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Colon cancer screening occurs at younger ages than osteoporosis screening. Bone density measurements using virtual colonoscopy performed for colon cancer screening can provide an early warning sign of patients at potential risk for osteoporosis-related fractures. Earlier identification may improve treatment and potentially fracture prevention. INTRODUCTION: Opportunistic osteoporosis screening with computed tomography colonography (CTC) offers an opportunity to capitalize on earlier colorectal cancer screening to identify patients at risk of future fractures. The purpose of this study is to evaluate 10-year fracture and specifically hip fracture risk based on Hounsfield units (HU) obtained from CTC. METHODS: We identified all CTC scans between 2004 and 2007 of patients 40 years and older with 10 years minimum follow-up. Hounsfield units were measured within the proximal femur and fractures identified via worldwide military records. Patients were stratified into two cohorts based on the presence or lack of a fracture in the wrist, spine, hip, or proximal humerus. Hounsfield unit measurements were compared between groups using Student's t test and the HU threshold was calculated that best approximated an 80% sensitivity to optimally screen patients for fracture risk. The odds ratio, negative predictive value, 10-year incidence of fracture, and survival curves were calculated. RESULTS: We identified 3711 patients with 183 fractures over 10 years. The HU threshold that corresponded with an 80% sensitivity to identify fractures was 112 HU. The negative predictive value (NPV) for overall fractures and hip fractures was over 97%. The 10-year fracture incidence was higher in patients below 112 HU compared to those above for both overall fractures (6.3% vs 1.7%) and hip fractures (2.7% vs 0.07%). The 112 HU threshold corresponds with an odds ratio for overall fracture and hip fractures of 2.5 (95% confidence interval (CI), 1.7-3.6) and 24.5 (95% CI, 3.3-175.5), respectively. CONCLUSION: In the 10 years following CTC, patients who experienced a fracture had lower hip HU. Decreasing HU on CTC may be an early warning sign of fracture potential.

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The outcome of coronary artery bypass grafting procedures is highly dependent on the technical adequacy of the distal anastomosis. Various methodologies, including flow measurement and imaging techniques, have been used by the cardiothoracic surgeon to assess the adequacy of the distal anastomosis. The limitations of these techniques outweigh their advantages and limit their widespread clinical applicability. Recent improvements in the technique for online measurement of regional myocardial pH provide a promising new metabolic approach to assessing the adequacy of the distal anastomosis in cardiac surgery.

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The search for effective adjuvant therapy for melanoma has resulted in the testing of a remarkably broad spectrum of therapeutic agents. Until recently, there was little evidence to suggest a benefit for any adjuvant therapy. The demonstration of activity for adjuvant high-dose interferon alfa in a cooperative group trial resulted in Food and Drug Administration approval and has dramatically changed the melanoma landscape. This article reviews all the randomized adjuvant trials conducted to date in melanoma, discusses pertinent studies still in progress or awaiting analysis, and offers recommendations for the adjuvant treatment of melanoma patients rendered clinically disease-free by surgery.

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Symptomatic relief of macromastia following reduction mammaplasty in the adult female population is well documented. Teenagers undergoing breast reduction may be at risk for recurrent symptoms secondary to postoperative breast development. The psychological consequences of prominent scars, sensory loss, and inability to breastfeed may overshadow the early symptomatic relief gained from reduction mammaplasty. Eighty-six patients who had undergone bilateral reduction mammaplasty prior to 20 years of age from 1970 to 1990 were identified from hospital and office charts. Forty-eight patients (56%) were successfully contacted and completed a detailed questionnaire evaluating preoperative, postoperative, and present symptoms as well as physical and psychological consequences of their surgery. Patient age ranged from 15.0 to 19.9 years with a mean of 17.8 years. Average length of follow-up time was 5.9 years, ranging from 1.4 to 20.4 years. Sustained relief of symptoms in those patients with preoperative back pain, neck pain, shoulder strap pain, and submammary rash occurred in 76%, 78%, 89%, and 93%, respectively, despite the fact that 72% reported at least some regrowth of breast tissue. Seventy-three percent reported being happy with their current breast size, 94% would have the procedure now if they had not had the surgery as teenagers, and 94% would recommend breast reduction to a friend with macromastia. Teenage patients who undergo reduction mammaplasty do not suffer from marked return of symptoms, and long-term satisfaction remains high.

