Biomedical subjects

K McCaul

Publications and source records attributed to K McCaul.

At least 19 recordsLinked to original sources

PubMed1998

Tumor microvascularity has no independent prognostic significance for breast cancer.

There is a continuing controversy regarding the value of estimating degree of intra-tumor vascularity to predict prognosis in breast cancer. In order to resolve this controversy, primary tumors from a cohort of 519 women with breast cancer were analysed to determine whether association exists between degree of vascularity and prognosis. Tumor vascularity was estimated by immunohistochemistry using a monoclonal antibody to the antigen CD31. The tumor area showing the highest degree of vascularity was chosen to score the number of microvessels per unit area. Issues such as the reproducibility of the microvascularity score and its association with tumor parameters including size, histological grade and hormone receptor levels were investigated. Although previously agreed criteria were used, consensus between two pathologists' estimations of the degree of vascularity was only moderate. There was no statistically significant association between tumor vascularity score and other currently established parameters of prognosis. After a median follow up of 71 months for axillary node negative patients, there was no association between tumor vascularity score and increased risk of relapse or death from breast cancer. In axillary node positive patients, tumor vascularity score was associated with increased risk of relapse and death from breast cancer. This association was not however independent of other established parameters of prognosis.

Adult↗

PubMed1998

Coverage of cancer patients by hospice services, South Australia, 1990 to 1993.

A population-based observational study of South Australian cancer patients was used to identify: the level of coverage of cancer patients by hospice services; the types of patients who miss out on hospice care; and the place of death of hospice and other cancer patients. We reviewed patients who died in 1990 and 1993 using the Central Cancer Registry database together with an identifier of hospice involvement. In 1990, 56 per cent of cancer patients who died had care from a hospice service, and this proportion increased to 63 per cent in 1993. Elderly patients, rural residents and those with a haematological malignancy were less likely than other patients to receive care from a hospice service, while patients aged between 40 and 60 years, longer survivors and those born in the United Kingdom and Europe were more likely to receive hospice care. Hospice involvement increased significantly between 1990 and 1993 for patients who died at home (59 to 73 per cent), in nursing homes (20 to 45 per cent), private hospitals (33 to 52 per cent) and public hospitals (48 to 55 per cent), but the proportion of patients with hospice involvement who died in country hospitals remained at 45 per cent. The increase in hospice coverage of terminal cancer patients reflects the continued integration of hospice care into the mainstream of health care delivery. The types of patients who miss out on hospice services should be given special consideration in the future planning of terminal care services.

Adult↗

PubMed1998

Elevated levels of versican but not decorin predict disease progression in early-stage prostate cancer.

Patients with clinically localized prostate cancer who might be cured by aggressive management are not easily identified using current clinical information. Additional, more accurate, biomarkers of tumor behavior need to be identified to improve clinical outcome. Our previous studies indicated that the concentration of the glycosaminoglycan chondroitin sulfate in prostatic stroma might be a useful biomarker of disease progression in early-stage prostate cancer. In this study, two chondroitin sulfate proteoglycans, versican and decorin, were investigated. Versican and decorin were immunolocalized to the periacinar and peritumoral fibromuscular stroma in sections of nonmalignant and malignant human prostate tissues. Video image measurements indicated that the concentrations of both proteoglycans were increased in the prostatic tissue of men with early-stage prostate cancer compared with tissue from men without cancer (P = 0.0006). Cox's univariate analysis indicated that increases in versican concentration but not in that of decorin were associated with increased risk of prostate-specific antigen (PSA) progression. Versican concentration was compared with other clinical or biological features of prognosis in two-variable regression analyses. Versican and serum PSA concentrations were independent predictors of PSA progression. Versican was a stronger prognostic factor than tumor grade, and it could predict outcome for patients with moderately differentiated tumors. Patients with low versican concentration had significantly better progression-free survival than patients with high levels of versican (Kaplan-Meier plot, 89% versus 27% PSA progression-free at 5 years, respectively; P = 0.0001). We conclude that the measurement of prostatic concentrations of versican, a molecule with reported anticellular adhesive properties, may be a useful marker of disease progression in patients with early-stage prostate cancer and that further study of versican in other patient cohorts is warranted.

Aged↗

PubMed1998

Analysis of p53 gene mutation by polymerase chain reaction-single strand conformation polymorphism provides independent prognostic information in node-negative breast cancer.

