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J Salter

Publications and source records attributed to J Salter.

35 records · Page 2Linked to original sources
PubMed1996

Comparison of MIB-1 proliferation index with S-phase fraction in human breast carcinomas.

The MIB-1 antibody has been raised against recombinant parts of the Ki-67 antigen and, unlike Ki-67, has wider application to routinely fixed specimens. The aim of this study was to compare the usefulness of MIB-1 with S-phase fraction (SPF) as a measure of proliferation. A total of 75 patients with operable breast cancer were studied, 44 (median age 56 years) before any treatment and 31 (median age 68 years) after primary medical hormonal therapy. Sections from formalin-fixed paraffin-embedded tissue were stained with the MIB-1 antibody and a percentage score of positively stained cells obtained. SPF was measured by flow cytometry in fine-needle aspiration samples taken from the same lesion in each patient. Median MIB-1 score was 9% and median SPF was 11.1%. A close correlation was found between MIB-1 score and SPF (rho=0.59, P<0.0001). There was a difference in the strength of the correlation found between the no treatment group and the treatment group, however, 95% confidence intervals for the rho values overlapped, indicating that there was no significant statistical difference. When analysed for ploidy status a correlation was found only in aneuploid tumours. MIB-1 immunostaining can be used as an effective method of assessing proliferation in human breast carcinomas. This can be done using simple, widely available technology and provides the opportunity to perform large-scale retrospective analyses of archival materials.

Aged↗
PubMed1996

Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer.

The purpose of this study was to determine the effect of the first rat monoclonal antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I clinical trial in patients with unresectable squamous cell carcinomas. This antibody effectively blocks the binding of EGF, transforming growth factor (TGF)-alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice. Eleven patients with squamous cell carcinoma of the head and neck and nine patients with squamous cell carcinoma of the lung, whose tumours expressed EGFR, were recruited. Groups of three patients were treated with 2.5 mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg. All patients were evaluated for toxicity using WHO criteria. Patients' sera were tested for the clearance of MAb ICR62 and the development of human anti-rat antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and two at 100 mg doses) and of these only the former two were anti-idiotypic responses. In four patients receiving doses of ICR62 at 40 mg or greater, biopsies were obtained from metastatic lesions 24 h later and examined for the localisation of ICR62 using anti-rat antibody reagent. In these patients we showed the localisation of MAb ICR62 to the membranes of tumour cells; this appeared to be more prominent at the higher dose of 100 mg. On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses.

Adult↗
PubMed1995

Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer.

Changes in estrogen receptor (ER) expression and function may explain the development of tamoxifen resistance in breast cancer. ER expression was measured by an immunohistochemical assay, validated for use in tamoxifen-treated tumors against a biochemical enzyme immunoassay, in 72 paired biopsies taken before treatment and at progression or relapse on tamoxifen. Progesterone receptor (PgR) and pS2 gene expression were also measured immunohistochemically as an indicator of ER function. Overall the frequency of ER expression was reduced from 37 of 72 (51%) pretamoxifen to 21 of 72 (29%) at progression or relapse, with a significant reduction in the quantitative level of ER (P < 0.0001; Wilcoxon signed rank sum test). Tumors treated with primary tamoxifen that responded but then developed acquired resistance frequently remained ER positive (ER+) at relapse: 16 of 18 (89%) were ER+ pretamoxifen (75% of these expressed either PgR or pS2) and 11 of 18 (61%) were ER+ at relapse (82% continued to express PgR or pS2). In contrast, only 3 of 20 (15%) tumors that progressed on primary tamoxifen with de novo resistance were ER+ pretamoxifen, and all tumors were ER- at progression. At progression, 6 of 20 (30%) of these tumors expressed high levels of PgR (mean H-score, 98) and/or pS2 (mean, 50% cells positive), despite being ER-. In tumors that recurred during adjuvant tamoxifen therapy, including locoregional and metastatic lesions, ER expression was significantly reduced from 18 of 34 (53%) in the original primary tumor to 10 of 34 (29%) at relapse (P = 0.002). PgR expression was likewise significantly reduced in this group (P = 0.001). This study confirms that expression of a functional ER in breast cancer is a strong predictor for primary response to tamoxifen. Although ER was reduced in tamoxifen-resistant tumors overall, the development of acquired resistance was associated with maintained ER expression and function in many tumors, whereas de novo resistance remained related to lack of ER expression. Recurrence during adjuvant tamoxifen was associated with development of an ER/PgR-negative phenotype in some tumors. These data imply that separate mechanisms of resistance may occur in these different clinical subgroups.

Aged↗
PubMed1995

The phenotypic changes in tumour infiltrating lymphocytes and tumour cells following intra-arterial infusion of interleukin-2 in patients with squamous cell carcinoma.

