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P R Taylor

Publications and source records attributed to P R Taylor.

At least 19 recordsLinked to original sources
PubMed1999

The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial.

BACKGROUND: Dietary components may be both causal and protective in cases of pancreatic carcinoma, but the preventive potential of single constituents has not been evaluated. The authors report the effects of alpha-tocopherol and beta-carotene supplementations on the rates of incidence of and mortality from pancreatic carcinoma in a randomized, controlled trial. METHODS: The 29,133 participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study were male smokers who were ages 50-69 years at the time they were randomized into 1 of the following 4 intervention groups: dl-alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both AT and BC, and placebo. The daily supplementation lasted for 5-8 years. Incident cancers were identified through the national Finnish Cancer Registry and death certificates of the Statistics Finland. Results were analyzed by supplementation with Cox regression models. RESULTS: Effects of both supplementations were statistically nonsignificant. The rate of incidence of pancreatic carcinoma was 25% lower for the men who received beta-carotene supplements (n = 38) compared with the rate for those who did not receive beta-carotene (n = 51) (95% CI, -51% to 14%). Supplementation with alpha-tocopherol (n = 51) increased the rate of incidence by 34% (95% CI, -12% to 105%) compared with the rate for those who did not receive alpha-tocopherol. Mortality from pancreatic carcinoma during the follow-up, adjusted for stage and anatomic location of the tumor, was 19% (95% CI, -47% to 26%) lower among those who received beta-carotene and 11% (95% CI, -28% to 72%) higher among those who received alpha-tocopherol as compared with those who did not receive supplementation. CONCLUSIONS: Supplementation with beta-carotene or alpha-tocopherol does not have a statistically significant effect on the rate of incidence of pancreatic carcinoma or the rate of mortality caused by this disease.

Aged↗
PubMed1999

Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation.

C1q-deficient (C1qa-/-) mice develop antinuclear Abs and glomerulonephritis (GN) characterized by multiple apoptotic bodies. To explore the contribution of C3 activation to the induction of spontaneous GN, C1qa-/- mice were crossed with factor B- and C2-deficient (H2-Bf/C2-/-) mice. GN was present in 64% of the 45 C1qa/H2-Bf/C2-/- mice compared with 8% of the 65 H2-Bf/C2-/- mice and none of the 24 wild-type controls. IgG was detected in the glomeruli of diseased C1qa/H2-Bf/C2-/- kidneys. However, glomerular staining for C3 was absent. Increased numbers of glomerular apoptotic bodies were detected in undiseased C1qa/H2-Bf/C2-/- kidneys. These findings support the hypothesis that C1q may play a role in the clearance of apoptotic cells without the necessity for C3 activation and demonstrate that the activation of C3 is not essential for the development of GN in this spontaneous model of lupus-like disease.

Animals↗
PubMed1999

Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers.

BACKGROUND: Few risk factors for pancreatic cancer have been identified, with age and cigarette smoking being the most consistent. The protective effect associated with consumption of fruits and vegetables-the major dietary sources of folate-is suggestive of a role for factors influencing cellular methylation reactions; however, to our knowledge, no study has investigated this relationship. Whether biochemical indicators of methyl-group availability are associated with exocrine pancreatic cancer risk was the focus of this investigation. METHODS: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29133 male Finnish smokers aged 50-69 years. One hundred twenty-six subjects with incident exocrine pancreatic cancer were matched by date of baseline blood draw (+/-30 days), study center, age (+/-5 years), trial intervention group, and completion of dietary history to 247 control subjects, who were alive and free from cancer at the time the case subjects were diagnosed. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined by use of conditional logistic regression. Reported P values are two-tailed. RESULTS: Serum folate and pyridoxal-5'-phosphate (PLP) concentrations showed statistically significant inverse dose-response relationships with pancreatic cancer risk, with the highest serum tertiles having approximately half the risk of the lowest (folate: OR = 0.45; 95% CI = 0.24-0.82; P for trend = .009, and PLP: OR = 0.48; 95% CI = 0.26-0.88; P for trend = .02). An increased pancreatic cancer risk was also observed with greater exposure to cigarettes (e.g., pack-years [number of packs smoked per day x number of years of smoking], highest versus lowest quartile: OR = 2.13; 95% CI = 1.13-3.99; P for trend = .04). CONCLUSIONS: These results support the hypothesis that maintaining adequate folate and pyridoxine status may reduce the risk of pancreatic cancer and confirm the risk previously associated with cigarette smoking.

