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Biomedical subjects

D M Barnes

Publications and source records attributed to D M Barnes.

At least 253 records · Page 14Linked to original sources
PubMed1985

The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast.

Recurrence and survival rates were studied in 175 women with breast cancer who, until the development of recurrent disease, received no treatment other than a modified radical (Patey) mastectomy, and in whom the oestrogen (REc) and progesterone (RPc) receptor content of the primary tumour was measured. At the time of first relapse most patients received endocrine therapy. At a minimum follow-up of 58 months post menopausal patients who possessed REc had an increased relapse-free survival (RFS) (P = 0.02). When examined by node status patients with 1-3 axillary nodes containing tumour also had an improvement in RFS (P = 0.02). There was no benefit for node-negative or premenopausal patients. In 163 patients in whom RPc was measured, RFS was unaffected by the possession of this receptor regardless of the degree of node involvement or menopausal status. Patients with REc had a significantly longer survival following mastectomy than patients without it (P = 0.006). This was most marked in post-menopausal (P = 0.003) and node-positive (P = 0.03) patients. Survival following mastectomy was also increased in patients possessing RPc (P = 0.04) and again was most marked for post-menopausal patients (P = 0.01), although no difference could be identified within node subgroups. There were significant differences in the post-relapse survival of REc and RPc positive and negative patients (REc P = 0.03, RPc P = 0.001). Patients with both receptors survived approximately 37 months longer than their receptor-negative counterparts. This study failed to confirm that the measurement of REc and RPc can reliably predict early relapse in breast cancer. The greater overall survival of receptor-positive patients is mainly due to an increase in survival following relapse. This may reflect the response of receptor-positive tumours to endocrine therapy given for recurrent disease.

Breast Neoplasms↗
PubMed1984

Steroid-hormone receptors and survival after first relapse in breast cancer.

Oestrogen receptors were measured in the primary breast tumours of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Response to tamoxifen or ovarian ablation was known in 65 of the 137 patients who relapsed. Survival from first relapse was significantly longer in patients who both responded to hormone therapy and had receptor-positive tumours. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.

Breast Neoplasms↗
PubMed1984

Steroid receptors in human meningioma.

It is well recognised that there is an increased frequency of meningioma in women compared with men and that rapid progression of the disease may occur during pregnancy. Recent studies have demonstrated steroid receptors in human meningioma. In this study we have looked for the presence of nuclear and cytoplasmic estrogen receptor (ER) and cytoplasmic progesterone receptor (PR) in 22 cases of meningioma. Radioreceptor assays using a six-point dextran-coated charcoal procedure failed to demonstrate specific ER, but 17 of 22 meningiomas did have specific PR (range 11-314 fmol/mg cytosol protein). Flat-bed isoelectric focusing in agarose gel was used to confirm the results in a few of these cases. We were not able to correlate the presence of receptor with age or sex of patient, or the site of tumour with receptor content. Of the five PR-negative tumors, one was a poor specimen when the histology was examined and two belonged to the angioblastic group (haemangiopericytic variety), a particularly aggressive tumour with a tendency to be more necrotic. The presence of PR in many of these tumours suggests a possible role for hormone therapy where total resection is not possible.

Adolescent↗
PubMed1984

Effects of ethosuximide and tetramethylsuccinimide on cultured cortical neurons.

In cultured cortical neurons, ethosuximide (ESM) had unexpected actions for an antiepileptic drug; it slightly diminished the effects of inhibitory neurotransmitters, GABA, and glycine. ESM had no direct membrane effects, did not change action potential characteristics or alter spontaneous activity, and did not reverse the effects of convulsants that are GABA antagonists. The structurally related convulsant tetramethylsuccinimide (TMSM) reduced the amplitude of GABA-mediated inhibitory postsynaptic potentials and antagonized responses to applied GABA, effects not reversed by ESM. The convulsant effects of TMSM include a blockade of postsynaptic GABA actions, but the antiepileptic effects of ESM are not due to an enhancement of GABA-mediated inhibition.

Animals↗
PubMed1983

Progesterone receptor measurement by isoelectric focusing: a potential microassay.

Sixty-two selected breast cancers were used to compare the conventional dextran-coated charcoal (DCC) assay with a new method of separating progesterone receptor by isoelectric focusing in flat beds of agarose gel. Ninety assays were performed. Isoelectric focusing indicated correctly the presence of receptor in 92% and the absence of receptor in 86% of assays, when compared with the DCC assay. The relationship between the results of the two methods was linear. Isoelectric focusing underestimated receptor to a variable extent, finding relatively less receptor at higher absolute levels of binding than at lower levels. The lower limit of sensitivity of isoelectric focusing was 30 fmol/ml cytosol. The protein concentrations of cytosols prepared from 46 needle biopsy samples (mean weight 25 mg) ranged from 0.5 to 30 g/l (median 4 g/l, 10th percentile 0.75 g/l). Isoelectric focusing is a satisfactory method of progesterone receptor measurement and can be applied to samples too small for conventional techniques.

