured. Mechanical tests were performed on the diaphysis of the femora in two loading configurations: (a) three-point bending to simulate loads that result in transverse fractures; and (b) torsion to simulate twisting injuries that result in spiral fractures. MAIN OUTCOME MEASURES: Correlation of radiographic data with the experimentally determined bone strength. RESULTS: Three-point bending consistently resulted in transverse fractures. Femoral diaphysis BMD (mean, 0.304 grams per square centimeter; SD, 0.028 grams per square centimeter) strongly correlated (r2 = 0.938) to fracture load in bending. Load at failure ranged from 530 to 1,024 N (mean, 726 N; SD, 138 N), consistent with the findings of Miltner. Empirically derived strength parameters coupling BMD with geometry accurately predicted bending loads (r2 = 0.84, p < 0.001) and energy to failure (r2 = 0.88, p < 0.05). Torsional loading failed to generate spiral fractures consistently, resulting in either end plate or diaphyseal fractures. Load at failure for torsion ranged from 1,383 to 3,559 Newton-millimeters (mean, 2,703 Newton-millimeters; SD, 826 Newton-millimeters). Because of these inconsistent fracture results, empirical strength parameters for torsion could not be derived. CONCLUSION: BMD coupled with geometry is a strong predictor of bending fracture loads in the immature femoral diaphysis. A similar relationship could not be shown for torsion because of inconsistent failure results. This study represents an initial attempt at developing a methodology for predicting the strength of young bones from radiographic measures. Further research is required to establish this methodology and to show the necessary correlation with immature human bone.

Partial correction of Cobb angle prior to posterior spinal instrumentation.

BACKGROUND: A substantial contribution to the overall surgical correction of Cobb angle has been observed to occur prior to securing the instrumentation. Knowledge specific to the amount of correction prior to instrumentation is scarce in the medical literature. If significant correction is due to the positioning and muscle stripping during exposure of the spine, questions arise about the usefulness and need for extensive rod-rotation maneuvers to further straighten the spine. This study quantifies the extent of correction achieved from standing to prone, with the spine exposed before and after instrumentation. MATERIALS AND METHODS: Eleven patients with the diagnosis of adolescent idiopathic scoliosis (AIS) and a right thoracic major curve were included in the study. Intraoperative changes in Cobb angle were measured before and after instrumentation, as well as postoperatively. The patients underwent posterior spinal instrumentation by the same surgical team using the rod-rotation techniques. Radiographs were taken prior to surgery, intraoperatively before and after instrumentation and postoperatively within one week from surgery. Cobb angle measurements were performed by the same examiner. RESULTS: The median preoperative Cobb angle of 60 degrees +/-14 degrees (48-90 degrees ) corrected to a median of 26 degrees +/-22 degrees (10-80 degrees ) on the right bend film, to a median of 55 degrees +/-12 degrees (30-70 degrees ) intraoperatively after exposure, and to a median 30 degrees +/-10 degrees (20-46 degrees ) after rod-rotation/instrumentation and fixation. The follow-up standing radiograph median Cobb angle was 40 degrees +/-14 degrees (9-56 degrees ). A median intraoperative correction of 28 degrees was obtained, 10 degrees of which was prior to the rod rotation and instrumentation. High variability was observed in the percentage contribution of pre-instrumentation release with a median of 42%+/-25% (0-67%). CONCLUSION: Approximately one-third of the total correction occurred prior to instrumentation being applied, and even though it was variable and substantial, the actual surgical rod rotation and instrumentation maneuver provided the majority of correction.

Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group.

OBJECTIVES: To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed. DESIGN: Prospective, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Intensive care units of 30 academic, teaching, and community hospitals in the United States. PATIENTS: Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization. INTERVENTIONS: Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm. MEASUREMENTS AND MAIN RESULTS: Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm. CONCLUSIONS: From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.

Anatomic variation of structural properties of periacetabular bone as a function of age. A quantitative computed tomography study.