Aged↗
PubMed1999

The results of routine primary closure in carotid endarterectomy.

PURPOSE OF STUDY: The aims of this study were to determine the incidence of restenosis following carotid endarterectomy with primary closure of the arteriotomy and to observe the natural history of disease progression in the 1st postoperative year. METHODS: The study group consisted of a consecutive series of 126 patients undergoing carotid endarterectomy. Duplex imaging was performed preoperatively and at 8 weeks, 6 months and 1 year postoperatively. RESULTS: Five patients (4%) had a residual stenosis. At 12 months, the overall restenosis rate was 15%: 8.5% for males and 28.9% for females. None of these restenoses were symptomatic. There was no significant difference in the diameter of the internal carotid artery between male and female patients (U = 896, P = 0.60) and no significant difference in the diameter of the arteries that had restenosed at 12 months and those that had remained patent (U = 391, P = 0.33). CONCLUSIONS: Carotid endarterectomy with primary closure is associated with a low incidence of restenosis in men, but not in women. Criteria for selective patching should consider both gender and vessel calibre.

Aged↗
PubMed1999

Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA).

OBJECTIVE: To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. METHODS: Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. RESULTS: Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. CONCLUSIONS: Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology.

Aged↗
PubMed1999

Patterns of care and survival for adolescents and young adults with acute leukaemia--a population-based study.

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.

Adolescent↗
PubMed1999

Carotid plaque characterization by duplex scanning: observer error may undermine current clinical trials.

BACKGROUND AND PURPOSE: Clinical studies currently in progress are using subjective methods to characterize plaque morphology from ultrasound images. However, there are few studies on the intraobserver and interobserver variability of these classifications. This study was designed to assess these variables. METHODS: Grading of plaque morphology from ultrasound images, stored both digitally and to hard copy, was performed by 2 classification schemes. Interobserver agreement was determined by 4 observers. Within-observer agreement was performed at intervals for up to 6 months. Accuracy of the 2 methods was determined by comparison with histology. RESULTS: Within- and between-observer agreement was moderate to good for full-color digital image analyses, with pooled kappa values of kappap=0.49+/-0.10 and kappap=0.62+/-0.07 for the 2-category method and kappap=0.53+/-0.06 and kappap=0.52+/-0.05 for the 4-category method, respectively. Hard copy data analyses gave lower kappa values. The more experienced observers produced higher within-observer agreements and higher correlation with histology. CONCLUSIONS: Reproducible grading of ultrasound images is not consistently achievable among experienced observers, and within-observer agreement may vary with time. The current subjective ultrasound characterization of carotid plaque morphology used in clinical trials may be associated with unacceptable levels of reproducibility in some centers. Variability between observers may be reduced by using the simpler 2-category grading of plaque morphology to interrogate full-color digitally stored images. Observer agreement should be audited regularly.

Aged↗
PubMed1998

Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants.

