Drug treatment for benign prostatic hyperplasia. Health authorities must audit use of finasteride.
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Cost-Benefit Analysis↗
Biomedical subjects
D Thompson
Publications and source records attributed to D Thompson.
Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups.
OBJECTIVE: To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis. DATA SOURCES: Published data and data on file at Merck Research Laboratories. STUDY SELECTION: All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). DATA EXTRACTION: All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. DATA SYNTHESIS: In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. CONCLUSION: In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.
Adult↗
Future development of extramural studies.
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Education, Veterinary↗
Structural analysis of membrane-bound retrovirus capsid proteins.
We have developed a system for analysis of histidine-tagged (His-tagged) retrovirus core (Gag) proteins, assembled in vitro on lipid monolayers consisting of egg phosphatidylcholine (PC) plus the novel lipid DHGN. DHGN was shown to chelate nickel by atomic absorption spectrometry, and DHGN-containing monolayers specifically bound gold conjugates of His-tagged proteins. Using PC + DHGN monolayers, we examined membrane-bound arrays of an N-terminal His-tagged Moloney murine leukemia virus (M-MuLV) capsid (CA) protein, His-MoCA, and in vivo studies suggest that in vitro-derived His-MoCA arrays reflect some of the Gag protein interactions which occur in assembling virus particles. The His-MoCA proteins formed extensive two-dimensional (2D) protein crystals, with reflections out to 9.5 A resolution. The image-analyzed 2D projection of His-MoCA arrays revealed a distinct cage-like network. The asymmetry of the individual building blocks of the network led to the formation of two types of hexamer rings, surrounding protein-free cage holes. These results predict that Gag hexamers constitute a retrovirus core substructure, and that cage hole sizes define an exclusion limit for entry of retrovirus envelope proteins, or other plasma membrane proteins, into virus particles. We believe that the 2D crystallization method will permit the detailed analysis of retroviral Gag proteins and other His-tagged proteins.
Amino Acid Sequence↗
Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease.
The CD31 monoclonal antibody, LYP21, binds to the CD31 domain 6 and inhibits the human mixed-lymphocyte reaction (MLR) in a specific and dose-dependent fashion. A synthetic CD31 peptide based on human CD31 epitope (amino acids 551 to 574) recognized by LYP21 is equally effective in inhibiting the MLR. In this study, we used the murine homolog of CD31 peptide 551 to 574 and a control peptide to study the role of CD31 molecule on T-cell activation. In vitro, CD31 peptide inhibited the MLR across several major and minor histocompatibility differences in a specific and dose-dependent fashion, similar to the results observed in the human system. Maximal inhibition was achieved at a dose of 200 microg/mL. In the cytotoxic T-lymphocyte (CTL) assay, CD31 peptide inhibited CTL responses by 97%. To study the in vivo effect of this peptide, graft-versus-host disease (GVHD) across minor histocompatibility barriers was induced in the B10.D2 (H-2d) --> BALB/c (H-2d) model. BALB/c recipients received CD31 peptide (100 microg/d), or phosphate-buffered saline (PBS), or control peptide (100 microg/d) intraperitoneally (IP) for the first 5 weeks. CD31 peptide delayed onset of graft-versus-host disease and significantly increased long-term survival. Twelve of 14 mice receiving CD31 peptide survived more than 100 days after transplantation, as compared with none of 10 mice receiving PBS and none of five mice receiving control peptide (P = .0001). Long-term engraftment of allogeneic bone marrow was documented in all transplanted mice by polymerase chain reaction (PCR) analysis of microsatellite region in the interleukin (IL)-1beta gene. Our data suggest that the CD31 molecule has an important functional role in T-cell activation in vitro and in vivo.
Amino Acid Sequence↗
Computerized scene segmentation for the discrimination of architectural features in ductal proliferative lesions of the breast.
