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Biomedical subjects

B Mayall

Publications and source records attributed to B Mayall.

At least 19 recordsLinked to original sources
PubMed2000

The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67.

Proliferation indices are intended to help patients and clinicians make treatment decisions. We have previously demonstrated that a proliferation index based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices. With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M2 BrdUrd during 30 min immediately preceding surgery. We used IU-4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 cases). Patients received standard surgical and adjuvant treatment. No patients were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had better disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall survival (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison, a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiority of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multivariate survival analyses we found that BrdUrd LI proliferative index significantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.

Adult↗
PubMed1999

Identification of Mycobacterium shimoidei by molecular techniques: case report and summary of the literature.

A 53-year-old woman from Melbourne, Australia, with squamous cell carcinoma of the oesophagus was shown by computed tomography (CT) scan to have a left apical cavity and inflammatory changes in the right lung consistent with aspiration. Acid-fast bacilli isolated from bronchial washings were identified biochemically first as Mycobacterium terrae, but later as M. shimoidei on the basis of 1) restriction fragment analysis and 2) sequencing of polymerase chain reaction (PCR) amplified 16S rDNA. Nine other descriptions of patients with M. shimoidei isolates were collated. The salient feature of isolates considered to be pathogenic was pulmonary cavitation. Most patients had underlying lung disease, including past tuberculosis or malignancy. Six of eight patients died of progressive respiratory illness, although the contribution of M. shimoidei was not always clear, and two patients improved. One patient with the acquired immune-deficiency syndrome (AIDS) died with Salmonella enteritidis and M. shimoidei isolated from blood cultures. One isolate was regarded as a coloniser. There are insufficient clinical or sensitivity data on which to base recommendations for therapy, but a combination of ethambutol, rifabutin and pyrazinamide could be considered.

AIDS-Related Opportunistic Infections↗
PubMed1998

The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer.

Proliferation indices are used, along with other parameters, to estimate the risk of recurrence of breast cancer for individual patients. Because it is unlikely one index will be practical for all patients, it is important to understand the relationship between various indices of proliferation. For this reason, we compared a proliferation index based on in vivo labeling of S-phase tumor cells with the thymidine analog bromodeoxyuridine (BrdUrd), to a proliferation index based on an estimate of the growth fraction with the MIB-1 antibody to the Ki-67 antigen. With informed consent, we gave 145 patients 200 mg/m2 BrdUrd intravenously just prior to surgical removal of breast cancer. On histology sections, we visually counted S-phase cells which had incorporated BrdUrd using the Br-3 antibody which is specific to DNA-incorporated BrdUrd, and we counted cells in the growth fraction using the MIB-1 antibody to the Ki-67 antigen. We found that both indices were positively correlated with tumor size, number of positive nodes, and tumor grade, and both were negatively correlated with age and estrogen-progesterone receptor positivity. Using a linear functional relationship model, we found that the best (i.e. the maximal) fit between the two indices (correlation coefficient 0.79; p < 0.0001) occurred when each index was square root transformed, as is appropriate when counts follow a Poisson distribution. When we used the median as a cutpoint for each index, the classification of 19 percent of data pairs changed depending upon which index was used. We also estimated that the Ki-67 intercept (1.02 +/- 0.25) was significantly greater than zero. We conclude that the BrdUrd index of DNA synthesis in S-phase correlates highly with the MIB-1 index of the growth fraction, and both indices correlate well with other parameters of tumor aggressiveness. Because this correlation is driven by concordance of the extremes of high and low counts, clinical comparison will be necessary to determine which is the better prognostic marker for human breast cancer.

Adult↗
PubMed1996

Blanket use of intranasal mupirocin for outbreak control and long-term prophylaxis of endemic methicillin-resistant Staphylococcus aureus in an open ward.

In December 1992, a thoracic ward in a Melbourne teaching hospital experienced an increase in patients infected with methicillin-resistant Staphylococcus aureus (MRSA). It was decided to attempt to control the outbreak by cohorting positive patients (infected and colonized), as well as nurse cohorting, emphasis on handwashing, and use of intranasal mupirocin initially three times a day for three days, then thrice weekly, for all patients in the ward (with or without MRSA). The campaign comprised for phases of 53, 45, 92 and 365 days, respectively. Patient and nurse cohorting stopped at the end of phase I. In phases I and II, surveillance nose swabs were taken on admission, then twice weekly; in phase III, on admission and weekly and in phase IV, on admission until the end of 1993. In phases I and II (98 days), only one patient acquired MRSA. When the frequency of mupirocin prophylaxis was decreased to once weekly (phase III), two patients acquired MRSA in 92 days (no significant difference): thrice weekly administration resumed (phase IV), during which there were three acquisitions in 365 days. The rates of nose colonization of admissions were 6.4%, 6.3%, 9.7% and 3.1% in phase I-IV, respectively. Only three patients were treated with vancomycin between July 1993 and June 1994 (significantly lower than historical rates, P = 0.0086). No mupirocin resistance was seen in MRSA isolates from this ward during phases I, II and III. In areas of low-level endemic MRSA, the blanket use of thrice-weekly intranasal mupirocin may be effective in decreasing serious infections with MRSA, and does not necessarily elicit mupirocin resistance.

