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Biomedical subjects

R M Bryan

Publications and source records attributed to R M Bryan.

69 records · Page 4Linked to original sources

Androgen receptors in breast cancer.

Androgen receptor assays have been performed on 1371 specimens of histologically confirmed primary and recurrent breast cancer. Forty-two patients who had received tamoxifen as treatment for advanced disease were assessed for objective response. Another 42 patients who had received chemotherapy were similarly studied. Patients with androgen receptor-negative tumors had a significantly poorer response rate to hormone therapy than those with receptor-positive tumors (P less than 0.05). This clinical correlation is supported by survival data of 1181 patients with primary breast cancer which showed that patients with androgen receptor-negative tumors had a highly significant trend toward shorter overall survival than those with receptor-positive tumors (P less than 0.001). Androgen receptor data added significantly to the information provided by estrogen receptor data both in terms of response to hormone treatment and survival.

Breast Neoplasms↗

Choroid plexus blood flow: evidence for dopaminergic influence.

Choroid plexus blood flow was measured in adult female sheep using the radioactive microsphere technique. The response of choroid plexus, renal and cortical blood flow to the infusion of dopamine (11 sheep), haloperidol (7 sheep) and propranolol (6 sheep) were compared. Choroid plexus and renal blood flow significantly increased after dopamine infusion (55% and 49% respectively). Choroid plexus and renal blood flow decreased significantly following haloperidol infusion (-24% and 29% respectively). Cortical blood flow did not significantly change. Propranolol infusion did not significantly change blood flow in these regions. These observations suggest that dopaminergic mechanisms play a role in the regulation of choroid plexus as well as renal blood flow.

Animals↗

Progesterone receptors in breast cancer.

Sixty-six women who had received hormonal therapy for advanced disease were assessed for objective response to treatment. Another 51 patients who had received chemotherapy were similarly studied. Progesterone receptor was of no value as a predictor of patients unlikely to respond to hormone therapy, though it may have a role in predicting patients likely to respond favourably. The addition of progesterone receptor data to oestrogen receptor data may increase prediction of response in the ER+ range but clinicians should be cautious in their interpretation of progesterone receptor results in the ER- range. Progesterone receptor was of no value in predicting response to chemotherapy in this series. Analysis of survival data of 1731 women with primary breast cancer showed a highly significant trend toward longer survival in patients with progesterone receptor positive tumours than in those with receptor negative tumours (P less than 0.001). This trend was evident in both pre- and post-menopausal women. Even though the prognostic discrimination provided by progesterone receptor was correlated with that of oestrogen receptor, the addition of progesterone receptor data to oestrogen receptor data significantly improved prediction of survival (P less than 0.05).

Adult↗

Hormone receptors in male breast cancer.

Hormone receptor assays were performed on specimens of breast cancer from 19 male patients over a six year period. Ninety-four per cent were positive for oestrogen receptor, 93% for progesterone receptor and 57% for androgen receptor. Eight patients had hormonal treatment for advanced disease and five (62.5%) responded. Duration of response ranged from six months to 23 months. There appeared to be no clear relationship between hormone receptor status or quantitative receptor level and response to treatment in this small series. It is unlikely that oestrogen and progesterone receptors will be of value as discriminators because of their high incidence and it is suggested that further study of androgen receptor is indicated.

Aged↗

Oestradiol receptor values in breast cancer and response of metastases to therapy.

Eighty-one women who had received hormonal therapy for advanced disease were assessed for objective response to treatment. Another 73 patients who had received chemotherapy were similarly studied. Patients with ER - tumours had a significantly poorer response rate to hormonal therapy than those with ER + tumours (P less than 0.05) and a significant trend toward an increasing rate of response occurred with increasing quantitative levels of receptor (P less than 0.01). This trend was even more significant when the assay had been performed on recurrent tumour (P less than 0.001), suggesting that this provides a more accurate index of response to hormonal treatment than assays performed on the primary lesion. These results suggest that whilst the quantitative receptor level used to discriminate between 'negative' or 'positive' assays is appropriate, this division is an over-simplification. Oestrogen receptor was not helpful in predicting response to chemotherapy.

