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Biomedical subjects

J M Harvey

Publications and source records attributed to J M Harvey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Aetiology and classification of small for gestational age infants.

OBJECTIVE: To determine important aetiological factors in small gestational age (SGA) infants and the effectiveness of anthropometric indexes in identifying patterns of growth retardation. METHODOLOGY: Eighty-four SGA infants and 81 controls were enrolled. Maternal biological, lifestyle and psychosocial factors were compared for the total group and the term Caucasian subset. Anthropometric indexes were also examined in relation to growth patterns. RESULTS: Decreased maternal size, poor weight gain, previous SGA infant and smoking were significantly associated with SGA status. Poor parental education and unemployment was increased in the study group. Mothers of SGA infants, especially the term Caucasian group, had a greater prevalence of hypertension and depressive and stress symptomatology. Ponderal index failed to identify discreet patterns of disproportionate/proportionate growth retardation. CONCLUSION: Biological, lifestyle and psychosocial differences remain important aetiological factors of intrauterine growth retardation. Identification of specific patterns of growth retardation by ponderal index remains controversial.

Body Height↗
PubMed1997

Biological predictors and co-morbidity of attention deficit and hyperactivity disorder in extremely low birthweight infants at school.

OBJECTIVE: To examine biological predictors and co-morbidity of Attention Deficit Hyperactivity Disorder (ADHD) and associated academic and social impairment in a cohort of extremely low birthweight of (ELBW) children attending school. METHODOLOGY: Eight seven (70%) of 125 ELBW children born between 1977 and 1986 were followed prospectively. Neonatal and biological data including cranial ultrasound for 62% of children, formal developmental assessment at 4 or 6 years of age, teacher and parent ADHD questionnaire, parental rating of health status and social impairment and school teacher rating of academic performance was recorded. RESULTS: Apart from grades 3 or 4 intraventricular haemorrhage in a minority of children, there was no evidence to suggest an association between ADHD and perinatal adversity in ELBW children. Social impairment, academic difficulty and atopic symptoms were significantly related to ADHD. CONCLUSIONS: Extremely low birthweight children presenting with symptoms of ADHD are likely to suffer social and learning impairment and these, rather than perinatal risk factors, should be the focus of clinical attention.

Adolescent↗
PubMed1997

The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells.

The small heat shock protein hsp27 is often expressed at high levels in clinical breast tumors; however, its biological role in this disease still remains unclear. Several laboratories have recently shown that hsp27 expression is associated with aggressive tumor behavior. We hypothesized that hsp27 may influence the metastatic tumor process since this is part of tumor 'aggressiveness'. Therefore, we stably transfected breast cancer cell lines with sense (MDA-MB-231) and antisense (MDA-MB-435) hsp27 constructs, respectively, and examined various cellular aspects associated with the metastatic process. We found that hsp27-overexpressing clones lost their protrusive morphology, but exhibited higher membrane ruffling as compared to low expressing cells. hsp27 overexpression also resulted in decreased cell motility, but invasiveness, adhesion, and growth in Matrigel were all significantly increased. Conversely, antisense suppression of hsp27 expression resulted in increased cell motility, but decreased in vitro invasiveness. The direct correlation of hsp27 levels with metastasis was confirmed by an in vivo assay measuring the number of lung metastases in mice injected with hsp27-transfected cells. Thus, we conclude that hsp27 overexpression may influence the invasive and metastatic potential of human breast cancer cells.

Animals↗
PubMed1996

Predicting axillary lymph node metastases in breast carcinoma patients.

Routine axillary dissection is primarily used as a means of assessing prognosis to establish appropriate treatment plans for patients with primary breast carcinoma. However, axillary dissection offers no therapeutic benefit to node negative patients and patients may incur unnecessary morbidity, including mild to severe impairment of arm motion and lymphedema, as a result. This paper outlines a method of evaluating the probability of harbouring lymph node metastases at the time of initial surgery by assessment of tumour based parameters, in order to provide an objective basis for further selection of patients for treatment or investigation. The novel aspect of this study is the use of Maximum Entropy Estimation (MEE) to construct probabilistic models of the relationship between the risk factors and the outcome. Two hundred and seventeen patients with invasive breast carcinoma were studied. Surgical treatment included axillary clearance in all cases, so that the pathologic status of the nodes was known. Tumour size was found to be significantly correlated (P < 0.001) to the axillary lymph node status in the multivariate anlaysis with age (P = 0.089) and vascular invasion (P = 0.08) marginally correlated. Using the multivariate model constructed, 38 patients were predicted to have risk of nodal metastases lower than 20%, of these only 4 (10%) patients had lymph node metastases. A comparison with the Multivariate Logistic Regression (MLR) was carried out. It was found that the predictive quality of the MEE model was better than that of the MLR model. In view of the small sample size, further verification of this model is required in assessing its practical application to a larger population.

