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C Reeves

Publications and source records attributed to C Reeves.

At least 19 recordsLinked to original sources
PubMed2001

Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing.

BACKGROUND & AIMS: The optimal strategy for the detection of hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers remains uncertain. We evaluated whether microsatellite instability (MSI) analysis or MSH2 and MLH1 protein immunostaining of tumors will screen individuals efficiently for germline MSH2 and MLH1 testing. METHODS: We performed a case-series study of 114 eligible families enrolled in our high-risk colorectal cancer (CRC) registry. Medical history data were collected on probands and relatives. MSI analysis was performed on proband tumors, and MSH2 and MLH1 protein immunostaining was assessed. Denaturing gradient gel electrophoresis was used to identify germline MSH2 or MLH1 mutations in probands found to have tumors with high-frequency MSI. RESULTS: Tumor tissue and adequate clinical data were available in 109 of the 114 families. Amsterdam criteria and Bethesda guidelines were met by 23% and 70% of the families, respectively. High-frequency MSI was identified in the proband tumors in 47 of the 109 families (43%). Germline MSH2 and MLH1 gene testing was carried out in the probands of 32 of 47 families with MSI-H tumors. Mutations were detected in 16 families (9 in MSH2 and 7 in MLH1) and sequence variants of uncertain significance in 5 families (1 in MSH2 and 4 in MLH1). Germline mutations or sequence variants of uncertain significance were detected in 15 of 19 (79%) of our Amsterdam families and in 6 of 13 (46%) of our non-Amsterdam families with MSI-H tumors. MSH2 and MLH1 protein immunostaining was assessed in 38 of the 47 MSI-H tumors. Unequivocal loss of hMLH1 expression was found in 20 tumors and loss of MSH2 expression in 9 tumors. Corresponding loss of protein expression was seen in 17 of 18 (94%) of tumors from probands with germline mutations or variants. CONCLUSIONS: The detection of high-frequency MSI or the loss of MSH2 or MLH1 immunostaining in CRCs are both useful criteria for selecting high-risk patients who should be tested for germline mutations in MSH2 or MLH1.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed2001

Eliciting public preferences for healthcare: a systematic review of techniques.