Controversy continues regarding the prognostic utility of detection of p53 gene abnormalities in node-negative breast cancer. To resolve this, we used a rapid and nonisotopic PCR-single strand conformation polymorphism method to screen for mutations in exons 4-8 of the p53 gene in primary tumors from 422 node-negative breast cancer patients. The prevalence of p53 mutation in the exons tested was 18%. p53 mutation was significantly associated with several markers of poor prognosis including larger tumor size, high tumor grade, low hormone receptor content, increased expression of MIB-1 (Ki-67), amplification of the HER-2/neu oncogene, and accumulation of the p53 protein. After a median duration follow-up period of 74 months, the parameters of tumor diameter > or =20 mm, HER-2/neu oncogene amplification, and p53 mutation were found to be associated with a statistically significant shortened duration of disease-free and overall survival, but not the parameters of tumor grade, hormone receptor levels, or p53 expression. The poor prognosis associated with p53 mutation was observed primarily in patients with a tumor diameter of > or =20 mm. In multivariate analysis, p53 mutation was a risk factor for increased risk of recurrence and death from breast cancer independent of tumor size, hormone receptor levels, HER-2/neu amplification, and MIB-1 expression. We conclude that a relatively simple and rapid single strand conformation polymorphism method of determining p53 mutation status in node-negative breast cancers can provide independent prognostic information.

Adult↗

PubMed1997

EMS1 amplification can occur independently of CCND1 or INT-2 amplification at 11q13 and may identify different phenotypes in primary breast cancer.

Chromosome 11q13 is amplified in about 13% of primary breast cancers. CCND1, encoding the cell cycle regulatory gene cyclin D1, and EMS1, encoding a filamentous actin binding protein, are favoured candidate onocogenes, whereas INT-2 is an unexpressed gene at this locus. In this study we tested the possibility that different regions of this large amplicon could be independently amplified and subsequently defined the phenotype of EMS1 amplified tumours in a series of 961 primary breast carcinomas. Using DNA slot blots, EMS1 was amplified in 15.2% of samples: 5.4% were coamplified for CCND1; 7.9% coamplified for INT-2 and 6.7% showed EMS1 amplification alone. The degree of amplification of CCND1 and INT-2 was highly correlated (P =0.0001). In contrast, no such relationship existed between EMS1 and CCND1 or INT-2 amplification, demonstrating independent amplification of EMS1 in 44% of amplified tumours. EMS1 amplification (> or = twofold increase in copy number) was positively correlated with patient age > or = 50 years (P = 0.025), ER positivity (P = 0.022), PgR positivity (P = 0.018), and was negatively correlated with HER-2/neu (c-erbB2) amplification (P = 0.01). In common with CCND1/INT-2, EMS1 amplification was associated with increased risk of relapse in patients with lymph node-negative disease (P = 0.028). In contrast, EMS1 and CCND1/INT-2 amplification appeared to confer different phenotypes in ER positive and negative tumours. A > or = threefold increase in EMS1 copy number was associated with an apparent increased risk of relapse and death in patients with ER negative tumours, but was without effect in ER positive tumours. In contrast, CCND1/INT-2 amplification had no effect in the patients with ER negative tumours but was associated with early relapse in ER positive patients. Thus EMS1 amplification may identify subgroups of breast cancer patients with increased probability of relapse and death distinct from those identified by CCND1/INT-2 amplification. Further studies are required to more clearly determine the functional consequences of EMS1 overexpression and a biological basis for the relationship between EMS1 amplification and phenotype in breast cancer.

Breast Neoplasms↗

PubMed1997

Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus.

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.

Adolescent↗

PubMed1997

A simple index to predict prognosis independent of axillary node information in breast cancer.

