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Biomedical subjects

M Ward

Publications and source records attributed to M Ward.

At least 145 records · Page 8Linked to original sources
PubMed1996

Myths and realities in clinical research.

It is often argued that clinicians should be more actively involved in research and that this inactivity is due to shortage of time and funds. This may be so, but more important and less obvious constraints are the differences in the philosophical foundations of clinical practice and research. Researchers must strive to abolish uncertainty, to be unwaveringly committed to truth and to rid themselves of all bias. Clinicians, in contrast, must frequently manage patients in the absence of certainty, handle truth creatively and be willing to be biased on their patients' behalf as part of a professional obligation. These differences constitute powerful selection pressures for individuals with particular skills, personalities and sources of job satisfaction. Clinical practice and research are instrinsically different activities and it is probably unreasonable to expect an individual talented in one to be similarly expert in the other.

Humans↗
PubMed1996

Risk of colorectal adenomas in patients with a family history of colorectal cancer: some implications for screening programmes.

BACKGROUND AND AIMS: Most colorectal cancers (CRC) arise in colorectal adenomas. A case-control study was conducted to see whether a family history of CRC is associated with a higher prevalence of colorectal adenomas. SUBJECTS: Subjects were drawn from all patients who underwent colonoscopy at the Royal Brisbane Hospital between 1980-1982 and 1985, and included 141 cases with colorectal adenomas diagnosed at colonoscopy and 882 controls who were free of polyps at colonoscopy. METHODS: The prevalence of family history of CRC was compared between patients with adenomas and negative colonoscopy controls. RESULTS: Overall, patients with one first degree relative with CRC were at no greater risk for adenomas at colonoscopy than patients with no family history (odds ratio (OR) = 0.8, 95% confidence intervals (CI) = 0.4, 1.5). Patients with two or more affected first degree relatives had a more than doubled risk for adenomas (OR = 2.3, 95% CI = 0.5, 8.2), and were also more likely to carry moderately or severely dysplastic adenomas (OR = 14.1, 95% CI = 2.0, 62.9). CONCLUSIONS: These findings are consistent with the hypothesis that some families, in addition to those with familial adenomatous polyposis, have an increased susceptibility to develop colorectal adenomas, and that adenomas in such families may have a greater tendency to undergo malignant transformation.

Adenoma↗
PubMed1996

Gene transfer-mediated generation of drug-resistant hemopoiesis.

Autologous- or allogeneic-bone marrow transplantation are increasingly used to overcome the myelosuppressive effects of high dose chemotherapy administered to cancer patients. Transfer of the multidrug resistance (MDR) gene in hemopoietic progenitors has been proposed as a tool to administer higher and possibly more curative doses of chemotherapy. Murine models have demonstrated that retrovirus-mediated MDR transfer in bone marrow cells can render animals resistant to myeloablative doses of Taxol, and in vitro studies have shown that MDR-transduced human CD34+ cells can generate drug-resistant multipotential hemopoietic progenitors such as long term culture-initiating cells. Given these results, phase I clinical trials are currently under way to evaluate feasibility and treatment-related toxicity of MDR gene transfer in cancer patients by means of safe retroviral vectors. Finally, Taxol treatment of MDR transduced mice and human CD34+ cells have indicated that MDR is a dominant selectable marker in vitro and in vivo, and vectors carrying both MDR and non selectable genes such as beta-globin or glucocerebrosidase could be used in the next future for gene therapy of inherited disorders like thalassemia or Gaucher disease.

Animals↗
PubMed1996

Temporal constraints on the McGurk effect.

Three experiments are reported on the influence of different timing relations on the McGurk effect. In the first experiment, it is shown that strict temporal synchrony between auditory and visual speech stimuli is not required for the McGurk effect. Subjects were strongly influenced by the visual stimuli when the auditory stimuli lagged the visual stimuli by as much as 180 msec. In addition, a stronger McGurk effect was found when the visual and auditory vowels matched. In the second experiment, we paired auditory and visual speech stimuli produced under different speaking conditions (fast, normal, clear). The results showed that the manipulations in both the visual and auditory speaking conditions independently influenced perception. In addition, there was a small but reliable tendency for the better matched stimuli to elicit more McGurk responses than unmatched conditions. In the third experiment, we combined auditory and visual stimuli produced under different speaking conditions (fast, clear) and delayed the acoustics with respect to the visual stimuli. The subjects showed the same pattern of results as in the second experiment. Finally, the delay did not cause different patterns of results for the different audiovisual speaking style combinations. The results suggest that perceivers may be sensitive to the concordance of the time-varying aspects of speech but they do not require temporal coincidence of that information.