BACKGROUND: Limited resources coupled with unlimited demand for healthcare mean that decisions have to be made regarding the allocation of scarce resources across competing interventions. Policy documents have advocated the importance of public views as one such criterion. In principle, the elicitation of public values represents a big step forward. However, for the exercise to be worthwhile, useful information must be obtained that is scientifically defensible, whilst decision-makers must be able and willing to use it. AIMS AND OBJECTIVES: The aim was to identify techniques that could be reasonably used to elicit public views on the provision of healthcare. Hence, the objectives were: (1) to identify research methods with the potential to take account of public views on the delivery of healthcare; (2) to identify criteria for assessing these methods; (3) to assess the methods identified according to the predefined criteria; (4) to assess the importance of public views vis-à-vis other criteria for setting priorities, as judged by a sample of decision-makers; (5) to make recommendations regarding the use of methods and future research. METHODS: A systematic literature review was carried out to identify methods for eliciting public views. Criteria currently used to evaluate such methods were identified. The methods identified were then evaluated according to predefined criteria. A questionnaire-based survey assessed the relative importance of public views vis-à-vis five other criteria for setting priorities: potential health gain; evidence of clinical effectiveness; budgetary impact; equity of access and health status inequalities; and quality of service. Two techniques were used: choice-based conjoint analysis and allocation of points technique. The questionnaire was sent to 143 participants. A subsample was followed up with a telephone interview. RESULTS: The methods identified were classified as quantitative or qualitative. RESULTS - QUANTITATIVE TECHNIQUES: Quantitative techniques, classified as ranking, rating or choice-based approaches, were evaluated according to eight criteria: validity; reproducibility; internal consistency; acceptability to respondents; cost (financial and administrative); theoretical basis; whether the technique offered a constrained choice; and whether the technique provided a strength of preference measure. Regarding ranking exercises, simple ranking exercises have proved popular, but their results are of limited use. The qualitative discriminant process has not been used to date in healthcare, but may be useful. Conjoint analysis ranking exercises did well against the above criteria. A number of rating scales were identified. The visual analogue scale has proved popular within the quality-adjusted life-year paradigm, but lacks constrained choice and may not measure strength of preference. However, conjoint analysis rating scales performed well. Methods identified for eliciting attitudes include Likert scales, the semantic differential technique, and the Guttman scale. These methods provide useful information, but do not consider strength of preference or the importance of different components within a total score. Satisfaction surveys have been frequently used to elicit public opinion. Researchers should ensure that they construct sensitive techniques, despite their limited use, or else use generic techniques where validity has already been established. Service quality (SERVQUAL) appears to be a potentially useful technique and its application should be researched. Three choice-based techniques with a limited application in healthcare are measure of value, the analytical hierarchical process and the allocation of points technique, while those more widely used, and which did well against the predefined criteria, include standard gamble, time trade-off, discrete choice conjoint analysis and willingness to pay. Little methodological work is currently available on the person trade-off. RESULTS - QUALITATIVE TECHNIQUES: Qualitative techniques were classified as either individual or group-based approaches. Individual approaches included one-to-one interviews, dyadic interviews, case study analyses, the Delphi technique and complaints procedures. Group-based methods included focus groups, concept mapping, citizens' juries, consensus panels, public meetings and nominal group techniques. Six assessment criteria were identified: validity; reliability; generalisability; objectivity; acceptability to respondents; and cost. Whilst all the methods have distinct strengths and weaknesses, there is a lot of ambiguity in the literature. Whether to use individual or group methods depends on the specific topic being discussed and the people being asked, but for both it is crucial that the interviewer/moderator remains as objective as possible. The most popular and widely used such methods were one-to-one interviews and focus groups. (ABSTRACT TRUNCATED)

Data Collection↗
PubMed2000

Stress grouping improves performance on an immediate serial list recall task.

Five experiments investigated whether perceptual patterning afforded by imposing a recurrent stress pattern on auditorially presented lists has a positive effect on list recall. The experiments also addressed whether the recall advantage reflected the salience that the stress pattern created for certain items or whether the recall advantage arose from the distinct grouping configurations that were produced by the stress pattern. The authors explored these issues by examining immediate serial-recall performance for spoken lists that either did or did not have a stress pattern imposed on them. Lists had an anapest or dactylic stress pattern or were monotone and consisted of two stimulus types, either digit names or common English nouns. Results showed that stress patterns enhanced serial-recall performance and that the recall benefit derived primarily from the perceptual grouping afforded by the stress patterns. Results also showed that the grouping benefit derived from stress patterning generalizes to monotone lists. In contrast, salience effects are attached to the stimulus per se and do not transfer.

Adult↗
PubMed1998

Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5.

We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal transferable fragment (STF) from 11p15.5 and the identification of nine known genes and four novel genes within this STF. We now report the isolation of a fifth novel cDNA, tumor-suppressing STF cDNA 5, designated TSSC5, located within the STF. TSSC5 encodes a predicted protein of 424 amino acids. Sequence analysis suggests that TSSC5 is a membrane protein with 10 transmembrane segments, and it is located between two imprinted genes, p57KIP2 and TSSC3. Northern blot hybridization revealed a 1.6-kb transcript in multiple adult tissues and in fetal liver and kidney, consistent with a potential role in embryonal tumors. We also found that TSSC5 is imprinted with preferential expression from the maternal chromosome. Reverse transcription-PCR analysis of TSSC5 revealed frequent occurrence of aberrant RNA splicing, which deleted exons 4, 5, and 6 in Wilms' tumors. Mutational analysis of TSSC5 by direct DNA sequencing of exons revealed a base substitution of G1120A in a Wilms' tumor, matched normal kidney, and the patient's mother, changed Arg at codon 309 to Gln. The G1120A substitution thus represents either a rare polymorphism or a tumor-predisposing mutation, because the mutant allele was of maternal origin and preferentially expressed in the patient's tissue. A second base substitution, C892T, was found in a lung cancer, changing Ser at codon 233 to Phe. This substitution was absent from the matched normal tissue and thus represented a somatic mutation. We also found loss of heterozygosity in the lung cancer, suggesting that TSSC5 may be a conventional tumor suppressor gene in the adult human lung and an imprinted tumor suppressor gene in the fetal kidney.

