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Biomedical subjects

D Thompson

Publications and source records attributed to D Thompson.

At least 127 records · Page 7Linked to original sources
PubMed1999

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.

OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.

Adenocarcinoma↗
PubMed1999

Distinguishing cortical adrenal gland adenomas from carcinomas by their quantitative nuclear features.

OBJECTIVE: To explore data from a set of cases of adrenal cortical adenomas with different endocrine syndromes and carcinomas to determine whether quantitative image analysis of nuclear features might be used to separate the groups. STUDY DESIGN: Fifteen adrenal cortical tumors in which clinical information and optimally preserved, paraffin-embedded tissue were available were used. There were 10 adenomas and 5 carcinomas. Among the adenomas, five were associated with primary hyperaldosteronism (Conn's syndrome) and five with Cushing's syndrome. Five-micrometer-thick sections were stained with hematoxylin and eosin. In each case 50 nuclei were measured, and a number of morphometric and densitometric features were extracted. The data were subjected to multivariate analysis. RESULTS: Quantitative analysis showed that nuclei from adrenal carcinomas are larger than those from adenomas. Total optical density (OD) had a near-diploid distribution in the adenomas, while it was clearly aneuploid in the carcinomas. The pixel OD histograms were almost identical for all groups. Differences in nuclear chromatin texture were found between adenomas and carcinomas and also between the two adenoma categories. Multivariate analysis showed good discrimination between carcinomas and adenomas (Wilks lambda = .628, P < .0001) and between adenomas. However, based on Bayesian decision boundaries, 20-25% of carcinoma nuclei could be expected to be in the range of adenoma, and about 12% of Cushing's adenoma nuclei and 15% of Conn's adenoma nuclei would be classified as carcinoma. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex.

Adenoma↗
PubMed1999

Case-based prediction of survival in colorectal cancer patients.

OBJECTIVE: To develop an approach to the prediction of survival in patients with colorectal cancer using nearest neighbor analysis and case-based reasoning. STUDY DESIGN: A total of 216 patients with full clinicopathologic records and five-year follow-up were the subjects of this study. They were divided into a core database of 162 cases and a test group of 54 cases, with follow-up on all patients. When the patient was still alive at the end of the follow-up period, censored survival time was used. For each of the test cases, the four closest neighbors from the database were retrieved and their median survival time recorded and used as the predicted estimate of survival. Case matching was based on a Euclidean multivariate distance measure for the three best predictor variables: patient age, Dukes stage and tubule configuration. Cases with the smallest distance from the test case were considered to be the most similar. The predicted survival times for the test cases were compared with the actual, observed survival in the test cases to determine the success of this approach. RESULTS: The results showed reasonable concordance between observed and predicted survival figures, although there was a large degree of spread. Classification of cases into < or = 60 and > 60 months' survival showed a correct classification rate of 63%. For the prediction of survival time, the distribution of differences between observed and predicted survival times for the uncensored test cases had a median value of--5 months but also showed a wide dispersion of values. Correlation of observed and predicted survival times, while not reaching statistical significance at P < .05, did show a strong positive association. CONCLUSION: Case-based approaches to the prediction of survival times in cancer patients are important. The results of the current study illustrate the difficulties in applying this approach to survival data and highlight the complexity of patient information and the inability to accurately predict patient outcome on a small subset of clinicopathologic features. While extensive work needs to be carried out to improve prediction power, this study illustrates the potential for case-based analyses. The ability to retrieve feature-matched cases from hospital patient databases has clear, independent advantages in patient management, but the ability to provide reliable, targeted prognostic estimates on individual cases should be a common goal in medical research.

Adult↗
PubMed1999

The prevention of playground injuries.

Playground accidents are the most common cause of injury to children in school. As the health professional who attends to these injured children, school nurses should be aware of safety practices that can help eliminate the risks that children encounter. The National Program for Playground Safety has identified four areas that can reduce the level of risk on school playgrounds: supervision, age-appropriate design of the play area, fall surfaces under and around playground equipment, and equipment and surface maintenance. The article discusses each of these, and recommends leadership methods and practices that nurses can implement that will eliminate or reduce risk factors. In addition, a comprehensive playground risk model is described, and suggestions for policy areas are outlined. Policy areas include assessment, education, and enforcement in relation to each of the risk factors.