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The hemostatic dysfunction induced by cardiopulmonary bypass is due, in part, to a platelet dysfunction evidenced by a postoperative extension of the bleeding time; it leads to increased postoperative blood loss and morbidity. This study, which was conducted in 85 patients undergoing cardiopulmonary bypass, was designed to characterize the hematologic changes during and after cardiopulmonary bypass and to elucidate the relationships between these changes, the extension of the bleeding time, and the magnitude of the postoperative nonsurgical blood loss. Variables were measured before, during, and 2, 24, 48, and 72 hours after cardiopulmonary bypass. Univariate and multivariate analyses were performed with either the 2-hour postbypass bleeding time or the 4-hour postbypass blood loss as the dependent variables. The reversal of the extension of the bleeding time in the postoperative period was accompanied by a significant increase in the mean platelet volume and by a significant increase in the level of thromboxane B2 measured in the blood shed from the site of the bleeding time determination. The postoperative bleeding time correlated with the postoperative blood loss, and both parameters were dependent on the duration of cardiopulmonary bypass. In addition, the postoperative bleeding time correlated with the skin temperature and the plasma level of D-dimer, while the postoperative blood loss also correlated with temperature and the plasma levels of C3. These data establish a direct relationship between the postoperative bleeding time, the postoperative blood loss, and temperature. They indicate that the reversal of the postoperative extension of the bleeding time is due in part to rewarming and to the release of larger platelets into the circulation, and they suggest that hyperfibrinolysis and complement activation may play an important role in the cardiopulmonary bypass-induced platelet dysfunction.

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Recent evidence suggests that the steady state level of prostaglandin (PG) endoperoxide synthase (PES) might regulate long term increases in PG synthesis, but the mechanism(s) regulating PES gene expression remains unclear. The present experiments investigated the regulation of PES expression in quiescent mesangial cells treated with serum. Serum induced time-dependent increases in PES steady state mRNA, protein level, and enzyme activity. Both the kinetics and cycloheximide sensitivity of PES mRNA induction suggest that PES was induced as a member of the delayed-early gene set. Beta-adrenergic-mediated cAMP accumulation was similar in Go and cycling cells, suggesting that the increase in PES expression did not reflect global up-regulation of signaling cascades in serum-treated cells. Three lines of evidence suggest that protein kinase-C (PKC) mediates serum-stimulated PES gene expression: 1) 12-tetradecanoyl phorbol 13-acetate mimicked the serum response; 2) PES gene expression by serum was attenuated in cells depleted of PKC; and 3) a PKC inhibitor, sangivamycin, blocked serum-stimulated PES gene induction. In addition, the ability of dexamethasone to block serum-induced PES enzyme activity without affecting the increase in PES mRNA points to posttranscriptional mechanisms of regulation. In summary, we conclude that in glomerular mesangial cells the PES gene is inducible, not constitutive, and that expression of this gene in Go cells is induced by serum and results in chronic elevations of PGE2. These findings are consistent with the hypothesis that differential regulation of PES gene expression might play a role in diverse cellular responses, such as mitogenesis and inflammation.

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The incidence of proliferative diabetic retinopathy was determined in the Pima Indians of the Gila River Indian Community in Arizona. Over 4 yr, this complication developed in 25 of 953 subjects greater than or equal to 9 yr of age with non-insulin-dependent diabetes. No cases were diagnosed in less than 35-yr-old subjects, and the incidence was strongly related to the duration of diabetes. The cumulative incidence of proliferative retinopathy after 20 yr duration was 14%. All cases of proliferative retinopathy occurred in subjects with background retinopathy. Younger age at diagnosis of diabetes was associated with a higher incidence of proliferation when subjects with diabetes of similar duration were compared. A higher incidence of proliferative retinopathy, after controlling for age, sex, and diabetes duration, was associated with hypertension, proteinuria, renal insufficiency, absence of Achilles tendon reflex, elevated total serum cholesterol concentration, and insulin therapy.

