Monkeybar injuries.
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Accident Prevention↗
Biomedical subjects
D Thompson
Publications and source records attributed to D Thompson.
Early onset baldness and prostate cancer risk.
Prostatic carcinoma is the leading cancer among American men, yet few risk factors have been established. Although increased androgen levels have long been associated with both prostatic carcinoma and baldness, to date no studies have shown an association between hair patterning and prostate cancer risk. A lack of standardized instruments to assess baldness or the assessment of hair patterning during uninformative periods of time may have precluded the ability of previous studies to detect an association. We hypothesized that baldness, specifically vertex baldness, should be assessed using standardized instruments and during early adulthood if an association with prostate cancer risk is to be found. To test this hypothesis, we included identical items related to hair patterning in surveys that were administered in two distinct prostate cancer case-control studies (Duke-based study, n = 149; 78 cases; 71 controls and community-based study, n = 130; 56 cases; 74 controls). In each, participants were provided with an illustration of the Hamilton Scale of Baldness and asked to select the diagrams that best represented their hair patterning at age 30 and again at age 40. From these data, the following five categories were created and compared: not bald (referent group); vertex bald early onset (by age 30); vertex bald later onset (by age 40); frontal bald early onset (by age 30); frontal bald later onset (by age 40); and frontal (at age 30) to vertex bald (at age 40). Separate analyses of the two studies are consistent and suggest an association between vertex baldness and prostate cancer [vertex bald early onset odds ratios, 2.44 [confidence interval (CI), 0.57-10.46)] and 2.11 (CI, 0.66-6.73), respectively; vertex bald later onset odds ratios, 2.10 (CI, 0.63-7.00) and 1.37 (CI, 0.47-4.06), respectively]. Although statistical significance was not achieved in either one of these studies, the concordance between the data suggests a need for future studies to determine whether early onset vertex baldness serves as a novel biomarker for prostate cancer and whether androgen production, metabolism, or receptor status differs among these men when compared to those who exhibit other types of hair patterning.
Adenocarcinoma↗
Image analysis of mesothelioma. I. differentiation of mesothelioma from adenocarcinoma of the lung.
OBJECTIVE: To explore the usefulness of nuclear micromorphometric analysis for the differentiation between epithelial mesothelioma and metastatic adenocarcinoma in the chest wall. STUDY DESIGN: High-resolution images of 2,100 nuclei from 27 cases of epithelial mesothelioma and 15 cases of adenocarcinoma of the lung were recorded. Stepwise discriminant analysis and a nonparametric classifier were applied to derive estimates for a case diagnosis correct classification rate. RESULTS: Nuclei from epithelial mesothelioma and adenocarcinoma of the lung showed statistically significantly different properties, but there was a region of overlap in feature space such that approximately 15-20% of cases could not be correctly classified. The lesion signatures derived from the mesothelioma cases with discriminant function scores that might result in case misclassification and the cases of adenocarcinoma of the lung spanned a similar range of degree of nuclear abnormality. However, the distribution of nuclear abnormality values for the mesothelioma cases has a mode at 0.87 SD from normal, whereas the distribution seen in lung adenocarcinoma cases had a mode at about 3.7 SD. CONCLUSION: Cases of epithelial mesothelioma and adenocarcinoma of the lung have nuclei with a wide range of deviation from normal in the spatial and statistical distribution of their nuclear chromatin. For approximately 80% of cases, correct case classification can be provided by nuclear micromorphometric analysis. Cases of epithelial mesothelioma with highly abnormal nuclei overlap in feature space with nuclei from adenocarcinoma of the lung. However, it is possible that characterization by a lesion signature may allow correct assignment for those cases.
Adenocarcinoma↗
Chromatin texture analysis of cortical adrenal gland adenomas, including incidentalomas, and adjacent normal-appearing cortical tissue.
