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Biomedical subjects

J Hayward

Publications and source records attributed to J Hayward.

At least 19 recordsLinked to original sources

A novel tumor-derived mediator that sensitizes cytokine-resistant tumors to tumor necrosis factor.

Therapeutic successes following treatment of murine tumors with tumor necrosis factor-alpha (TNF) have not been easily applied to clinical oncology because the concentrations of TNF required in humans induces systemic toxicity. This has led us to identify mediators which could sensitize tumors to the effects of TNF, permitting administration of lower doses and possible realization of the therapeutic potential of this cytokine. Our study reports the ability of a novel cytokine, endothelial-monocyte-activating polypeptide II (EMAP II), to sensitize initially resistant murine and human tumors to TNF-induced regression employing a murine model. Recombinant (r) EMAP II was purified from Escherichia coli transformed with a plasmid expressing mature EMAP II. The B16 melanoma, raised in C57BL/6 mice, or a human fibrosarcoma (HT-1080), grown in immunocompromised mice, was injected intratumorally with either vehicle or rEMAP II/heat-treated EMAP II (50-100 micrograms) followed by systemic TNF/heat-treated TNF (5 micrograms) and assessed for tumor volume, hemorrhage, and histologic appearance. Both the B16 melanoma and the HT-1080 human fibrosarcoma underwent thrombohemorrhagic and acute inflammatory changes concomitant with regression or significantly slowed growth after administration of intratumor EMAP II followed by systemic TNF. Omission or inactivation of either cytokine abrogated this effect. These results demonstrate that local treatment of certain tumors with EMAP II results in enhanced susceptibility to TNF-mediated induction of thrombohemorrhage and regression.

Animals

Career guidance during nurse training: findings from an exploratory study.

This research into the career guidance experiences of nurses during their training was undertaken as an exploratory study upon which a series of larger studies will subsequently be based. Additionally, it contributed to a national cohort study of the careers of newly qualified registered general nurses. One hundred and twelve nurses were involved in the development and testing of questions for a postal questionnaire to be used in the cohort study of careers. Some problems encountered when investigating career guidance by questionnaire are described, in the light of which a revised research design is proposed and the career guidance experiences of 31 nurses presented. Twenty-one aspects of guidance were investigated, covering information and advice about applying for first post, post-basic courses and longer-term plans.

Career Choice

Duplex ultrasonography and pulse-generated run-off in selecting claudicants for femoropopliteal angioplasty.

Non-invasive assessment of lower limb vasculature may avoid unnecessary angiography in claudicants. Colour duplex ultrasonography of the femoral and popliteal arteries was performed to assess patency and the presence of any stenoses, and pulse-generated run-off (PGR) was used to assess the distal vasculature. In 65 legs colour duplex scanning was successful, compared with angiography, in identifying the site and type of disease in the femoropopliteal segment and 23 lesions were correctly identified as suitable for angioplasty. More patent distal vessels were demonstrated by PGR than by angiography; no vessels patent on angiography were missed by PGR. The estimated cost of diagnostic angiography was 330 pounds per test compared with 52 pounds for non-invasive assessment. By using duplex examination as a screening test, a potential saving of 8062 pounds could have been made in this series. Duplex ultrasonography offers a non-invasive and cost-effective alternative to diagnostic angiography for clinically suspected infrainguinal arterial disease presenting as claudication. PGR was not of clinical value in assessing suitability for angioplasty.

Aged

SIDS: race as a factor.

In Wisconsin, the rate of postneonatal deaths attributed to sudden infant death syndrome (SIDS) for the period 1978-1987 was 6.7 per 1,000 live births for Native Americans, 3.6 for blacks, and 1.4 for whites. To investigate racial differences in case ascertainment and risk for SIDS mortality, this study used matched birth-death certificate data for the 1,111 reported SIDS deaths during the 10-year period. At least 90% of all SIDS deaths occurred before 6 months of age; seasonal variation in time of death and autopsy rates were similar by race. The reported higher risk of SIDS for male infants and those with low birth weights did not occur among Native Americans. Low birth weight was a stronger risk for SIDS among whites than blacks. Our findings suggest that diagnostic practices may not account for racial differences in SIDS mortality. Patterns of risk, however, appear to vary by race.

Black People

Estrogen receptors and human bone cells: immunocytochemical studies.