Administration, Intranasal↗
PubMed1995

Selection and implementation of a laboratory computer system.

The process of selection of a pathology computer system has become increasingly complex as there are an increasing number of facilities that must be provided and stringent performance requirements under heavy computing loads from both human users and machine inputs. Furthermore, the continuing advances in software and hardware technology provide more options and innovative new ways of tackling problems. These factors taken together pose a difficult and complex set of decisions and choices for the system analyst and designer. The selection process followed by the Microbiology Department at Heidelberg Repatriation Hospital included examination of existing systems, development of a functional specification followed by a formal tender process. The successful tenderer was then selected using predefined evaluation criteria. The successful tenderer was a software development company that developed and supplied a system based on a distributed network using a SUN computer as the main processor. The software was written using Informix running on the UNIX operating system. This represents one of the first microbiology systems developed using a commercial relational database and fourth generation language. The advantages of this approach are discussed.

Clinical Laboratory Information Systems↗
PubMed1994

The association of p53 immunopositivity with tumor proliferation and other prognostic indicators in breast cancer.

Abnormal accumulation of the p53 tumor suppressor gene product was analyzed in 198 primary invasive human breast carcinomas. In 47 of these cases, single-strand conformational polymorphism was used to detect mutations in the highly conserved exons 5-9 of the gene. Mutations as determined by single-strand conformational polymorphism were found in 15 of 15 strongly immunopositive cases (100%) and 3 of 23 immunonegative cases (13%). There were also nine cases with < 1% immunopositive cells (borderline immunopositivity); p53 mutations were detected in seven of these cases. The results suggest that p53 immunopositivity is a highly specific, albeit somewhat insensitive surrogate for p53 mutations. p53 accumulation, detected by immunohistochemical methods using antibody PAb 1801, was noted in 29.8% of the cases and was associated with estrogen receptor (ER) negativity (P = 0.0003), progesterone receptor (PR) negativity (P = 0.008), and high histological grade (P = 0.037) by univariate analysis. Incorporation of bromodeoxyuridine was used to determine the percentage of cells synthesizing DNA (proliferative fraction). When bromodeoxyuridine was administered either in vivo (n = 93) or in vitro (n = 79), p53 accumulation was only marginally related to proliferative fraction (P = 0.067 by chi 2; P = 0.055 by Mann-Whitney). When tumors were segregated by ER status, the aforementioned associations of p53 immunopositivity with PR negativity, high histological grade, and increased proliferation rate lost their significance. p53 accumulation did not correlate with tumor size, clinical stage, axillary node metastases, or age at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Tumor labeling indices of primary breast cancers and their regional lymph node metastases.

BACKGROUND: Tumor labeling index has emerged as a strong predictor of the clinical course of women with breast cancer. This study investigated whether labeling index of primary tumors correlates with labeling indices of concurrent regional node metastases. METHODS: With appropriate written consent, preoperative in vivo infusion of the thymidine analogue 5-bromodeoxyuridine (BrdUrd) was used to label 109 human breast cancers. Labeled S-phase cells were identified immunohistochemically with an antibody specific to DNA-incorporated BrdUrd. Labeling index was the fraction of labeled nuclei in 2000 tumor nuclei. For 30 women, there was sufficient cancer in axillary lymph nodes to compare labeling indices in primary breast cancer and regional lymph node metastases. RESULTS: The 30 women were from 25 to 82 years of age. Tumors were from 1 to 12 cm in size and there were from 1 to 26 positive nodes. Tumor labeling index ranged from 0.1% to 34%, (mean, 11.1%; median, 10.3%) and axillary lymph node metastasis labeling index ranged from 0.1% to 27.7% (mean, 10.8%; median, 10.0%). There was strong correlation between primary tumor labeling index and regional lymph node metastases labeling index (r = 0.82, with 95% confidence interval 0.65-0.91). The correlation persisted within subgroups according to age, tumor size, number of positive nodes, and hormone receptor status. Primary tumor and lymph node metastases labeling indices also had statistically similar relationships with age, level of hormone receptors, tumor size, and number of positive nodes. CONCLUSIONS: Primary tumor and regional node labeling indices correlate strongly; the relationship is not influenced by age, level of hormone receptors, tumor size, or number of positive nodes.

Adult↗
PubMed1993

Keeping children healthy--the intermediate domain.