OBJECTIVE: To describe, by morphometric and chromatin texture analysis, a series of adrenal gland lesions, including Cushing's and Conn's adenomas and incidentalomas. STUDY DESIGN: The material for the study consisted of five consecutive cases of incidentaloma, three cases of Conn's adenoma and three cases of Cushing's adenoma. Also included were five cases of adrenal carcinoma. Sections were stained according to the Feulgen procedure. Measurements were taken from the nodules and from two different zones, identified as outer and inner parts, of the normal-appearing adrenal cortex adjacent to the tumor. Data on approximately 50 nuclei were recorded for each of these three sites (tumor and outer and inner normal-appearing adrenal cortex). The nuclei were subjected to feature extraction and were analyzed by identification procedures--i.e., establishing nuclear and lesion signatures. RESULTS: The total optical density (OD) distributions of the nuclei from the normal-appearing adrenal cortex pointed to their diploid or near-diploid nature. In incidentalomas there was a very small increase in the number of nuclei, with increased total OD. In Conn's adenoma there was a noticeable but modest extension of the total OD distribution into the higher OD range. This trend continued for Cushing's adenoma. The pixel OD histograms for nuclei from normal-appearing tissue and from incidentalomas were hardly distinguishable. Starting with nuclei from Conn's adenoma, a shift toward lower pixel OD values began. The trend continued for nuclei from Cushing's adenoma and was very pronounced for nuclei from carcinoma. The nuclear signatures showed no appreciable difference between nuclei from normal-appearing cortex and from incidentaloma. Nuclei from Conn's adenoma were more similar to those from normal tissue in their signatures than nuclei from Cushing's adenoma. In fact, the nuclear signatures from Cushing's adenoma were almost identical to those of carcinoma. The lesion signatures for normal tissue, incidentaloma and Conn's adenoma confirmed the results seen in the nuclear signatures. There was a very modest increase in the number of nuclei with greater deviation from normal in incidentalomas, and the trend was more obvious in Conn's adenoma. However, in Cushing's adenoma there was a very substantial increase in the number of nuclei, with large deviations of their nuclear chromatin texture from normal. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex and highlighted the similarity between incidentalomas and adjacent normal-appearing cortex and between Cushing's adenoma and adrenal carcinoma.
Adenoma↗
Image analysis of mesothelioma. II. Discrimination of mesothelioma from metastatic serous ovarian adenocarcinoma.
OBJECTIVE: To examine the utility of karyometric measurements in the differentiation of mesothelioma from metastatic serous ovarian adenocarcinoma. STUDY DESIGN: High-resolution images of 1,631 nuclei from 32 cases of mesothelioma and 742 nuclei from 15 cases of ovarian adenocarcinoma were recorded. A stepwise discriminant analysis and nonparametric classifier were applied. RESULTS: Nuclei from these two diagnostic categories appear very similar and occupy feature space with significant overlap. A nonparametric classification procedure provided acceptable correct classification. CONCLUSION: For certain regions in feature space, cases could be unequivocally classified.
Cell Nucleus↗
The clinical and economic burden of obesity in a managed care setting.
OBJECTIVE: To estimate the clinical and economic burden of obesity in a managed care setting. STUDY DESIGN: Prevalence-based cost-of-illness evaluation using modeling techniques and data from secondary sources. PATIENTS AND METHODS: The health and economic burden of obesity was estimated for a hypothetical health plan with 1 million members between the ages of 35 and 84 years, based on projections of the numbers of cases of 8 diseases for which obesity is an established risk factor (coronary heart disease, hypertension, hypercholesterolemia, gallbladder disease, stroke, type 2 diabetes, osteoarthritis of the knee, and endometrial cancer), obesity-attributable "etiologic fractions," and estimates of associated medical care costs. Our analysis was based on data from a variety of secondary sources, including a large managed care plan in the Pacific Northwest region of the United States. RESULTS: In a population of 1 million persons aged 35 to 84 years, it was estimated that obesity would account for approximately 132,900 cases of hypertension (45% of all cases), 58,500 cases of type 2 diabetes (85%), 51,500 cases of hypercholesterolemia (18%), and 16,500 cases of coronary heart disease (35%). Healthcare costs attributable to obesity were estimated to total $345.9 million annually (or 41% of the total for the 8 diseases of interest). CONCLUSION: The clinical and economic burden of obesity in a managed care setting is substantial.
Adult↗
Quantitative study of ductal breast cancer progression: signatures of nuclei in proliferating breast lesions and in situ cancer.
AIMS: The objective of this study is to derive highly specific nuclear signatures (NS's) for the characterization of nuclei of ductal breast epithelium in proliferative lesions and in situ cancers in order to evaluate if nuclear structural changes are able to describe the main events of ductal cancer progression and if the method can be used for objective grading. METHODS: A total of 82 different features descriptive of the nuclear chromatin patterns were computed in nuclei from normal glandular breast tissue, florid hyperplasia, and ductal carcinoma in situ (DCIS) and of DCIS with microinfiltration. The feature values were arranged to form a profile or signature. Measures of difference to a standard profile derived from normal glandular breast tissue were defined. One may then compute a standardized distance measure for a nucleus from "normal". Lesions can be characterized in the same manner, on the basis of the mean profile for all of their nuclei, and on the basis of the distribution of distances of their constituent nuclei from normal. RESULTS: The selected histopathologic patterns on which the diagnostic categories for DCIS are based were found to have corresponding distinctive patterns in the chromatin of the lesion's nuclei. A monotonic trend of ductal neoplastic progression was found. In addition, lesions histologically assessed as belonging to the same diagnostic category were found to offer substantially different distribution patterns. CONCLUSIONS: The full utilization of nuclear texture features allows the derivation of highly specific signatures for nuclei so that a reproducible grading can be performed for prognostic purposes.