In this immunocytochemical study we have probed a number of human bone cell types and bone preparations for the presence of the estrogen receptor (ER) with two distinct monoclonal antibodies. Using a well-validated antibody (H222) that recognizes human ER and standard peroxidase-antiperoxidase methodology, we were unable to demonstrate nuclear staining for ER in cultured primary or transformed human bone-derived cells or in fetal bone sections. Attempts to visualize ER in osteosarcoma cell lines (TE85C and HTB96) using a silver enhancement procedure were also unsuccessful. Additionally, we failed to detect immunocytochemical staining for the progesterone receptor (using monoclonal antibody mPR1) in control or estrogen-treated human bone cell cultures. Estrogen and progesterone receptor staining was readily detectable in MCF7 human breast cancer cells. In contrast, with a monoclonal antibody that recognizes a 29 kDa cytoplasmic component (p29) closely related to human ER, we observed specific staining in all the osteoblastlike cells studied. Cytoplasmic staining for this p29 antigen was most intense in primary cultures of human bone-derived cells. It is possible that the relatively abundant but as yet undefined p29 antigen may act as a sensitive marker for the presence of ER in cells at levels below the detection limit of the anti-ER monoclonal antibody. If so, our results are consistent with the presence of ER in osteoblastlike cells at very low concentrations.

Adult

The significance of local control in the primary treatment of breast cancer. Lucy Wortham James clinical research award.

Two sequential clinical trials were carried out to compare wide excision with radical mastectomy in patients with early breast cancer with clinically negative nodes. In the first study there was an increased incidence of local recurrence in patients who had wide excision, but distant recurrence and survival were unaltered. In the second study, the distant recurrence and survival rates were also significantly impaired. A new analysis showed that there were significantly more patients with T1 tumors in the second study than in the first. Comparison of treatments by T status indicates that radical mastectomy gives significantly better results in patients with T1 tumors. There is no difference between the results of the two treatments in patients with T2 tumors. We comment on the implications of these findings for conservation treatment of early breast cancer.

Awards and Prizes

A hospital discharge code review of toxic shock syndrome in Wisconsin.

The Wisconsin Division of Health conducted a review of discharge coding for 142 (97%) of the state's general care hospitals for the period 1980-1983 to evaluate the use of International Classification of Diseases codes for toxic shock syndrome and to estimate completeness of reporting of recognized hospitalized cases of the syndrome to the Division of Health. Hospital use of code 040.89 (other bacterial diseases-other) recommended for toxic shock syndrome by the National Center for Health Statistics in January 1981 increased from 23% of Wisconsin hospitals in 1980 to 92% in 1983. The sensitivity of this code for toxic shock syndrome increased from 54% to 85% from 1981 to 1983; study population specificity was stable at approximately 95%, and the predictive value was 65% in 1981 and 70% in 1983. The use of codes 785.50 (shock, unspecified) and 785.59 (nontraumatic shock-other) frequently assigned to toxic shock syndrome was also assessed; all measures of their utility decreased in proportion to the increasing use of 040.89. The coding review identified 20 previously unreported cases of toxic shock syndrome; the 10 confirmed and 10 probable cases represent 4% and 21% of the state's 223 confirmed and 47 probable cases with onsets in 1980-1983. Results indicate that a National Center for Health Statistics coding recommendation for a disease of emerging significance can result in relatively uniform coding of the illness, which can provide a tool for case finding and surveillance evaluation for hospitalized cases.

Adolescent

Effects of imidazole- and triazole-derivative antifungal compounds on the growth and morphological development of Candida albicans hyphae.

Six azole-derivative antifungal compounds affected several aspects of Candida albicans hyphal development with only a relatively small degree of inhibition of growth rate, measured in terms of ATP concentration, whereas amphotericin B and 5-fluorocytosine affected morphology only when they also substantially inhibited fungal growth rate. At 10(-8) M, all the azoles tested inhibited branch formation by C. albicans hyphae. At 10(-7) M and higher concentrations, clotrimazole and miconazole strongly suppressed emergence of new hyphal outgrowths from parent yeast cells, whereas ICI 153066 and itraconazole had little effect on this phenomenon and ketoconazole and tioconazole had intermediate effects. At the highest concentrations tested (10(-5) M) hyphal development was ultimately arrested by the azole compounds and the fungus grew predominantly in the form of budding yeast cells; however, none of the azole antifungals prevented initial emergence of an apparently normal germ tube. The antifungals only exerted their morphological effects when they were present in the culture medium: removal of the compounds after exposure of C. albicans to them led to reversion to normal growth.

Amphotericin B

The principles of breast cancer surgery.

The rationale for the treatment of patients with early breast cancer has changed considerably over the last 20 years. The management of the disease must now involve an integral approach taking into consideration the many developments that have occurred and how these have affected orthodox therapy. Because of advances in radiation technology, and also because patients are now presenting with tumors of much smaller size, the trend in treatment has been towards more conservative surgery. However, techniques have had to take into account a number of developments which have materially changed our concepts of what needs to be accomplished: 1) treatment must ensure local control of disease; 2) it must supply sufficient tumor tissue for histological and biochemical analysis; 3) it must be compatible with the use of adjuvant therapy; 4) it must give full information on axillary node status. At present only the radical mastectomy or its modified version has been proved to be effective whilst fuftilling all these criteria for treatment. Nevertheless new conservation techniques are now being tested which may allow the breast to be conserved whilst at the same time safely treating the patient and providing the surgeon with all the information needed for future management.

