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Biomedical subjects

I Mitchell

Publications and source records attributed to I Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1987

The effects of interferons on the activity of alpha-glycerolphosphate dehydrogenase in benign prostatic hyperplasia cells in primary culture.

Human benign prostatic hyperplasia (BPH) tissues were obtained from patients undergoing transurethral resection of the prostate and viable cells from these were successfully maintained in primary cultures grown on collagen gel. The prostatic origin of the cells was confirmed by the measurement of prostate specific acid phosphatase and by scanning and transmission electron microscopy before and after immunostaining with human prostate specific antigen-antibody. The cell cultures were treated with various interferons (IFNs), both in the presence and absence of testosterone propionate (TP), for 72 hours and the activities of seven enzymes of carbohydrate metabolism were estimated in the cytosolic fraction of the cells. Treatment with TP induced a significant decrease in the activity of alpha-glycerolphosphate dehydrogenase (alpha-GPDH). Using this enzyme activity as a marker, the effects of various types of IFNs were investigated. IFN-alpha (wellferon) increased the activity of the enzyme both in the presence of one microgram./ml. of TP and in its absence whereas IFN-gamma inhibited the activity under similar conditions. The effect of treatment with IFN-beta in the presence of TP was biphasic in that there was an increase in the activity of the enzyme at the lowest concentration while at higher concentrations an inhibition of enzymic activity was observed. In the absence of TP IFN-beta inhibited the activity. The significance of these findings in terms of the clinical usefulness of IFNs is discussed and it is postulated that IFN-alpha (wellferon) might be effective in the treatment of metastatic carcinoma of the prostate in selected patients.

Cells, Cultured↗
PubMed1986

The activity of phosphohexose isomerase in primary breast carcinomas and response to chemotherapy in patients with metastatic disease.

The activity of phosphohexose isomerase [PHI] was measured in 48 primary carcinomas from patients with breast cancer, and its usefulness as a predictor of response to cytotoxic drugs at the metastatic stage was evaluated. There was a statistically significant difference in the activity of PHI between responders and non-responders to these treatments. These preliminary findings are currently being evaluated in an extended series.

Antineoplastic Agents↗
PubMed1985

The effects of the administration of tamoxifen, ethynyloestradiol, and prednisolone on the activities of certain enzymes of carbohydrate metabolism in primary human breast carcinomas in vivo.

Postmenopausal patients with primary breast cancer were treated with tamoxifen, ethynyloestradiol or prednisolone for up to 12 days before mastectomy and the effects of pretreatments with these drugs on the activities of phosphofructokinase (PFK), 6-phosphogluconate dehydrogenase (6PGDH) and alpha-glycerolphosphate dehydrogenase (alpha-GPDH) in the carcinomas were compared with age, stage and menopausal status matched untreated controls. The administration of tamoxifen or prednisolone resulted in a significant increase in the activity of alpha-GPDH and the alpha-GPDH/6PGDH ratio, whereas ethynyl-oestradiol treatment produced a significant decrease in the activity of the enzyme and the ratio. When tamoxifen and ethynyl-oestradiol were administered together, it was found that tamoxifen failed to reverse the oestrogen-induced reduction in the activity of alpha-GPDH. Since increased activity of the enzyme or a higher alpha-GPDH/6PGDH ratio are associated with a lower risk of recurrence (Deshpande et al., 1981), it is postulated that the beneficial effects of tamoxifen or prednisolone in terms of prolongation of the relapse free interval might be mediated via alterations in the activity of alpha-GPDH in micrometastases. The activities of PFK and 6PGDH remained unaffected by these treatments.

Aged↗
PubMed1985

Adverse effects of racemic epinephrine in epiglottitis.

Acute epiglottitis, a potentially fatal disease, may be difficult to diagnose if the presentation is atypical. We present three such patients who were initially diagnosed as acute laryngotracheitis. They deteriorated rapidly after administration of racemic epinephrine via nebulizer. We caution that: diagnosis of acute epiglottitis should be considered in similar patients; and appropriate precautions must be taken prior to visualization of the airway.