Axilla↗
PubMed1996

School performance of ELBW children: a controlled study.

This paper examines the prevalence of learning difficulty in reading, spelling, mathematics and writing and the prevalence of attention deficit disorder (ADD) in extremely low-birthweight (ELBW) children at school compared to their peers. Parents of 87 eligible ELBW children completed an educational questionnaire and questionnaire for ADD. Teachers of the ELBW children completed a detailed educational and ADD questionnaire for the study child and two control children in the same class, matched for age and nearest in birth date to the study child. Parents reported that 4% of the ELBW children born between 1977 and 1986 were in a special education unit, 46% received remedial help and 21% repeated a grade. Teacher assessment of six aspects of reading and spelling and five aspects of mathematics and writing skills indicated that the ELBW children experienced marked problems in all areas compared to control children and were approximately 3 times more likely to be delayed by more than a year in all areas. Prevalence of ADD was not increased in the ELBW children compared to the control group, though males in both groups had a higher prevalence of symptoms. Early intervention and special education resources must be available for ELBW children attending school.

Adolescent↗
PubMed1995

Extremely low birth weight and control infants at 2 years corrected age: a comparison of intellectual abilities, motor performance, growth and health.

A 2-year cohort of 63 surviving extremely low birth weight (ELBW) infants was prospectively studied and 60 of these infants, together with 44 normal birth weight control infants, were assessed at 2 years of age for intellectual abilities, motor skills, growth and health. The total ELBW group differed significantly from controls on overall Griffiths developmental quotient (99.3 vs. 103.8 P = 0.02) and in the personal/social subscale (100.7 vs. 106.7 P = 0.01). A subset of 43 of the ELBW infants was identified as low risk at discharge. No statistically significant differences were present between the low risk ELBW subset and controls in intellectual abilities though both the total ELBW group and the low risk ELBW subset differed from controls in fine and gross motor abilities, and in weight at 2 years. The total ELBW group also experienced more frequent ill health and hospital readmission.

Child, Preschool↗
PubMed1995

Breast cancer in Western Australia in 1989: IV. Summary of histopathological assessment in 655 cases.

This study was part of a population-based survey of all cases of breast cancer diagnosed in Western Australia in 1989. The paper concerns histopathology reporting by pathologists in 655 cases of carcinoma of the breast in that year, before the introduction of mammographic screening programmes. Pathological features of the neoplasms are documented, and the extent to which information known to be of clinical or prognostic importance was included in the reports is analysed. 96.5% of all pathology reports included information on breast cancer subtype and, in 98.6% of cases with axillary dissection, the number of lymph nodes dissected, and the number containing metastatic tumor was stated. In 83.7% of cases of invasive carcinoma exact tumor dimensions were recorded. In 44.9% of cases histological grade was recorded, and information about excision margins was present in 60% of reports overall. The reporting of pathological features in many instances was limited by the way in which the specimen was handled prior to reception. At the time of the study, views about the importance of many aspects of histological assessment were still evolving. Even now, for example, consensus is still being reached on the value of histological grading in predicting prognosis and whether reliable histological assessment of such factors as extent of DCIS and completeness of excision of DCIS is possible. The introduction of mammographic screening since 1989 has provided a focus for wider discussion about the value of histological information in prognostication and patient management. A case is made to support the use of "check lists" for surgical pathology reports in cases of breast cancer.

Adolescent↗
PubMed1995

Do 'social relief' admissions have any effect on patients or their care-givers?

Dependent patients and their care-givers were studied before and 1 week after a social relief admission in order to assess the effects on physical and psychological problems. Data about care-givers stress and mental health were gathered, as well as patient data. Patients' self-care abilities improved slightly but care requirements remained constant. Care-giver stress levels did not change, but there was a highly significant improvement in their mental health. The results suggest that social relief admissions enabled care-givers to continue to look after very dependent people in the community.

Aged↗
PubMed1994

c-erbB-2 amplification in breast cancer: detection in formalin-fixed, paraffin-embedded tissue by in situ hybridization.

