Biomedical subjects
Publications and source records attributed to D R Anderson.
We present the MRI findings in a case of subcutaneous fat necrosis of the newborn. To our knowledge, the MRI findings of this entity have not been reported. Subcutaneous fat necrosis of the newborn is an uncommon, benign process in full-term infants. Hypercalcemia may be a potentially life-threatening complication of this otherwise self-limiting process.
It is widely suspected that tissue ischemia initiates or participates in optic disk damage in glaucoma. The details are not well delineated. Particularly puzzling is the clear separation of the clinical appearances of glaucoma and anterior ischemic optic neuropathy, which is also a presumed ischemic disease. When venous pressure at the exit point from the eye is elevated by intraocular pressure (IOP), the arteriovenous pressure difference is reduced. Nutrition is maintained only because of blood flow autoregulation. Intraocular pressure-induced ischemia can result if autoregulation is impaired in an individual, either because of an innate deficiency or, perhaps, as a result of vasospastic disease. Autoregulation can also be impaired if another disease (e.g., an atheroma) has caused much of the autoregulatory capacity to be already utilized, so that little or none is left to respond to the additional challenge of IOP. Ischemia might also result from microvascular occlusion with platelet or clotting abnormalities, perhaps inducing glaucomatous optic neuropathy that is not dependent on IOP. A better understanding of the pathogenic mechanism (and how it may be different in various cases) is needed to predict more successfully an individual's risk of glaucomatous damage, to make decisions about the aggressiveness of treatment, and, one day, to direct therapy at the type of vascular abnormality present, in addition to or instead of lowering IOP.
The conceptual and computational structure of a performance assessment (PA) for the Waste Isolation Pilot Plant (WIPP) is described. Important parts of this structure are (1) maintenance of a separation between stochastic (i.e., aleatory) and subjective (i.e., epistemic) uncertainty, with stochastic uncertainty arising from the many possible disruptions that could occur over the 10,000-year regulatory period that applies to the WIPP, and subjective uncertainty arising from the imprecision with which many of the quantities required in the analysis are known, (2) use of Latin hypercube sampling to incorporate the effects of subjective uncertainty, (3) use of Monte Carlo (i.e., random) sampling to incorporate the effects of stochastic uncertainty, and (4) efficient use of the necessarily limited number of mechanistic calculations that can be performed to support the analysis. The WIPP is under development by the U.S. Department of Energy (DOE) for the geologic (i.e., deep underground) disposal of transuranic (TRU) waste, with the indicated PA supporting a Compliance Certification Application (CCA) by the DOE to the U.S. Environmental Protection Agency (EPA) in October 1996 for the necessary certifications for the WIPP to begin operation. The EPA certified the WIPP for the disposal of TRU waste in May 1998, with the result that the WIPP will be the first operational facility in the United States for the geologic disposal of radioactive waste.
Television viewing at home by 50 individuals in 5 age groups (2-, 5-, 8-, 12-year-olds, and adults) was recorded on 1-s time-lapse videotapes over 10-day periods. Coding was based on 5-min point samples. Analysis examined looking at the TV screen in relation to the visual presence of the features cuts, movement, animation, man, woman, child, and nonhuman; content features were child vs. adult programming and overt purposeful character behavior. Cuts, movement, and overt purposeful character behavior were positively related to looking independent of child vs. adult programming. Associations with looking for the remaining features depended on the viewer's age or sex or type of content within which they occurred.
Compression US is the imaging procedure of choice for patients with clinically suspected DVT of the lower and upper extremities. Clinical trials have validated the safety of the approach of relying on two negative US studies obtained 1 week apart to safely exclude the diagnosis of DVT. In selected low-risk patients, the diagnosis of DVT may be excluded by a single negative US study. US has a role to play in the management of patients with suspected pulmonary embolism who have nondiagnostic pulmonary imaging studies.
Deep vein thrombosis is a relatively common disease, amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with the non-invasive imaging procedure ultrasonography, but limitations exist. As with all tests, there is a potential for false-positive and false-negative results. The latter are especially an issue for calf vein thrombi, and this in part has led to the concept of serial testing of the proximal venous system rather than imaging the calf. The premise of the repeat (serial) test is that only thrombi that extend to the proximal system are clinically relevant and such thrombi will be detected on the repeat test. However, despite the safety of the serial-testing concept, it is inconvenient and expensive. In the last few years, the diagnostic process has been improved by the validation of a clinical model that accurately categorizes patients as having low, moderate or high probability of deep vein thrombosis. Among the improvements this provides is the elimination of serial testing if the ultrasound is normal and the clinical probability low. The fibrin degradation product D-dimer has been demonstrated to have a high negative predictive value and has also proven useful in diagnostic algorithms. The combination of the D-dimer with clinical model assessment will enable diagnostic-testing strategies that are more safe, effective and convenient for patients.
