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Biomedical subjects

J A Olson

Publications and source records attributed to J A Olson.

At least 37 records · Page 2Linked to original sources

Sight-threatening varicella zoster virus infection after fludarabine treatment.

Varicella zoster virus (VZV) infection involving the posterior segment of the eye after fludarabine treatment has not previously been described. Two patients, who had completed fludarabine treatment 3 and 18 months previously, presented with visual loss that had been preceded by a recent history of cutaneous zoster. The use of the polymerase chain reaction (PCR) for VZV DNA from ocular specimens allowed rapid confirmation of clinical diagnosis and treatment with a good outcome in one patient. With the increasing use of fludarabine and other purine analogues, an awareness of such complications is important because of their potentially sight-threatening consequences.

Acyclovir↗

Automated detection of microaneurysms in digital red-free photographs: a diabetic retinopathy screening tool.

AIMS: To develop a technique to detect microaneurysms automatically in 50 degrees digital red-free fundus photographs and evaluate its performance as a tool for screening diabetic patients for retinopathy. METHODS: Candidate microaneurysms are extracted, after the image has been modified to remove variations in background intensity, by algorithms that enhance small round features. Each microaneurysm candidate is then classified according to its intensity and size by the application of a set of rules derived from a training set of 102 images. RESULTS: When 3,783 individual images were analysed and the results compared with the opinion of a clinical research fellow examining the same images, the program achieved a sensitivity of 81% and a specificity of 93% for the detection of images containing microaneurysms. Nine hundred and twenty-five sets of 4 images per patient were then analysed and the total number of microaneurysms detected compared with the overall patient retinopathy grade derived by the clinician examining the same images. In this context, intended to mimic a screening situation, the program achieved a sensitivity of 85% and a specificity of 76% for the detection of patients with (any) retinopathy (positive predictive value 0.71, negative predictive value 0.88). CONCLUSIONS: An automated technique was developed to detect retinopathy in digital red-free fundus images that can form part of a diabetic retinopathy screening programme. It is believed that it can perform a useful role in this context identifying images worthy of closer inspection or eliminating 50% or more of the screening population who have no retinopathy.

Algorithms↗

beta-carotene is converted primarily to retinoids in rats in vivo.

beta-Carotene might be converted oxidatively to vitamin A- active products in animals by the following three possible routes: 1) central cleavage, 2) sequential excentric cleavage or 3) random cleavage. Central cleavage is strongly favored by stoichiometric studies with tissue homogenates in vitro. To examine the relative importance of these pathways in rats in vivo, an oral dose (5.6 micromol) of all-trans beta-carotene in oil was given to vitamin A-deficient (-A) and to vitamin A-sufficient (+A) adult female Sprague-Dawley rats. Serum and several tissues were analyzed before and 3 h after dosing. The primary products of beta-carotene found in the intestine, serum and liver were retinol, retinyl esters and retinoic acid. Two minor oxidation products of beta-carotene, namely, 5,6-epoxy-beta-carotene and a partially characterized hydroxy-beta-carotene, were present in the stomach and its contents as well as in intestinal preparations. In the intestine, including its contents, of -A rats, very minor amounts of 5,6-epoxyretinyl palmitate and of beta-apocarotenals (8', 10', 12', 14') were identified. The total amount of the beta-apocarotenoids, however, was <5% of the retinoids formed in the intestine from beta-carotene during the same period. Another beta-carotene derivative, with a spectrum similar to that of semi-beta-carotenone, citranaxanthin and beta-apo-6'-carotenal, was also found in the intestinal extract of a -A rat. beta-Apocarotenals, beta-apocarotenols, beta-apocarotenyl esters and beta-apocarotenoic acids were not detected in tissues of +A rats nor in other tissues of -A rats. These findings agree with the view that central cleavage is by far the major pathway for the formation of vitamin A from beta-carotene in healthy rats in vivo.

Animals↗

Staging work-up and post-treatment surveillance of patients with melanoma.

Strategies based on evidence are required to accurately stage and effectively follow patients with melanoma. The goal of staging is to define the extent of disease at the time of presentation to direct and assign prognosis. Patient surveillance is performed to assess treatment results and detect recurrences amenable to further treatment. Staging and surveillance require careful use of resources to be cost effective. This article addresses preoperative staging and post-treatment surveillance of patients with melanoma and outlines a method of follow-up based on available data.

Follow-Up Studies↗

Asthma hospitalizations in Wisconsin: a missed opportunity for prevention.