Breast Neoplasms↗

The prognostic value of oestrogen receptors in breast cancer.

Survival data for 2006 women who had oestrogen receptor assay carried out on primary breast cancer tissue between 1976 and 1982 are presented. There was a significant trend to shorter survival in patients with low ER levels than in those with high ER levels (P less than 0.01). This trend was evident in both pre- and post-menopausal women. The point of maximum discrimination between prognostic groups occurred at 8 fm in premenopausal women and the four year survival rates of patients above and below this level were 84% and 48%, respectively. In post-menopausal women, maximum discrimination occurred at 90 fm, and the four year survival rates above and below this level were 82% and 64%, respectively.

Adult↗

Wound healing following mastectomy.

Local complications following mastectomy are of considerable importance if peri-operative chemotherapy is to be used. A retrospective survey of 100 patients following Patey mastectomy was therefore undertaken to investigate problems associated with wound healing in the absence of such therapy. The survey showed that 18% of patients developed postoperative wound infection, this being severe in 50% of cases. Varying degrees of total wound breakdown occurred in 9% of patients while delayed healing occurred in a further 5%. The incidence of seroma was 25%, and the majority of these patients required further drainage. There was a significant association between seroma formation and wound infection (P less than 0.05). The mean length of hospital stay in patients without wound infection was 11.7 days, but was increased to 27.3 days when infection occurred (P less than 0.001).

Female↗

The cerebral redox state in cats during severe insulin induced hypoglycemia.

The cerebral metabolic state was studied in cats during insulin-induced hypoglycemia and the recovery after glucose infusion. Changes in the redox state of nicotinamide adenine dinucleotide (NAD) were monitored from the surface of the exposed cerebral cortex using microfluorometry. After insulin injection blood glucose fell from 6.85 mumol/ml to 0.45 mumol/ml at EEG isoelectricity and was accompanied by an oxidation of NADH+. Upon intravenous glucose infusion EEG activity rapidly returned and NAD became more reduced. The oxidation of NADH+ during severe hypoglycemia demonstrated that the in vivo redox state of mitochondria behave in a similar manner as isolated mitochondria when reducing equivalents become limiting to the respiratory chain.

Animals↗

Regional cerebral glucose utilization in rats with portacaval anastomosis.

Regional cerebral glucose utilization was measured using [2-14C]glucose in rats with an end-to-side portacaval anastomosis. The experiments were conducted in two groups of rats 4 to 8 weeks after portacaval shunting was established. One group was paralyzed and given N2O:O2 (70:30), whereas the other was conscious, unstressed, and unaware of the experiment. In both groups the rate of glucose utilization was decreased in almost all brain structures by an average of 20% after portacaval shunting. The results showed definitively that cerebral energy metabolism was reduced at a time when there were no obvious neurological abnormalities.

Animals↗

Cerebral glucose utilization in awake unstressed rats.

Regional cerebral glucose utilization (rCMRGlc) was measured in awake unstressed rats by use of [2-14C]glucose autoradiography. Rats prepared by chronic catheterization of the jugular and epigastric veins were placed in specially designed chambers after surgery. The catheters were passed through the top of the chambers. Seven days after surgery, plasma glucose was normal (7.5 mM), plasma ketone bodies were low (0.13 mM), and body weight was maintained. Plasma epinephrine was 31 pg/ml; approximately 3% of the level for stressed (immobilized) rats. Injections and blood sampling through the catheters did not produce changes in heart rate, blood pressure, plasma catecholamines, or blood metabolites. Visual observations did not reveal any signs that the rats were aware of the [2-14C]glucose injections and the subsequent blood sampling. The rCMRGlc in stressed rats was significantly greater than in unstressed rats. This method provides a model for physiological studies in unstressed unanesthetized rats.

Animals↗

Cerebral energy metabolism in diving and non-diving birds during hypoxia and apnoeic asphyxia.