Acute Disease↗
PubMed1985

Sodium cromoglycate-induced changes in the dose-response curve of inhaled methacholine in cystic fibrosis.

Fifteen patients with cystic fibrosis (CF) (aged 7 to 20 years, mean 12.3 years), all known to respond to a methacholine (MCh) challenge, had two MCh challenges preceded by an inhalation of normal saline on one occasion and sodium cromoglycate (SCG) on another. The variation in baseline FEV1 between the two days of the study was 10% or less in all patients. Four patients (27%) gained significant protection with SCG against this non-allergenic challenge and, in two patients, SCG completely blocked the effects of MCh. These results would support clinical studies of SCG in some patients with CF but not the widespread use of SCG in CF.

Adolescent↗
PubMed1985

Deoxyribonucleic acid (DNA) content of primary carcinoma and response to endocrine or cytotoxic drug therapies in patients with advanced breast cancer.

The DNA content of primary carcinomas was estimated colorimetrically in 111 patients with carcinoma of the breast who subsequently developed metastatic disease. The data were analysed to investigate whether these measurements will assist clinicians in predicting: survival from mastectomy or recurrence, the likelihood of response to the first endocrine or the first cytotoxic drug therapy, duration of response amongst responders to these treatments, and time to treatment failure (TTTF). The DNA content of primary carcinomas failed to predict the clinical course of the disease for patients who underwent endocrine treatments. In patients who were treated by cytotoxic drug therapies, only the duration of response amongst responders to these therapies was significantly shorter in cases where the DNA content was high. The DNA content of carcinomas failed to give any useful information on other parameters. It is concluded that these measurements are unlikely to be of prognostic value in these cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Drug effects on certain enzymes of carbohydrate metabolism in MCF-7 cells in culture.

The effects of treatments with ethinyl-estradiol, tamoxifen, prednisolone, cyclophosphamide, methotrexate, 5-fluorouracil and Adriamycin on the activities of PFK, 6PGDH, alpha-GPDH and alpha-GPDH/6PGDH ratios were investigated in MCF-7 cells in monolayer cultures. The following findings are recorded. Both ethinyl-estradiol and prednisolone failed to induce alterations in the activities of these enzymes. Tamoxifen increased the activities of PFK, alpha-GPDH and alpha-GPDH/6PGDH ratios whereas ethinyl-estradiol inhibited the tamoxifen-induced rise in the activity of PFK. Treatment with cyclophosphamide alone was without any effect but in combination with either methotrexate or 5-fluorouracil induced increases in the activities of 6PGDH and alpha-GPDH. Adriamycin at a lower dose increased the activities of 6PGDH and alpha-GPDH and the alpha-GPDH/6PGDH ratio and decreased the activity of PFK. At a higher dose level it reduced the activities of all the enzymes whilst increasing the alpha-GPDH/6PGDH ratio. These data encourage us to undertake a project to test the sensitivity of individual tumours to these drugs in vitro thereby enabling the selection of appropriate drugs for adjuvant therapy.

Antineoplastic Agents↗
PubMed1983

Deoxyribonucleic acid (DNA) content of carcinomas and prognosis in human breast cancer.

DNA content was estimated in 705 breast carcinomas from patients with stage I or stage II disease undergoing mastectomy, to investigate whether it would predict the clinical course of the disease. The patients were then followed for up to 84 months during which time 166 of them developed recurrences. There were no statistically significant differences in the DNA content of carcinomas between stage I and stage II patients or between those with various numbers of involved nodes. The tumours from pre-menopausal patients as a group had significantly higher DNA content than those from post-menopausal cases. There was a gradual rise in DNA content with the malignancy grade of the carcinoma which showed significant differences between Grades I and III and between II and III. Life-table analyses showed that the measurement of DNA would not be an aid to prognosis. Furthermore, when the data were stratified according to menopausal status, stage, malignancy grade or numbers of lymph nodes involved, the results indicated that these estimation do not add significantly to the information obtained through established prognostic factors. Survival data were available on III patients with recurrent disease. There were no significant differences in tumour DNA content between short- and long-term survivors. It is concluded that these measurements seem unlikely to be a prognostic factor in human breast cancer.