A high-affinity IgG1 kappa murine monoclonal anti-CD20 antibody (IDEC-2B8) was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma. A stable immunoconjugate (Zevalintrade mark) was prepared by reacting IDEC-2B8 with a derivative of diethylenetriaminepentaacetic acid, designated MX-DTPA, a chelator exhibiting high affinity and retention for 90Y. Zevalin exhibited antigen specificity, human tissue reactivity, and preclinical safety profile comparable to the native antibody. The conjugate radiolabeled with 90Y (90Y-Zevalin) or 111In (111In-Zevalin) exhibited excellent retention of immunoreactivity with radioincorporations >95%. The radiolabeled conjugates formulated in PBS containing human serum albumin were stable in vitro at 4 degrees C for 48 h as indicated by negligible loss of radioisotope and retention of binding to CD20+ cells. In vitro human serum stability studies at 37 degrees C with 90Y-Zevalin indicated that loss of 90Y from the conjugate was minimal, averaging 1% per day. Biodistribution studies in BALB/c mice confirmed the in vitro stability of 90Y-Zevalin and 111In-Zevalin. In particular, excellent in vivo retention of 90Y by the conjugate was demonstrated by minimal bone accumulation (</=3% of the injected dose over three days). Radiation dose estimates to normal organs calculated from mouse biodistribution studies with 90Y-Zevalin were comparable to those determined in a phase I/II clinical trial and below generally accepted safe radiation levels. Studies in athymic mice bearing CD20+ tumors demonstrated that 111In-Zevalin accumulated in the tumors preferentially compared with normal organs. 90Y-Zevalin is currently being evaluated in phase III clinical trials for treatment of relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin's lymphoma.
The purpose of this study was to evaluate whether the determination of pretest probability using a simple clinical model and the SimpliRED D-dimer could be used to improve the management of hospitalized patients with suspected deep-vein thrombosis. Consecutive hospitalized patients with suspected deep-vein thrombosis, had their pretest probability determined using a clinical model and had a SimpliRED D-dimer assay. Patients at low pretest probability underwent a single ultrasound test. A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography. Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound one week later. Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography. All patients were followed for three months for the development of venous thromboembolic complications. Overall, 28% (42/150), and 10% (5/50), 21% (14/71) and 76% (22/29) of the low, moderate and high pretest probability patients. respectively, had deep vein thrombosis. Two of 111 (1.8%; 95% CI = 0.02% to 6.4%) patients considered to have deep vein thrombosis excluded had events during three-month follow-up. Overall 13 of 150 (8.7%) required venography and serial testing was limited to 58 of 150 (38.7%) patients. The negative predictive value of the SimpliRED D-dimer in patients with low pretest probability was 96.2%, which is not statistically different from the negative predictive value of a negative ultrasound result in low pretest probability patients (97.8%). Management of hospitalized patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible.
OBJECTIVE: To determine the pharmacologic and physical modalities used by orthopedic surgeons in Canada to prevent venous thromboembolism (deep venous thrombosis and pulmonary embolism) after total hip or knee arthroplasty. DESIGN: Mail survey sent to all members of the Canadian Orthopaedic Association. SETTING: A nation-wide study. METHODS: A total of 828 questionnaires, designed to identify the type and frequency of prophylaxis against venous thromboembolism that were used after hip and knee arthroplasty were mailed to orthopedic surgeons. OUTCOME MEASURES: Demographic data and the frequency and type of thromboprophylaxis. RESULTS: Of the 828 surveys mailed 445 (54%) were returned, and 397 were included in this analysis. Of the respondents, 97% used prophylaxis routinely for patients who undergo total hip or knee arthroplasty. Three of the 397 (0.8%) did not use any method ofprophylaxis. Warfarin was the most common agent used (46%), followed by low-molecular-weight heparin (LMWH) (36%). Combination therapy with both mechanical and pharmacologic methods were used in 39% of patients. Objective screening tests were not frequently performed before discharge. Extended prophylaxis beyond the duration of hospitalization was used by 36% of physicians. CONCLUSION: Prophylaxis for venous thromboembolism with warfarin or LMWH has become standard care after total hip or knee arthroplasty in Canada.
Recent advances in the management of patients with suspected VTE have resulted in improvements in the diagnostic testing accuracy and the development of management algorithms that are safer and more accessible. Ongoing clinical trials are evaluating whether these diagnostic management strategies can be made even simpler and less expensive. Diagnostic procedures for VTE continue to be refined, and modalities, such as magnetic resonance imaging and spiral CT, have the potential to further increase the accuracy of the investigation approach. There is still need to improve management strategies for the diagnosis of recurrent venous thrombosis and to determine whether diagnostic testing results may be correlated with long-term patient treatment needs.