It is now well known that the initial phase of graft-versus-host disease (GVHD) involves cytokine release during preconditioning of the recipient of an allogeneic bone marrow transplant (BMT). Tumor necrosis factor (TNF), in particular, has been implicated in pathological damage and is released pretransplant due to irradiation and cytotoxic preconditioning regimens. Interleukin-10 (IL-10), a natural immunosuppressant of TNF, may be involved in downregulation of these responses, which may be an individual patient-specific effect. In this study, we determined the genotype for polymorphisms associated with TNF and IL-10 in 80 potential allo-BMT recipients and correlated the genotype with the severity of GVHD in 49 patients for whom clinical data relating to GVHD was available. The widely studied TNF -308 polymorphism does not show any significant associations, but the d3 homozygous allele of the TNFd microsatellite is preferentially associated with grade III/IV GVHD (7 of 11 patients) compared with its occurrence in 8 of 38 patients with grade 0/II GVHD (P =.006). Alleles of the IL-10 (-)1064 promoter region microsatellite polymorphism that possess greater numbers of dinucleotide (CA) repeats also significantly associate with more severe GVHD. This region has been demonstrated to be important in the regulation of the IL-10 promoter. Eighteen of 38 patients with grade 0-II GVHD possessed alleles with greater numbers (12 or more) of dinucleotide repeats, compared with 9 of 11 cases with grade III-IV GVHD (P <.02). Of the 38 patients with grade 0-II GVHD, 3 of 38 had a both TNFd3/d3 and IL-10 (12-15) genotype, compared with 6 of 11 patients with grade III-IV GVHD (P <.001). There was no association of either the TNFd or IL-10 microsatellite polymorphisms with mortality (P =.43 and.51, respectively). Our results suggest that patient cytokine gene polymorphism genotypes may influence GVHD outcome by affecting cytokine activation during the pretransplant conditioning regimens, and these results are the first to suggest a genetic predisposition to this important transplant-related complication.

Acute Disease↗
PubMed1998

Predicting graft-versus-host disease in HLA-identical bone marrow transplant: a comparison of T-cell frequency analysis and a human skin explant model.

BACKGROUND: Graft-versus-host disease (GVHD) occurring after HLA-identical sibling bone marrow transplantation (BMT) is considered to be mainly caused by minor histocompatibility antigen (mHag) disparities between the recipient and donor. In our laboratory, a human skin explant model has been successfully used to predict acute GVHD in HLA-identical sibling BMT. More recently, the frequency analysis of host-reactive helper and cytotoxic T lymphocyte precursors (HTLp and CTLp, respectively) has been shown to have potential application for predicting GVHD. In the present study, HTLp and CTLp frequency analysis and the skin explant model were directly compared for their ability to predict acute GVHD in HLA-identical sibling BMT. METHODS: Host-reactive HTLp and CTLp frequencies were determined using a combined limiting dilution assay. A human skin explant model was used to detect graft-versus-host reactions in vitro. The results from the skin explant model (graft-versus-host reaction grades I-IV) and T cell frequency analysis (>/< 1:100,000) were correlated with posttransplant GVHD outcome, respectively. RESULTS: The skin explant model correctly predicted GVHD outcome in 77% of cases (P=0.03). HTLp frequencies were very low in all patient/donor pairs tested. None of them exceeded 1:100,000, although 9/18 recipients developed GVHD (> or =clinical grade II) after transplant. In all patients tested, the relationship between either high (>1:100,000) or low (<1:100,000) CTLp frequency and occurrence of GVHD appeared to be random (P=1.0). CONCLUSIONS: HTLp and CTLp frequency analysis did not predict the occurrence of acute GVHD after HLA-identical sibling BMT. The human skin explant model, however, remained an accurate indicator of acute GVHD and probably detects mHag disparities.

Acute Disease↗
PubMed1998

Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China.