This paper draws on two recent research studies to consider negotiations and relationships between parents and health staff as regards child health care and child rearing, to which each side contributes. The value of the concept of an intermediate domain, located between the public world of paid work and the private world of the family is explored to throw light on the character of these negotiations and relationships. The implications of gender for relationships between parent and health staff are considered.

Child↗
PubMed1993

Correlation of bromodeoxyuridine (BRDU) labeling of breast carcinoma cells with mitotic figure content and tumor grade.

Tumor proliferation is inversely associated with survival in patients with breast carcinoma. Labeling of tumor cells with bromodeoxyuridine (BRDU) correlates highly with that seen with [3H]thymidine, the current "gold standard" for measuring tumor S-phase. However, the relationship of BRDU labeling to mitotic figure content and tumor grade remains incompletely defined. To determine this, we labeled 55 breast carcinomas with BRDU in vivo and correlated the results with mitotic figure content. The BRDU labeling index was the number of BRDU-positive cells/2,000 tumor cells, the mitotic figure index was the number of mitotic figures per 1,000 tumor cells, and the mitotic figure count was the number of mitotic figures per 10 high-powered fields. BRDU labeling was also correlated with tumor grade (Scarff-Bloom-Richardson). The BRDU labeling index correlated highly with the mitotic figure index (r = 0.814, p = 7.0 x 10(-14)), mitotic figure count (r = 0.725, p = 6.0 x 10(-10)), and tumor grade (r = 0.68, p = 1.1 x 10(-8)). The correlation of BRDU labeling with mitotic figure content was strong enough to suggest that a very carefully measured mitotic figure index provides an estimate of tumor growth fraction equivalent to the BRDU labeling index. Also, analysis of variance showed that the mitotic figure index was twice as precise as the mitotic figure count in estimating BRDU labeling, and thus was a more accurate measure of tumor proliferation. Moreover, measurements made by the mitotic figure index were as precise as those made by BRDU labeling. However, which method is optimal for estimating tumor proliferation rate remains unclear. Further studies are indicated.

Adult↗
PubMed1993

Epithelial markers to detect occult microinvasion in serous ovarian tumors.

Ovarian serous lesions with severe cytological and architectural atypia without obvious destructive stromal invasion may be diagnosed as serous borderline malignant tumor or as serous cystadenocarcinoma, depending on the criteria that individual pathologists use. The recent introduction of the diagnosis "serous borderline tumors with stromal microinvasion" seems an important improvement for the accuracy of the diagnosis of serous ovarian tumors. The aim of this study was to determine if immunohistochemical epithelial markers could help to detect stromal microinvasion in serous ovarian tumors and to compare these findings with the occurrence of "eosinophilic metaplastic" cells. Therefore, we studied the presence of eosinophilic metaplastic cells. Three immunohistochemical epithelial markers were applied in a group of 42 borderline and invasive serous tumors. The histopathologic diagnosis of the tumors was established by a reference center for gynecologic pathology in the Netherlands. We found that "eosinophilic metaplastic" cells were a constant feature in the serous borderline tumor lesions both with and without microinvasion. The presence of these cells should therefore not be considered as pathognomonic for microinvasion. The three investigated antibodies against epithelial epitopes helped to detect microinvasion, with the monoclonal antikeratin (CAM5.2) the best of these antibodies. Serous tumors diagnosed as carcinoma with dubious invasion showed no evidence of microinvasion in 83% of cases. In 13% of serous borderline malignant tumors, microinvasion was detected by the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Use of ribosomal RNA gene restriction patterns to investigate two outbreaks of Campylobacter enteritis in Melbourne, Australia.

The analysis of ribosomal RNA (rRNA) gene patterns (ribotyping) has been used to differentiate strains within bacterial species. We used this method to investigate two outbreaks of campylobacter enteritis that occurred recently in Melbourne, Australia. The first outbreak involved seven patients although isolates from only five patients were available for typing. The second outbreak consisted of three patients infected with human immunodeficiency virus (HIV) on the same ward of a hospital. Analysis of the rRNA gene patterns revealed identical patterns for the isolates from five patients in the first outbreak, suggesting that these isolates were from the same source. However, ribotyping of the four isolates from the second outbreak showed three distinct ribotypes indicative of contact with unrelated sources. This study demonstrated that ribotyping is a useful, reliable and convenient typing scheme for epidemiological purposes.

Australia↗
PubMed1991

Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis may be fatal.