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Endomyocardial biopsy specimens from 96 patients with unexplained congestive heart failure or dysrhythmia were evaluated by standard histologic techniques and by direct immunofluorescence and immunoperoxidase cell marker analysis for mononuclear cell infiltration. Control specimens derived from normal autopsy hearts (n = 8) and autopsy hearts with severe coronary artery disease (n = 9) were analyzed in a similar fashion. The results were correlated with functional data obtained from cardiac catheterizations as well as the clinical history. The objectives of the study were to assess the sensitivity and specificity of immunoperoxidase identification of lymphocytes for the diagnosis of myocarditis and to correlate clinical parameters such as degree of cardiac dysfunction and symptom duration with the extent of inflammatory changes. No control biopsies (neither normal nor ischemic) had a T-cell concentration of one or more cells per high-power field (HPF:200X), whereas 32% of the study cases had more than one T-cell per HPF. Heavy T-cell infiltration (greater than or equal to 3 per HPF) was present in 7% of the study cases and occurred most commonly when the symptoms were of recent onset. The results demonstrate that lymphocytes are not present (less than 1 per HPF) in normal myocardium, in viable myocardium from hearts with generalized coronary artery disease, and in most endomyocardial biopsies (68%) from patients with unexplained heart failure or dysrhythmia. Thus, lymphocyte infiltration is not a nonspecific response to cardiac dysfunction. Immunoperoxidase identification of lymphocytes provides a quantitative assessment of inflammatory cell infiltration that is useful in the detection of myocarditis.

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On the basis of recent investigation, controversy has arisen regarding which of several cardiopulmonary resuscitation methods optimizes hemodynamics. The present study was designed to compare five recently described chest compression techniques: high-impulse manual chest compression at 150/min, mechanical compression at 60/min with simultaneous ventilation, mechanical compression at 60/min with simultaneous ventilation and either systolic or diastolic abdominal compression, and pneumatic vest compression at 60/min. Eight dogs were chronically instrumented with electromagnetic flow probes in the ascending and descending aorta while matched micromanometers measured aortic, left ventricular, and pleural pressures. At study, each dog was anesthetized with morphine, intubated, and the heart was fibrillated by rapid ventricular pacing. The five cardiopulmonary resuscitation methods were performed randomly in each preparation within 7 to 10 minutes of arrest. In four dogs, brachiocephalic blood flow was computed as total cardiac output minus descending aortic blood flow, and in all dogs coronary perfusion pressure was calculated as mean diastolic aortic pressure minus mean diastolic left ventricular pressure. Average cardiac output for seven studies was 662 +/- 61 ml/min with high-impulse manual compression, 340 +/- 46 ml/min with mechanical compression and simultaneous ventilation, 336 +/- 45 ml/min with mechanical compression and simultaneous ventilation with systolic abdominal compression, 366 +/- 52 ml/min with mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 196 +/- 29 ml/min with vest resuscitation (high-impulse manual compression significantly greater than other techniques by multivariate analysis, p less than 0.05). Brachiocephalic blood flow generally followed cardiac output and was statistically the greatest with high-impulse manual compression at 273 +/- 47 ml/min (p less than 0.05). Finally, high-impulse manual compression provided the highest coronary perfusion pressure of 31 +/- 4 mm Hg (p less than 0.05) compared to 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation, 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation with systolic abdominal compression, 23 +/- 3 mm Hg for mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 11 +/- 2 mm Hg for vest resuscitation. These data demonstrate that high-impulse manual compression generated physiologically and statistically superior hemodynamics when compared with other methods in this model of cardiopulmonary resuscitation.

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Adequate coronary blood flow is a major determinant for successful resuscitation from cardiopulmonary arrest. To develop compression techniques that optimize coronary blood flow, we implanted in eight dogs electromagnetic flow probes that measured circumflex coronary blood flow and ascending aortic blood flow. Micromanometers measured left ventricular and aortic pressures. Each dog was anesthetized and intubated, and the heart was fibrillated electrically. High-impulse manual chest compressions were performed with the dog in the supine position, and compression rate was varied from 60/min to 150/min. Antegrade coronary blood flow occurred primarily during artificial diastole, and there was a brief period of retrograde coronary blood flow with compression during artificial systole. Cardiac output and diastolic aortic pressure increased with compression rate, significantly augmenting peak coronary blood flow velocity. However, diastolic perfusion time decreased linearly with compression rate and limited coronary perfusion at rates greater than 120/min. As a result, net coronary blood flow during high-impulse manual chest compression was determined primarily by diastolic aortic pressure and diastolic perfusion time. Coronary blood flow was optimized in this model at a compression rate of 120/min.

