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Biomedical subjects

William Ellis

Publications and source records attributed to William Ellis.

9 recordsLinked to original sources
PubMed2006

Determinants of aflatoxin levels in Ghanaians: sociodemographic factors, knowledge of aflatoxin and food handling and consumption practices.

Aflatoxins are among the most potent of carcinogens found in staple foods such as groundnuts, maize and other oil seeds. This study was conducted to measure the levels of aflatoxin B(1) (AFB(1)) albumin adducts in blood and aflatoxin M(1) (AFM(1)) metabolite in urine of people in a heavy peanut and maize consuming region of Ghana and to examine the association between aflatoxin levels and several socio-demographic factors and food handling and consumption practices. A cross-sectional study was conducted in four villages in the Ejura Sekyedumase district of Ghana. A socio-demographic survey was administered to 162 participants. Blood samples were collected from 140 and urine samples from 91 of the participants and AFB(1) albumin-adduct levels in blood and AFM(1) levels in urine were measured. High AFB(1) albumin-adduct levels were found in the plasma (mean+/-SD=0.89+/-0.46pmol/mg albumin; range=0.12-3.00pmol/mg; median=0.80pmol/mg) and high AFM(1) levels in the urine (mean+/-SD=1,800.14+/-2602.01pg/mg creatinine; range=non-detectable to 11,562.36pg/mg; median=472.67pg/mg) of most of the participants. There was a statistically significant correlation (r=0.35; p=0.007) between AFB(1)-albumin adduct levels in plasma and AFM(1) levels in urine. Several socio-demographic factors, namely, educational level, ethnic group, the village in which participants lived, number of individuals in the household, and number of children in the household attending secondary school, were found to be significantly associated with AFB(1) albumin-adduct levels by bivariate analysis. By multivariate analyses, ethnic group (p=0.04), the village in which participants live (p=0.02), and the number of individuals in the household (p=0.01), were significant predictors of high AFB(1) albumin-adducts. These findings indicate strongly that there is need for specifically targeted post-harvest and food handling and preparation interventions designed to reduce aflatoxin exposure among the different ethnic groups in this region of Ghana.

Aflatoxin B1↗
PubMed2005

Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.

WR182393, a guanidinoimidazolidinedione derivatives with potent causal prophylactic antimalarial activity by intramuscular injection, was previously prepared by treatment of chloroproguanil and diethyl oxalate, yielding a mixture of two closely related isomers. Poor solubility of the mixture made the separation and purification impossible. To overcome the separation problem, new and facile unambiguous syntheses of the two active components were reported. The new synthetic methods facilitate the synthesis of not only the active components, but also their derivatives. To search for compounds with good oral efficacy, a series of carbamate derivatives of the active components were prepared by the new procedure, many of which showed profound causal prophylactic antimalarial activity against Plasmodium yoelii in mouse by oral administration.

Administration, Oral↗
PubMed2004

Clinical and neuropsychological features in autopsy-defined vascular dementia.

Studies reporting that ischemic vascular dementia (IVD), compared to Alzheimer's disease (AD), is associated with relatively greater impairment of executive function and relatively preserved episodic memory raise the question of whether there is a distinctive neuropsychological profile of impairment associated with IVD and whether this might be useful in clinical diagnosis. However, prior reports are almost all based on clinically diagnosed cases, raising obvious issues of possible circularity and leaving unanswered questions of validity. Here we report on clinical and neuropsychological findings in 18 prospectively studied cases that had substantial pathology-defined cerebrovascular disease (CVD) at autopsy. Nine cases had minimal AD pathology, while the remainder had moderate or severe degrees of AD pathology. Cognitive status at last evaluation ranged from mild cognitive impairment to moderate dementia. Clinical features were quite variable; only 40% of cases with high CVD levels had elevated Hachinski Ischemia Scale scores and neither abrupt onset nor stepwise progression was found in most high CVD cases, even when AD changes were essentially absent. The presence of dementia was predictably related to the level of neurofibrillary pathology, but was not related to the severity of CVD. Neuropsychologists expert in the evaluation of dementia used a priori criteria to diagnose neuropsychological protocols (blind to all other data) from cases with pathology-informed diagnoses of AD, IVD, and mixed dementia. Sensitivity and specificity were both high for AD, sensitivity for detecting pure IVD was poor, and values were intermediate for detecting IVD irrespective of AD levels. A illustrative case example is included. We conclude that the profile of cognitive impairment in IVD is highly variable, but that in clinical settings neuropsychological readings may contribute to the differential diagnosis of dementia.

Aged↗
PubMed2003

Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases.

Cyclin dependent protein kinases (CDKs) have become attractive drug targets in an effort to identify effective inhibitors of the parasite Plasmodium falciparum, the causative agent of the most severe form of human malaria. We tested known CDK inhibitors for their ability to inhibit two malarial CDKs: Pfmrk and PfPK5. Many broad spectrum CDK inhibitors failed to inhibit Pfmrk suggesting that the active site differs from other CDKs in important ways. By screening compounds in the Walter Reed chemical database, we identified oxindole-based compounds as effective inhibitors of Pfmrk (IC(50) = 1.5 microM). These compounds have low cross-reactivity against PfPK5 and human CDK1 demonstrating selectivity for Pfmrk. Amino acid comparison of the active sites of Pfmrk and PfPK5 identified unique amino acid differences that may explain this selectivity and be exploited for further drug development efforts.

Amino Acid Sequence↗
PubMed2003

Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone.