Adult↗
PubMed1998

Treatment of human immunodeficiency virus-positive patients with complementary and alternative medicine: a survey of practitioners.

OBJECTIVE: To investigate complementary and alternative medicine (CAM) practices provided to human immunodeficiency virus (HIV)-infected individuals, provider experience in HIV disease, patients' characteristics, provider perceptions of treatment effectiveness, and feasibility and interest in future studies. DESIGN: Mailed survey. PARTICIPANTS: 117 providers, recruited from professional associations and conferences, who offer CAM therapies to HIV-infected individuals. OUTCOME MEASURES: Provider credentials, patient descriptors, treatments prescribed and their perceived effectiveness, health service information, medical information charted, and research participation capability and interest. RESULTS: Providers are treating patients at all stages of HIV disease with a variety of CAM practices, claiming a mean of 6.5 years of HIV disease treatment experience and 105 HIV-positive patients in treatment per provider (solo practice or clinic). Eighty percent of respondents report holding state licenses to practice. A total of 115 different CAM therapies with an average of 12 treatments per provider were used. Ninety percent of providers claimed their therapies were "somewhat" to "very effective" on all disease stages, indicating effectiveness for symptom management (96%), quality of life (98%), raising or maintaining CD4+ lymphocyte levels (66%), slowing progression to acquired immunodeficiency syndrome (AIDS) (69%), and extending survival (73%). Research readiness and willingness was reported by a majority of respondents. CONCLUSIONS: Providers with substantial experience treating HIV disease with a range of CAM practices claim effectiveness for their methods. Providers are generally willing to participate in studies that would examine such claims and appear to have the capacity meaningfully to contribute. These claims should be investigated.

Complementary Therapies↗
PubMed1998

Constitutional WT1 mutations in Wilms' tumor patients.

PURPOSE: Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation. METHODS: We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who had specific clinical risk factors compared with those who did not. RESULTS: Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. CONCLUSION: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs.

Adolescent↗
PubMed1997

A scientific plan for the evaluation of alternative medicine in the treatment of HIV/AIDS.

The Bastyr University AIDS Research Center was established in October 1994 through a 3-year cooperative grant with the Office of Alternative Medicine, National Institutes of Health. The mission of the Center is to (1) describe forms and patterns of use of alternative medical therapies for HIV infection and AIDS prescribed by practitioners and self-administered by HIV-positive patients in the United States, (2) screen and evaluate therapies for HIV/AIDS from five program areas of alternative medicine, and (3) provide consultation and support in the scientific evaluation of alternative therapies. To meet these goals, the Center has established a network of cooperating alternative medicine clinics and is recruiting HIV-positive men and women who are using alternative medicine to participate in the study. It is collecting data every 6 months from 1500 HIV-positive patients throughout the United States and has created a centralized database to compare outcomes (CD4+ lymphocytes, HIV RNA, CDC class progression, weight, quality of life, and survival) for a variety of alternative therapies. The Center will determine whether patients who use both conventional medicine and alternative medicine have different outcomes from patients who use only conventional medicine. The occurrence of AIDS-related opportunistic infections and neoplasms in HIV-positive patients who are using specific alternative therapies will be compared with the incidence in those who use other medical treatment. This article describes the scientific plan for the study.