Biopsy, Needle↗
PubMed1983

The association of cytosol oestrogen and progesterone receptors with histological features of breast cancer and early recurrence of disease.

Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of oestrogen (REc) and progesterone (RPc) receptors. Analysis has shown a relative interdependence between the steroid receptor status of primary breast cancer and other prognostic variables such as histological grade, lymphocytic infiltration and tumour elastosis. There were significant associations between epithelial cellularity, stromal fibrosis and the value of REc in those tumours in which the receptor was present. Cellularity and fibrosis were unrelated to the presence or absence of oestrogen receptor. By contrast, neither the presence or absence nor the value of RPc could be related to cellularity or fibrosis. The value of REc and RPc analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy. Overall relapse-free survival (RFS) was no different for those patients with receptors compared to those without them (REc P = 0.11, RPc P = 0.7). There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account.

Age Factors↗
PubMed1983

Variation of receptor status in cancer of the breast.

One hundred and nineteen patients with breast cancer had 2 or more lesions removed for oestrogen (REc) or progesterone receptor (RPc) assay, either synchronously (on 38 occasions) or after an interval (on 91 occasions). In all but 7 both receptors were assayed for each lesion. The assays did not agree on the presence or absence of REc alone, RPc alone or the combination of both receptors in 11, 13 and 16% respectively of the synchronous samples, compared with 23, 30 and 43% of the asynchronous samples. The differences between the synchronous and asynchronous samples were significant for the combined receptors (P = 0.007) but not for REc (P = 0.176) or RPc alone (P = 0.077). Variation between asynchronous biopsies was greater when the earlier lesion contained RPc (18/37 disagreed) than when it did not (8/50) disagreed, P = 0.0023). This was not true for oestrogen receptor. In those remaining receptor positive there was only a weak correlation between the first and second values (Spearman rank correlation coefficient, rho = 0.39 for REc, P less than 0.02, and 0.45 for RPc, 0.05 less than P less than 0.1). Receptor levels and receptor status may change with time. Biopsy is most appropriate at the time when systemic treatment is proposed.

Biopsy↗
PubMed1983

Etazolate (SQ20009): electrophysiology and effects on [3H]flunitrazepam binding in cultured cortical neurons.

The actions of etazolate (SQ20009) on cultured cortical neurons have been examined in electrophysiological experiments and in receptor binding studies. Etazolate (0.3 to 100 microM) prolongs the duration of spontaneously occurring IPSPs. Higher concentrations of etazolate produce an increase in membrane chloride conductance, an effect which is picrotoxinin and bicuculline sensitive. Etazolate potentiates the response to exogenously applied GABA and acts synergistically with diazepam to enhance GABA-mediated conductance. Etazolate does not increase glycine-mediated conductance changes. Etazolate increases [3H]flunitrazepam binding and stimulates the GABA enhancement of [3H]flunitrazepam binding. In addition, GABA stimulates the etazolate enhancement of [3H]flunitrazepam binding. The etazolate-mediated increases in binding are Cl- dependent and picrotoxinin and bicuculline sensitive. The dose response relationships for etazolate-mediated effects are similar in physiological experiments and in binding studies. These data suggest that etazolate interacts with the postsynaptic GABA receptor complex at a site distinct from either the GABA recognition site or the benzodiazepine binding site to enhance GABA-mediated inhibition and to increase benzodiazepine binding.

Animals↗
PubMed1982

Isoelectric focusing of oestradiol receptor protein from human mammary carcinoma--a comparison with dextran coated charcoal assay.

Two simple methods for the detection of specific oestradiol--17 beta protein in breast tumour tissue were investigated. Isoelectric focusing of receptor protein in polyacrylamide gel was examined as an alternative micromethod to dextran-coated charcoal receptor assay. In a series of 32 cytosols prepared from unselected breast tumour tissue, assay results agreed on the presence or absence of receptors in 97% of cases. Quantitative analysis of the positive results showed a correlation coefficient, r = 0.88. Isoelectric focusing gave significantly lower receptor concentrations than the dextran-coated charcoal method. Twenty-six Tru-Cut biopsy tumour specimens were analyzed for receptor by isoelectric focusing and the results were compared with those obtained by the dextran-coated charcoal method on the same tumour. In 88% of the specimens examined, both methods agreed as to the presence or absence of receptor protein. A correlation coefficient, r = 0.62, was calculated from the 15 positive results. There was no significant difference between the results from the two methods. Quantitative results were related to total protein concentration in the cytosol. Negative receptor status was defined as less than 5 fmol/mg cytosol protein for both methods.