BACKGROUND: The low specificity of ventilation-perfusion lung scanning complicates the management of patients with suspected pulmonary embolism. OBJECTIVE: To determine the safety of a clinical model for patients with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Five tertiary care hospitals. PATIENTS: 1239 inpatients and outpatients with suspected pulmonary embolism. INTERVENTIONS: A clinical model categorized pretest probability of pulmonary embolism as low, moderate, or high, and ventilation-perfusion scanning and bilateral deep venous ultrasonography were done. Testing by serial ultrasonography, venography, or angiography depended on pretest probability and lung scans. MEASUREMENTS: Patients were considered positive for pulmonary embolism if they had an abnormal pulmonary angiogram, abnormal ultrasonogram or venogram, high-probability ventilation-perfusion scan plus moderate or high pretest probability, or venous thromboembolic event during the 3-month follow-up. All other patients were considered negative for pulmonary embolism. Rates of pulmonary embolism during follow-up in patients who had a normal lung scan and those with a non-high-probability scan and normal serial ultrasonogram were compared. RESULTS: Pretest probability was low in 734 patients (3.4% with pulmonary embolism), moderate in 403 (27.8% with pulmonary embolism), and high in 102 (78.4% with pulmonary embolism). Three of the 665 patients (0.5% [95% CI, 0.1% to 1.3%]) with low or moderate pretest probability and a non-high-probability scan who were considered negative for pulmonary embolism had pulmonary embolism or deep venous thrombosis during 90-day follow-up; this rate did not differ from that in patients with a normal scan (0.6% [CI, 0.1% to 1.8%]; P > 0.2). CONCLUSION: Management of patients with suspected pulmonary embolism on the basis of pretest probability and results of ventilation-perfusion scanning is safe.
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BACKGROUND: The aim of this study was to assess by angiography the late effects of both classic and modified Blalock-Taussig shunts in terms of growth and development of stenosis and distortion. METHODS: At a mean of 51 months postoperatively, we retrospectively reviewed the results in 78 patients who underwent creation of Blalock-Taussig shunts (25 classic and 71 modified). RESULTS: At the level of the anastomosis, the shunt caused a reduction in diameter of the pulmonary artery in 49% of all shunts, major stenosis (>50% narrowing of the lumen) in 14%, and distortion of the pulmonary artery in 19%, findings that did not correlate with the type of shunt. Distortion did correlate with younger age at the time of shunt operation (p=0.01). CONCLUSIONS: After a Blalock-Taussig shunt, growth of the pulmonary arteries occurred but did not exceed the normal growth of the pulmonary arterial tree. Moreover, a shunt procedure can cause distortion and stenosis of the pulmonary artery, which may have important implications for future corrective surgical intervention. All these findings support earlier complete surgical repair of correctable congenital cardiac defects.
OBJECTIVES: We recently demonstrated the utility of a clinical model combined with ultrasonography to assist the diagnostic approach in patients with suspected deep-vein thrombosis (DVT). In this study we also sought to demonstrate that the model is useful with impedance plethysmography, a less accurate and less utilized diagnostic test. The original clinical model is slightly cumbersome to use; thus at the completion of the study we attempted to develop a simpler scoring system with a goal of maintaining accuracy. DESIGN: An open, nonrandomized, multicentre trial. SETTING: Three centres, two in Canada, and one in Italy. SUBJECTS: Ambulatory patients with suspected deep-vein thrombosis. INTERVENTIONS: All patients were assessed clinically to determine the probability for deep-vein thrombosis prior to performing impedance plethysmography and venography. We compared the accuracy of impedance plethysmography between the three pretest probability categories of high, moderate and low. All of the above were performed and interpreted by independent observers. When the study was completed, we revised the clinical model by first performing a simple regression analysis then a multiple logistic regression analysis; a scoring system was devised using the latter. RESULTS: Impedance plethysmography is significantly more sensitive and less specific for all DVT in patients with high pretest probability for deep-vein thrombosis (P = 0.001). The post- test probability (positive predictive value) for deep-vein thrombosis with an abnormal impedance plethysmography result was significantly different (P = 0.0001) between the three pretest probability categories. Multiple regression analysis has provided a new model with only nine variables and a simple scoring system. The retrospective application of the revised clinical model, which is simpler to use, suggests it will provide similar results as the original clinical model when combined with impedance plethysmography. The combination of impedance plethysmography and the clinical model suggests patients are likely to have false positive results if they have a low or moderate pretest probability for deep-vein thrombosis and false negative results if the pretest probability is high. The combination of a low pretest probability and a normal impedance plethysmography result may exclude the need for serial testing, and represented more than 50% of our patient population. CONCLUSIONS: The use of the clinical model in conjunction with impedance plethysmography would decrease the number of false positive and negative diagnoses and could markedly decrease the need for serial impedance plethysmography. Combining the clinical model with impedance plethysmography could overcome the fact that impedance plethysmography is clearly less accurate than venous ultrasound imaging. The use of the revised clinical model may increase acceptability and utility, but prospective testing is required before widespread use.