BACKGROUND: Since the course of breast cancer is often unpredictable, we wished to develop a model using characteristics of the primary tumour alone to predict prognosis. METHODS: Several tumour features were determined, and after a median follow-up duration of 65 months, multivariate analysis identified tumour size and grade, oestrogen receptor concentration, axillary lymph node metastasis and tumour cell proliferation fraction (MIB-1 count) as being independently associated with increases in risk for both relapse and death from breast cancer. A prognostic model was constructed using tumour size and grade, oestrogen receptor concentration and MIB-1 count only. A score of 1 for each was given to tumour size > 20 mm, tumour grade 2 or 3, oestrogen receptor concentration < 10 fmol/mg cytosol protein and MIB-1 count > 9%. Five groups established by assigning a combined score of 0, 1, 2, 3 or 4 for each patient were analysed for their associations with disease-free and overall survivals. RESULTS: This preliminary model predicted 5-year survival rates of 97, 91, 85, 68 and 50% for the five groups. The model was further simplified by excluding tumour grade from the analysis. The revised model identified four risk groups with predicted 5-year survival rates of 91, 86, 66 and 52%. This model, the Adelaide prognostic index, was also able to identify four risk groups in both node-negative and node-positive patients. CONCLUSIONS: The Adelaide prognostic index can be used to predict prognosis even in the absence of axillary lymph node information.

Antigens, Nuclear↗

PubMed1997

Risk factors for repeat attendance at hospital emergency departments among adults and children with asthma.

BACKGROUND: Acute asthma attacks are frequent causes of attendance at hospital Emergency Departments (EDs) and a subgroup of these patients repeatedly present for such treatment. AIMS: This study sought to characterise patients who were repeat attenders at EDs, to assist the targetting of appropriate future interventions aimed at reducing avoidable presentation. METHODS: A cross-sectional survey was undertaken of patients presenting with an asthma attack to the EDs of six teaching hospitals in Adelaide, South Australia between 14 May and 30 June 1994. Patients were interviewed within six weeks of their attendance about aspects of their asthma history, severity, medications, self-management, attitudes and environment. Repeat attenders, defined as two or more visits over the course of the preceding year, were compared with those who reportedly attended on one occasion only, using logistic regression analyses. RESULTS: Sixty-two per cent of 272 patients aged under 15 years and 40% of 165 patients aged 15 years or more reported having attended two or more times over the course of the preceding year. Among adults, the variables independently associated with repeat attendance principally related to asthma severity. Among children, repeat attendance was associated with parental attitudinal variables relating to appraisal of their child's asthma severity, management of asthma attacks and parental worry. CONCLUSIONS: The factors underlying repeated presentations at EDs differ between adults and children and interventions to minimise avoidable presentation will require different emphasis for these patient subgroups.

Adolescent↗

PubMed1997

Continuous passive motion after primary total knee arthroplasty. Does it offer any benefits?

We report a prospective randomly controlled trial to examine the effectiveness of continuous passive motion (CPM) in improving postoperative function and range of movement after total knee arthroplasty (TKA). We allocated 53 patients (57 knees) to one of three postoperative regimes: no CPM (n = 19); CPM at 0 to 40 degrees (0 to 40 CPM; n = 18); and CPM at 0 to 70 degrees (0 to 70 CPM; n = 20). Those in the CPM groups had CPM for 48 hours and all patients had an identical regime of physiotherapy. There was an even distribution of various cemented and cementless TKAs in each group. Patients were assessed preoperatively and at one week and at one year postoperatively. At one week, there was a statistically significant increase in the range of flexion and total range of movement in the 0 to 70 CPM group compared with the no-CPM group. At one year we found no significant differences in mean flexion, overall range of movement, fixed flexion deformity or functional results in the three groups. Those who had CPM had a significant increase in analgesic requirement (p = 0.04). There was an increased mean blood drainage postoperatively in those who had 0 to 70 CPM (1558 ml) compared with those with no CPM (956 ml) (t = 2.96, p = 0.005) and with 0 to 40 CPM (1017 ml) (t = 2.62, p = 0.01). Our findings show that CPM had no significant advantage in terms of improving function or range of movement, and that its use increased blood loss and analgesic requirements.

Aged↗

PubMed1997

A risk screening questionnaire for adult asthmatics to predict attendance at hospital emergency departments. South Australian Asthma Reference Panel.

STUDY OBJECTIVES: To develop a practical screening tool that could identify adult patients highly likely to attend a hospital emergency department (ED) in a 1-year period. DESIGN: Retrospective case-control study of patients who did and did not attend a hospital ED for asthma in the past year. SETTING: Adelaide, South Australia. PARTICIPANTS: One hundred sixty-five adults attending an ED for asthma were compared with 260 adults with asthma from a community survey who had not attended an ED in the previous year. MEASUREMENTS AND RESULTS: The following variables were independently related to ED attendance: having been woken from sleep by asthma in past month; having been admitted to hospital because of asthma in the past year; having seen more than one general practitioner for asthma in the last 12 months; a moderate or severe self-rating of asthma in the last month; and having taken oral steroid medication for asthma in past month. A risk screening questionnaire using the weighted responses to these five variables with a cutoff score of 30/100 demonstrated a sensitivity of 90% and specificity of 88%. CONCLUSIONS: These findings agree with those of previous studies that markers of asthma severity and discontinuity of care are risk factors for adverse asthma outcomes. Validation of the risk screening questionnaire is required in a prospective study.