Breast Neoplasms↗
PubMed1981

The evolution of white matter disease as seen on computed tomography.

The evolving computed tomographic (CT) findings in three patients with different types of dysmyelinating white matter diseases (Krabbe, Canavan, ketotic hyperglycinemia) are presented. Serial CT scans suggested that the abnormal, low density white matter, which is characteristic of many white matter diseases, is present for only a limited time, corresponding to active dys- or demyelination. The low density abnormality gives way to a nonspecific final common pathway manifested as severe atrophy on CT. Ventricular enlargement is accentuated in this form of atrophy which appears to be the final stage in a wide variety, if not all, of white matter diseases.

Atrophy↗
PubMed1981

Feline mammary hypertrophy/fibroadenoma complex: clinical and hormonal aspects.

Abnormal mammary enlargement, characterized microscopically by hyperplasia of both epithelial and mesenchymal tissues, was studied in 26 cats which were mostly young, sexually intact females. Clinicopathologic data indicated that mammary hypertrophy was likely progesterone-dependent. Administration of progestins preceded this condition in 5 cats, 4 of which were neutered. Serum progesterone concentrations (6.7 ng/ml) were increased in 1 of the 3 cats tested. Estrogen receptors were not found in the cytosols or nuclei of mammary tissues in the 2 cats studied. However, there were convincing 4S [3H]progesterone or 5S [3H]R5020 binding peaks which were suppressible by nonlabeled progestins. Progesterone receptors were measured at 14.9 and 8.6 fm/mg of protein, respectively. The apparent influence of progesterone, whether present as exogenous therapy in the male or female or as endogenous steroid of ovarian origin, has thus been demonstrated directly and indirectly in cats with mammary hypertrophy.

Adenofibroma↗
PubMed1980

The clinical value of multiple steroid receptor assays in breast cancer management.

Measurement of cytoplasmic estrogen (REc) and progesterone (RPc) receptors in human breast tumors together with estrogen receptor activity in the residual pellet ("nuclear" REN) provides a more accurate prediction of hormonal dependence that REc alone. Of 74 patients with advanced metastatic breast cancer, 57% of those with REc+ tumors had an objective response to endocrine manipulation. Of 51 patients whose tumor was assayed for both REc and RPc activity, 9 of 12 patients with REc+ RPc+ tumors showed remission, whereas only 3 of 30 patients with REc- RPc-, 2 of 6 with REc+ RPc-, and 2 of 3 with REc- RPc+ tumors had a clinical response. In a group of 19 patients where triple assay was performed, 5 of 6 with tumors positive for all three receptors responded, whereas 9 patients with triple negative tumors all showed no remission. Fifty-nine percent of primary and 60% of metastatic tumors with REc+ activity were also shown to be RPc+. Thirteen percent of REc- tumors were RPc+. Patients with REc+ RPc+ primary tumors tended to have a longer disease-free interval than patients with RPc- tumors, irrespective of whether the tumors were REc+ or REc-. In the light of the possibility of employing receptor status of the primary tumor to predict hormonal responsiveness in subsequent recurrences, a comparison is made of receptor status measured in primary tumors and metastases.

Adult↗
PubMed1980

Clostridial myonecrosis in a black bear associated with drug administration.

Clostridial myonecrosis is described for the first time in a black bear (Ursus americanus). This fatal condition appeared within three days following immobilization with parenterally administered promazine hydrochloride and phencyclidine hydrochloride. Clostridial myonecrosis may be responsible for other unexplained deaths of animals following recovery from immobilizing drugs. Administration of prophylactic antibiotics to immobilized animals might be considered.

Animals↗
PubMed1979

Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer?

In a group of 74 patients with advanced metastatic breast cancer, 57% of those with cytoplasmic oestrogen receptor activity in their tumours (REC+) showed a clinical response to endocrine therapy. Of 51 patients whose tumour was assayed for both REC and cytoplasmic progesterone (RPC) activity, 9/12 patients with REC+ RPC+ tumours responded to hormone treatment, whereas only 3/30 patients with REC-RPC-tumours had a clinical response. In a group of 19 patients in whom nuclear oestrogen receptor (REN) was also estimated in the pellets from tumour-tissue homogenates, 5/6 with tumours positive for all 3 receptors showed a clinical response. None of the 9 patients with triply negative tumours responded. Addition of the REN assay appears to reinforce the greater precision of prediction when RPC as well as REC are estimated in breast tumours.

Breast Neoplasms↗