BACKGROUND: In previous studies in the high risk population of Linxian, China, the majority of foci of high grade (moderate and severe) squamous dysplasia (HGD) and invasive squamous carcinoma (CA) of the esophagus were associated with endoscopically visible lesions that could be targeted for biopsy, but some foci of HGD were missed by routine endoscopic examination. This study examined whether spraying the mucosa with Lugol's iodine solution, which stains normal epithelium brown but leaves dysplasia and carcinoma unstained, could improve endoscopic detection and delineation of these lesions. METHODS: Two hundred twenty-five Linxian adults with balloon cytologic evidence of dysplasia or carcinoma underwent endoscopy. All visible lesions were described and photographed before and after staining with 1.2% Lugol's iodine solution. Biopsies were taken from all lesions visible before staining, from all unstained lesions (USLs) after applying the stain, and from representative control areas of stained mucosa. RESULTS: Two hundred fifty-three USLs and 255 control sites were biopsied. No complications occurred. Ninety-four biopsy sites contained HGD and 20 contained CA. Before staining, the sensitivity of visible lesions for identifying HGD or CA was 62%, and the specificity was 79%. After staining, the sensitivity of USLs for identifying HGD or CA was 96%, and the specificity was 63%. Eighty-eight percent of the HGD and CA lesions were larger or more clearly defined after staining. The diagnostic lesions in 17 of 31 patients with moderate dysplasia (55%), 8 of 35 patients with severe dysplasia (23%), and none of the 19 patients with invasive carcinoma (0%) were identified only after staining. CONCLUSIONS: Mucosal iodine staining improved endoscopic detection and delineation of HGD and CA in these patients. This simple technique is highly sensitive for identifying these precursor and invasive squamous lesions, and it should be used whenever optimal visualization of squamous mucosal abnormalities is required.

Adult↗
PubMed1998

Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease.

BACKGROUND: Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis. In epidemiological studies antioxidants have been inversely related with coronary heart disease. Findings from controlled trials are inconclusive. METHODS: We studied the primary preventive effect of vitamin E (alpha tocopherol) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial undertaken primarily to examine the effects of these agents on cancer. A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infarction were randomly assigned to receive vitamin E (50 mg), beta carotene (20 mg), both agents, or placebo daily for 5 to 8 years (median, 6.1 years). The end point was the first major coronary event, either nonfatal myocardial infarction (surviving at least 28 days; n = 1204) or fatal coronary heart disease (n = 907). RESULTS: The incidence of primary major coronary events decreased 4% (95% confidence interval, -12% to 4%) among recipients of vitamin E and increased 1% (95% confidence interval, -7% to 10%) among recipients of beta carotene compared with the respective nonrecipients. Neither agent affected the incidence of nonfatal myocardial infarction. Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8% (95% confidence interval, -19% to 5%), but beta carotene had no effect on this end point. CONCLUSIONS: Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infarction, but no influence on nonfatal myocardial infarction. Supplementation with beta carotene has no primary preventive effect on major coronary events.

Aged↗
PubMed1998

Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial.

BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers. METHODS: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.

Anticarcinogenic Agents↗
PubMed1998

A targeted disruption of the murine complement factor B gene resulting in loss of expression of three genes in close proximity, factor B, C2, and D17H6S45.

Factor B is a serine protease, essential for the function of the alternative pathway of complement activation. To study further the importance of the alternative pathway of complement activation in vivo and to help elucidate any additional functions of factor B or its activation fragments we developed, by homologous recombination in embryonic stem cells, mice with a disrupted factor B gene. Factor B-deficient mice produced no detectable factor B mRNA or protein and had no detectable factor B enzymatic activity or alternative pathway function in their serum. Further studies revealed that the two adjacent genes, complement component C2 and D17H6S45, had been down regulated as a result of the disruption. The down-regulation of C2 gene expression was sufficient to cause a complete loss of classical pathway function as determined by the failure of sera from the deficient mice to opsonize antibody-sensitized sheep erythrocytes and by impairment of immune complex processing in vivo. The resulting mouse is deficient in both factor B and C2, and hence the alternative and classical pathways of complement activation, and adds to the repertoire of models for studying the in vivo role of complement in the immune system.

Animals↗
PubMed1998

Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: potential clues to an etiologic exposure?

Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.

Adenocarcinoma↗