The distinction between ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS) still remains a problem in the histological diagnosis of non-invasive breast lesions. In this study, a method was developed for the automatic segmentation and quantitative analysis of breast ducts using knowledge-guided machine vision. This permitted duct profiles and intraduct lumina to be identified and their shape, size, and number computed. These were used to derive measures of duct cribriformity and architectural complexity which were examined as an objective tool in the characterization of duct pattern in proliferative lesions. A total of 215 images of ducts were digitally captured from 22 cases of DCIS and 21 cases of DH diagnosed independently by two pathologists. The cribriformity index proved to be a useful measure of duct architecture, showing a nosotonic increase with increasing duct complexity. The number of lumins also increased with increasing overgrowth of ductal epithelium until the duct was filled. Discriminant analysis of the duct characteristics for benign and malignant groups selected the lumen area/duct area ratio and the duct area as significant discriminatory variables and they were combined into a discriminant function. Of the lumens features, the mean area of the lumen and the polar average (mean of the distribution of the number of events with an increasing spiral from the centre of the duct) were combined into a second discriminant function. Plotting cases against these two functions provided good separation of DH and DCIS groups, with correct classification estimated on the training sample as being over 80 per cent. With an increasing incidence of complex proliferative lesions arising from mammography, the ability to diagnose these lesions correctly is more important than ever. The use of expert system-guided machine vision facilitates the quantitative evaluation of breast duct architecture; along with established histological and cytological criteria, it is hoped that this will lead to a more objective means of diagnosis and disease classification.
Aged↗
Automated location of dysplastic fields in colorectal histology using image texture analysis.
Automation in histopathology is an attractive concept and recent advances in the application of computerized expert systems and machine vision have made automated image analysis of histological images possible. Systems capable of complete automation not only require the ability to segment tissue features and grade histological abnormalities, but, must also be capable of locating diagnostically useful areas from within complex histological scenes. This is the first stage of the diagnostic process. The object of this study was to develop criteria for the automatic identification of focal areas of colorectal dysplasia from a background of histologically normal tissue. Fields of view representing normal colorectal mucosa (n = 120) and dysplastic mucosa (n = 120) were digitally captured and subjected to image texture analysis. Two features were selected as being the most important in the discrimination of normal and adenomatous colorectal mucosa. The first was a feature of the co-occurrence matrix and the second was the number of low optical density pixels in the image. A linear classification rule defined using these two features was capable of correctly classifying 86 per cent of a series of training images into their correct groups. In addition, large histological scenes were digitally captured, split into their component images, analysed according to texture, and classified as normal or abnormal using the previously defined classification rule. Maps of the histological scenes were constructed and in most cases, dysplastic colorectal mucosa was correctly identified on the basis of image texture: 83 per cent of test images were correctly classified. This study demonstrates that abnormalities in low-power tissue morphology can be identified using quantitative image analysis. The identification of diagnostically useful fields advances the potential of automated systems in histopathology: these regions could than be scrutinized at high power using knowledge-guided image segmentation for disease grading. Systems of this kind have the potential to provide objectivity, unbiased sampling, and valuable diagnostic decision support.
Adenomatous Polyps↗
Subtle changes in benign tissue adjacent to prostate neoplasia detected with a Bayesian belief network.
The aim of this paper was to test the usefulness of a Bayesian belief network (BBN) as a decision support system in the uncertainty assessment of benign prostatic tissue, either associated or not with inflammation or adjacent to prostatic adenocarcinoma (PAC) or prostatic intraepithelial neoplasia (PIN). A shallow network was used with eight first-level descendant nodes for the diagnostic clues, each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives. One diagnostic evidence node was based on the tissue architecture and the others were based on cell features. The efficacy of the network was tested on a series of 45 simple prostatectomy specimens, subdivided as follows; benign prostatic tissue not associated with other diseases (15 cases), associated with acute and/or chronic inflammation (15 cases), and adjacent to accidentally discovered PAC or PIN (15 cases). The highest belief values for the diagnostic alternative normal prostate (NP) were obtained in the 15 cases not associated with other diseases, the mean value being 0.996. The 15 cases evaluated in areas with inflammation showed the lowest belief values for NP (mean 0.774). For the 15 cases evaluated in specimens with PAC or PIN, the belief values for NP were intermediate between those from normal prostatic tissue associated with inflammation and those not associated (mean 0.925). Moreover, it was found that subtle changes were also present at a certain distance from the tumour. In conclusion, the network can be used as a decision support system to differentiate with high certainty benign prostate adjacent to PAC or PIN from benign prostatic tissue either associated or not with inflammation. The subtle morphological alteration detected with the BBN may be considered malignancy-associated changes.
