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Biomedical subjects

D S Wilkinson

Publications and source records attributed to D S Wilkinson.

At least 19 recordsLinked to original sources
PubMed2004

Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation.

Acute rejection (AR) and recurrence of hepatitis C virus (HCV) infection are complications after liver transplantation (LTx). Genetic factors play a role in cytokine production as a consequence of polymorphisms within cytokine genes. Our goal was to identify genetic factors that might be associated with AR and recurrence of HCV in liver transplant recipients (LTxRs). We studied 77 Caucasian LTxRs and 100 Caucasian healthy individuals. We studied single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha[TNF-alpha, interleukin-6 (IL-6), IL-10, transforming growth factor-beta1, and angiotensin-converting enzyme genes by SNaPSHOT trade mark Multiplex assay. SNPs were classified as high producers (HP), intermediate producers (IP), or low producers (LP), and their association with AR and recurrence of HCV were studied. The frequency of TNF-alpha IP and HP genotypes was significantly higher in LTxRs with AR in comparison to patients without AR (TNF-alpha HP -238: 63 vs 20%, p < 0.001; TNF-alpha HP -308: 47.4 vs 20%, p = 0.02). The frequency of IL-6 IP and HP genotypes was higher in patients with AR episodes, but the difference was not statistically significant (p = 0.14). However, when we analyzed the simultaneous presence of pro-inflammatory genotypes in the same patient, we found a significant difference between patients with and without AR, respectively (42.1 vs 14.6%, p = 0.012). Moreover, the frequency of the IL-10 LP genotype was higher in LTx patients with AR (p = 0.001) compared to patients without AR. There was an association between pro-inflammatory genotypes and HCV recurrence. Our data suggest that cytokine gene polymorphisms might play a role in AR and HCV recurrence in LTxRs.

Adult↗
PubMed2000

Genetic changes in solid tumors.

Although most solid tumors are treated surgically, determining the genetic changes present in the tumor of an individual patient is becoming increasingly important for managing the oncology patient. Our knowledge of the genetic alterations that characterize and predispose to solid tumors continues to expand. Concurrently, the advent of newer technologies such as DNA chips has the potential to enable a more rapid and comprehensive assessment of these changes. The ultimate goal of this new information and technology is to provide sensitive and specific tests that reduce unnecessary procedures and optimize therapy. This review addresses the utility of molecular testing in evaluating cancer. A review of the current technology and hereditary cancer syndromes is also presented.

Breast Neoplasms↗
PubMed2000

Detection of a novel truncated WT1 transcript in human neoplasia.

BACKGROUND: The Wilms' tumor 1 (WT1) gene encodes a transcription factor critical in urogenital development. Using a new model of prostate cancer progression that permits comparison of the cellular and molecular properties of increasingly aggressive sublines of simian virus 40 large T-antigen-immortalized human prostate epithelial cells within the same lineage, the role of WT1 in tumorigenesis was investigated. METHODS AND RESULTS: Using RT-PCR and northern blotting, we identified a novel truncated WT1 transcript in these prostate cancer cell lines. This 2.1-kb transcript consisted of the coding region of the zinc-finger domain of WT1, together with a portion of intron 5 at the 5' end of the transcript. Furthermore, two peptides were detected by western blotting using antibodies to epitopes of the COOH terminus of WT1. Using RT-PCR, the 2.1-kb transcript was also detected in leukemia cell line K562, breast cancer cell line MCF7, and blood samples from patients with acute leukemia. CONCLUSION: These novel findings in both cell lines and patient-derived specimens suggest this new WT1 gene alteration has a potential role in the development of new diagnostic assays for some human malignancies.

Blotting, Northern↗
PubMed2000

Validation of a multiplex methylation-sensitive PCR assay for the diagnosis of Prader-Willi and Angelman's syndromes.

BACKGROUND: Prader-Willi (PWS) and Angelman's (AS) syndromes are two distinct clinical entities caused by alterations in an identical but differentially methylated region of DNA on chromosome 15q. Highly complex laboratory tests are required for diagnosis because the disorders are caused by several genetic mechanisms. Methylation-specific PCR (MSPCR) is a relatively simple alternative method to detect the methylation status of the PWS/AS region. METHODS AND RESULTS: DNA was treated with sodium bisulfite, with alterations to the published method in which a neutralization step after the alkali treatment of the modified DNA enabled the use of the modified product directly in the PCR, eliminating the need for ethanol precipitation. Multiplex MSPCR using primers to methylated and unmethylated DNA was optimized to yield equal amplification efficiency for both products. Complete concordance was observed during the clinical validation of 40 previously characterized samples, except for one patient with mosaic AS detected by fluorescence in situ hybridization. CONCLUSION: We have developed and validated a multiplex MSPCR assay with alterations of the original published protocol that is technically robust and reproducible and can be used as a screening assay to detect PWS and AS.