To better understand the clinical and pathologic features of end-stage, androgen-independent carcinoma of the prostate (CaP), we performed rapid autopsies on 14 men who died of progressive CaP and recorded relevant clinical data. The timing of tumor progression varied widely. The median time to androgen independence was 2 years (range, 4 months to 13.6 years). The median survival after androgen independence was 1 year (range, 1 month to 3.6 years). Because osseous metastases are prevalent in progressive CaP, up to 20 bone sites were systematically sampled in each patient. Bone metastases were widespread; tumor filled the marrow in an average of 14 bone sites. Tumor histology and expression of prostate-specific antigen (PSA) and chromogranin A (CGA) were examined in all metastases and were compared with the primary tumor. Five histological patterns of metastatic tumor were observed: solid (10 patients), macroacinar (1 patient), microacinar (1 patient), clear cell (1 patient), and comedocarcinoma (1 patient). Gleason grade of the primary tumor did not predict the histological pattern of the metastases. Although >70% of tumor cells expressed PSA, the fraction of PSA-positive cells varied widely in separate metastases in some patients (standard deviation >25). Likewise, the fraction of neuroendocrine (NE) (CGA-positive) tumor cells in different metastases varied widely. For example, between 0 and 95% of tumor cells in different metastases in 1 patient had a NE phenotype. The present study highlights the heterogeneity--histologically and immunophenotypically--of metastatic CaP. Consequently, therapy directed to the phenotype of 1 metastasis may have no effect on other metastases in the same patient because of phenotypic heterogeneity.

Adenocarcinoma↗
PubMed2002

Risk factors for acute urinary retention requiring temporary intermittent catheterization after prostate brachytherapy: a prospective study.

PURPOSE: We prospectively investigated prognostic factors for men undergoing transperineal radioactive seed implantation for prostate cancer at the University of Washington. METHODS AND MATERIALS: Between February and April, 1998, 62 consecutive unselected patients were prospectively followed after brachytherapy for early-stage prostate adenocarcinoma. Pretreatment variables included age, American Urological Association (AUA) score, uroflowimetry, and prostate volume by ultrasound. Nonrandomized variables included hormonal therapy, seed type, and use of pelvic radiotherapy. Patients were contacted by phone at one week postoperatively and at one-month intervals thereafter. Follow-up continued until all patients provided the date of last catheterization. RESULTS: Urinary retention rate at one week was 34% (21 of 63 patients). At one month, 29%; at three months, 18%; and at six months, 10%. Preoperative flow rate and post-void residual did not predict for retention (p =.48 and p =.58). Use of alpha blockers, hormonal therapy, type of seed (103Pd or 1251), or external beam radiotherapy had no impact on risk of retention at any followup point. Preimplant volume and AUA score predicted for retention on univariate analysis, but on multivariate analysis only postimplant volume remained significant (p =.02) for predicting retention risk and duration. CONCLUSION: Patients with large prostate size (>36 g) and higher AUA score (>10) appear to be at greater risk of risk of retention as well as duration of retention as defined in our study. Further investigation will be needed to clarify the risk of urinary retention for men undergoing brachytherapy.

Adenocarcinoma↗
PubMed2002

A neuroendocrine/small cell prostate carcinoma xenograft-LuCaP 49.

The late stages of progression of prostate carcinoma are typically characterized by an androgen-insensitive, rapidly proliferative state. Some late-stage tumors are composed predominantly of neuroendocrine cells. Virtually no animal models of a neuroendocrine/small cell variant of prostate carcinoma are available for experimental studies. We report a human neuroendocrine/small cell prostate carcinoma xenograft that was developed from a nodal metastasis of a human prostate carcinoma and that has been propagated as serial subcutaneous implants in severe combined immunodeficient mice for >4 years. Designated LuCaP 49, all tumor passages exhibit a neuroendocrine/small cell carcinoma phenotype-insensitivity to androgen deprivation, expression of neuroendocrine proteins, lack of expression of prostate-specific antigen or androgen receptor, and an unusually rapid growth (a doubling time of 6.5 days) for prostate cancer xenografts. Genetically this tumor exhibits loss of heterozygosity for the short arm of chromosome 8 and has a complex karyotype. This xenograft should prove to be useful in the investigation of mechanisms underlying the androgen-insensitive state of progressive prostate carcinoma.

Aged↗
PubMed2002

Late urinary function after prostate brachytherapy.

PURPOSE: To determine the relationship between short term and longer term morbidity following prostate brachytherapy. METHODS AND MATERIALS: Patients completed the American Urological Association (AUA) questionnaire at the time of initial clinical evaluation. Most patients underwent pre-implant uroflowmetry and postvoid residual (PVR) via transcutaneous ultrasound. Seventeen patients were treated with palladium-103 (29%) and 44 were treated with iodine-125 (71%). Follow-up ranged from 31 to 35 months. RESULTS: Twenty-one of 52 patients (43%) developed postimplant urinary retention, almost always within 24 h of the procedure, and were generally managed by intermittent self-catheterization. By 2 years, all cases of retention had resolved spontaneously, and no patient required a surgical procedure to relieve urinary obstruction. Preimplant AUA score, age, and transrectal ultrasound volume did not correlate with time in retention. There was no clear relationship between long-term changes in AUA scores and preimplant transrectal ultrasound volume, age, preimplant AUA scores, postvoid residual, maximum urinary flow rates, or use of beam radiation or hormonal therapy. CONCLUSIONS: Although there is no shortage of unsubstantiated claims regarding predisposing factors to postimplant morbidity, the risk of urinary retention and long-term urinary dysfunction is probably multifactorial in nature and only crudely defined by known clinical variables.

Adult↗