US Food and Drug Administration's monitoring and surveillance programs for mycotoxins, pesticides and contaminants in food.
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Data Collection↗
Biomedical subjects
K Egan
Publications and source records attributed to K Egan.
Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease.
The aims of this study are to assess the efficacy of hepatitis B virus (HBV) vaccination using an accelerated schedule and double dose of recombinant vaccine in liver transplant recipients and identify factors associated with seroconversion and persistence of antibody to hepatitis B surface antigen (anti-HBs). Three hundred fifty-six patients were enrolled. Exclusion criteria were previous HBV infection, fulminant liver failure, or less than 2 years of follow-up after orthotopic liver transplantation (OLT). The vaccination schedule was 0, 2 weeks, 4 weeks, and 6 months using double-dose recombinant vaccine. Seroconversion was evaluated prospectively by measuring anti-HBs on the day of OLT and 1 and 2 years after OLT. Quantitative analyses of anti-HBs were performed retrospectively on stored sera. Geometric mean concentrations (GMCs) were calculated using a standard formula. All patients completed the full vaccination schedule, and 129 patients (36%) completed the schedule before OLT. The overall prevalence of anti-HBs was 128 of 356 pre-OLT samples (36%) compared with 41 of 353 (11.6%) and 26 of 325 post-OLT samples (8%) 1 and 2 years after OLT, respectively (both P =.001). The pre-OLT GMC was 86.7 compared with 0.32 and 0.33 at 1 and 2 years after OLT, respectively (P =.001). Patients with high titers of anti-HBs before OLT were more likely to have persistence of antibodies 1 or 2 years after OLT. Younger age (P =.02), low Child-Pugh score (P =.02), underlying chronic hepatitis C (P=.03), and specific host HLA subtypes were most strongly associated with seroconversion and/or persistence of anti-HBs. Thus, (1) seroconversion before or after OLT using double-dose accelerated-schedule vaccination against HBV is low, (2) there is a rapid, significant decrease in antibody titer after OLT, (3) pre-OLT anti-HBs titer potentially may be useful in predicting persistence of protective antibodies after OLT, and (4) several factors (age, genetic predisposition, severity of liver disease, and underlying liver disease) may have a role in poor vaccine responsiveness.
Adolescent↗
Comparison of donepezil-, tacrine-, rivastigmine- and metrifonate-induced central and peripheral cholinergically mediated responses in the rat.
There are now several acetylcholinesterase inhibitors in clinical use for the treatment of Alzheimer's disease, however, no systematic comparative studies of their central and peripheral cholinergic mediated effects in rats appear to have been reported. The present study investigated the dose-response characteristics of donepezil, tacrine, rivastigmine and metrifonate in inducing tremor, lacrimation, salivation and hypothermia and the duration of action of these compounds in Lister hooded rats. Data obtained were compared with the clinical observations on these drugs. Three doses of each compound were given orally to establish a dose-response curve for each behaviour, Tremor and lacrimation were scored, salivation was measured by weighing swabs applied to the mouth area and hypothermia was measured with a rectal probe. ED50 values were calculated for tremor. Using a just sub-maximal tremorigenic dose, the duration of response was examined. All four compounds produced dose-dependent increases in tremor and hypothermia. Only tacrine also produced marked salivation and lacrimation. The order of potency (ED50 value in micromol/kg) was rivastigmine (3.7), donepezil (18.0), tacrine (37.5), metrifonate (470). Tremor following tacrine (150 micromol/kg) and donepezil (20 micromol/kg) was prolonged (> 6 h) with a similar hypothermic response. The duration of these responses following metrifonate (777 micromol/kg) and rivastigmine (12.5 micromol/kg) did not exceed 3 h. Tacrine had poor selectivity for central (tremor) versus peripheral (salivation/lacrimation) effects compared to the other compounds. Donepezil also had a sustained duration of action. The data are consistent with clinical results and indicate that simple in-vivo models may assist in the selection of acetylcholinesterase inhibitors with a suitable response profile for use in the symptomatic treatment of Alzheimer's disease.
Animals↗
Cyclo-oxygenase products and atherothrombosis.
The advent of selective inhibitors of the cyclo-oxygenase (COX)-2 enzyme has afforded the opportunity to reduce the incidence of gastrointestinal complications of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). The widespread use of these drugs has increased interest in their role in the cardiovascular system. Although deletion of the prostacyclin receptor (the IP) accelerates atherogenesis in the mouse, retention of one copy of the IP is atheroprotective. This is consistent with the failure of biochemically defined, selective doses of a COX-2 inhibitor to accelerate atherogenesis in the mouse, despite suppressing prostacyclin biosynthesis by roughly 60%. Inhibition of both COX isozymes, by contrast, markedly retards atherogenesis. Consistent with these observations, antagonism of the thromboxane receptor (the TP) retards atherogenesis and diminishes the proliferative response to vascular injury in the mouse. Even partial suppression of prostacyclin (without coincident inhibition of platelet COX-1-dependent thromboxane formation) by COX-2 inhibitors may be undesirable in acute vascular occlusive syndromes. However, these drugs are unlikely to accelerate progression of the underlying vascular disease. By contrast, the effects of TP antagonists, aspirin, and even traditional NSAIDs on atherosclerotic plaque progression merit further evaluation in humans.