Angelman Syndrome↗
PubMed2000

Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation.

STUDY OBJECTIVE: To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical pharmacy anticoagulation service in a group model health maintenance organization. SUBJECTS: Thirty nonbleeding patients with international normalized ratios (INRs) ranging from 6.0-10.0. INTERVENTIONS: Patients were randomized to receive either a single oral dose of phytonadione 2.5 mg or placebo. Both groups omitted warfarin doses until the INR became less than or equal to 4.0. MEASUREMENTS AND RESULTS: The mean calculated time to reach an INR of 4.0 was significantly greater in the placebo than the phytonadione group (2.6 vs 1.4 days, p=0.006). Overcorrection of anticoagulation was significantly more common in patients receiving phytonadione. Overt warfarin resistance was not observed in either group after reinitiating warfarin therapy. No major bleeding or thromboembolic complications occurred, and minor bleeding episodes were similar in both groups. CONCLUSION: The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone. Adverse events did not differ between the two groups. Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0. Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection.

Aged↗
PubMed2000

Enhanced analytical sensitivity of a quantitative PCR for CMV using a modified nucleic-acid extraction procedure.

Accurate and rapid diagnosis of CMV disease in immunocompromised individuals remains a challenge. Quantitative polymerase chain reaction (QPCR) methods for detection of CMV in peripheral blood mononuclear cells (PBMC) have improved the positive and negative predictive value of PCR for diagnosis of CMV disease. However, detection of CMV in plasma has demonstrated a lower negative predictive value for plasma as compared with PBMC. To enhance the sensitivity of the QPCR assay for plasma specimens, plasma samples were centrifuged before nucleic-acid extraction and the extracted DNA resolubilized in reduced volume. Optimization of the nucleic-acid extraction focused on decreasing or eliminating the presence of inhibitors in the pelleted plasma. Quantitation was achieved by co-amplifying an internal quantitative standard (IS) with the same primer sequences as CMV. PCR products were detected by hybridization in a 96-well microtiter plate coated with a CMV or IS specific probe. The precision of the QPCR assay for samples prepared from untreated and from pelleted plasma was then assessed. The coefficient of variation for both types of samples was almost identical and the magnitude of the coefficient of variations was reduced by a factor of ten if the data were log transformed. Linearity of the QPCR assay extended over a 3.3-log range for both types of samples but the range of linearity for pelleted plasma was 20 to 40,000 viral copies/ml (vc/ml) in contrast to 300 to 400,000 vc/ml for plasma. Thus, centrifugation of plasma before nucleic-acid extraction and resuspension of extracted CMV DNA in reduced volume enhanced the analytical sensitivity approximately tenfold over the dynamic range of the assay.

Centrifugation↗
PubMed1999

Clinical utility of a quantitative polymerase chain reaction for diagnosis of cytomegalovirus disease in solid organ transplant patients.

BACKGROUND: Accurate and rapid diagnosis of human cytomegalovirus (HCMV) disease in solid organ transplant patients remains a challenge. We evaluated the clinical utility of a quantitative polymerase chain reaction (QPCR) method to diagnose transplant patients with HCMV disease. METHODS: A total of 429 plasma samples from 121 solid organ transplant patients were prospectively collected and evaluated for HCMV using a QPCR assay. To enhance the sensitivity of the QPCR assay, plasma samples were centrifuged in a manner designed to concentrate the virions before nucleic acid extraction. Quantitation was achieved by co-amplifying an internal quantitative standard (IS) that contained the same primer sequences as for HCMV. Polymerase chain reaction products were detected by hybridization to 96-well microtiter plates coated with either a HCMV- or an IS-specific probe. RESULTS: A total of 103 patients had all samples negative by QPCR. None of the 103 patients developed HCMV disease during the study. In contrast, 18 patients showed at least 1 sample positive by the QPCR assay, but only 8 of these developed HCMV disease. The mean viral load value for patients without HCMV disease was 93 viral copies (vc) per ml of plasma (range: 35-325 vc/ml plasma) and for the 8 patients with HCMV disease was 67,686 vc/ml plasma (range: 167-1,325,000 vc/ml plasma) (P<0.001). Using a cut-off value of 100 vc/ml plasma and clinical diagnosis of HCMV disease, the QPCR assay showed a sensitivity of 100% and specificity of 99.1%. CONCLUSION: HCMV viral load may be useful in the diagnosis of HCMV disease in solid organ transplant patients.

Adolescent↗
PubMed1999

What families know about funeral-related costs: implications for social work practice.