This investigation estimates the impact of ten modifiable health risk behaviors and measures and their impact on health care expenditures, controlling for other measured risk and demographic factors. Retrospective two-stage multivariate analyses, including logistic and linear regression models, were used to follow up 46,026 employees from six large health care purchasers for up to 3 years after they completed an initial health risk appraisal. These participants contributed 113,963 person-years of experience. Results show that employees at high risk for poor health outcomes had significantly higher expenditures than did subjects at lower risk in seven of ten risk categories: those who reported themselves as depressed (70% higher expenditures), at high stress (46%), with high blood glucose levels (35%), at extremely high or low body weight (21%), former (20%) and current (14%) tobacco users, with high blood pressure (12%), and with sedentary lifestyle (10%). These same risk factors were found to be associated with a higher likelihood of having extremely high (outlier) expenditures. Employees with multiple risk profiles for specific disease outcomes had higher expenditures than did those without these profiles for the following diseases: heart disease (228% higher expenditures), psychosocial problems (147%), and stroke (85%). Compared with prior studies, the results provide more precise estimates of the incremental medical expenditures associated with common modifiable risk factors after we controlled for multiple risk conditions and demographic confounders. The authors conclude that common modifiable health risks are associated with short-term increases in the likelihood of incurring health expenditures and in the magnitude of those expenditures.
Coxsackievirus B3 (CVB3), an enterovirus in the family Picornaviridae, induces cytopathic changes in cell culture systems and directly injures multiple susceptible organs and tissues in vivo, including the myocardium, early after infection. Biochemical analysis of the cell death pathway in CVB3-infected HeLa cells demonstrated that the 32-kDa proform of caspase 3 is cleaved subsequent to the degenerative morphological changes seen in infected HeLa cells. Caspase activation assays confirm that the cleaved caspase 3 is proteolytically active. The caspase 3 substrates poly(ADP-ribose) polymerase, a DNA repair enzyme, and DNA fragmentation factor, a cytoplasmic inhibitor of an endonuclease responsible for DNA fragmentation, were degraded at 9 h following infection, yielding their characteristic cleavage fragments. Inhibition of caspase activation by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD.fmk) did not inhibit the virus-induced cytopathic effect, while inhibition of caspase activation by ZVAD.fmk in control apoptotic cells induced by treatment with the porphyrin photosensitizer benzoporphyrin derivative monoacid ring A and visible light inhibited the apoptotic phenotype. Caspase activation and cleavage of substrates may not be responsible for the characteristic cytopathic effect produced by picornavirus infection yet may be related to late-stage alterations of cellular homeostatic processes and structural integrity.
Clinical trials evaluating antithrombotic therapy for the treatment of deep vein thrombosis require that the diagnosis is confirmed by objective testing prior to patient entry into the study. Two basic approaches may then be taken for defining endpoints to assess the efficacy of antithrombotic treatment. In the first approach, the diagnostic test is repeated at a predetermined time following the initiation of the interventional therapy. In the second approach, no further diagnostic testing is routinely performed for a minimum of 3 months following patient enrolment after the diagnosis of venous thromboembolism for evidence of symptomatic recurrent deep vein thrombosis or pulmonary embolism. This approach is used in later-phase clinical trials to examine whether a novel therapeutic agent is as safe and effective as the drugs currently used for management of venous thromboembolism. Symptomatic recurrent deep vein thrombosis and pulmonary embolism confirmed by objective testing are clinically important causes of patient morbidity, place patients at increased risk of fatal pulmonary embolism, cause increased rates of chronic thromboembolic complications and have resource consequences. Studies utilizing symptomatic recurrent deep vein thrombosis or pulmonary embolism as endpoints have been responsible for most of the treatment advances in the management of patients with venous thromboembolism that have been observed in the past 40 years. Although confirmation of recurrent venous thromboembolism is not possible in all patients, clinical trials using rigorous methodology can minimize the potential bias caused by the limitations of diagnostic test results. There is a need to develop better objective tests in the future, to distinguish previous from recurrent venous thromboembolism.