This study evaluates the morphological and phenotypic changes that occur in squamous cell carcinoma of the head and neck when local infusions of interleukin-2 (IL-2) are given. Twelve patients were treated with a range of doses of IL-2 (3 x 10(3) to 3 x 10(6) international units/day) by continuous intra-arterial infusion for 10 days. Biopsies of the tumour were taken pre- and 48 h post-therapy, snap-frozen, cut, and examined histologically and immunocytochemically. Local infusions of IL-2 increase the numbers of antigen-presenting Langerhans cells (CD1a-positive) and infiltrating lymphocytes, predominantly of the CD3 and CD4 (T-helper) phenotypes. Locally infused IL-2 results in the expression of MHC (major histocompatibility complex) class II antigens on the surface of the tumour cells, capillary and post-capillary endothelial cells, and peri-tumoural macrophages. Intratumoural NK (natural killer) cells and CD8-positive (T-cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25 (IL-2 receptor) was only increased in those patients treated at the lower dose levels. The system of intra-arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cytokines, since in vivo they are mainly produced and act locally. Furthermore, the infused tumours are easily accessible to biopsy. The results from studies such as this may influence the design of tumour-targeted cytokine gene therapy programmes.

Adult↗
PubMed1995

Effects of the pure anti-oestrogen ICI 182780 on oestrogen receptors, progesterone receptors and Ki67 antigen in human endometrium in vivo.

The new steroidal pure anti-oestrogen ICI 182780 was studied for the first time in pre-menopausal women. A total of 30 patients requiring hysterectomy for benign gynaecological disease were randomized to ICI 182780, 12 mg/day i.m. (n = 19) or no treatment (n = 11) for 7 days prior to surgery. Immunohistochemical measurements were made in the snap-frozen, resected endometrium for oestrogen receptors (ER), progesterone receptors (PgR) and Ki67, a nuclear antigen whose expression is closely related to proliferation. Five control patients ovulated prior to surgery and, as expected, the secretory endometria had lower Ki67 antigen concentrations than endometria had lower proliferative phase. The endometria from patients treated with ICI 182780 had reduced Ki67 compared with controls. This demonstration of reduced proliferative activity indicates that the pharmacological effectiveness of the treatment was maintained despite increased plasma oestradiol concentrations. In contrast to results from rodents, ICI 182780 did not markedly reduce ER expression, although there was significantly lower ER in the myometrial cells of the treated group. The lack of effect on PgR shows a dissociation between the drug's effect on this oestrogen-dependent protein and its effects on proliferation.

Adult↗
PubMed1995

The histological and immunohistochemical changes in the skin of patients with melanoma who develop changes in skin pigmentation following immunotherapy.

The histological and immunocytochemical appearances of skin with altered pigmentation from two patients receiving chemoimmunotherapy for melanoma were examined. In both patients, there was a clinical response to treatment coincident with depigmentation of skin and hair. Skin biopsies showed extensive infiltration with CD8+ and CD4+ lymphocytes rather than CD57+ in the depigmented areas suggestive of a specific MHC-related cytotoxic T-cell activity against melanocytes. In keeping with this, MHCII expression was markedly up-regulated. These observations suggest the development of a simultaneous anti-tumour and anti-melanocyte immune response stimulated by chemoimmunotherapy, possibly against the same or similar antigens.

Adult↗
PubMed1994

Modulation of Bcl-2 and Ki-67 expression in oestrogen receptor-positive human breast cancer by tamoxifen.

The expression of the bcl-2 proto-oncogene, which is associated with prolonged cell survival and prevention of programmed cell death, was investigated in human primary breast carcinomas prior to and following endocrine therapy with the anti-oestrogen, tamoxifen. Using the BCL-2-100 antibody, a 26-kD protein was detected by western immunoblot in the cytosols of oestrogen receptor (ER)+ve human breast cancers. In a cross-sectional study, the immunohistochemical expression of Bcl-2 was observed in 32% of invasive breast cancers, but in 65% of tumours treated with tamoxifen (P = 0.009). There was a significant association of Bcl-2 with ER status, with 64% of untreated and 88% of tamoxifen-treated Bcl-2-positive tumours being ER+ve. A significantly lower Ki-67 score was found in tamoxifen-treated tumours which were Bcl-2-positive compared with Bcl-2-negative (9.3 versus 24.6%, P = 0.01). In a separate series of sequential Trucut biopsies from 18 patients, the frequency of Bcl-2 expression was increased in ER+ve tumours from 3/12 to 8/11 following tamoxifen (P = 0.04). This was also associated with a significant reduction in mean Ki-67 score from 32 to 12% (P = 0.0004). The observations from this study clearly indicate that Bcl-2 in human breast cancer is associated with ER status, and that expression is enhanced in ER+ve tumours following tamoxifen, in association with reduced cell proliferation.