Social workers provide essential services in the area of end-of-life care to individuals who are dying and their families. Results reported here suggest that social work's role be expanded to provide basic information about local final arrangement (funeral and burial) options and costs. This study was undertaken to determine the knowledge and experience level of people responsible for funeral and cemetery arrangements and to investigate factors affecting familiarity with final costs. Survey responses from 163 survivors of older adults in Kansas City showed that adult children play an important role in the final arrangements of a parent and that half the survivors responsible for final arrangements had no idea what to expect in terms of costs.

Aged↗
PubMed1999

The role of perceived stress on prenatal care utilization: implications for social work practice.

Data from the National Institute of Child Health and Human Development/Missouri Maternal and Infant Health Survey on about 2,828 mothers were used to examine the relationship between perceived stress and prenatal care utilization. Major life events that contribute to stress also were examined in relation to adequacy of prenatal care. Women who received inadequate prenatal care were more likely to have reported that they almost always felt stress during pregnancy. Odds ratios were statistically significant for women who were not black and Medicaid recipients but not for black women and women who were not covered by Medicaid. Social work intervention for stress reduction on behalf of pregnant women has the potential to contribute to improved prenatal care utilization, but further analysis of the kinds of stress women experience will enhance social work's ability to target specific interventions.

Adolescent↗
PubMed1998

A performance indicator of psychosocial services in enhanced prenatal care of Medicaid-eligible women.

OBJECTIVE: Psychosocial services for low-income pregnant women vary widely in practice, and validated indicators of effective performance are lacking. The study presented here aims to determine whether a measure of provider compliance with a psychosocial service delivery guideline is associated with improved birth outcomes and therefore meets an important validity criterion of a performance indicator. METHODS: Data on psychosocial services delivered to 3467 pregnant women came from 27 sites certified by the California Department of Health Services to provide enhanced perinatal services to Medicaid-eligible women. Multivariate regression analyses were used to test the association of adequate service delivery according to a performance guideline with birth outcomes and the dependence of the association on the credentials of the provider and the type of practice setting. RESULTS: Women who received at least one psychosocial assessment each trimester of care according to the guideline were half as likely as women with inadequate services to have a low birthweight (OR = 0.49; CI 0.34, 0.71) or preterm birth (OR = 0.53; CI 0.40, 0.72) outcome. The effect did not depend on the credentials of the provider or the practice setting type. CONCLUSIONS: The indicator of the adequacy of psychosocial services according to a performance guideline appears to meet a fundamental criterion for a performance indicator, an association with improved outcomes. This indicator may be useful in monitoring performance of enhanced perinatal services for continuous quality improvement of services to low-income pregnant women.

Birth Weight↗
PubMed1998

Pregnancy intentions, pregnancy attitudes, and the use of prenatal care in Missouri.

OBJECTIVES: This study uses data from 2378 mothers of live-born infants from the NICHD/Missouri Maternal and Infant Health Survey to examine the relationship between pregnancy intention and adequacy of prenatal care. METHODS: Pregnancy intention was measured using traditional classifications of mistimed and unwanted pregnancies as well as additional measures of women's attitudes about their pregnancies. Odds ratios for inadequate prenatal care and its component parts (initiation of care and receipt of services) were calculated using multiple logistic regression in separate models and in a combined model for the measures of intention and attitude. RESULTS: Women's attitudes about their pregnancies were associated with inadequate prenatal care, including both inadequate initiation of care and inadequate receipt of services. Traditional measures of intendedness were significantly related only to inadequate initiation of care. Women who were unhappy about the pregnancy (OR = 1.44), unsure that they wanted to be pregnant (OR = 2.81), or denied their pregnancies (OR = 4.82) were more likely to have inadequate prenatal care than women who did not have these attitudes. Women who were unhappy about being pregnant (OR = 1.86), unsure that they wanted to be pregnant (OR = 3.44), or who denied the pregnancy (OR = 6.69) were more likely to have inadequate initiation of care. Women who were unsure that they wanted to be pregnant (OR = 1.95) or who denied their pregnancies (OR = 2.47) were more likely to have received inadequate care once they had entered care. CONCLUSIONS: This study suggests that attitudes about pregnancy may be a psychosocial barrier to women obtaining early and continuous prenatal care. Pregnancy attitudes should be assessed and appropriate services provided to improve women's utilization of prenatal care. New measures of pregnancy attitude, beyond the traditional intention measures, can be useful in assessing pregnancy wantedness and identifying women to target for these services.

Adolescent↗
PubMed1998

Going home: community reentry of light care nursing facility residents age 65 and over.

Issues of consumer choice, and rising public expenditures of nursing facility care for the rapidly increasing elderly population have fueled interest in community reentry of nursing facility residents. The Minimum Data Set Plus (MDS+) contains a wealth of information which can be used to provide a better understanding of nursing facility residents including those who discharge. This study employs the Andersen model of health services utilization and logistical regression on MDS+ data to examine characteristics of higher functioning nursing facility residents age 65 and over related to community reentry in one midwestern state. Findings include having Medicaid as a payer source significantly decreased the likelihood of discharge. In contrast, being younger than 85, retaining decision making responsibilities, and having no cognitive impairments were found to increase the likelihood of discharge. Policy and program implications related to identifying and assisting nursing facility residents in resuming community living are discussed.