The shape of the acetabulum, the volume of the periacetabular bone, and its density for 125 patients with a wide age range have been quantified using quantitative computed tomography. The goals were to study the relationship between geometric and densitometric properties and provide normative data for finite-element analysis. Significant correlations were found between acetabular diameter and (1) depth, (2) cancellous periacetabular bone density, and (3) periacetabular total bone volume. Only changes in densitometric properties significantly correlated with age. Sphericity of the acetabulum did not increase with age. Variability in bone morphology and density was found for both male and female groups. Surgeons using purely geometric measures to quantify the integrity of acetabular bone should be aware of their limitations when selecting hardware for total hip arthroplasty.

Observer variation in the detection of acetabular bone deficiencies.

To determine observer variation in the detection of acetabular bone deficiencies, 42 pairs of frontal (AP) and lateral hip radiographs and CT studies for total hip arthroplasty patients obtained within an average of 4 weeks of each other were reviewed separately by five radiologists and one orthopedic surgeon. Interobserver variations were calculated for each individual reading the films using kappa values. The individual film readings were then compared with a consensus reading of the CT data. When separate observers were analyzed, agreement on plain film readings was slight to fair (av. kappa = 0.1440 +/- 0.1047). The individual observers were not able to give readings which were very consistent with the CT consensus reading, resulting in a low sensitivity (65%) and specificity (74%) for acetabular defect classification with plain radiographs. The identification of acetabular bone defects from the AP and lateral views of the hip is highly subjective and variable from observer to observer.

Curved beam model of the proximal femur for estimating stress using dual-energy X-ray absorptiometry derived structural geometry.

The investigation of individual differences in hip strength requires a method to measure structural geometry in vivo and a valid analytical approach to calculate mechanical stress. We developed a method for deriving structural geometry of the femur from the proximal shaft through the femoral neck, using data from dual energy X-ray absorptiometry. The geometric properties are employed in a two-dimensional curved beam model of the proximal femur to estimate stresses on the lateral and medial bone surfaces. Stresses calculated by this method are compared with those from the conventional flexure formula and with results produced from a cadaver femur with use of three-dimensional finite element analysis of computed tomography data. Loading conditions simulating a one-legged stance and a fall on the greater trochanter are employed. Stresses calculated by curved beam theory are in much better agreement with three-dimensional finite element analysis than are those for which the conventional straight beam formula was used. In simulation of a fall on the greater trochanter, all three methods show peaks of stress at the femoral neck but only the curved beam and finite element analysis methods show an additional peak at the medial intertrochanteric margin. Both neck and trochanter regions correspond to common failure sites for hip fractures in the elderly. The curved beam treatment of hip structure derived from dual-energy X-ray absorptiometry provides an approach for the in vivo engineering analysis of hip structure that is not practical by other methods.

Absence of abnormal hyperphosphorylation of tau in intracellular tangles in Alzheimer's disease.

Adult human nerve cells contain tau protein, a phosphorylated microtubule-associated protein, that is hyperphosphorylated in the fetus and in patients with Alzheimer's disease. Hyperphosphorylation, which diminishes the microtubule-binding capacity of tau, destabilizes microtubules and may enhance the formation of paired helical filaments that constitute neurofibrillary tangles in Alzheimer's disease. Here, we use phosphorylation-dependent anti-tau antibodies to detect specific epitopes that characterize hyperphosphorylated tau. Our demonstration of intracellular tangles containing full-length tau that are not immunolabeled by these antibodies suggests that hyperphosphorylation of tau is not obligatory in the formation of neurofibrillary tangles in Alzheimer's disease.

An algorithm for improving the accuracy of discrete ROI integrals.