Accidental Falls↗
PubMed1998

A week in the life of a hospital.

The same urgency and intellect that America's teaching hospitals apply to saving lives is now also going into saving the institutions themselves. All across the country, academic medical centers are trying to figure out how to marry progress with profits. At the Duke University Medical Center, TIME visits the front line in the war between money and medicine.

Budgets↗
PubMed1998

Organization of HIV-1 capsid proteins on a lipid monolayer.

In an in vitro system that mimics the assembly of immature human immunodeficiency virus (HIV) particles, ordered arrays of HIV-1 capsid (CA) proteins encoded by the viral gag gene have been obtained by incubation of histidine-tagged capsid proteins (His-HIVCA) beneath lipid monolayers containing the nickel-chelating lipid, 1,2-di-O-hexadecyl-sn-glycero-3-(1'-2"-R-hydroxy-3'-N-(5-amino-1- carboxypentyl)iminodiacetic acid)propyl ether. The membrane-bound His-HIVCA proteins formed small crystalline arrays of primitive (p1) unit cells with dimensions of a = 74.2 A, b = 126.2 A, gamma = 89.3 degrees. The image-analyzed two-dimensional projection of His-HIVCA assemblies shows a cage-like lattice, consisting of hexamer and trimer units, surrounding protein-free cage holes. The hexamer-coordinated cage holes of 26.3-A diameter are spaced at 74. 2-A intervals: these distances, and the hexamer-trimer arrangement, are consistent with previous, lower resolution studies on immature HIV-1 virus particles produced in vivo. Additionally, HIV-1 matrix protein trimer unit structures align to the His-HIVCA trimer units such that residues previously shown to interact with the HIV-1 gp120/gp41 envelope protein complex are oriented toward the hexamer cage holes. Our results form a bridge between results from conventional methods for the analysis of HIV particle structure.

Capsid↗
PubMed1998

Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.

BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.

Alendronate↗
PubMed1998

Holmium laser enucleation of the prostate (HoLEP) combined with transurethral tissue morcellation: an update on the early clinical experience.

The preliminary experience with 64 patients who have undergone HoLEP combined with intravesical morcellation is presented. The mean preoperative prostate volume was 75.3 cc. The mean laser time was 46.9 minutes and the morcellator time a further 10.5 minutes. A mean total of 35.5 g of tissue was obtained, and 93% of the patients were discharged the day after their surgery without a catheter. The American Urological Association Symptom Score at 1 month was 8.6 and the peak flow rate 23.4 mL/sec. This combination of procedures allows prostate glands of virtually any size to be safely treated transurethrally, and a complete anatomic enucleation of the prostatic adenoma is achieved.

Aged↗
PubMed1998

Efficacy of ivermectin in a controlled-release capsule for the control of breech strike in sheep.

OBJECTIVE: To investigate the efficacy of ivermectin in an intraruminal controlled-release capsule (CRC) against blowfly strike. DESIGN: Pen and field trials with controls. ANIMALS: Pen studies: Two breech strike trials involving 60 Romney and 60 Merino sheep. One body strike trial using 100 Merino sheep. Field trials: Eight trials in New Zealand used 1000 Romney and Romney-cross sheep. Fifty Merino lambs in one trial in Australia. PROCEDURE: Pen studies: Sheep were allocated to two equal groups. One was not treated, the other sheep received a CRC that delivered ivermectin at > or = 20 micrograms/kg/day for 100 days. In the breech strike trials, each animal was given an oral laxative 2 days before exposure to adult Lucilia cuprina. In the body-strike trial, the sheep sheep were kept wet to increase susceptibility prior to the release of blowflies. Field trials: Fifty or 200 sheep allocated to equal groups of nontreated or treated with the CRC and grazed at pasture exposed to natural blowfly challenge. RESULTS: Pen studies: Breech strikes developed in 24 of 60 controls but in none of 60 CRC-treated sheep. There was a 35% reduction in the number of CRC-treated sheep struck on the body. Field trials: The average number of breech strikes in CRC-treated sheep was reduced by 86% (P < 0.001). The number of body strikes in the treated groups was a reduced by 27% (P < 0.05). CONCLUSION: The ivermectin CRC is a useful aid in controlling breech strike, but provides only moderate reduction in the incidence of body strike.