We describe a sensitive and practical in situ hybridization method, using a digoxigenin-labeled probe, for the detection of c-erbB-2 amplification in breast cancer in formalin-fixed, paraffin-embedded tissue sections. Forty-six primary breast carcinomas were studied. Nuclear hybridization signal was observed in 36 of 46 carcinomas. Signal was confined to malignant cells. Normal breast epithelium and stromal and inflammatory cells were uniformally negative. DNase predigestion, no-probe preparations, and competitive hybridization confirmed the specificity of the reaction. The hybridization reaction was localized to multiple discrete foci in tumor cell nuclei, suggesting multiple sites of gene copy and transcriptional activity in the nucleus. Considerable cell-to-cell variation in hybridization signal was evident within individual tumors and positive reactions were observed in several cases in which amplification could not be detected by either Southern or slot blot analysis. The high sensitivity and specificity of the reaction and its use in a tissue-based system will allow the study of a range of possible precursor lesions of breast cancer for evidence of c-erbB-2 amplification.

Breast Neoplasms↗
PubMed1994

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1993

Stromelysin-3 expression in breast cancer biopsies: clinico-pathological correlations.

Stromelysin-3 expression was studied by Northern blotting in 222 tissue samples including primary and metastatic breast carcinoma and normal breast tissue. Uninvolved breast tissue from mastectomy specimens, normal breast tissue from reduction mammoplasties and normal lymph nodes did not contain stromelysin-3 mRNA. About 62% of primary and metastatic breast carcinomas, but only 1 of 10 in situ ductal carcinomas, expressed stromelysin-3. Stromelysin-3 mRNA was found more often in estrogen-receptor-positive carcinomas and in histological grade-1 carcinomas. There was no significant correlation between stromelysin-3 expression and other prognostic factors, including tumor size, lymph-node involvement, age of patient, vascular invasion and cathepsin-D.

Axilla↗
PubMed1993

What's new in breast cancer? Molecular perspectives of cancer development and the role of the oncogene c-erbB-2 in prognosis and disease.

The oncogene c-erbB-2 is frequently amplified in human breast carcinoma. The c-erbB-2 gene is present as a single copy in normal cells, and has been mapped to chromosome 17 in the region 17q 12-21.32. c-erbB-2 encodes a transmembrane glycoprotein known as p185. The intracellular component of p185 has tyrosine kinase activity; the extracellular domain has a structure resembling a growth factor receptor. c-erbB-2 amplification, p185 overexpression and levels of transcribed c-erbB-2 specific messenger RNA have been studied in a large number of breast carcinomas using a variety of techniques. In general, overexpression of p185 oncoprotein reflects various levels of DNA amplification, though in some cases amplification can be detected in the absence of overexpression of p185 and similarly overexpression of p185 can be present without detectable levels of c-erbB-2 amplification. This findings suggests that multiple mechanisms may be responsible for overexpression. c-erbB-2 amplification and/or overexpression occurs in almost all cases of high grade duct carcinoma in-situ, but has been reported in only 10%-40% of infiltrating duct carcinoma. c-erbB-2 amplification or overexpression occurs rarely in invasive lobular carcinoma, and has not been detected in ductal or lobular epithelial hyperplasia, or in atypical ductal or atypical lobular hyperplasia. It is generally believed that c-erbB-2 amplification/overexpression is an important independent prognostic indicator in breast carcinoma, identifying a subset of patients with poor prognosis tumours, particularly if axillary node metasases are present. However, many unanswered questions remain regarding c-erbB-2 and its role in breast cancer development and progression. The causes of c-erbB-2 amplification are unknown. There is no evidence of mutations in the human gene which might cause amplification or overexpression. The significance of the differences in levels of c-erbB-2 amplification/overexpression in in-situ duct carcinoma and associated invasive duct carcinoma has not been established. Amplification or overexpression have not been reported in atypical duct hyperplasia, a proposed precursor of duct carcinoma in-situ, yet overexpression occurs almost always in high grade duct carcinoma in-situ. c-erbB-2 may play a critical role in the development of a clonal in-situ, proliferation of high histological grade, yet does not obviously influence the acquisition of an invasive phenotype. We would postulated that this instability in amplification/overexpression is of biological significance, and if better understood may aid in the study of progression of human breast carcinoma.

Blotting, Southern↗
PubMed1993

Breast cancer in Western Australia in 1989. I. Presentation.

This study was designed as a population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989. Cases were identified from the State Cancer Registry and from computerized hospital inpatient records. Data were obtained from the records of surgeons and oncologists managing the patients, hospital medical records, and pathology and cytology reports. A total of 701 histologically proven tumours were documented in 692 women. Of these 6.8% were not known to the State Cancer Registry. Two-thirds (68%) of tumours were first detected by the woman herself, 11% were found by a doctor and 11% were detected by mammographic screening. Stage I tumours accounted for 40% of tumours and Stage II 39%. The estimated lifetime risk of a WA woman developing at least one malignant breast tumour is 10%. Passive surveillance based upon a legal obligation on doctors to notify cases of cancer may be resulting in a significant under-estimation of the incidence of cancer in WA. Mammographic screening played only a small role in the detection of breast cancer in WA in 1989, but its contribution and the proportion of stage I tumours should both increase as a population-based mammographic screening programme is established. This survey will provide a yardstick against which changes can be measured. Eighty-four per cent of tumours presently occur in women who would have access to mammographic screening although only 44% occur in the 50-69 age bracket that is to be actively recruited. The lifetime risk of breast cancer in WA women is greater than has been appreciated previously.