Adenocarcinoma↗
Specific Contributions of Politics, Economics, and Toxicology in Setting Socially Consensual Limit Values
/ Limit values are legal limits for the concentrations of substances in the environment. They must be agreed upon in a consensual procedure between science, economics/technology, and political forces. This is a crucial political precondition for their social acceptance. The arguments put forward to justify their expediency and numerical level are based not only on risk-benefit considerations but also on the aspect of the technical avoidability of direct and indirect exposure. The critical assessment of the direct benefit of specified exposures falls within the responsibility of economics/technology, whereas criteria for their potential adverse effects (direct and indirect) are provided by medicine/biochemistry and/or ecology. Within this concept, the avoidance of nonbeneficial-even if not openly adverse-exposure is the essential aim of environmental hygiene and should be promoted by politics/science. In general, society or segments thereof reject adverse, accept beneficial, and tolerate unavoidable exposure. Conflicts of interest arise when different groups of society simultaneously define a given exposure as being adverse, beneficial, and unavoidable. Therefore, from the viewpoint of society as a whole, an optimal exposure lies as far as reasonably achievable at a level lower than known or plausible adverse effect thresholds (as defined by toxicology or ecology). This optimal level of exposure must be determined using a transparent and, hence, public procedure.KEY WORDS: Legal limit values; Benefit threshold; Social acceptance; Social tolerability; Adverse effect threshold; Avoidable exposure; Tolerance threshold; Environmental hygiene
Journal Article↗
Quantitative study of ductal breast cancer--patient targeted prognosis: an exploration of case base reasoning.
Current analytic methodologies allow the extraction, even from small tumor masses, of extensive information on the biologic characteristics of malignant lesions, such as tumor aggressivity, metastatic potential, drug resistance, and host interactions. Clinical practice now offers a wide range of therapeutic strategies. Information technological advances offer the opportunity to refer to very large data bases of patient anamnestic data, response to treatment and clinical outcome. There is a need to formulate therapy and prognosis for each individual case. Case based reasoning is a knowledge based methodology where the outcome for complex situations can be predicted by referring to a large data base of cases of known outcomes. The preliminary data obtained from this study suggest that case based reasoning may offer a promising approach to individual targeted prognosis.
Breast Neoplasms↗
An analysis of playground surface injuries.
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Accidental Falls↗
Scrotal pathology as the cause for hip pain. Diagnostic findings on bone scintigraphy.
Scrotal scintigraphy has become a relatively uncommon examination in many nuclear medicine departments. However, scrotal perfusion is visualized during three-phase bone imaging of the pelvis and hips. The authors present a compilation of three cases of hip pain secondary to unsuspected scrotal pathology documented on routine three-phase bone scintigraphy, discussing this topic for the first time in the literature. A short review of the pathophysiology of referred hip pain, differential diagnosis, and imaging alternatives emphasize the unique contribution of nuclear imaging.
Adolescent↗
Value-adding in the rural training stream: a release program for hospital-based rural training stream registrars.
This paper describes a release program developed in 1995 for year I hospital based GP registrars in the Rural Training Stream of the Royal Australian College of General Practitioners Training Program in South Australia. Background, objectives, content and organisation, and evaluation are described. The 1996 program that developed from this pilot is also described.
Australia↗
The soluble interleukin-2 receptor predicts mortality in older hospitalized men.
BACKGROUND: There is an inverse relationship between the soluble interleukin-2 receptor (sIL-2R) and serum albumin, cholesterol, transferrin, prealbumin, and hemoglobin. Inasmuch as low serum albumin and cholesterol have been associated with excess mortality, we hypothesized that elevated sIL-2R would predict mortality in older adults. OBJECTIVE: To determine if elevated sIL-2R predicts mortality in patients on a geriatric rehabilitation unit. DESIGN: Prospective cohort. SETTING: University-affiliated VA medical center. PARTICIPANTS: Seventy-two male patients aged greater than 60 years admitted to a geriatric rehabilitation unit. Patients with severe hepatic or renal disease were excluded. MEASUREMENTS: We measured serum albumin, prealbumin, cholesterol, transferrin, hemoglobin, body mass index (BMI), C-reactive protein (CRP), and sIL-2R upon admission. Subjects were followed for 1 year. RESULTS: Low serum albumin, prealbumin, and hemoglobin and high sIL-2R and CRP predicted 1-year mortality on univariate analysis. When these predictors were included as covariates in a Cox regression model, only sIL-2R was a significant independent predictor of mortality (P = .043). Multiple linear regression with the above covariates revealed that only sIL-2R predicted time to death at (P = .003). CONCLUSIONS: High sIL-2R and CRP and low albumin, prealbumin, and hemoglobin predicted mortality using univariate analysis on a rehabilitation unit. However, with multivariate analysis, sIL-2R was the sole predictor of mortality.