Acquired Immunodeficiency Syndrome↗
PubMed1994

dT diaphorase: increased enzyme activity and mRNA expression in oxidant stress of skin.

DT diaphorase is a flavoprotein that enzymatically transfers two electrons from quinones as intermediate substrates and has been reported to increase its activity in the liver after exposure to toxicants. In this series of experiments, we tested the hypothesis that DT diaphorase also increases its activity after exposure to oxidants following gradient ischemia in skin. Using dorsal rat flaps, oxidant stress was induced immediately or during a 7-day period of preconditioning as a bipedicle flap before the distal attachment was divided. DT diaphorase activity (delta Abs/min/100 g) or expression of message was measured during the period of preconditioning to determine the relationship between skin survival, enzyme activity, and expression of message. There was 4.7 +/- 0.8 cm of skin necrosis in the distal end of acute flaps while the preconditioned flaps had no skin necrosis after the distal attachment was divided. In the acute flaps, the DT diaphorase activity was equal throughout the flap for the first 6 hr. After 24 hr of ischemia, the DT diaphorase activity was significantly higher in the proximal end of the flap (1.83 +/- 0.21 delta Abs/min/100 g) than that in the distal end (0.005 +/- 0.01 delta Abs/min/100 g), which was significant (P < 0.05). In the preconditioned flaps, enzyme activity did not increase but there was as 50-fold increase in DT diaphorase activity at the distal end 24 hr after they were divided (P < 0.05). Maximal enzyme induction of DT diaphorase activity occurred after 4 days of preconditioning and correlated with the maximal expression of mRNA. These studies provide the first evidence that DT diaphorase enzyme activity is inducible after oxidant stress. The data also suggests that DT activity remains elevated for at least 6 hr of ischemia and may be a potential source of anti-oxidant activity in ischemic skin.

Animals↗
PubMed1994

Mutants of Streptomyces cattleya defective in the synthesis of a factor required for thienamycin production.

Thienamycin non-producing mutants of Streptomydes cattleya were identified that displayed a cross-feeding relationship. A diffusible product from one of these mutants (RK-11) resulted in restoration of thienamycin production when fed to cultures of another mutant (RK-4). In vivo radiolabeling experiments were conducted to test whether the RK-11 mutant produced a late biosynthetic intermediate which contained a carbapenem ring and a cysteaminyl and/or a hydroxyethyl side chain. Both [35S]cystine and [methyl-3H]methionine were used to label the RK-11 product which was then fed to RK-4 cultures. None of the thienamycin subsequently produced by RK-4 converter cells was labeled, implying the lack of either side chain of the thienamycin molecule in the RK-11 product. Further stability studies suggested that the RK-11 product does not contain a carbapenem ring. Additional feeding experiments with RK-4 cells also ruled out the possibility that the RK-11 product is a co-factor necessary for thienamycin production. It is concluded that the RK-11 product may regulate expression of the thienamycin gene cluster.

Chromatography, High Pressure Liquid↗
PubMed1993

Summing up.

Explore the source record for details and available documents.

Budgets↗
PubMed1991

Isolation and sequencing of a genomic DNA clone containing the 3' terminus of the 6-methylsalicylic acid polyketide synthetase gene of Penicillium urticae.

A 7.7-kilobase (kb) Penicillium urticae genomic DNA fragment containing the 3' terminus of the 6-methylsalicylic acid polyketide synthetase gene was cloned using a 41-mer mixed oligodeoxynucleotide probe which was based on a cyanogen bromide cleavage peptide of 35 amino acids obtained from pure synthetase. Nucleotide sequence analysis of a 2.2-kb region of the cloned fragment revealed a large open reading frame of 1866 bases which was devoid of introns and which corresponded to amino acids of the carboxyl terminus of the enzyme. This was followed by a putative transcription termination--polyadenylation signal. A putative acyl carrier protein domain at the 3' terminus was preceded by a beta-ketoreductase domain. These functionalities were identified by amino acid sequences known to be characteristic of the active sites of fatty acid synthetase functional domains. Their relative positions contrast with those in yeast and P. urticae fatty acid synthetase genes where the two functional domains are located at the 5' terminus and in reverse order. Furthermore, amino acid sequence identities indicated a striking homology with vertebrate rather than either yeast or P. urticae fatty acid synthetases.