Asthma is the most common chronic disease of children and the third leading cause of preventable hospitalizations in the United States. To assess the impact of this disease on Wisconsin, we examined 1996-1998 state-wide and county-specific asthma hospitalization rates and compared these rates to Wisconsin 1990-1992 rates, national rates, and United States Healthy People 2010 asthma target objectives. Wisconsin's average asthma hospitalization rate has decreased from 13.4/10,000 during 1990-1992 to 12.1/10,000 during 1996-1998. Wisconsin children 0-4 years of age had the highest asthma-related hospitalization rate (38.0/10,000) of all age groups, during 1996-1998. Wisconsin African American residents had an average asthma hospitalization rate 6.6 times higher than whites (58.5 vs. 8.8 per 10,000, respectively) during 1996-1998. Milwaukee County had the highest county-specific asthma hospitalization rate in the state (26.4/10,000). Unless significant reductions are achieved, Wisconsin will not reach the Healthy People 2010 target objectives. Interventions should be directed to preventing asthma hospitalizations, especially among Wisconsin's youth and African American population.

Adolescent↗

Effects of epoxycarotenoids, beta-carotene, and retinoic acid on the differentiation and viability of the leukemia cell line NB4 in vitro.

Three all-trans epoxides of beta-carotene (beta-Car), namely, 5,6-epoxy-beta-carotene (5,6-EC), 5,8-epoxy-beta-carotene (5,8-EC) and 5,6,5',6'-diepoxy-beta-carotene (5,6,5',6'-DEC) were synthesized by treatment of beta-carotene with 3-chloroperoxybenzoic acid, were purified chromatographically, and were characterized. The relative potencies (mean +/- S.D.) of 1 microM compounds in inducing the differentiation of NB4 cells, a cell line that contains the chromosomal transposition t(15;17) characteristic of acute promyelocytic leukemia, after 4 days of incubation were: RA: 1.35 +/- 0.16, 5,6-EC: 0.29 +/- 0.01, 5,8-EC: 0.22 +/- 0.05, 5,6,5',6'-DEC: 0.11 +/- 0.02, beta C: 0.09 +/- 0.01, and the control: 0.06 +/- 0.01. The same order of potencies existed at other concentrations tested and at other incubation times. P values for the differences between the inducing activities of successive pairs of compounds at 1 microM were: RA vs. 5,6-EC, < 0.001; 5,6-EC vs. 5,8-EC, < 0.01; 5,8-EC vs. 5,6,5',6'-DEC, < 0.01; 5,6,5',6'-DEC vs. beta-Car, < 0.10; beta-Car vs. control, < 0.005. Similar P values were also obtained for studies at other concentrations and at other incubation times. The viable cell mass at 4 days was inversely proportional to the extent of differentiation (rs = -1.0). The inducing activities of all compounds were dose-dependent. Thus, the 5,6-monoepoxide of beta-carotene, which has not previously been studied as an inducer, showed higher activity in NB4 cell differentiation than the 5,8-monoepoxide, the 5,6,5',6'-diepoxide, or beta-carotene. Possible explanations of these observations are discussed.

Cell Differentiation↗

The preprocessing of retinal images for the detection of fluorescein leakage.

Images of the human retina are routinely used in clinical practice for the diagnosis and management of eye disease. Increased permeability of retinal blood vessels, which is a clinically significant feature, can be visualized with a process known as fluorescein angiography as leakage of fluorescence dye into the surrounding tissues. Analyses of such images can be quantified but significant degradation of images due to uneven illumination or occluded optical pathways is often incurred during image capture. We describe a procedure to restore fluorescein angiographic retinal images so that quantitative computation can be reliably performed. Analysis of the image acquisition system reveals that captured images are composed of two functions, one describing the true underlying image and the other the degradation incurred. These two functions are independent of one another and it is possible to estimate the degradation from an isolated captured image and restore it appropriately. Any leakage of fluorescein dye is then detected by analysing the restored angiographic sequence over time and finding areas of the image that do not have the usual decrease in fluorescence intensity.

Eye Diseases↗

Who is "62 enough"? Identifying respondents eligible for Social Security early retirement benefits in the Health and Retirement Study.

Workers are not instantly eligible for Social Security retirement benefits on their 62nd birthdays, nor can they receive benefits in the month they turn 62. This note discusses how well researchers can do using data from the Health and Retirement Study (HRS) to identify respondents old enough to receive and report early Social Security retirement benefits. It shows that only some workers aged 62 at the time of an HRS interview will be "62 enough" to have received a Social Security benefit and reported it in the survey. In general, workers become eligible for a retirement benefit the month after they turn 62, and they may receive their first payment the month after that. Until recently, payments were received very early in the month, but in mid-1997 and later, the Social Security Administration (SSA) staggered benefit payments over the course of a month. Therefore, many beneficiaries will not be able to report the receipt of their first benefit payment until the third month after their birthday in more recent HRS interviews. This note describes the best approach for approximating the pool of HRS respondents who are old enough to have reported the receipt of their first retirement benefit. It then applies the procedure to an analysis by Burkhauser, Couch, and Phillips, who used the 1994 HRS data to distinguish between those who took early retirement benefits upon turning 62 and those who postponed the receipt of benefits. Because these authors did not provide for respondents who were not "62 enough" to receive a benefit at the time of the interview, they understated the proportion of respondents who took retirement benefits at age 62.

Age Factors↗

Carotenoids and human health.