Aged↗
A descriptive analysis of children's playground injuries in the United States 1990-4.
OBJECTIVES: To review playground injury statistics over a five year period in order to develop an awareness of how and where children in the United States are being injured. METHODS: All data are based on the United States Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) for playground related injuries during 1990-4. The surveillance data includes injuries recorded in more than 90 hospital emergency departments located throughout the United States. RESULTS: Each year there are roughly 211,000 preschool or elementary school-children in the United States who receive emergency department care for injuries associated with playground equipment. On average, 17 of these cases result in death. 70% of all injuries occur on public playgrounds, with nearly one third classified as severe. Swings, climbers, and slides are the pieces of playground equipment associated with 88% of all NEISS reported injuries. Falls to the surface are responsible for 70%. CONCLUSIONS: NEISS playground injury statistics contribute to our understanding of playground injuries. By identifying where and how children are injured, suggestions can be made in an attempt to make playgrounds safer.
Adolescent↗
Diagnostic distance of high grade prostatic intraepithelial neoplasia from normal prostate and adenocarcinoma.
OBJECTIVE: To develop a distance measure based methodology to support the morphological evaluation of high grade prostatic intraepithelial neoplasia (PIN), a direct precursor of prostate cancer. METHODS: Eight morphological and cellular features were analysed in 20 cases of high grade PIN found in radical prostatectomy specimens from patients with adenocarcinoma. The diagnostic distance was evaluated to measure the extent to which the feature outcomes of the individual high grade PIN cases differed from the expected outcome profile of normal prostate, low and high grade PIN, and cribriform and large acinar adenocarcinoma. The belief value for high grade PIN was evaluated with a Bayesian belief network (BBN). RESULTS: Complete separation existed between the cumulative absolute diagnostic distances of these 20 cases from the prototype feature outcomes of high grade PIN and normal prostate the values for which were < or = 3 (range 0 to 3) and > or = 9 (range 9 to 15), respectively. The distances from low grade PIN (range 3 to 9), cribriform adenocarcinoma (range 2 to 8), and large acinar adenocarcinoma (range 5 to 10) were intermediate and showed overlap in their distribution. When taking into consideration whether the severity of feature changes was increasing or decreasing in comparison with the category prototype outcomes, the cumulative directional diagnostic distances from high grade PIN ranged from -3 to +3. Positive distance values were seen relative to low grade PIN (range +3 to +9) and relative to normal prostate (range +9 to +15). Negative values were found relative to cribriform adenocarcinoma (range -8 to +2). The distance values from large acinar adenocarcinoma ranged from -2 to +4 and partly overlapped with those from the high grade PIN category. A bivariate scattergram derived from both diagnostic distance measures showed excellent separation between the groups' distances. BBN analysis confirmed the morphology based diagnosis. The distance evaluation resulted in 18 cases whose belief value for high grade PIN ranged from 0.60 to 0.87. In the remaining two cases the results of the BBN analysis showed a belief value of 0.50 and 0.57 for low grade PIN and of 0.49 and 0.38 for high grade PIN, respectively. CONCLUSIONS: Distance measure based methodology represents a useful diagnostic decision support tool for the accurate evaluation of high grade PIN.
Adenocarcinoma↗
Herpes zoster encephalomyelitis associated with low dose methotrexate for rheumatoid arthritis.
We describe herpes zoster encephalomyelitis occurring 9 days after the onset of cutaneous zoster in an elderly patient taking low dose weekly methotrexate without concomitant prednisolone.
Aged↗
C-arm manipulation using a sterile disposable lamp handle.
Portable C-arm fluoroscopy is often used in the operating room. We describe a sterile technique that enables the physician to position the C-arm without requiring the use of a sterile drape.
Disposable Equipment↗