Animals↗
Assessment of the bacterial flora of the proximal part of the small intestine in healthy cats, and the effect of sample collection method.
OBJECTIVE: To investigate the bacterial flora of the proximal part of the small intestine of healthy cats and determine the effect of sample collection method on results of bacteriologic culture. ANIMALS: 25 healthy barrier-maintained specific-pathogen-free-derived cats. PROCEDURE: Aspirated, undiluted samples of proximal small intestinal juice were obtained via oral endoscopy (UEA), and a second sample was collected after instillation of 1 ml of sterile saline solution (diluted, DEA). Undiluted juice also was obtained by direct needle aspiration (NA) from the intestinal lumen. Samples for quantitative and semiqualitative bacteriologic examination were grown aerobically and anaerobically. RESULTS: Mean (range) log10 colony-forming units of total bacteria/ml were 6.2 (2.0 to 8.3) for NA, 6.0 (2.0 to 7.9) for UEA, and 4.9 (2.0 to 7.5) for DEA samples. One cat had no growth (< or = 2.0 colony-forming units/ml) for samples obtained using all 3 methods, and another cat had no growth for the DEA sample only. Mean total aerobic, anaerobic, and bacterial counts were not significantly different between NA and UEA methods, but these techniques yielded significantly higher mean counts than did DEA samples (P < or = 0.002, ANOVA). As a percentage of the total bacteria isolated, anaerobes constituted a median 35, 32, and 50% of the NA, UEA, and DEA samples, respectively. Good correlation was found between the NA and UEA samples for total bacteria, aerobes, and anaerobes (r > or = 0.830). CONCLUSIONS: Compared with human beings, healthy cats carry high numbers of bacteria in the proximal part of the small intestine. By comparison with NA samples, UEA samples accurately reflected bacterial populations in the small intestine, whereas DEA samples significantly underestimated these populations.
Animals↗
Effect of dietary supplementation with fructo-oligosaccharides on fecal flora of healthy cats.
OBJECTIVE: To investigate changes in the fecal flora of healthy cats after dietary supplementation with fructo-oligosaccharides (FOS). ANIMALS: 12 healthy, barrier-maintained, specific-pathogen-free-derived adult cats. PROCEDURE: Fresh fecal samples for quantitative and qualitative bacteriologic examination were collected from each cat after ingestion of a replete dry (basal) diet for a minimum of 8 weeks. The diet was then supplemented with 0.75% FOS, and another fecal sample was collected after 12 weeks. RESULTS: Mean +/- SD fecal aerobic, anaerobic, and total bacterial counts (log10 colony-forming units per gram of feces [CFU/g]) did not differ significantly between diets (8.3 +/- 0.8, 9.2 +/- 0.6, 9.4 +/- 0.4, respectively, for the basal diet; and 8.4 +/- 0.8, 9.7 +/- 0.7, and 9.8 +/- 0.7, respectively, for the FOS diet), although there was a trend for higher numbers of anaerobes and total bacteria associated with the FOS diet. Members of the genus Bacteroides, Clostridium perfringens, Escherichia coli, lactobacilli, and Plesiomonas shigeloides were the most prevalent bacteria isolated. Compared with samples from cats fed basal diet, there was a trend for increased mean counts of lactobacilli (P = 0.02) and Bacteroides spp (P = 0.05) after FOS supplementation, and a trend for decreased mean numbers of Escherichia coli (P = 0.03) and Clostridium perfringens (P = 0.08) to be associated with the FOS diet. Supplementation of FOS resulted in a median 164-fold increase in numbers of lactobacilli, 13.2-fold increase in Bacteroides spp, 98% reduction in numbers of C perfringens, and 75% reduction in numbers of E coli. CONCLUSIONS: Supplementation of the diet with FOS resulted in alteration of the fecal flora of cats.
Analysis of Variance↗
Evidence that adult life risk factors influence the expression of familial propensity to breast cancer.