Breast↗
A multi-state outbreak of tuberculosis among members of a highly mobile social network: implications for tuberculosis elimination.
SETTING: Baltimore, Maryland. OBJECTIVE: To describe a tuberculosis (TB) outbreak among a highly mobile population and the efforts required to control it. DESIGN: Epidemiologic outbreak investigation. RESULTS: Between June 1998 and January 2000, 20 TB outbreak cases were identified, of which 18 were culture-confirmed. Seventeen isolates of Mycobacterium tuberculosis had an identical 11-band DNA fingerprint; another isolate had one additional band and was considered a match. Two cases were diagnosed in New York City; another patient lived primarily in Atlanta, but was diagnosed in Baltimore. Persons in the outbreak were predominantly young (median age 24 years), black, male, infected with the human immunodeficiency virus (HIV), and gay, transvestite or transsexual. Activities common among many TB cases included attending two nightclubs, membership in one of three social 'Houses', attending balls or pageants in East Coast cities, marijuana use, and prostitution. Community outreach, extended contact tracing, DNA fingerprinting, directly-observed therapy, and expanded use of preventive therapy were utilized to assess and control the outbreak. During the outbreak period the Baltimore City TB rate declined by 10%. However, additional public health personnel were required to control the outbreak, resulting in a 17% increase in TB clinic staff. CONCLUSION: As TB rates decline, remaining cases are likely to occur in difficult-to-reach populations. Increased resources per case of TB treated will be required to eliminate TB.
AIDS-Related Opportunistic Infections↗
Diagnostic quiz #41. Case no. 1. Dentigerous cyst.
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Adolescent↗
Diagnostic quiz #37. Case no. 1. Squamous cell carcinoma.
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Aged↗
Managed care: how one big HMO capitulated.
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Eligibility Determination↗
Constraints on the Space Density of Methane Dwarfs and the Substellar Mass Function from a Deep Near-Infrared Survey.
We report preliminary results of a deep near-infrared search for methane-absorbing brown dwarfs; almost 5 yr after the discovery of Gl 229b, there are only a few confirmed examples of this type of object. New J-band, wide-field images, combined with preexisting R-band observations, allow efficient identification of candidates by their extreme (R-J) colors. Follow-up measurements with custom filters can then confirm objects with methane absorption. To date, we have surveyed a total of 11.4 deg2 to J approximately 20.5 and R approximately 25. Follow-up CH4 filter observations of promising candidates in one-fourth of these fields have turned up no methane-absorbing brown dwarfs. With 90% confidence, this implies that the space density of objects similar to Gl 229b is less than 0.012 pc-3. These calculations account for the vertical structure of the Galaxy, which can be important for sensitive measurements. Combining published theoretical atmospheric models with our observations sets an upper limit of alpha</=0.8 for the exponent of the initial mass function power law in this domain.
Journal Article↗
Lifetime health and economic consequences of obesity.
BACKGROUND: Obesity is an established risk factor for several chronic diseases. The lifetime health and economic consequences of obesity for individual patients have not been documented. OBJECTIVE: To estimate the lifetime health and economic consequences of obesity. METHODS: We developed a dynamic model of the relationship between body mass index and the risks and associated costs of 5 obesity-related diseases: hypertension, hypercholesterolemia, type 2 diabetes mellitus, coronary heart disease, and stroke. The model was estimated using data from the Third National Health and Nutrition Examination Survey, the Framingham Heart Study, and other secondary sources. We used this model to estimate (1) risks of hypertension, hypercholesterolemia, and type 2 diabetes mellitus at future ages; (2) lifetime risks of coronary heart disease and stroke; (3) life expectancy; and (4) expected lifetime medical care costs of these 5 diseases for men and women aged 35 to 64 years with body mass indexes of 22.5, 27.5, 32.5, and 37.5 kg/m2 (nonobese and mildly, moderately, and severely obese, respectively). RESULTS: Disease risks and costs increase substantially with increased body mass index. The risk of hypertension for moderately obese 45- to 54-year-old men, for example, is roughly 2-fold higher than for their nonobese peers (38.1% vs 17.7%), whereas the risk of type 2 diabetes mellitus is almost 3-fold higher (8.1% vs 3.0%). Lifetime risks of coronary heart disease and stroke are similarly elevated (41.8% vs 34.9% and 16.2% vs 13.9%, respectively), whereas life expectancy is reduced by 1 year (26.5 vs 27.5 years). Total discounted lifetime medical care costs for the treatment of these 5 diseases are estimated to differ by $10,000 ($29,600 vs $19,600). Similar results were obtained for women. CONCLUSIONS: The lifetime health and economic consequences of obesity are substantial and suggest that efforts to prevent or reduce this problem might yield significant benefits.