Attention↗
PubMed1996

Retroviral transfer and expression of the human multiple drug resistance (MDR) gene in peripheral blood progenitor cells.

The multiple drug resistance (MDR) gene P-glycoprotein product is a transmembrane efflux pump that prevents toxicity of a variety of chemotherapeutic agents, including the anthracyclines, Vinca alkaloids, podophyllins, and taxol. The bone marrow toxicity of these drugs is due to the low or absent expression of MDR in marrow cells. Transfer and expression of the human MDR gene into bone marrow progenitors should prevent this toxicity. We report here the efficient transfer and expression of the MDR gene by retroviral-mediated gene transfer into CD34(+) cells isolated from peripheral blood progenitor cells (PBPCs), comparable to that obtained using bone marrow-derived progenitors. Optimal MDR transduction of these PBPC-derived cells requires exposure to growth factors and a period of preincubation. In addition, we demonstrate that we can transduce up to 100% of progenitor cells derived from PBPCs and can protect up to 25% of these progenitors from a dose of taxol toxic to untransduced controls.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas.

BACKGROUND: Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans. PURPOSE: We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily). METHODS: We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance. RESULTS: There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03). CONCLUSIONS: Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.

Adenoma↗
PubMed1995

How accurate is self-reported family history of colorectal cancer?

Much of the evidence that supports a relation between a positive family history of and increased risk for colorectal cancer is based on information obtained exclusively from patients. There have been few assessments of the accuracy of such data. The validity of self-reported family history of colorectal cancer was assessed in the course of a case-control study of colorectal adenomas conducted among patients aged 20-75 years who underwent colonoscopy in Brisbane, Australia between 1980 and 1985. Family histories reported by a subsample of 237 colonoscopy patients (74 cases and 163 controls) were compared with relatives' medical records and death certificates. Patients' reports of colorectal cancer in 90 relatives were confirmed for 70 (77.8%; 95% confidence interval (CI) 67.8-85.9). Among 124 reports by patients of relatives who had other abdominal cancer or bowel conditions, 114 (91.9%; 95% CI 85.7-96.1) were confirmed to be correct, while 10 (8.1%) were found to be colorectal cancer. Finally, 105 (99.1%; 95% CI 94.9-100.0) of a random sample of 106 completely negative reports by patients were confirmed to be correct. Overall, 77% of positive family histories (any positive relatives) were confirmed, and it was estimated that 98% of negative family histories (no positive relatives) were correct. Cases were slightly more accurate than controls in reporting both positive and negative histories among their relatives. By extrapolation of these results to the total sample of 1,244 patients in the larger case-control study, sensitivity of self-reported positive family history was estimated to be 0.87 among cases and 0.82 among controls, and specificity was estimated to be 0.97 in both groups.

Adult↗
PubMed1995

An Alu VpA marker on chromosome I demonstrates that replication errors manifest at the adenoma-carcinoma transition in sporadic colorectal tumors.

Widespread mutations in simple tandemly repeated (STR) DNA sequences are frequently found in colorectal tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) and less frequently in sporadic colorectal cancers. This aims of this study were to determine the type of DNA sequence most commonly affected by such mutations and to examine the point in the natural history of the tumor where replication errors (RERs) appear. An unselected series of colorectal tumors (49 adenomas and 108 carcinomas) was examined with 4 different STR markers: one Alu VpA polymorphism (MYCLI), one tetranucleotide repeat (D17S846), one dinucleotide repeat (D3S1029), and one polyA repeat (AP delta 3 delta). All 3 positive adenomas and 18 of 20 positive carcinomas showed replication errors in the Alu VpA sequence at the MYCLI locus, making this marker more than twice as sensitive as the best of the other 3 markers. Importantly, all positive adenomas showed small foci of carcinoma in situ. This suggests that replication errors manifest at the adenoma/carcinoma transition in sporadic colorectal tumors.