Axilla

Post-operative serum sialyltransferase levels and prognosis in breast cancer.

Serum sialyltransferase (SST) activity was measured 10 days after mastectomy in 153 patients with operable breast cancer. Enzyme activity declined with time in storage (1-42 months). After correction for loss of activity in storage, patients with SST activity below the median value had a longer disease-free interval (DFI) than those with SST activity above the median, and this difference remained when patients were stratified by axillary nodal status, tumor size, and tumor grade. Survival was longer in patients with low SST activity. Post-operative elevation of SST indicates a poor prognosis in patients with operable breast cancer.

Breast Neoplasms

Estrogen and progesterone receptors: correlation of response rates, site and timing of receptor analysis.

156 patients with advanced breast cancer of known estrogen receptor (ER) and progesterone receptor (PgR) status treated by endocrine therapy were studied. Regarding values for ER and PgR greater than or equal to 5 fmole/mg cytosol protein as positive, patients were divided into 4 phenotypic subgroups: ER+PgR+ (43%), ER+PgR- (26%), ER-PgR+ (8%), and ER-PgR- (23%). In patients with tumor phenotype ER+PgR+, responses were seen in 20/30 (67%) assessable initial treatments when receptor assays were performed on tumor recurrence or on primary tumor immediately before endocrine therapy, and in only 11/32 (34%) assessable initial treatments when receptor analysis was performed on primary tumor and there was intervening local therapy before endocrine therapy was started for tumor recurrence (P less than 0.05). Responses to first endocrine therapy for each tumor phenotype were ER+PgR+ 50%, ER+PgR- 27%, ER-PgR+ 27%, and ER-PgR- 6%. Four of 16 (25%) patients with ER+PgR+ tumors responded to subsequent secondary endocrine therapy, but such responses were not observed in 20 patients with other tumor phenotypes. Duration of response was similar for each phenotype, but patients with ER-PgR- tumors had a significantly shorter survival from time of initial endocrine treatment than patients of any other phenotype. These results suggest that repeat steroid receptor assays on accessible tumor immediately before endocrine therapy may result in improved predictability.

Aged

Universities and nursing education.

Trends reflected by Department of Health and Social Security statistics on the nursing workforce are examined and the ratios between grades discussed. Recruitment into nursing degree courses in the UK is considered in relation to overall recruitment into nursing. The somewhat ambiguous position of nursing degree courses in the UK leads into consideration of policy statements by the universities and the nursing profession. The importance of such policies is emphasized in the current financial climate, as are the potential contributions of university departments to professional debate, for example standards of care. Comparisons are drawn between the goals of courses involving full-time studentships as opposed to part-time apprenticeships and the present boundaries between these noted, especially in relation to the expanding roles of courses. On-going research into the preparation of nurse-tutors in the UK is mentioned, together with a preliminary analysis of the academic basis in the biological sciences possessed by learners and tutors. Out of this is derived a suggestion that the present-day shortage of nurse teachers could be helped by varying the existing patterns of recruitment, especially involving subject specialists in the biological, behavioural and social sciences.

Education, Nursing

The surgeon's role in primary breast cancer.

During the 1960s, it was suggested that, at least in clinical stage I disease, simple mastectomy or even wide excision, plus radiotherapy to the breast and gland fields resulted in the same distant recurrence rate and survival as the orthodox radical operation. It was thought that local control of the disease was not important in terms of ultimate prognosis and it was felt that minimal surgery incurred no penalty. It was forecast that breast cancer would soon be treated by radiotherapy alone, possibly even without removal of the tumour. Four developments have materially affected the situation. 1. It has been shown that assays of hormone receptors should be carried out on all primary tumours. 2. In clinical stage II disease, it has been demonstrated that restricted surgery results in a penalty in terms of distant recurrence and survival. 3. It is now realised that the number of involved axillary lymph nodes must be known to evaluate future prognosis. 4. Adjuvant chemo or endocrine therapy have proved to be effective in treating patients with heavy axillary node involvement. These developments mean that the effective treatment of early breast cancer must entail removal of the tumour, achieve local control of disease and include axillary node dissection. Currently, only the modified radical mastectomy effectively equates with these three aims. Nevertheless, it is possible that tumour excision, irradiation to the tumour bed and breast, and axillary node dissection would achieve the same object whilst conserving the breast.

Axilla