1. Cerebral energy metabolism during apnoeic asphyxia and steady-state hypoxia was compared in ducks and chickens; ducks tolerate apnoeic asphyxia 3-8 times longer than chickens. 2. Fluctuations in the reduced form of respiratory chain nicotinamide adenine dinucleotide (NADH) were monitored from the left cerebral hemisphere by a noninvasive fluorometric technique and used as an indicator of mitochondrial hypoxia. NADH fluorescence was expressed in aribtrary units (a.u.) where 100 a.u. was defined as the fluorescence change from normoxia to anoxia. Electroencephalogram (e.e.g.) and surface Po2 were recorded from the right hemisphere. 3. After 1 min of asphyxia NADH fluorescence increased by 37 a.u.+/-3.60 S.E. of mean (n=54) in paralysed chickens and 8 a.u.+/-1.41 (n=55) in aralysed ducks. After 2 min the fluorescence increased by only 15 a.u.+/-1.95 in ducks. 4. Both species showed an isoelectric e.e.g. when fluorescence increased by approximately 35 a.u., indicating that anaerobic ATP production in ducks did not maintain brain function (e.e.g.) for a greater accumulation of respiratory chain NADH. 5. At a given decrease in tissue Po2 ducks and chickens showed the same level of NADH increase, indicating that both species are equally dependent on tissue Po2 for the maintenance of redox state. 6. We conclude that biochemical adjustment which enhance anaerobic ATP production and/or prolong oxidative phosphorylation during progressive hypoxia are not responsible for increased cerebral tolerance to apnoeic asphyxia in the duck.

Anaerobiosis↗

Cerebral energy metabolism in mallard ducks during apneic asphyxia: the role of oxygen conservation.

Cerebral energy metabolism during apneic asphyxia was studied in ducks. Fluctuations in the reduced form of respiratory chain nicotinamide adenine dinucleotide (NADH) were monitored from the left cerebral hemisphere and used as an indicator of mitochondrial hypoxia. Electroencephalogram (EEG) and surface PO2 were recorded from the right hemisphere. Forced dives of 4- to 7-min duration on restrained ducks were characterized by bradycardia and an accumulation of NADH, which increased throughout the diving period. NADH returned to the preasphyxic level when breathing was resumed. In later experiments, asphyxia was produced by stopping artificial ventilation in paralyzed ducks. Asphyxia produced by this means caused similar changes in the measured variables (heart rate, blood pressure, and NADH fluorescence) to those obtained in forced submergence of nonparalyzed ducks. The inhibition of cardiovascular adjustments by atropine caused NADH to increase faster and tissue PO2 to decrease faster during apneic asphyxia than in nonatropinized ducks. We conclude that the oxygen-conserving cardiovascular adjustments play a key role in the increased cerebral tolerance to apneic asphyxia in ducks.

Animals↗

Occupational exposure to ethylene oxide: effects and control.

Ethylene oxide (EO) is widely used in the health care industry as a gas sterilant for medical products that cannot withstand the high temperature and humidity associated with conventional steam sterilization. As a consequence, approximately 100,000 health care workers are exposed to residual EO each year. The acute toxicity of exposure to EO has been well documented, and recent concern about the mutagenic potential of occupational exposure to EO has resulted in an effort to further reduce workplace exposure levels to EO. The Environmental Protection Agency has issued a rebuttal presumption against registration of EO as a pesticide and the American Conference of Governmental Industrial Hygienists (ACGIH) has proposed a sharp reduction in the threshold limit value permitted for EO. Recognizing the need for environmental health personnel to become more familiar with this workplace hazard, it is appropriate to briefly review the toxic effects of acute and chronic exposure to EO residuals. The authors describe a gas sterilization system successfully utilized at the U.S. Public Health Service Hospital in New Orleans, La., which has demonstrated exposure concentrations well below the EO threshold limit value recently proposed by the ACGIH, while preserving the principal goal of assuring the sterility of reusable medical products which cannot be subjected to steam sterilization.

Central Supply, Hospital↗