Adenoma↗
PubMed1995

Brief child assessment battery to assist with treatment planning and program evaluation.

A brief battery of self-report measures was constructed to discriminate effectively 45 matched clinic versus nonclinic subjects, ages 8 to 15. The battery consisted of measures from six domains, including externalizing problems, child and parent report of internalizing problems, peer relations, school functioning, and family relationships. Data on subjects and their families were provided by various sources, including parents, teachers, and the children. In an effort to facilitate interpretation and use of this information by unsophisticated staff, within domain scores were converted to bivariate risk scores. Results indicated effective classification (82%) of groups using the bivariate risk scores alone. This constituted only a small loss of information when the risk scores replaced t-scores. Implications for the use of the risk scores to facilitate treatment planning and program evaluation are discussed.

Adolescent↗
PubMed1995

Judicial decision-making in contested custody cases: the influence of reported child abuse, spouse abuse, and parental substance abuse.

This study examined the relationship between allegations of maltreatment and substance abuse, and custody awards in Florida. Information concerning the presence, or absence, of these reports was collected on 60 contested initial disposition, or disposition modification cases, and was used to model judicial decision-making. Substantiated reports of child and spouse abuse occurred very infrequently in our sample. Conversely, substance abuse allegations occurred much more frequently. Judges appeared responsive to allegations of abuse with regard to awards of primary physical residence, despite the lack of substantiated evidence. Maltreatment allegations had no apparent impact, however, on awards of shared, versus sole, custody. Additionally, reports of parental substance abuse also had no apparent impact on judicial decision-making. Implications of these results are discussed.

Adolescent↗
PubMed1995

Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17 with evidence for a specific target region.

Allelic loss is a common mechanism of inactivation of tumour-suppressor genes in colorectal carcinomas. A number of known or putative tumour-suppressor genes including NF1, BRCA1, NME1, NME2 and prohibitin are present on the long arm of chromosome 17, and this region has not been extensively analysed in colorectal tumours. In this study 72 colorectal carcinomas were examined for allelic loss at eight loci on chromosome 17. Allelic loss was frequent both at the p53 locus, which is known to be important in colorectal carcinoma, and also telomeric to p53 on 17p. Allelic loss continued to be present in more than 50% of cases in the pericentromeric region and on proximal 17q to the marker LEW101 (D17S40) at 17q22-23. The most telomeric markers on 17q showed lower rates of allelic loss. Analysis of cases with partial deletions which did not include the p53 locus showed a common region of overlap of the deletions centred on D17S40. This suggests the target of allelic loss on 17q is a tumour-suppressor gene in this region.

Alleles↗
PubMed1995

Coupled glucose transport and metabolism in cultured neuronal cells: determination of the rate-limiting step.

In brain and nerves the phosphorylation of glucose, rather than its transport, is generally considered the major rate-limiting step in metabolism. Since little is known regarding the kinetic coupling between these processes in neuronal tissues, we investigated the transport and phosphorylation of [2-3H]glucose in two neuronal cell models: a stable neuroblastoma cell line (NCB20), and a primary culture of isolated rat dorsal root ganglia cells. When transport and phosphorylation were measured in series, phosphorylation was the limiting step, because intracellular glucose concentrations were the same as those outside of cells, and because the apparent Km for glucose utilization was lower than expected for the transport step. However, the apparent Km was still severalfold higher than the Km of hexokinase I. When [2-3H]glucose efflux and phosphorylation were measured from the same intracellular glucose pool in a parallel assay, rates of glucose efflux were three- to-fivefold greater than rates of phosphorylation. With the parallel assay, we observed that activation of glucose utilization by the sodium channel blocker veratridine caused a selective increase in glucose phosphorylation and was without effect on glucose transport. In contrast to results with glucose, both cell types accumulated 2-deoxy-D-[14C]glucose to concentrations severalfold greater than extracellular concentrations. We conclude from these studies that glucose utilization in neuronal cells is phosphorylation-limited, and that the coupling between transport and phosphorylation depends on the type of hexose used.

Animals↗