OBJECTIVE: To review experience with neutropenia related to low-dose methotrexate therapy in patients with psoriasis and rheumatoid arthritis. DESIGN: Retrospective review of medical records. SETTING: A 509-bed Melbourne teaching hospital. PATIENTS: Five patients admitted in 1987 and 1988, with neutrophil counts of less than 1 x 10(9)/L, given low doses of methotrexate for psoriasis or rheumatoid arthritis. MAIN OUTCOME MEASURES: Death, or length of hospital admission. FINDINGS: Four patients were women, and one a man; three had been treated for psoriasis, and two for rheumatoid arthritis. Ages ranged from 56 to 91 years. The eldest patients, aged 77, 81 and 91 years, died. The other two were discharged after 43 and 48 days. Prior to or shortly after admission, four patients were treated with penicillin antibiotics which may have interfered with methotrexate excretion. CONCLUSIONS: Methotrexate clearances (related to creatinine clearance rates and presumably low) were probably reduced sufficiently by concomitant therapy to result in neutropenia. Practitioners using methotrexate should be aware of drug interactions resulting in delayed methotrexate excretion. Blood counts should be monitored after changes in therapy, especially in patients with impaired renal function, such as the elderly.

Aged↗
PubMed1991

Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations.

Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines. Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant. Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed. Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors. Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole. Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes. The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole. The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.

Blotting, Western↗
PubMed1991

In vivo measurement of breast cancer growth rate.

S-phase cells of 66 primary breast cancers were labeled in vivo by preoperative infusion of the thymidine analogue bromodeoxyuridine. A monoclonal antibody specific for DNA-incorporated bromodeoxyuridine was used to identify positive cells and compute a labeling index on histologic sections. The labeling index (the percentage of cells in S-phase) ranged from 0.1% to 23.9%; it correlated positively with poorly differentiated cancer, higher mitotic counts on routine histologic examination, and tumor size; and it correlated inversely with estrogen and progesterone receptors. The labeling index did not correlate with nodal involvement or ploidy. Of the 15 patients with a labeling index greater than 12%, three died and one had systemic disease after a median follow-up of 19 months. No other patients had recurrences. There were no clinical complications of bromodeoxyuridine infusion.

Breast Neoplasms↗
PubMed1991

Characterization by image cytometry of duct epithelial proliferative disease of the breast.

To develop a morphometric model of premalignant breast epithelium, we evaluated 120 lesions classified as nonproliferative disease (n = 20), hyperplasia (n = 20), moderate hyperplasia (n = 20), atypical hyperplasia (n = 20), carcinoma in situ (n = 20), and carcinoma (n = 20) in tissue from surgical biopsy or mastectomy. Atypical hyperplasia, a component of duct epithelial proliferative disease, has frequently been described in breasts with carcinoma. Atypical hyperplasia is generally viewed as premalignant or as a marker of increased risk for breast cancer. Measurements of nuclei in breast lesions were obtained with the Leitz TAS Plus on 4-microns sections stained for DNA with the Azure A Feulgen reaction. Nuclei of duct epithelial lesions had morphometric features that displayed changes from nonproliferative disease to carcinoma. The morphometric data from each lesion were compared among the six disease groups. Means of nuclear area, perimeter, maximum and minimum diameter, and large dark and large light intranuclear areas increased with higher degrees of proliferative abnormality. When the six groups of lesions were compared using the means of the first four nuclear features, atypical hyperplasia was significantly different (P less than 0.05) from carcinoma and non-proliferative lesions, but not from hyperplasia, moderate hyperplasia, or carcinoma in situ. These findings suggest that objective morphometric descriptors for characterizing significant proliferative lesions can be established using image cytometry. The progressive increases also suggest that proliferative breast disease is a continuum that includes premalignant lesions.

Azure Stains↗
PubMed1991

A comparison between bromodeoxyuridine and 3H thymidine labeling in human breast tumors.

The fraction of tumor cells in the DNA synthesis (S) phase of the cell cycle is a strong prognostic indicator in human breast cancer. Most studies measuring S-phase in primary tumors have used either in vitro labeling with 3H thymidine or DNA flow cytometry. The former involves a cumbersome and time-consuming radioactive assay, while the latter is heavily dependent on the quality of the preparation and the effectiveness of the algorithms used. In this study, in vivo or in vitro labeling with bromodeoxyuridine (BrdUrd) was compared with in vitro labeling using 3H thymidine in a series of 33 human breast tumors. Thymidine labeling showed strong correlation with both in vitro (r = 0.96) and in vivo (r = 0.83) BrdUrd incorporation. The reliability between observers was higher for BrdUrd counting (r = 0.94) than for thymidine counting (r = 0.87). The mean labeling index of 15 tumors labeled in vivo with BrdUrd was 5.9% compared to 4.7% for 18 tumors labeled in vitro (p = 0.34). There was poor correlation between flow cytometric and microscopic analysis of BrdUrd incorporation (r = 0.37). We conclude that microscopic analysis of in vivo or in vitro BrdUrd incorporation is a rapid and reliable method to estimate breast tumor proliferation.

Analysis of Variance↗