Many problems in the analysis of medical digital images, e.g., digitized x-ray radiograph, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET), require a detailed and precise analysis of user chosen regions of interest (ROIs). Examples of their use include calculating integrals of area, volume, mass, structural moments, and statistical measures for either organs, tumors, or the musculoskeletal system. Among various ROI scan conversion schemes, binary approximate scan conversion is usually preferred due to its efficiency. In this paper, geometric area error is tabulated for typical scan conversion techniques, including whole pixel (WP) approximation and subpixel (SP) approximation methods, and compared to exact pixel (EP) coverage methods for medical ROIs. A new efficient and general EP method for scan conversion of these ROIs is presented. The algorithm traverses the boundary of the polygon while simultaneously scan converting the ROI, and calculates the fractional area of each pixel covered at the perimeter. The resultant geometric area is substantially more accurate than the SP or WP methods, without a significant loss of speed. The numerical results for a ROI with a large ratio of boundary to polygon area demonstrated that the geometric error for a SP method was 40% of the total polygon area, and 150% of the total polygon area for a WP method. The new algorithm could "exactly" calculate the pixel coverage area, in addition to being four times faster than the widely used EP method of Catmull. Efficient and accurate calculation of ROI integrals is essential for comparative analysis.

Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's disease.

Antibodies to different phosphorylated and non-phosphorylated tau epitopes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughout the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed extracellular tangles (Type 3) were characterized by the presence of epitopes associated with the microtubule binding region and the COOH-terminus. These three types of tangles, found in situ in hippocampus, could be created experimentally by proteolytic treatment of brain sections. These findings suggest that three stages of neurofibrillary degeneration can be understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phosphorylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.

Evidence of subtypes of Alzheimer's disease and implications for etiology.

OBJECTIVE: Because age of onset does not reliably define two subtypes of Alzheimer's disease, classification based on the severity of neuronal degeneration was tested. DESIGN: Numbers of extracellular tangles and pyramidal neurons in the hippocampus were used to group patients. PATIENTS: The study population consisted of 46 elderly patients satisfying DSM-III criteria for dementia and NINCDS-ADRDA criteria for definite Alzheimer's disease after death. RESULTS: Univariate logistic regression analysis showed the numbers of neurofibrillary tangles and pyramidal neurons and the duration of dementia were significantly associated with grouping based on the presence of abundant extracellular tangles. Ninety-one percent of patients were correctly classified as compared with 85% correctly classified by age of onset data. Odds ratios showed that increasing numbers of neurofibrillary tangles predicted greater severity of neuronal loss. CONCLUSION: The results of the study indicate the importance of neurofibrillary degeneration, not the deposition of amyloid, in the pathogenesis of Alzheimer's disease. They support a classification of Alzheimer's disease related more closely to the severity of neurofibrillary degeneration than to age at onset.

Magnetic resonance imaging and the severity of dementia in older adults.

Periventricular white-matter lesions were visualized in the brains of elderly patients being assessed for possible Alzheimer's disease. The magnitude of these lesions, expressed as lesion-brain ratios, correlated closely with the severity of dementia indicated by scores on the Blessed Dementia Scale and the Folstein Mini-Mental State Examination. Impairment in several domains of cognitive functioning tested by the Mini-Mental State Examination was also correlated with the relative quantity of periventricular lesions. Correlations were significant with systolic blood pressure, approached significance with age, and were not significant with duration of dementia or the magnitude of the lateral ventricles. These findings indicate the potential utility of structure-function correlations that are possible with magnetic resonance imaging in identifying mechanisms underlying dementia. They suggest that magnetic resonance imaging may be more useful than computed tomography in following the course of dementia.

Neurofibrillary degeneration and neuronal loss in Alzheimer's disease.

Neuronal loss in Alzheimer's disease, especially in cerebral cortex and hippocampus, appears closely associated with the process of neurofibrillary degeneration. In certain noncortical nuclei neuronal loss appears not to depend upon the formation of neurofibrillary tangles. Neurofibrillary tangles and neurons were counted in the same populations of neurons in five brain regions. In the locus ceruleus and nucleus basalis, where tangles have a loose or globose structure, correlations with neuronal counts were not significant. In cerebral cortex and hippocampus, tangles have a more dense and often a flame-like appearance and their correlations with neuronal counts were significant. The relationships between tangles and noncortical neurons reported here suggest that the appearance of tangles does not necessarily herald the demise of a neuron in Alzheimer's disease. It can be reasonably anticipated that these relationships depend upon the clinical heterogeneity of Alzheimer's disease, regional differences in the brain and/or the macromolecular composition of neurofibrillary tangles.