In the context of a study in Athens comprising 692 cases and 1,261 controls, we have evaluated the effect on breast cancer risk of the joint action of first-degree relative family history and established adult life risk factors. We created a risk score by assigning the value of 1 to women at high risk with respect to any of these risk factors and 0 otherwise, and summing these values, using weights equal to the excess odds ratio. The odds ratio for a tertile increment in the risk score was 1.5 [95% confidence interval (CI) = 1.3-1.8] among women without family history, and 2.3 (95% CI = 1.1-5.1) for women with family history. Our findings imply that women with a family history of breast cancer may benefit disproportionately by reduced exposure to adult life risk factors.
Adult↗
An abattoir-based study of the prevalence of subclinical Johne's disease in adult cattle in south west England.
The prevalance of subclinical Johne's disease was estimated in adult cattle slaughtered at three major abattoirs in south west England. A polymerase chain reaction (PCR) based on IS900 was used to detect Mycobacterium paratuberculosis in intestinal lymph nodes of 1553 cattle. Culture was also carried out on all PCR positive and inconclusive samples. The prevalence of subclinical disease in adult cattle was 3.5% (95% confidence intervals (CI) 2.6-4.7) by PCR and 2.6% (CI 1.8-3.6) by culture. The proportion of the disease in each month ranged from 1.6% (CI 0.2-5.5) in April to 4.6% (CI 2.8-6.9) in November, but the difference was not significant (P > 0.05). The proportion of PCR positive lymph nodes in each abattoir ranged from 2.8% (CI 1.6-4.6) to 4.9% (CI 2.9-7.6), this difference was not significant either (P > 0.05). The prevalence in young cattle was 2.0% (CI 0.6-4.5). The difference between age groups was not statistically significant (P > 0.05).
Abattoirs↗
Ocular blood flow velocity in age-related macular degeneration.
BACKGROUND: Changes in the structure of the ocular blood vessels associated with age-related macular degeneration (AMD) have been described in some detail, but comparatively little is known of the concomitant circulatory changes. The goal of this study is to evaluate changes in the ocular circulation that may be associated with AMD. METHODS: Ocular blood flow velocities and vessel pulsatilities were measured in volunteers with and without AMD using a color Doppler imaging unit. Spectral analyses were recorded from the ophthalmic artery, central retinal artery and vein, the temporal and nasal short posterior ciliary arteries, and the four vortex veins. RESULTS: Adjusting for age, pulsatility indices of all arteries were higher in subjects with AMD (central retinal artery [P = 0.02]; temporal and nasal short posterior ciliary arteries [P = 0.06 and 0.002, respectively]; and ophthalmic artery [P = 0.24]). End-diastolic blood flow velocity of the short posterior ciliary arteries tended to decrease in the presence of AMD. CONCLUSIONS: The combination of increased pulsatility and decreased velocity of the short posterior ciliary arteries, observed in the presence of AMD, are interpreted as evidence of increased vascular resistance. The clinical signs of AMD may be related to degradation of the metabolic transport function of the retinal pigment epithelium, resulting from impaired choroidal perfusion.
Aged↗
Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma.
PURPOSE: Vitamin D compounds have been shown to inhibit tumor growth in a transgenic retinoblastoma murine model. The mechanism of action has not been defined clearly, although an antiangiogenic action has been proposed. METHODS: Transgenic retinoblastoma mice received high (0.05 microgram) and low (0.025 microgram) doses of vitamin D3 by intraperitoneal injection 5 times per week for 5 weeks. Control animals were injected with mineral oil vehicle alone. At 5 months of age, the animals were killed and eyes were enucleated and processed for light microscopy. Paraffin-embedded sections were stained with an immunoperoxidase stain (GS-1) specific for mammalian vascular endothelium. Sections were graded by a single masked reviewer, and intraobserver reliability was assessed. Mean vessel counts were made for each group. RESULTS: The high-dose group had the lowest mean vessel count (8.5), followed by the low-dose group (10.1). The control group had the highest mean vessel count (14.1). Vitamin D-treated animals (high- and low-dose groups combined) had significantly fewer vessels P = 0.001) than untreated controls. CONCLUSIONS: These results support the hypothesis that inhibition of angiogenesis is a mechanism of action for vitamin D in the transgenic retinoblastoma mouse model.
Animals↗
A practice-based survey of the frequency of Johne's disease in south west England.
The frequency of Johne's disease in cattle in south west England was estimated from data collected by telephone interviews with veterinarians and farmers. The response rate was 81.6 per cent. The disease frequency was expressed as the proportion of farms with clinical disease and the cumulative incidence in the infected herds. The proportion of farms affected was 1.0 per cent and the cumulative incidence on those farms was 1.9 per cent per year. Similar values were obtained when diagnosis by faecal examination, post mortem examination and histology was taken into consideration; 0.9 per cent of farms were affected and the cumulative incidence in the infected herds was 2.0 per cent per year. The survey was validated against three external reference points. There was good agreement between the use of vaccine and MAFF records, and the total number of holdings and census data. When the responses of the veterinarians were compared with those of farmers there was also good agreement on the use of vaccine (kappa = 77.8 per cent), the number of cases reported in the last year of diagnosis (r = 0.78) and the total number of cattle in the herds (r = 0.75). However, the results suggested that the total number of cattle holdings was overestimated and consequently the proportion of farms affected may have been underestimated.