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From 1966 through 1985, a total of 640 patients received 739 renal transplants at a single center transplantation program. Of 245 total deaths, a slide and chart review of all 116 autopsied cases (47%) identified the major causes of death as pneumonia (n = 43), sepsis (n = 32), hemorrhage (n = 15), peritonitis (n = 11), meningitis (n = 7), and pulmonary embolism (n = 5). Eighty-five (73.3%) of these patients died of complications directly associated with immunosuppression, almost all (n = 82) as a result of infection. Organisms most frequently identified at death were gram-negative bacilli (n = 72), Candida species (n = 23), cytomegalovirus (n = 17), enterococcus (n = 14), Staphylococcus aureus (n = 11), Aspergillus species (n = 10), Pneumocystis carinii (n = 5), and mycobacteria (n = 5). Significant associations were found between bolus steroid antirejection therapy and infection with Aspergillus cytomegalovirus. Diabetics had a higher incidence of fungal infections and bowel perforation than nondiabetics. During this 20-year period, overall one-year actual patient survival rates for the four respective five-year intervals increased dramatically (69.9%, 68.2%, 83.3%, and 91.8%), but the normalized death rate showed a smaller decrease for infectious vs noninfectious causes.

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Analyses of leaf megafossil and dispersed leaf cuticle assemblages indicate that major ecologic disruption and high rates of extinction occurred in plant communities at the Cretaceous-Tertiary boundary in the Raton Basin. In diversity increase, the early Paleocene vegetational sequence mimics normal short-term ecologic succession, but on a far longer time scale. No difference can be detected between latest Cretaceous and early Paleocene temperatures, but precipitation markedly increased at the boundary. Higher survival rate of deciduous versus evergreen taxa supports occurrence of a brief cold interval (<1 year), as predicted in models of an "impact winter."

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Since abnormalities in regional myocardial function and nucleotide metabolism persist for a prolonged period after a brief coronary occlusion the temporal relation between the resolution of myocardial dysfunction and repletion of nucleotide pools in postischaemic myocardium was studied in conscious mildly sedated animals. In a second experiment 5-amino-4-imidazolecarboxamide riboside (AICAriboside) was infused in an attempt to influence myocardial function by altering the rate of adenine nucleotide synthesis. Conscious dogs mildly sedated with morphine underwent coronary occlusion for 15 min followed by reperfusion for 30 min or 12 h, at which time a myocardial sample was obtained for nucleotide analysis. Segment shortening averaged 62% of control values at 15 min of reperfusion and increased to 81% of control by 12 h of reperfusion (p less than 0.05). Adenine nucleotide content was 75(5)% of control after 30 min of reperfusion and did not change significantly over the next 12 h of reperfusion. Thus the early return of systolic function was not accompanied by a detectable increase in total adenine nucleotide content. In the second experiment a pronounced stimulation of the proximal purine nucleotide synthetic pathway occurred as evidenced by a 13-fold to 25-fold increase in inosine monophosphate content. One branch of the distal purine pathway was also stimulated as evidenced by complete repletion of guanine nucleotide pools, but the product of the other branch (adenine nucleotides) did not increase significantly. These results indicate a selective limitation of the distal adenine nucleotide synthetic pathway in postischaemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

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The association of inflammatory cell infiltration with orthotopic rat liver transplant rejection was studied by immunopathologic evaluation of allografts at different time points using high- and low-responder strain combinations. PVG(RT-1c) recipients of ACI (RT-1a) liver transplants had prolonged survival (greater than 100 days) without immunosuppression. In contrast, Lewis (RT-1l) recipients of ACI liver transplants had severe acute rejection with mean survival of 10.7 +/- 0.5 days (n = 9). Graft recipients of both strain combinations, as well as control syngeneic PVG-to-PVG and Lewis-to-Lewis graft recipients were sacrificed at various time points posttransplant. Sections of livers were evaluated in a masked fashion for histologic changes as well as the extent and phenotype of cellular infiltrates, as determined by immunoperoxidase labeling using monoclonal antibodies OX1 (pan leukocyte), W3/13 (pan T cell), W3/25 (T helper cell:Th), and OX8 (T cytotoxic-suppressor:Tc-s). The results suggest that: the intensity and relative distribution of rat hepatic allograft T cell infiltrates at a given time point do not necessarily correlate with eventual outcome; the intensities of W3/25 (Th) and OX1 (pan-leukocyte) cell infiltrates parallel each other in both high- and low-responder strain combinations; the relative ratio of T cells (W3/13) to non-T cells increases over time in low-responder strains but remains relatively constant in high-responder strains during active rejection; and the relative ratio of W3/25:OX8 (Th:Tc-s) decreases in high-responder strains but increases in low-responder strains.

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