Activities of Daily Living↗
PubMed1997

Detection of a common mutation in factor V gene responsible for resistance to activate protein C causing predisposition to thrombosis.

Hereditary predisposition to thrombosis due to activated protein C resistance (APCR) has been attributed to a missense mutation in the factor V gene at nucleotide 1691 (G to A), causing replacement of arginine at codon 506 with glutamine. Using an RFLP-PCR assay to detect this mutation, we measured a prevalence of 3.3% in healthy Caucasians and 1.25% in healthy African-Americans. In addition, we evaluated a total of 90 consecutive specimens submitted to the coagulation laboratory at the Medical College of Virginia for the presence of this mutation. We compared our results for 78 of these specimens with the values measured by a modified partial thromboplastin assay, the COATEST. Twelve of the 90 samples could not be tested using the COATEST because the patients were undergoing anticoagulant therapy. One of the latter 12 specimens was positive by the RFLP-PCR test. Using the genetic test as the definitive assay and the cutoff value established for distinguishing between normal and abnormal results by the COATEST, the COATEST had a sensitivity of 50% and specificity of 93% for the detection of factor V mutation. Analysis of the 90 samples stratified by ethnic groups revealed a frequency of mutation of 13.3% for Caucasians and 6.88% for African-Americans, although with the present sample size, the difference was not statistically significant. Although the COATEST is technically simpler to perform than the genetic test for diagnosing the presence of the factor V mutation, its use for this purpose is limited due to low sensitivity. Thus where this disorder is clinically suspected, submission of the specimen directly for genetic testing by RFLP-PCR or equivalent assay should be considered.

Black People↗
PubMed1996

Red cells and platelets. Modifications for special patients.

Blood components are modified to meet the clinical requirements of specific patient populations. The clinical indications for some well-established components have narrowed with the development of new technology. Leukoreduced blood components are being considered for a variety of clinical applications. Published data support the use of leukoreduced components to prevent febrile nonhemolytic transfusion reactions. The routine use of such components for other indications should be considered experimental, and the cost effectiveness of experimentally validated indications should be evaluated.

Blood Component Removal↗
PubMed1995

Chemistry and sintering behaviour of thin hydroxyapatite ceramics with controlled porosity.

Hydroxyapatite ceramic tapes (several hundred micrometres thick), have been prepared at different porosity levels, using the tape casting technique. The reactions, which occur during processing and sintering of the tapes, have been characterized by power X-ray diffraction analysis, differential thermal analysis (DTA), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Volume changes have been measured during different stages of heat treatment. These can be attributed to phase transformations of the starting materials, which determine the sintering behaviour and final porosity of the samples. Measurements of the elastic modulus were performed by the resonant frequency method. A cubic dependence on the relative density is found. Finally, some possible improvements for the technique and selection of powders are suggested, based on the reported results.

Ceramics↗
PubMed1995

Carcinoma of the gall-bladder: an experience and review of the literature.

This paper summarizes the treatment results of 28 cases of gall-bladder carcinoma at Toowoomba Base Hospital, Toowoomba, Queensland, Australia. The literature is reviewed in order to determine whether more extensive resection is improving the outcome of a disease generally understood to have a deplorable prognosis. The complete records of 28 patients with this malignancy were obtained from the period 1978 to 1994 and analysed retrospectively. Twenty-three patients had cholecystectomy, but only one underwent formal lymph node dissection. Overall, the 5 year survival rate was 13%, and long-term survivors all had stage I or II disease. Those with stage III or IV disease had a median survival of 46 days. Recent literature confirms that simple cholecystectomy is not always curative for early lesions discovered incidentally and also that some patients with advanced disease can achieve long-term survival if treated with radical resection. Wedge resection of the liver and nodal clearance of the hepatoduodenal ligament at least has been recommended in patients with T2 lesions (subserosal/perimuscular), and in selected patients with stage III disease.

Cholecystectomy↗
PubMed1994

Nonclient factors in the reporting of prenatal psychosocial risk assessments.

Psychosocial and nutrition risk assessments at 27 randomly selected sites of a Medicaid-funded enhanced prenatal program were examined for completeness and uniformity of reporting. The recording of psychosocial data, but not of nutrition data, was found to be associated with a substantial number of nonclient factors, including geographical location and abstractor, assessor, and service provider characteristics. The variability in recording of psychosocial problems reflects the numerous ways that assessments are performed and the subsequent difficulty in interpreting the practice of psychosocial assessment. A uniform system of defining and classifying risks is needed to improve both service delivery and service evaluation.

Female↗