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Biomedical subjects

J Bryant

Publications and source records attributed to J Bryant.

At least 73 records · Page 4Linked to original sources
PubMed1998

Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. METHODS: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. RESULTS: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). CONCLUSION: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.

Antimetabolites, Antineoplastic↗
PubMed1998

erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.

BACKGROUND: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. METHODS: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. RESULTS: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P=.02), lack of estrogen receptors (P=.008), and the number of positive lymph nodes (P=.0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors--DFS: relative risk of failure (RR)=0.60 (95% confidence interval [CI]=0.44-0.83), P=.001; survival: RR=0.66 (95% CI=0.47-0.92), P =.01; RFS: RR=0.58 (95% CI=0.42-0.82), P=.002; DDFS: RR=0.61 (95% CI=0.44-0.85), P=.003. However, it was not significant for patients with erbB-2-negative tumors-DFS: RR=0.96 (95% CI=0.75-1.23), P=.74; survival: RR =0.90 (95% CI=0.69-1.19), P=.47; RFS: RR=0.88 (95% CI=0.67-1.16), P=.37; DDFS: RR=1.03 (95% CI=0.79-1.35), P=.84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P=.02) and DDFS (P=.02) but not for survival (P= .15) or RFS (P=.06). CONCLUSIONS: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.

Adult↗
PubMed1998

Microbial contamination of meat during the skinning of beef carcass hindquarters at three slaughtering plants.

The microbiological effects on the product of the series of operations for skinning the hindquarters of beef carcasses at three packing plants were assessed. Samples were obtained at each plant from randomly selected carcasses, by swabbing specified sites related to opening cuts, rump skinning or flank skinning operations, randomly selected sites along the lines of the opening cuts, or randomly selected sites on the skinned hindquarters of carcasses. A set of 25 samples of each type was collected at each plant, with the collection of a single sample from each selected carcass. Aerobic counts, coliforms and Escherichia coli were enumerated in each sample, and a log mean value was estimated for each set of 25 counts on the assumption of a log normal distribution of the counts. The data indicated that the hindquarters skinning operations at plant A were hygienically inferior to those at the other two plants, with mean numbers of coliforms and E. coli being about two orders of magnitude greater, and aerobic counts being an order of magnitude greater on the skinned hindquarters of carcasses from plant A than on those from plants B or C. The data further indicated that the operation for cutting open the skin at plant C was hygienically superior to the equivalent operation at plant B, but that the operations for skinning the rump and flank at plant B were hygienically superior to the equivalent operations at plant C. The findings suggest that objective assessment of the microbiological effects on carcasses of beef carcass dressing processes will be required to ensure that Hazard Analysis: Critical Control Point and Quality Management Systems are operated to control the microbiological condition of carcasses.

Abattoirs↗
PubMed1998

Relationship of stable integration of herpes simplex virus-2 Bg/II N subfragment Xho2 to malignant transformation of human papillomavirus-immortalized cervical keratinocytes.

Transfection of the right end Xho2 subfragment of Bg/II N of herpes simplex virus-2 (HSV-2) into human genital keratinocytes immortalized by human papillomavirus (HPV) type 16 or 18 resulted in invasive and noninvasive indolent cystic squamous carcinomas when cells were injected into immunocompromised mice. Retention and expression of the right end portion of the Bg/II N fragment correlated with malignancy, as the corresponding HSV-2 sequences were integrated and transcribed in the tumorigenic cell lines. HPV-immortalized cells alone were not tumorigenic. In contrast, previous results have shown that using the entire Bg/II N region can malignantly transform HPV-immortalized cells, although HSV2 DNA was not retained. Together, these observations localize the transforming activity of Bg/II N to Xho2 and suggest that the remaining sequences have an inhibitory effect on stable integration. The Xho2 sequence is 2480 bp long and contains an open reading frame (ORF) extending from nucleotides 559 to 1797. The ORF encodes a putative protein of 412-aa with a m.w. of 42-43 kDa and is highly homologous to UL43 of HSV-I. The correlation of tumorigenicity with stable integration and expression of Xho2 DNA in HPV-immortalized cells indicates that HSV-2 should be investigated further for a possible role in cervical cancer.

Amino Acid Sequence↗
PubMed1998

Dysfunction of natural killer activity in a family with chronic fatigue syndrome.

A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry. NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood. Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.

Adolescent↗
PubMed1998

Early stopping of a clinical trial when there is evidence of no treatment benefit: protocol B-14 of the National Surgical Adjuvant Breast and Bowel Project.