Animals↗
PubMed1998

Predictors of a medical-offset effect among patients receiving antidepressant therapy.

OBJECTIVE: Characteristics of patients receiving antidepressant therapy were examined to identify factors that may be associated with a medical-offset effect. METHOD: In a retrospective study, the authors analyzed claims data from a large health insurer in New England. The study subjects included 1,661 persons initiating treatment for depression with selective serotonin reuptake inhibitors or tricyclic antidepressants between July 1991 and June 1993. RESULTS: Patients with anxiety disorders, coronary heart disease, cancer, and chronic fatigue syndrome and those remaining on their initial regimens of antidepressant therapy for at least 6 months were more likely to experience significant reductions in the costs of medical care services. The number of visits to mental health providers had no effect on the costs of medical services. CONCLUSIONS: Specific comorbid conditions and sustained use of antidepressant drugs may be associated with a medical-offset effect for patients receiving treatment for depression.

Adult↗
PubMed1998

Breathing patterns in children with craniofacial dysostosis and hindbrain herniation.

In the past few years, hindbrain herniation has become recognized as a frequent feature of the child with syndromic craniofacial dysostosis. The clinical significance of hindbrain herniation in these disorders is unclear. Abnormalities of respiratory control have frequently been reported. The aim of the present study was to document the incidence of obstructive and central respiratory abnormalities during sleep in craniofacial syndromes with hindbrain herniation. We performed cardiorespiratory sleep studies during unsedated night-time sleep in a group of 13 children. Hindbrain herniation was confirmed by magnetic resonance imaging (MRI) and ranged 1.5-26.9 mm below the cranial base. Sleep studies revealed central respiratory pauses associated with important reduction of the arterial oxygen saturation (Sa,O2) in only two of 13 cases (minimum Sa,O2 86% and 87%). In contrast 10 of 13 children had some degree of upper airway obstruction (four mild, three moderate and three severe). Of the remaining three children, two had previous long-term tracheostomies. Changes in the breathing pattern were proportional to the severity of the obstruction and comprised increased respiratory efforts and arterial oxygen desaturation. Infrequent mixed apnoeas were observed in five patients, and their severity reflected the severity of the obstructive component. In conclusion, obstruction of the upper airways was the predominant sleep-related respiratory problem in this group of patients. Hindbrain herniation was not associated with a high incidence of central sleep apnoea.

Airway Obstruction↗
PubMed1998

Nuclear morphometry in solar keratosis.

OBJECTIVE: To carry out a feasibility study for the development of procedures for the objective characterization and grading of solar keratotic skin lesions. STUDY DESIGN: Imagery from sections of skin shave biopsies from 12 light-skinned individuals were digitized. A minimum of 25 nuclei from a solar keratotic lesion and 25 nuclei from a location in histologically normal appearing skin adjacent to the lesion were recorded for each case. Values of karyometric features were computed, and a discriminant function distinguishing normal nuclei from nuclei exhibiting solar irradiation damage was derived. RESULTS: Approximately 50% of nuclei in solar keratotic lesions were markedly affected by solar irradiation, but even in biopsies from histologically normal appearing skin, 3-30% of nuclei showed signs of such damage. Nuclei from solar keratotic lesions exhibiting such damage had numerous morphometric and karyometric features commonly found in malignant cells. The state of progression of a solar keratotic lesion can be graded by a plot of proportion of nuclei exhibiting solar damage versus the average discriminant function score of the most affected nuclei. This plot provides a monotonically rising progression curve and a numeric grading score. CONCLUSION: Karyometry of nuclei from skin biopsies allows objective assessment of the progression of solar keratotic lesions. Similarity of feature values in nuclei from solar keratotic lesions to those in malignant lesions was noted. The progression curve derived in this study could serve to measure the efficacy of chemopreventive or therapeutic intervention.