Animals↗
Circulating levels of cytokines that modulate bone resorption: effects of age and menopause in women.
Interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are cytokines with potent bone-resorbing effects; some of these biologic effects are opposed by interleukin-1 receptor antagonist (IL-1ra). In vitro and animal model studies suggest that these cytokines are paracrine mediators of the increased bone resorption associated with estrogen deficiency, and increases in their production also could contribute to age-related bone loss. Therefore, we measured serum concentrations of these cytokines in 80 normal women who were 24-87 years old. IL-6 concentration correlated highly with age (p < 0.001) and increased three-fold during life. However, multiple-regression analysis showed no significant correlation between serum IL-6 levels and menopausal status, serum estradiol concentration, or markers for bone turnover (serum bone alkaline phosphatase, osteocalcin, carboxyl-terminal telopeptide of type I collagen, or 24 h urinary free pyridinoline excretion). Serum IL-1 alpha, IL-1 beta, or IL-1ra level did not change with age and, by multiple-regression analysis, did not correlate with markers of bone turnover, except IL-1ra weakly with ICTP. We found no relationship between bone-resorbing cytokines and ovarian function. Although the large age-related increase in serum IL-6 concentration could contribute to age-related bone loss, the lack of correlation with markers for bone turnover argues against this. However, based on the strong evidence in experimental animals that these cytokines are involved in estrogen action on bone, further studies in humans are warranted.
Adult↗
Circulating cytokine levels in osteoporotic and normal women.
Interleukin-1 (IL-1) and IL-6 have been postulated to play roles in the pathogenesis of postmenopausal osteoporosis. To test this hypothesis, we measured circulating levels of IL-6, IL-1 alpha, and IL-1 beta in 40 age-matched normal and 40 osteoporotic women with vertebral fractures and increased bone turnover. Since IL-1 activity is modulated by the IL-1 receptor antagonist (IL-1ra), we also measured circulating IL-1ra levels in these women. Despite having higher rates of bone turnover as assessed by bone biochemical markers, the osteoporotic women had serum levels of IL-6, IL-1 alpha, and IL-1 beta that were similar to the normal women. IL-1ra levels (mean +/- SEM) tended to be lower in the osteoporotic women (143 +/- 21 pg/mL) vs. the normal women (189 +/- 22 pg/mL; P = 0.08). The IL-1 alpha/IL-1ra ratio, an index of IL-1 alpha bioactivity, was higher in the osteoporotic women (6.4 +/- 1.1) than in the normal women (4.4 +/- 0.5; P < 0.05). There were nonsignificant trends for increased IL-1 beta/IL-1ra and (IL-1 alpha + IL-1 beta)/IL-1ra ratios in the osteoporotic vs. normal women. None of the cytokines correlated with markers of bone resorption in either group of women. In summary, although there was a trend for a higher IL-1/IL-1ra ratio in the osteoporotic women, we were unable to demonstrate unequivocal abnormalities of cytokines affecting bone resorption in peripheral serum of women with postmenopausal osteoporosis. However, it is possible that increased production of these cytokines occurs in the local environment of bone or bone marrow and is not detected by analysis of peripheral serum. Thus, further studies will be required to exclude this possibility.
Aged↗
Standardized data collection and coding in eye disease epidemiology: the Uveal Melanoma Data System.
The Uveal Melanoma Data System of the Massachusetts Eye and Ear Infirmary is a computerized data-base designed for data management and analysis with a broad range of clinical research applications. The system was created in 1980 and has evolved to include standardized data collection forms for all aspects of uveal melanoma patient care such as initial examination, treatment, and follow-up, as well as precoded forms for computer entry, which facilitate quality control measures and data analysis. Excerpts from current versions of these forms are presented. The Uveal Melanoma Data System has been used for a variety of clinical epidemiologic investigations. Examples of its application, including descriptive studies, prognostic factor studies, and treatment evaluations, are discussed. The model has potential broad application for clinical ophthalmic research in other specialty areas.
Data Collection↗
Opioids: mediators of fear or mania.
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Bipolar Disorder↗
Long-term results of proton beam irradiated uveal melanomas.
The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis.
Eye Diseases↗
Reducing death from translocation syndrome.
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Aged↗
Echographic and histologic tumor height measurements in uveal melanoma.
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Humans↗