Adolescent↗

PubMed1996

Vimentin expression is not associated with poor prognosis in breast cancer.

The clinical significance of vimentin intermediate filament (VIF) expression was studied in relation to other established prognostic parameters in primary breast cancer. Archival tumour samples embedded in paraffin were examined by immuno-histochemistry with monoclonal antibodies (MAbs) to VIF, p53 protein and cell proliferation marker MIB-I. The vimentin staining pattern was heterogeneous, but in vimentin-positive areas > 80% of the tumour cells were positive. There was no association between vimentin expression and tumour size or the number of axillary lymph nodes involved. Vimentin expression was significantly associated with high-grade tumours, absence of hormone receptors, increased p53 expression and high tumour proliferation fraction as estimated by MIB-I count. Despite these associations with several recognised features of tumour aggressiveness, vimentin expression was not associated with increase in risk of relapse or death from breast cancer.

Antibodies, Monoclonal↗

PubMed1996

Relationship between minimal residual disease and outcome in adult acute lymphoblastic leukemia.

In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (> 10(-3) leukemic cells per marrow cell) nearly always relapse, whereas those with low levels (<2 x 10(-5)) seldom do. However, the importance of MRD in adult ALL is unclear. We studied 27 patients aged 14 to 74 who were treated with a standard protocol and who attained morphological remission. MRD in the marrow at first remission was quantified by using the polymerase chain reaction (PCR), with the rearranged immunoglobulin heavy chain gene as a molecular marker. Levels of MRD varied from 3 x 10(-1) to <7 x 10(-7). The probability of long-term relapse-free survival was significantly related to the level of MRD and only one of nine patients with MRD >10(-3) did not relapse. For patients who did relapse, there was an inverse relationship between MRD level and the length of remission. Overall, MRD in adults in whom a translocation had not been identified was significantly higher than in comparably-treated children, suggesting that ALL in adults is more drug-resistant than in children.

Adolescent↗

PubMed1996

Relationship between p53 gene abnormalities and other tumour characteristics in breast-cancer prognosis.

The prognostic significance of p53 gene abnormalities was investigated in 919 primary breast-cancer patients. p53 expression and tumour-cell proliferation fraction determined by MIB-1 count, p53 exon 5 and 6 mutations and HER-2/neu oncogene amplification were detected by immunohistochemistry, PCR-SSCP and slot-blot hybridization, respectively. Increased MIB-1 count, p53 expression, HER-2/neu oncogene amplification and p53 mutations were detected in 33%, 29%, 10% and 8% of tumours, respectively. Statistically significant associations were observed between p53 expression or MIB-1 count and age below 50 years, high-grade tumours, medullary carcinomas, and absence of hormone receptors. p53 mutations were associated with increased MIB-1 count, HER-2/neu oncogene amplification and absence of hormone receptors, but not with age, tumour size or grade, histological subtype, or the number of axillary nodes involved. After a median follow-up of 66 months, p53 expression was observed to be associated with significant increases in risk of both relapse and death from breast cancer, but not after adjusting for the effect of other parameters. In these analyses, MIB-1 count, and not HER-2/neu oncogene amplification, was an independent predictor of prognosis. In node-negative patients, only p53 exon 5 and 6 mutations and MIB-1 count were associated with a statistically significant increase in risk of death from breast cancer, independent of tumour size and ER concentration. We conclude that tumour-cell proliferation fraction, as measured by MIB-1 count, is the most useful parameter of breast-cancer prognosis, with the exception of ER, tumour size and the number of axillary nodes involved.

Adult↗

PubMed1996

Prospective study of the prognostic significance of epidermal growth factor receptor in primary breast cancer.