Although several randomized clinical trials in the 1980s indicated a benefit from the use of tamoxifen in the treatment of early-stage breast cancer, questions have remained regarding the optimal duration of drug administration. In 1982, the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial to compare 5 years of tamoxifen to placebo among breast cancer patients with estrogen receptor-positive tumors and no evidence of axillary node involvement. By 1987, evidence of a substantial benefit for tamoxifen led the NSABP to extend this trial to determine whether longer duration tamoxifen therapy would be additionally beneficial. This study randomized patients who had completed 5 years of tamoxifen free of breast cancer recurrence or other events to either tamoxifen or placebo for an additional 5 years. By 1994, 1172 women had entered the study and accrual was closed. In late 1995, the trial was terminated on the basis of interim findings indicating that a benefit for continuing tamoxifen would not be realized. The closure has prompted controversy among cancer researchers, because there are currently at least three tamoxifen duration trials in progress, whereas results from two other studies evaluating 5-year duration therapy versus longer therapy were recently published. Here, we provide details of the statistical rationale contributing to our decision to recommend early closure of the study. We then consider other possible approaches to assessing the appropriateness of early termination in the face of evidence against a benefit, including Bayesian methods, which can be used to incorporate a range of prior beliefs regarding the efficacy of a treatment with accruing information from the trial. We also briefly discuss results of the other published studies.

Antineoplastic Agents, Hormonal↗
PubMed1998

S-phase fraction combined with other patient and tumor characteristics for the prognosis of node-negative, estrogen-receptor-positive breast cancer.

Women with estrogen-receptor (ER)-positive breast cancer and no axillary lymph-node involvement are considered to have excellent overall prognosis. However, this population is not homogeneous with regard to risk of recurrence; in fact, some of these patients have a prognosis no better than that of many women with ER-negative tumors or positive axillary nodes. Consequently, better tumor markers and better use of those currently available are needed to distinguish patients who would benefit from more aggressive therapy from those for whom such therapy is unnecessary. A well-defined cohort of over 4000 breast cancer patients from National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-14 who had ER-positive tumors and no axillary lymph-node involvement was analyzed to ascertain the usefulness of tumor cell S-phase fraction for prognosis. The significance of clinical tumor size, patient age at surgery, ER and progesterone receptor (PgR) expression, and nuclear grade was also explored. Statistical methods based on smoothing splines were used to relate treatment failure and mortality rates to patient and tumor characteristics. Models for 5- and 10-year disease-free survival (DFS) and overall survival were developed and summarized. The attenuation of the prognostic importance of covariates over time was investigated. After other characteristics were accounted for, a strong association was found between S-phase fraction and DFS, as well as survival. Tumor size, patient age at surgery, and PgR status were also significantly associated with outcome. The diversity of risk in the B-14 population was more extreme than is generally recognized. The prognostic capabilities of S-phase, tumor size, and PgR status were sharply attenuated as the time from surgery increased.

Aged↗
PubMed1998

Evaluation of the hygienic performances of the processes for beef carcass dressing at 10 packing plants.

The hygienic performances of the carcass dressing processes at 10 beef packing plants were assessed from small sets of microbiological data. For each process, a single sample was obtained from a randomly selected site on each of 25 randomly selected beef sides leaving the process. In addition, during a period of about a year, a further nine such sets of samples were obtained from each of two of those processes. The aerobic bacteria, coliforms and Escherichia coli recovered from each sample were enumerated. For each set of 25 counts, values for the mean log and standard deviation were calculated on the assumption that the log values were normally distributed, and the log of the arithmetic mean was estimated for each set from the mean log and the standard deviation. The processes were ranked with respect to the log mean numbers of E. coli, coliforms and total counts estimated for the products. Log mean numbers of E. coli, coliforms and total counts ranged from about 2 to < 100 cm-2, from about 3 to < 100 cm-2, and from about 5 to about 2 cm-2, respectively. For one of the processes, 8, 7, and 8 of the log mean values for the replicated sets of aerobic, coliform and E. coli counts, respectively, differed by < 1 log unit. For the other process 5, 7, and 9 of the log mean values for the replicated sets of aerobic, coliform and E. coli counts, respectively, differed by < 1 log unit. These results indicate that the first process was generally consistent in the contamination of carcasses with aerobes, coliforms and E. coli. The contamination of carcasses in the second process with coliforms and E. coli was also generally consistent, but contamination of those carcasses with aerobes was inconsistent. The findings suggest that beef carcass dressing processes can be operated consistently with respect to the bacterial contamination of carcasses, and that log mean numbers of 1 +/- 0.5 to 100 cm-2, 1 +/- 0.5 to 100 cm-2 and 3 +/- 0.5 cm-2 for E. coli, coliform and total counts, respectively, may be appropriate, commercially attainable acceptance criteria for the hygienic performance of beef carcass dressing processes.