Aged↗
PubMed1994

Comparison of new immunohistochemical assay for oestrogen receptor in paraffin wax embedded breast carcinoma tissue with quantitative enzyme immunoassay.

AIM: To validate the use of a new mouse monoclonal antibody (1D5) directed against the N-terminal domain (A/B region) of the oestrogen receptor in an immunohistochemical assay (ER-IHA) for paraffin wax embedded tissue. METHODS: Breast cancer specimens were surgically obtained from 119 previously untreated patients. For comparison, oestrogen receptor was measured from cytosol fractions using an established oestrogen receptor enzyme immunoassay (ER-EIA) method. Oestrogen receptor "H-scores" were obtained from the ER-IHA after antigen retrieval using microwave treatment. Where discrepancies occurred between the two methods, further immunohistochemistry was performed using the H222 antibody from the Abbott Laboratories ER-ICA kit. RESULTS: The correlation between the two methods was non- linear, but despite this there was an 86% concordance between ER-EIA and ER-IHA using the 1D5 ER antibody. Fifty four per cent of tumours (64/119) were oestrogen receptor positive and 32% (38/119) were negative by both assays. A mismatch between the ER-EIA and ER-IHA occurred in 17 cases. Seven tumours were IHA positive but EIA+, but five of these were borderline negative by EIA, having values of > 5 and < 10 fmol/mg protein. Ten tumours were IHA negative and EIA+; four of these tumours were completely negative by IHA in the section studied. A further IHA assay, carried out on the 17 tumour mismatches with H222 antibody, showed that three tumours remained substantially discordant. These three tumours were strongly positive with the 1D5 antibody and negative with the H222 antibody. Two of these discordant tumours were of the rare ER negative and PgR positive phenotype and may contain oestrogen receptor that is of biological interest but which lacks the hormone binding epitope. CONCLUSIONS: The concordance between the classic enzyme immunoassay technique and the new immunohistochemical method on paraffin wax embedded sections was good. Moreover, the IHA technique using the 1D5 antibody against the N-terminal was easily reproducible. This technique may allow oestrogen receptor content to be determined in large cohorts of patients in whom archival tumour material is available.

Adult↗
PubMed1994

Immunohistochemical and biochemical analysis of the oestrogen regulated protein pS2, and its relation with oestrogen receptor and progesterone receptor in breast cancer.

AIMS: (i) To assess the validity of an immunocytochemical technique for detecting pS2 protein in paraffin wax embedded tissue; (ii) to provide further data on the relation between pS2 protein and oestrogen receptor (ER) and progesterone receptor (PgR). METHODS: Breast cancer excision biopsy specimens were obtained from 35 previously untreated patients. An immunoradiometric assay was compared with an immunohistochemical method for measuring pS2 protein. ER and PgR were measured in cytosol fractions by enzyme immunoassay and the relation between the presence of these receptors and pS2 protein was assessed before and after subdivision of the women into groups of over or under 50 years of age. RESULTS: A good correlation was seen between the immunoradiometric and immunohistochemical methods for pS2 protein measurement (r = 0.84; p = 0.0001). Log-transformed data showed a significant correlation between increasing values of ER and pS2 protein (r = 0.45; p = 0.006) and to a lesser extent between pS2 protein and PgR (r = 0.38; p = 0.03). Correlations were also shown between pS2+ and PgR+ status (p = 0.01), and between ER and PgR positivity (p = 0.05; Fisher's exact test). pS2+ protein status was only associated with ER+ status in patients aged 50 years or less. CONCLUSIONS: The two methods for pS2 analysis are virtually interchangeable. This provides strong support for using immunohistochemistry for pS2 in paraffin wax embedded tissue. The association with ER positivity and pS2+ protein status only in the premenopausal patients may be due to the higher levels of oestrogenic stimuli in that group.

Adult↗
PubMed1991

Isocratic reversed-phase HPLC method to measure pyrimethamine extracted from plasma of infants treated for toxoplasmosis.

An isocratic HPLC method for measuring pyrimethamine extracted from infant plasma is reported. The method is an improvement over previously published methods by requiring lower volumes of plasma (100 microL) and having increased sensitivity to pyrimethamine at 210 nm. The procedure, which entails a basic organic extraction and subsequent HPLC chromatography of the reconstituted extract, can detect 1.4 ng and quantify 4.0 ng of pyrimethamine per 40-microL injection, with two analyses per 100-microL sample. Analytical recovery of pyrimethamine added to plasma at 10, 50, and 125 ng/100 microL averaged 80%, 92%, and 101%, respectively (n = 20). Within- and between-day CVs were less than 7%. Studies of various plasma samples from adults and infants (n = 15) revealed no interference from other plasma peaks with the analyte of interest.