Acyltransferases↗
PubMed1990

Noninvasive cardiac output: simultaneous comparison of two different methods with thermodilution.

The authors attempted to simultaneously measure cardiac output by thermodilution (COtd), thoracic bioimpedance (CObi), and suprasternal Doppler ultrasound (COdopp) in 68 patients. Subgroups separately compared included patients whose lungs were mechanically ventilated, patients undergoing cardiac surgery, aortic surgery, patients with dysrhythmias, and patients with sepsis. The authors also studied the value of the ventricular ejection time (VET) in evaluating the agreement of CObi and COdopp with COtd. Simultaneous CObi and COtd were available in a total of 56 patients (416 data sets) with an overall correlation coefficient r = 0.61, regression slope (m) of 0.52, intercept (y) of 2.46, and mean (CObi-COtd) difference (bias) of -0.67 +/- 1.72 (SD) l/min. Simultaneous COdopp and COtd were available in 59 patients (446 data sets) with an overall r = 0.51, m of 0.53, y of 2.05, and bias of -0.79 +/- 1.95 l/min. CObi agreed most closely with COtd in patients whose lungs were mechanically ventilated, who had not undergone cardiac or aortic surgery, and with VET difference less than 40 ms (16 patients, 99 data sets; r = 0.74; m = 0.97; y = 0.15; bias = -0.02 +/- 1.53 l/min). COdopp agreed most closely with COtd in patients whose lungs were mechanically ventilated, who had not undergone cardiac or aortic surgery, and in sinus rhythm with VET difference less than 40 ms (10 patients, 45 data sets; r = 0.82; m = 0.98; y = -0.07; bias = -0.82 +/-1.03 l/min). VET by radial artery can help evaluate the reliability of CObi and COdopp.

Aorta↗
PubMed1989

Thoracic bioimpedance and Doppler cardiac output measurement: learning curve and interobserver reproducibility.

Nine previously untrained health professionals learned to measure cardiac output (Qt) by suprasternal continuous-wave Doppler ultrasound (QtDopp) and by thoracic bioimpedance (Qtbi). Each received standardized written, videotaped, and individual instruction. First the novice, then the reference examiner, measured QtDopp or Qtbi in triplicate in an adult male subject. The reference examiner was blind to the novice measurements and the novice was not informed of the reference measurements. Each novice repeatedly measured QtDopp or Qtbi in different subjects until the mean novice QtDopp or Qtbi was within 10% of the corresponding mean reference measurement in three of four consecutive subjects. The novice observers required an average of 12.9 +/- 3.5 trials to learn to measure QtDopp, and an average of 8.4 +/- 4.5 trials to learn to measure Qtbi. The likelihood of novice agreement with the reference improved with experience. The same degree of intraobserver variability as reported for Qt measured by thermodilution (coefficient of variance less than or equal to 10%) was achieved with Qtbi in 150 (99%) of 152 triplicate measurements and QtDopp in 216 (97%) of 222 triplicate measurements. More importantly, interobserver agreement (within 10%) was achieved with both Qtbi and QtDopp. Reproducible noninvasive Qt measurement will allow these techniques to be used to monitor trend changes in Qt.

Cardiac Output↗
PubMed1989

Gastroview--a touring medical roadshow.

'Gastroview' is the title of a touring medical roadshow which offers invited medical audiences the opportunity to view live endoscopic proceedings with two-way sound communication, enabling dialogue between the audience and the endoscopist. It is particularly targeted at general practitioners. The project is funded by an International Pharmaceutical Company and the paper gives an insight into the practicalities of organizing and administering such a show.

Audiovisual Aids↗