Adult↗
PubMed1993

Breast cancer in Western Australia in 1989. II. Diagnosis and primary management.

This study was designed as a population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989. Cases were identified from the State Cancer Registry and from computerized hospital inpatient records. Data were obtained from the records of surgeons and oncologists managing the patients, hospital medical records and pathology and cytology reports. A total of 701 tumours in 692 women were treated by 105 different surgeons of whom 25 saw 10 or more cases. Over 70% were proven by cytology or biopsy within 2 weeks of presentation to a doctor. The first diagnostic investigation was fine needle aspiration in 45%, open biopsy in 28% and diagnostic mammogram in 24.4%. A definitive procedure involving breast conservation was performed in 31.3% of patients with operable tumours; 35.6% of those under 50 years of age. If axillary dissection or sampling was part of such treatment, 93.5% of those under 50 years and 75% of those 50 years and over had radiotherapy to the residual breast. Although less than one-third of patients were referred to a medical oncologist almost a half had adjuvant systemic therapy (92% of node positive and 23% of node negative patients). Tamoxifen was prescribed as part of adjuvant therapy in 93% of those over 50 years and cyclophosphamide, methotrexate and 5-fluorouracil in 71% of those under 50 years. Less than 10% of patients treated with mastectomy and axillary dissection had postoperative radiotherapy to the chest wall and drainage areas. The patterns of care of patients with breast cancer in WA prior to the introduction of population-based mammographic screening have been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Nuclear DNA content of human breast carcinoma: a comparison of results obtained by microspectrophotometry and flow cytometry of paraffin embedded tissue.

This study compares 2 techniques for estimating the nuclear DNA content of tumor cell lines: (i) static cytometry of smears taken from fresh tissue and (ii) flow cytometry of cells extracted from paraffin embedded tissue. Parallel determinations of DNA content, using both techniques, were made on samples of tissue taken from 130 female patients with breast carcinoma. Using a simple classification into diploid and non-diploid groups, the 2 techniques yielded discrepant results in 11% of cases. The most frequent causes of disagreement were (a) the inability of static cytometry to distinguish between a diploid and a near-diploid peak and (b) for flow cytometry, the difficulty of determining whether a minor peak in the tetraploid region represented the G2 peak of a diploid cell line or the G0/G1 peak of a tetraploid cell line. If it is deemed necessary to accurately assess ploidy status, flow cytometry on paraffin embedded tissue, using modern statistical programmes, would seem to be most practical for routine use, but some neoplasms, particularly those with an equivocal ploidy peak in the tetraploid range by this method, will require static cytometry to accurately assess nuclear DNA content. Using this approach, it appears that the disagreement between the 2 techniques would be less than 5%.

Adult↗
PubMed1993

c-erbB-2 amplification and overexpression in breast cancer: evaluation and comparison of Southern blot, slot blot, ELISA and immunohistochemistry.

The oncogene c-erbB-2 has been shown to be amplified in 17-30% of breast cancers, with similar levels of overexpression of the oncogene product p185, a transmembrane growth factor receptor glycoprotein. Amplification of c-erbB-2 is now generally considered to be a significant prognostic indicator in patients with breast cancer. A series of 74 consecutive breast carcinomas were analysed for c-erbB-2 amplification and p185 overexpression. The procedures of Southern blotting and slot blot were used for the analysis of oncogene amplification, while immunoperoxidase (IPOX) staining and enzyme-linked immunosorbent assay (ELISA) were used for the analysis of p185 overexpression. Detection of c-erbB-2 oncogene amplification by both the conventional Southern blotting technique and by the slot blot technique showed complete accord, with the amplified c-erbB-2 oncogene being detected in 14 of the 74 patients (18.9%). The c-erbB-2 oncoprotein, as measured by IPOX and ELISA, was found to be overexpressed in 21% and 19% of patients, respectively. Comparison was made between the results attained by all four methods, and further comparison of the techniques was made from the point of view of ease of use, expense and ease of introduction into routine diagnostic laboratories. Immunocytochemistry in combination with slot blotting procedures were considered to be the most cost effective methods for evaluation of overexpression and amplification in routine pathology laboratories.

Blotting, Southern↗