Adult↗
Cure crusader. How a cancer patient waged a determined quest for a medical miracle--and may still achieve it.
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Adenomatous Polyposis Coli↗
The physiological structure of human C-reactive protein and its complex with phosphocholine.
BACKGROUND: Human C-reactive protein (CRP) is the classical acute phase reactant, the circulating concentration of which rises rapidly and extensively in a cytokine-mediated response to tissue injury, infection and inflammation. Serum CRP values are routinely measured, empirically, to detect and monitor many human diseases. However, CRP is likely to have important host defence, scavenging and metabolic functions through its capacity for calcium-dependent binding to exogenous and autologous molecules containing phosphocholine (PC) and then activating the classical complement pathway. CRP may also have pathogenic effects and the recent discovery of a prognostic association between increased CRP production and coronary atherothrombotic events is of particular interest. RESULTS: The X-ray structures of fully calcified C-reactive protein, in the presence and absence of bound PC, reveal that although the subunit beta-sheet jellyroll fold is very similar to that of the homologous pentameric protein serum amyloid P component, each subunit is tipped towards the fivefold axis. PC is bound in a shallow surface pocket on each subunit, interacting with the two protein-bound calcium ions via the phosphate group and with Glu81 via the choline moiety. There is also an unexpected hydrophobic pocket adjacent to the ligand. CONCLUSIONS: The structure shows how large ligands containing PC may be bound by CRP via a phosphate oxygen that projects away from the surface of the protein. Multipoint attachment of one planar face of the CRP molecule to a PC-bearing surface would leave available, on the opposite exposed face, the recognition sites for C1q, which have been identified by mutagenesis. This would enable CRP to target physiologically and/or pathologically significant complement activation. The hydrophobic pocket adjacent to bound PC invites the design of inhibitors of CRP binding that may have therapeutic relevance to the possible role of CRP in atherothrombotic events.
Binding Sites↗
Inference network-based analyses of the histopathological effects of androgen deprivation on prostate cancer.
The evaluation of prostate cancer histology following hormonal therapy often represents a diagnostic problem for the pathologist. Previous studies have shown that an inference or Bayesian belief network (BBN) offers a descriptive classifier useful for the accurate analysis of morphological changes in individual cases of prostate neoplasia. Three different BBNs were evaluated in 94 cancer foci present in 20 radical prostatectomy (RP) specimens and in the matching biopsies in which the initial diagnosis of prostatic adenocarcinoma was made. Ten RP specimens were from patients treated with total androgen ablation or combination endocrine therapy (CET) before surgery. The first and second BBN allowed the identification with high certainty of the cancer foci present in the biopsies and RP specimens, as well as their Gleason grade, the belief value often being close to 1.0. The results of the second BBN showed a good correspondence between the Gleason grade given in the biopsies and that in the RP specimens, except in the surgical material of the treated patients, in which upgrading was always present. The third BBN showed the existence of three subgroups in treated RP specimens, one with morphological effect, another with poor effect, and the third with the histology of untreated (i.e. unaffected) cancer. In conclusion, an inference network-based analysis allows the characterization of treated prostate cancers according to the degree of histopathological change.
Adenocarcinoma↗
Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group.
OBJECTIVE: To investigate whether the incidence of vertebral fractures is related to the magnitude of change in bone mineral density (BMD) during alendronate treatment. METHODS: Women in this study were age 55-81 years (n = 2,984). While participating in the Fracture Intervention Trial, they received 5 mg/day of alendronate for 2 years followed by 10 mg/day for the remaining 12-30 months of the study. Their BMD was measured at baseline and at 12 and 24 months, and spine radiographs were obtained at baseline and again at 36 or 48 months to identify new vertebral fractures. RESULTS: After 12 months of alendronate treatment, 35% of participants had increases of > or =3% in total hip BMD, and 21% had either decreased total hip BMD or no change. Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period. Only 3.2% of women with increases of > or =3% in total hip BMD experienced new vertebral fractures, whereas twice as many women (6.3%) whose BMD declined or stayed the same experienced new fractures (adjusted odds ratio 0.45, 95% confidence interval 0.27-0.72). Similar patterns were observed for spine BMD at 12 months, and for both sites using change in BMD at 24 months. CONCLUSION: Women with increases of > or =3% in BMD during the first 1 or 2 years of alendronate treatment had the lowest incidence of new vertebral fractures. These findings suggest that, among women taking antiresorptive agents, greater increases in BMD are associated with lower risk of new vertebral fractures.
Aged↗