After the discovery of vitamin A in 1913, the yellow pigments of fruits and vegetables were soon implicated as compounds with similar nutritional effects. beta-Carotene was shown to be converted into vitamin A by Moore in 1929, and the chemical structures of both vitamin A and beta-carotene were determined two years later. Thus, the sole function of beta-carotene in human health was considered to be its conversion into vitamin A. On the basis of observational epidemiologic studies, conducted in the mid-1970s, however, carotenoids were implicated as protective agents, first against lung cancer and then against a variety of other chronic diseases. Intervention trials employing beta-carotene, however, either have shown no preventive effect or indeed, in two cases, have enhanced the incidence of lung cancer in middle-aged male smokers and asbestos workers. The possible protective action of carotenoids can be attributed to their properties as singlet oxygen quenchers and as antioxidants, whereas their cancer-enhancing actions in lung can be ascribed to the prooxidant action of carotenoid free radicals in damaged cells. Apart from chronic diseases, beta-carotene has shown significant therapeutic value in individuals suffering from photosensitivity disorders and provides temporary relief to persons afflicted with leukoplakia. A part from a medical context, the colored carotenoids found in many living organisms and in many foods delight both the eye and the palate. Thus, human health and the enjoyment of life are greatly benefited by the presence of these interesting pigments in nature, whether or not they ultimately prove to have more specific protective effects against chronic diseases.

Antioxidants↗

Bioavailability of carotenoids.

Our current knowledge about the bioavailability of provitamin A carotenoids in foods is insufficient, fragmentary and difficult to interpret. Past methods of estimating the vitamin A value of food carotenoids suffer both from uncertainty about the meaning of bioavailability and from the inadequacy of the indicators used in its determination. Reported conversion ratios of beta-carotene to vitamin A in humans in vivo, depending on conditions, range from 2:1 to 26:1 (microgram/microgram). Thus, the ratio of 6:1, devised by the World Health Organization, must be considered as a rough average estimate that is not applicable to all diets. Strategies to increase the dietary intake of carotenoid-containing foods should include measures to enhance carotenoid bioavailability.

Absorption↗

Reversed-phase gradient high-performance liquid chromatographic procedure for simultaneous analysis of very polar to nonpolar retinoids, carotenoids and tocopherols in animal and plant samples.

A reversed-phase gradient high-performance liquid chromatographic (HPLC) procedure, which utilizes gradient elution and detection by a photodiode-array detector, has been developed to analyze simultaneously very polar retinoids, such as 4-oxo-retinoyl-beta-glucuronide, retinoyl beta-glucuronide and 4-oxo-retinoic acid; polar retinoids, such as retinoic acid and retinol; nonpolar retinoids, such as retinyl esters; along with xanthophylls, monohydroxy carotenoids, hydrocarbon carotenoids, and tocopherols. The procedure has been applied to the simultaneous analysis of retinoids, carotenoids, and tocopherols present in human serum and liver, rat serum and tissues, and for carotenoids in a number of fruits and vegetables. Bilirubin present in human serum can also be simultaneously analyzed. By this gradient HPLC procedure, 3.4-didehydroretinyl ester (vitamin A2 ester) has been identified as a minor constituent in a human liver sample. Lycopene was identified as a major carotenoid in one specimen of papaya fruit, and 5,6,5',6'-diepoxy-beta-carotene was characterized as a major carotenoid in one specimen of mango fruit.

Animals↗

Lethality of multiple endocrine neoplasia type I.

The lethality of the endocrine tumors associated with multiple endocrine neoplasia type I (MEN-I), particularly the pancreatic islet cell tumors, has been controversial. We evaluated the cause and age of death in MEN-I kindreds. Our database contains 34 distinct kindreds with 1838 members. Reliable death data are available for 103 people (excluding accidents and age < 18 years). We compared survival curves of MEN-I patients who died from causes related to MEN-I with those from MEN-I carriers who died from a nonendocrine cause and unaffected kindred members. We also compared ages of death between affected and unaffected members of MEN-I kindreds. Of 59 MEN-I-affected patients, 27 died directly of MEN-I-specific illness and 32 of non-MEN-I causes. The MEN-I-specific deaths occurred at a younger age (median 47 years) than either MEN-I patients whose death was from some nonendocrine cause (median 60 years, p < 0.02) or than all kindred members who did not die of MEN-I disease (median 55 years, p < 0.05). The causes of death of the MEN-I patients included islet cell tumor (n = 12), ulcer disease (n = 6), hypercalcemia/uremia (n = 3), carcinoid tumor (n = 6), and nonendocrine malignancies (n = 9). There was no difference in survival between MEN-I carriers and unaffected kindred members. Of our MEN-I patients, 46% died from causes related to their endocrine tumors after a median age of 47 years, which was younger than family members who did not die from these tumors. Pancreatic islet cell tumors were the most common cause of death of MEN-I patients. Management of kindreds with MEN-I should include an aggressive screening program with early therapeutic intervention when a tumor is identified.

Adult↗