Biopsy↗
PubMed1998

Machine vision in the detection of prostate lesions in histologic sections.

OBJECTIVE: To explore the utility of N-gram encoding for the automated detection and delineation of regions of histologic abnormality in tissue sections of prostate. STUDY DESIGN: Digitized imagery of tissue sections from normal prostate glandular tissue, stroma and regions of well- and poorly differentiated lesions was recorded and successively subdivided into square subregions of 256 x 256 to 16 x 16 pixels. N-grams of N = 2 to N = 6 were computed, with each element assuming a value representing an optical density interval 0.30 units wide, covering the range from optical density = 0.0 to 1.80. Then, from a large database, prototype frequency histograms of the different N-grams were established. For each subregion the Euclidean distances to the different prototype histograms were computed and defined as "distance to prototype" features. Standard discriminant analyses and a nonparametric classifier were used to assign subregions to the different tissue categories. RESULTS: Classification of subregions was achieved for most discrimination tasks at a correct recognition rate ranging from 85% to 100% on both training set and test set data, with a few exceptions. N-grams of N > 4 had considerable discriminatory power. CONCLUSION: N-gram encoding has the potential to provide highly discriminating, texture-based characterization of subregions of digitized imagery of prostate lesions and may be very useful in the development of decision procedures for the automated detection of prostate lesions by a machine vision system.

Algorithms↗
PubMed1998

Statistical histometry of the basal cell/secretory cell bilayer in prostatic intraepithelial neoplasia.

OBJECTIVE: To delineate the sampling requirements for a histometric assessment of progression in low grade and high grade prostatic intraepithelial neoplasia (PIN) lesions. STUDY DESIGN: Images of whole glands from normal prostates, low grade PIN lesions and high grade PIN lesions were digitized. The images were processed by a machine vision system and automatically segmented, and a number of histometric characteristics descriptive of the disruption of the basal cell layer were extracted. Next, high-resolution images of secretory cell nuclei still facing or no longer facing intact segments of the basal cell layer were recorded and karyometrically analyzed. RESULTS: For the characterization of an individual lesion a minimum of 20-30 glands should be analyzed to provide an estimate of a progression index. Then, a change in progression, or due to regression, of approximately 16% can be documented. The disruption of the basal cell layer is accompanied by statistically highly significant changes in the chromatin texture and spatial distribution in secretory cell nuclei no longer facing an intact segment of that layer. CONCLUSION: Automated histometry by machine vision can provide valuable quantitative data for diagnostic assessment and for monitoring the efficacy of chemopreventive treatment.

Analysis of Variance↗
PubMed1998

Nuclear chromatin texture in prostatic lesions. I. PIN and adenocarcinoma.

OBJECTIVE: To document changes in the chromatin pattern in secretory cell nuclei from prostates with prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. STUDY DESIGN: High-resolution images of nuclei were recorded, and a set of features descriptive of the chromatin texture and spatial distribution was computed. From this data set, features undergoing a monotonic trend of progression were selected and plotted to reveal trends in lesion progression. RESULTS: The nuclear chromatin in secretory cells in prostates with either PIN or malignant adenocarcinoma undergoes distinct and statistically significant changes in its texture and spatial distribution. Two trends of progressive change were observed. First, the values of a number of features descriptive of the clumpiness of the chromatin increase from values found in normal prostates to those recorded for nuclei from low grade to high grade PIN lesions. The second trend is a decrease in the values of the same features from those found in nuclei from high grade PIN still facing an intact basal cell layer to those no longer facing such a layer. This may be the first detectable step in progression towards development of a malignant lesion. There is a further decrease in nuclei in glands immediately adjacent to adenocarcinoma and in malignant lesions themselves. CONCLUSION: The described changes may lend themselves to the monitoring of lesion progression or of response to treatment or to chemopreventive intervention.

Adenocarcinoma↗