Bearing in mind the continuing controversy over the prognostic significance of epidermal growth factor receptor (EGF-r) expression, we investigated its clinical significance prospectively in 345 primary breast cancer patients. The prognostic significance of EGF-r expression, as measured by a radioligand binding assay, was determined by Cox's multivariate analysis using EGF-r concentration as a continuous or dichotomous variable. Increased EGF-r expression was detected in 20-32% of tumours, depending on the cut-off in concentration used. EGF-r expression, irrespective of the cut-off, was not associated with tumour size or grade or the number of axillary nodes involved. There was, however, a strong inverse association between EGF-r expression and the absence of hormone receptors. After a median follow-up period of 57 months, multivariate analysis suggested that EGF-r expression was associated with increases in risk for both relapse and death from breast cancer, even after adjusting for oestrogen receptor (ER) concentration, tumour size and the number of axillary nodes involved. Patients with ER-positive tumours, which also expressed EGF-r, had increases in risk for both relapse and death from breast cancer compared with tumours without EGF-r. Expression of EGF-r was not a predictor of poor prognosis in either node-negative or ER-negative subgroups of patients.

Adult↗

PubMed1996

A population-based study of the coverage of cancer patients by hospice services.

The aims were to determine the proportion of terminal cancer patients in South Australia who had involvement with a programme of hospice care, to identify the predictors of hospice involvement, and to consider the influence of hospice services, along with other variables, on the place of death. A file of patients of the State's hospice services who died in 1990 was compiled and linked to the population-based Central Cancer Register. We found that 1561 (56%) of the 2800 cancer patients who died in 1990 had care from a hospice service. Patients were less likely to be involved with a hospice service if they were 80 years or older, lived in a rural region, or had a haematological malignancy, and more likely to have hospice care if they had a survival time of more than six months, or were born in the UK or Europe. Patients of hospice services were more likely than other patients to die at home or in an inpatient hospice, and less likely to die in a nursing home or private hospital. A range of other factors were also found to be associated with place of death. We conclude that there has been a rapid acceptance of hospice care in South Australia, with a majority of the target population of cancer patients covered by services. Epidemiological research methods are useful for identifying gaps in the provision of care, and for determining the impact of various factors on where people die. This research is, therefore, important for the formulation and evaluation of policy for the delivery of terminal care.

Adult↗

PubMed1994

The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group.

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.

Adult↗

PubMed1993

Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group.

PURPOSE: To determine prospectively the prognostic significance of HER-2/neu oncogene amplification in the primary tumors of breast cancer patients. METHODS: HER-2/neu amplification in tumor DNA was determined by the slot-blot technique in 1,056 patients with breast cancer (stage I to III) diagnosed between 1987 and 1990. Parameters such as estrogen receptor (ER) and progesterone receptor (PgR) levels, tumor size, axillary nodal involvement, tumor grade, and time to relapse were prospectively obtained. RESULTS: HER-2/neu oncogene amplification, > or = 2, > or = 3, and > or = 5 copy number, was detected in 21%, 11%, and 7% of patients, respectively. In a test set of 529 patients, Cox multivariate analysis showed HER-2/neu copy number > or = 3 or > or = 5 was associated with shorter disease-free survival (DFS) duration. HER-2/neu copy number > or = 3 correlated significantly with pathologic stage of disease, number of axillary nodes with tumor, histologic type, and absence of ER and PgR. For all patients, after a median follow-up duration of 39 months, Kaplan-Meier univariate analysis indicated that tumor oncogene copy number > or = 3 correlated with shorter DFS in both node-negative and node-positive patients. In Cox multivariate analysis, HER-2/neu copy number > or = 3 was associated with shorter DFS, independent of nodal status, ER level, and tumor size. CONCLUSION: Although the follow-up duration of this study is relatively short, we conclude that HER-2/neu amplification is an independent predictor of shorter DFS in both node-negative and node-positive patients.

Adult↗

PubMed1990

Body-image distortion among male and female college and high school students, and eating-disordered patients.

For 179 male and female college and high school students, and 26 female eating-disordered patients body-image distortion was measured using a computer-based image-analysis of redrawn images of standardized human figures. Statistical analysis indicated that body-image distortion was the same for all groups. Body-image distortion was significantly and negatively related to weight:height ratio as a function of a simple polynomial. These results suggest this evaluation of distortion of body-image yields a quantitative measure reliably related to weight status but also suggests the technique, and possibly measurement of body-image distortion in general, may not be a valid discriminator between eating-disordered and normal persons.

Adolescent↗