Quantitative magnetic resonance imaging and the severity of dementia in Alzheimer's disease.

The T2 component of the magnetic resonance imaging (MRI) signal was measured in 11 brain loci in six elderly patients diagnosed as having probable Alzheimer's disease. T2 values and relative amount of periventricular high-intensity foci were significantly correlated with dementia severity, indicated by the Blessed-Roth Dementia Scale score. Although the mean T2 value for left hemispheric structures was more closely correlated with the dementia score, T2 values did not differ significantly in the right and left hemispheres or in gray and white matter. These findings suggest that more severe dementia in Alzheimer's disease is associated with more water in the brain.

Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease.

Relationships were examined between neuronal degeneration in the nucleus locus ceruleus (nLC), a parameter of central noradrenergic impairment, and neocortical markers of Alzheimer disease (AD). The loss of nLC neurons was found to correlate significantly with norepinephrine concentration, choline acetyltransferase (ChAT) activity, and numbers of plaques and tangles on Brodmann area 24 (cingulate); ChAT and plaque counts in area 21 (temporal); and with ChAT activity in area 10 (frontal). In addition, nLC neuronal counts were correlated significantly with the severity and estimated duration of dementia. The number of neurofibrillary tangles in nLC, which did not correlate significantly with neocortical markers of AD, correlated with the estimated duration and severity of dementia. These data suggest that changes in central noradrenergic pathways are related to the pathophysiology of AD.

Field size dependence of radiation sensitivity and dose fractionation response in skin.

Four sets of data from the literature were analyzed to assess the effects of field size on dose tolerance and dose fraction size dependence in irradiated skin. The data consisted of combinations of total dose and dose per exposure (or number of fractions) required to yield a given degree of visible damage to the skin, for fields of different sizes. Putative cell survival curves were constructed, under the assumptions that the isoeffect represents a fixed cell survival, and that each exposure during a course of fractionated irradiation has equal effect on cell survival. The analysis showed that overall sensitivity to radiation, and dependence on dose per exposure, both increase with field size. To account for these results we describe a model that can be qualitatively related to the geometric properties of the dermal vascular network. First, vascular function after irradiation should depend on the length of the vessels exposed to the radiation. This directly predicts an increasing sensitivity in large irradiated fields. Furthermore, if vascular function determines radiation response, the shape of the shoulder (low-dose) region of the effective survival curve will depend on the average number of vessels nourishing each cell, with a more pronounced shoulder for a high multiplicity of vessels. The model predicts a greater fractionation sensitivity in large than in small fields, in agreement with our analysis of the isoeffect data. It is therefore possible that the advantages of hyperfractionation in reducing late effects in normal tissues may be related to vascular architecture, and not to inherent differences between late and acutely responding cell populations.

Lack of correlation between basal cell survival and gross response in irradiated swine skin.

The relationship between basal cell survival and gross response in irradiated swine skin was tested by comparing dose survival curves derived from time-dose isoeffect data with curves obtained directly from basal cell counts in histological sections. Assuming equal effect per exposure and constant cell survival at isoeffect, best-fitting single-hit multi-target and linear-quadratic response curves were determined for time-dose schedules resulting in non-healing of 50% of irradiated fields. Basal cell survivals for single doses of 970, 1649, 2231, and 2619 rad were estimated 1) by counting regenerating islands and 2) by monitoring total basal cell counts through time. The dose survival curve derived from the isoeffect data was steeper than the curve obtained from direct basal cell counts. Furthermore, the direct basal cell survival curve extrapolates to less than 100% at zero dose, indicating the presence of a resistant basal cell subpopulation. The data show that the isoeffect in this case is not strongly coupled to basal cell survival. Rather, the probability of healing of an irradiated field is more sensitive to the dose per fraction than is basal cell survival, implying a contribution to non-healing from damage to stromal elements such as the capillary endothelium.