Adult↗
PubMed1983

Frequency and severity of apnoea in lower respiratory tract infection in infancy.

Twenty four hour recordings of heart rate and respiration were made on 60 infants with lower respiratory tract infection (LRTI) during the acute phase of the illness, on 20 infants with upper respiratory tract infection (URTI) and on 21 control infants. Infants with LRTI and URTI had more apnoeic episodes of longer than 10 seconds compared with controls. The length of apnoeic episodes was greatest in the LRTI group but their frequency decreased with age. In both the LRTI and URTI groups apnoea was associated with bradycardia but the LRTI group also suffered an appreciable number of episodes of bradycardia without apnoea.

Age Factors↗
PubMed1983

Corticotropin and morphine interaction in the regulation of phosphofructokinase activity in rat mammary gland.

The roles of corticotropin and morphine in the regulation of phosphofructokinase (PFK) activity in rat mammary glands were investigated by the administration of corticotropin, morphine and dexamethasone. Corticotropin increased the activity of PFK in the mammary glands of intact and hypophysectomised animals but was without any effect in tissues from ovariectomised and adrenalectomised animals. Morphine administration resulted in a significant decrease in the enzyme's activity in intact animals only. A combined dose of corticotropin and morphine significantly reduced the corticotropin-induced increase in the activity in both intact and hypophysectomised animals. Dexamethasone treatment resulted in a significant increase in the activity in hypophysectomised and ovariectomised plus adrenalectomised animals and morphine was able to reduce the glucocorticoid-induced rise. It is postulated that endogenous opioids might be playing a dual role in the regulation of glycolysis by inhibiting the release of corticotropin and regulating the action of glucocorticoids at the cellular level in the mammary gland.

Adrenocorticotropic Hormone↗
PubMed1983

Transpyloric feeding in the newborn: use in neonates with and without respiratory failure.

In a peripheral maternity hospital providing Intensive Care for 5274 deliveries per annum, NJ feeding was attempted, in one year, in 57 neonates. One third of these weighed less than 1500 g at birth and 41 (71.9%) had respiratory disease. A standard technique, and a commercially available tube was used, and the tube was passed to the jejunum within 24 hours in 46 (80.7%) of the babies. NJ feeding was continued for varying periods, up to 50 days. The volume of milk given varied with the duration of the feed but feeds of up to 244 ml of milk/Kg body weight/day were achieved. Thirty-eight (66.6%) of the babies regained their birthweight by 20 days and major complications were uncommon. We have shown that NJ feeding can be used in low birthweight babies with serious respiratory illness, even when resources are limited.

Enteral Nutrition↗
PubMed1983

Enzyme studies in human prostatic tissues.

The activities of six enzymes associated with carbohydrate metabolism were measured in 24 benign prostatic hyperplasias and 29 carcinomas of the prostate with the intention of investigating whether these measurements might eventually predict the clinical course of the disease. The following findings are recorded: the activities of PFK, alpha-GPDH and PHI were significantly lower in carcinomas. Comparison between well and poorly-differentiated carcinomas indicated a significantly lower activity of 6PGDH and higher alpha-GPDH/6PGDH ratios in the latter. These findings are the opposite of those observed in carcinomas of the breast.

Aged↗
PubMed1982

Effects of opiates and naloxone on certain enzymes of carbohydrate metabolism in human breast carcinomas.

The effects of administration of opiates and naloxone on the activities of PFK, 6PGDH and alpha-GPDH and alpha-GPDH/6PGDH ratios in human breast carcinomas were investigated in patients awaiting mastectomy. Injection of naloxone or fentanyl into an antecubital vein resulted in a statistically significant reduction in the activity of alpha-GPDH. Fentanyl was also effective in reducing the activity of 6PGDH. Injection of morphine into a branch of the internal mammary artery during mastectomy failed to induce changes in the activities of any of the enzymes but injection of naloxone resulted in a significant rise in the activity of 6PGDH. It is postulated that these alterations in the activities might not be associated with the binding of these drugs to opiate receptor proteins in the carcinoma. Furthermore opiate agonists or antagonists might not produce the required changes in the activities of any of the enzymes.

Breast Neoplasms↗