Animals↗
PubMed1998

Acclimation of photosynthesis to elevated CO2 under low-nitrogen nutrition is affected by the capacity for assimilate utilization. Perennial ryegrass under free-Air CO2 enrichment

Acclimation of photosynthesis to elevated CO2 has previously been shown to be more pronounced when N supply is poor. Is this a direct effect of N or an indirect effect of N by limiting the development of sinks for photoassimilate? This question was tested by growing a perennial ryegrass (Lolium perenne) in the field under elevated (60 Pa) and current (36 Pa) partial pressures of CO2 (pCO2) at low and high levels of N fertilization. Cutting of this herbage crop at 4- to 8-week intervals removed about 80% of the canopy, therefore decreasing the ratio of photosynthetic area to sinks for photoassimilate. Leaf photosynthesis, in vivo carboxylation capacity, carbohydrate, N, ribulose-1,5-bisphosphate carboxylase/oxygenase, sedoheptulose-1,7-bisphosphatase, and chloroplastic fructose-1, 6-bisphosphatase levels were determined for mature lamina during two consecutive summers. Just before the cut, when the canopy was relatively large, growth at elevated pCO2 and low N resulted in significant decreases in carboxylation capacity and the amount of ribulose-1,5-bisphosphate carboxylase/oxygenase protein. In high N there were no significant decreases in carboxylation capacity or proteins, but chloroplastic fructose-1,6-bisphosphatase protein levels increased significantly. Elevated pCO2 resulted in a marked and significant increase in leaf carbohydrate content at low N, but had no effect at high N. This acclimation at low N was absent after the harvest, when the canopy size was small. These results suggest that acclimation under low N is caused by limitation of sink development rather than being a direct effect of N supply on photosynthesis.

Journal Article↗
PubMed1998

Lipophilic versus hydrophilic beta(1) blockers and the cardiac sympatho-vagal balance during stress and daily activity in patients after acute myocardial infarction.

OBJECTIVE: To compare the effects of a lipophilic and a hydrophilic beta(1) blocker on cardiac sympatho-vagal balance during daytime activity and stress in patients four to six weeks after myocardial infarction. DESIGN: Randomised, double blind, crossover study comparing the effect of atenolol (50 mg once daily) with metoprolol CR (100 mg once daily) with treatment periods of four weeks. SETTING: Large teaching hospital. PATIENTS: 50 patients (45 male, 5 female, age range 40 to 75 years), four to six weeks after an acute myocardial infarction. METHODS: At the end of each treatment period the 24 hour heart rate variability, heart rate variability power spectra during head up tilt and mental stress, baroreflex sensitivity, and exercise performance were evaluated. RESULTS: During daytime activity and during orthostatic and mental stress, both heart rate and the ratio between the low and high frequency spectral components of the heart rate variability were significantly lower with atenolol. Conversely, there was no difference between treatments in baroreflex sensitivity and resting plasma catecholamines. Exercise duration and peak oxygen consumption did not differ between treatments, but the heart rate during submaximal and peak exercise was significantly lower with atenolol. CONCLUSIONS: At the doses used in this study, atenolol achieved greater beta(1) adrenergic blockade than metoprolol CR and this was associated with significant inhibition of vagal withdrawal during stress. This suggests that peripheral blockade of beta(1) adrenergic receptors may be more important than central blockade in preventing stress induced vagal withdrawal in patients after myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1998

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Unexpected sudden death during propranolol therapy in a patient with mild mesenteric venous myointimal hyperplasia.

Propranolol, a beta-adrenergic blocking agent commonly used in the treatment of hypertension, decreases mesenteric blood flow during exercise, at rest, and in cirrhosis. Widespread idiopathic myointimal hyperplasia of mesenteric veins produces intestinal ischemia in otherwise healthy individuals. This report describes a 42-year-old woman who died suddenly and unexpectedly while attending a ball game. She had hypertension treated with propranolol and no other clinically apparent disorders. Autopsy revealed mild mesenteric venous myointimal hyperplasia and segmental jejunal infarction. Recent clinical and experimental studies are used to propose possible mechanisms for this death which combine the effects of propranolol and mesenteric venous myointimal hyperplasia.

Adult↗
PubMed1997

Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer.

BACKGROUND: The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. METHODS: Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received tamoxifen alone; 767 received methotrexate, fluorouracil, and tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. RESULTS: Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen [P = .01]; 89% for CMFT versus 85% for tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen [P = .008]; 91% for CMFT versus 87% for tamoxifen [P = .006]) and survival (97% for MFT versus 94% for tamoxifen [P = .05]; 96% for CMFT versus 94% for tamoxifen [P = .03]). Compared with tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. CONCLUSIONS: Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.

Antimetabolites, Antineoplastic↗