Chromatography, High Pressure Liquid↗
PubMed1990

Renal insufficiency in sarcoidosis. A clinical and pathologic study.

The relationship of sarcoidosis to renal insufficiency is not widely known by pathologists or clinicians. During an 8-year period beginning in 1980, we observed six patients with sarcoidosis and clinically significant renal insufficiency (serum creatinine, greater than 260 mumol/L). In one of these patients with long-standing sarcoidosis, renal insufficiency was attributed to unrelated primary renal disease until renal biopsy specimen showed interstitial noncaseating granulomas. The four patients with renal insufficiency at presentation differed from the typical patient with sarcoidosis because they were white men who lacked the usual clinical constellation of skin, eye, and pulmonary involvement. All four had noncaseating granulomas on their initial biopsy (bone marrow [3 patients], and lymph node [1 patient]), suggesting each had sarcoidosis, yet each had two or more follow-up biopsies before the diagnosis of sarcoidosis was accepted and appropriate therapy initiated. One of these four patients underwent long-term antifungal and antituberculous therapy. The major causes of renal insufficiency in these six patients were complications of hypercalcemia and interstitial granulomatous nephritis. Except in one patient with nephrocalcinosis, prednisone therapy resulted in a dramatic fall in serum creatinine level with resolution of hypercalcemia. Sarcoidosis is a rare, but treatable, cause of renal insufficiency. Early recognition by clinicians and pathologists may spare patients from undergoing unnecessary biopsies and result in more timely initiation of therapy.

Biopsy↗
PubMedDate not supplied

Rehabilitation nursing approaches to cerebrovascular accident: a comparison of two approaches.

The purpose of this study was to compare patients receiving neurodevelopmental therapy (NDT) to patients receiving a traditional approach. The study took place on two separate medical rehabilitation units, each using just one approach. Patients were assigned to each unit based upon bed availability. The charts of 43 cerebral vascular accident (CVA) patients who received the traditional approach and of 37 CVA patients who received NDT were audited for demographic, functional, and disposition data. No significant differences at admission were found between the two groups, except that the NDT group had higher scores in dressing (p = .04) and toileting (p = .02). At discharge, the NDT group had higher functioning scores on toileting only (p = .03). Length of stay was almost identical between the two groups. Eighty-six percent of the NDT sample were discharged home compared to 78% of the traditional sample, but this was not statistically significant. Thus, the NDT approach does not appear to be superior to the traditional approach. These results imply that there needs to be more careful study of rehabilitation approaches before committing to one specific approach in the nursing care of CVA patients.

Activities of Daily Living↗
PubMedDate not supplied

Critical care elements in a rehabilitation nursing course.

This article describes a specialized rehabilitation education program, based on adult learning theory, that was developed to promote retention of rehabilitation nurses at MetroHealth Center for Rehabilitation in Cleveland. The curriculum encompasses the skills required to care for rehabilitation patients needing both advanced rehabilitation nursing and critical care nursing. Critical care and rehabilitation nurses collaborated in the presentation of topics and were guided by the course coordinators. Learners were chosen based on experience in rehabilitation, with priority given to those certified in rehabilitation nursing. A variety of evaluation methods elicited positive responses. A 6-month postcourse survey also was completed to assess the long-term effects of the course.

Critical Care↗
PubMedDate not supplied

Competency-based nursing in a rehabilitation setting.

The success of achieving a competency-based rehabilitation nursing practice is shared in this article. An education day provided a comprehensive approach to ensure that practicing staff nurses stay abreast of the knowledge and skills necessary to provide quality patient care. This article details the decision-making process, competency development, strategies, and evaluation of the competency program. Formal documentation of competency testing is an asset for follow-up and accreditation review.

Clinical Competence↗
PubMedDate not supplied

Clinical nursing judgment related to reducing the incidence of falls by elderly patients.

The incidence of falls among elderly patients has been and continues to be a major challenge for nurses. Falls add physical injury and mental stress to patients' existing health problems, are a deterrent to rehabilitation, and increase healthcare costs. This study describes the variables that nurses identify as influencing their clinical decision making and the nursing behaviors associated with preventing patient falls. The study was grounded in the theory that discretionary nursing behaviors are related to nursing expertise, and the study was guided by the assumption that such behaviors are proactive and anticipatory. An analysis of interviews of registered nurses (n = 14) working on a geriatric rehabilitation unit in a medical center in Ohio focused on the zones of association and the contextual meanings of language used by the nurses when discussing patient falls. Four themes emerged: the reasons for patient falls, identifying patients who are likely to fall, preventing falls, and nurses' feelings when patients fall.

Accidental Falls↗