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Biomedical subjects

A Turkes

Publications and source records attributed to A Turkes.

At least 37 records · Page 2Linked to original sources
PubMed1989

Pharmacokinetics of three bioequivalent norethindrone/mestranol-50 micrograms and three norethindrone/ethinyl estradiol-35 micrograms OC formulations: are "low-dose" pills really lower?

We have examined the pharmacokinetic parameters derived from the analysis of plasma ethinyl estradiol (EE) and norethindrone levels after administration of a single dose of three bioequivalent norethindrone-1mg/mestranol (ME)-50 micrograms formulations (Ortho-NovumR 1/50, NorinylR 1/50 and Norcept-MR 1/50) and three norethindrone-1mg/ethinyl estradiol-35 micrograms formulations (Ortho-Novum 1/35R, NorinylR 1/35, Norcept-ER 1/35) in a randomized crossover design involving 24 women for the 35 micrograms and 27 women for the 50 micrograms agents. Differences between the AUC-EE of pairs from the same manufacturer (1 + 35 and 1 + 50) were not significantly different, indicating that 50 micrograms of mestranol was equivalent to 35 micrograms ethinyl estradiol with respect to this pharmacokinetic parameter. The Cmax values were also similar. Inter-individual coefficients of variation (C.V.) for the AUC-EE were 47% and 57% for the 1 + 35 and 1 + 50 agents, respectively. Intra-individual C.V.s were 41% and 42%, respectively. For norethindrone, the AUC was larger with the 1 + 50 formulations than with the 1 + 35 group (87.9 vs. 72.8 pg hr/ml). Additionally, the Cmax values were larger for the 1/50 group (17.7 vs. 14.0). Since the amount of norethindrone in the two dosage groups was the same, this difference in the pharmacokinetics between the 35 micrograms EE and the 50 micrograms ME formulations remains unexplained. The inter-individual C.V. averaged 56% for both dosage groups. The intra-individual C.V.s were 17% and 46% for the 1 + 35 and 1 + 50 groups, respectively. The large variation in blood levels of ethinyl estradiol and norethindrone between and within individuals may overshadow clinical differences attributable to differences in dosage.

Adult↗
PubMed1989

Endocrine effects of combination antioestrogen and LH-RH agonist therapy in premenopausal patients with advanced breast cancer.

Thirty-eight premenopausal breast cancer patients were treated for periods up to 12 months with a sustained-release formulation of the luteinizing hormone-releasing hormone agonist goserelin [Zoladex, (D-Ser(But)6Azgly10-LH-RH); 3.6 mg depot every 4 weeks] either alone or in combination with the antioestrogen tamoxifen citrate (Nolvadex 40 mg/day). In both treatment groups serum gonadotrophin concentrations fell durig the first month of therapy and were suppressed on continued treatment. In patients treated with the combination therapy FSH concentrations were significantly reduced in comparison with goserelin alone. Relatively normal ovarian activity was observed during the first few weeks of therapy. Thereafter, oestradiol and progesterone concentrations rapidly declined in both treatment groups. Slightly lower serum oestradiol concentrations were recorded in patients receiving combination therapy. No significant adverse side-effects were recorded in either group of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Review of the endocrine actions of luteinising hormone-releasing hormone analogues in premenopausal women with breast cancer.

The endocrinological actions of the luteinising hormone-releasing hormone (LHRH) analogue, Zoladex (goserelin) in premenopausal women with advanced breast cancer are reviewed. LHRH analogues are an interesting addition to the currently available treatments for hormone-sensitive breast cancer in premenopausal women. Their modest side effects and ease of administration are in contrast to the risks and morbidity of surgical endocrine therapy.

Adult↗
PubMed1989

Progesterone concentrations in samples of saliva from adolescent girls living in Britain and Thailand, two countries where women are at widely differing risk of breast cancer.

Menstrual-cycle patterns of salivary progesterone concentration were obtained for 131 and 245 adolescent girls up to 4 years postmenarche living in Britain and Thailand respectively. These patterns were graded on a scale of 1 (little or no activity) to 5 (activity similar to that exhibited by the mature premenopausal woman) and the frequency of these grades within groups of girls from each centre was analysed. The major finding was that British girls exhibited a predominance of higher grades of progesterone activity when compared with their Thai counterparts (n = 2 x 58) when matched for chronological and gynaecological ages (P approximately 0.002). This was particularly so for the girls from these two matched groups in the gynaecological age range 2-4 years (P approximately 0.03). The major contribution to this significant difference between the two groups is attributed to the greater effect of chronological age on progesterone secretion in the British girls (P approximately 0.03) compared with the Thai girls (P approximately 0.29). These findings may have implications for facilitating our understanding of the reason for the differing risk of breast cancer in women in both countries.

Adolescent↗
PubMed1988

Comparison of prostate-specific antigen and prostatic acid phosphatase in the management of prostatic cancer.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostatic cancer. All patients, who participated in a phase III trial (n = 110), had disseminated disease and received first line endocrine treatment of either orchidectomy or a monthly injection of a depot luteinizing hormone-releasing hormone analogue (Zoladex). Serum samples were analyzed for PSA and PAP at 0, 3, 6, and 12 months and patients were clinically assessed at 6 and 12 months. At diagnosis, 72 and 97% of all patients had elevated PAP and PSA concentrations (greater than 4 ng/ml), respectively. Patients with progressive disease had significantly higher PSA and PAP levels at both assessments. A small number of patients in the "complete remission" group had both PSA and PAP levels within the normal range after 3 months of treatment. Similarly, both PSA and PAP levels steadily declined in the group of patients who had partial regression of the disease. The patients with stable disease, however, had a significant rise only in their PSA levels at the 12-month assessment. This data suggest that PSA is more sensitive than PAP in those patients who have a "slow progression" of the disease.

Acid Phosphatase↗
PubMed1988

Chemiluminescence immunoassay for progesterone in plasma incorporating acridinium ester labelled antigen.

A sensitive, solid-phase chemiluminescence immunoassay suitable for determining progesterone concentrations in plasma has been developed. The solid-phase antiserum was prepared by coupling a monoclonal progesterone-antibody, raised against a progesterone-11 alpha-hemisuccinyl/bovine serum albumin conjugate, to cyanogen bromide activated cellulose. An 11 alpha-progesteryl-2-carboxymethyltyramine-4-(10-methyl)-a cri dinium-9-carboxylate conjugate was used as the chemiluminescent label. The assay had a lower limit of sensitivity of 3 pg/assay tube and satisfied accepted validation criteria. Progesterone concentrations determined by chemiluminescence assay were in good agreement not only with a radioimmunoassay in routine use but also with a gas chromatography-mass spectrometry procedure.

Acridines↗
PubMed1988

Hormonal counterregulatory responses to human (semi-synthetic and recombinant DNA) and porcine insulin induced hypoglycaemia.

Controversy exists over differences in hormonal counterregulatory (CR) responses to human and porcine insulins with conflicting reports regarding the adrenaline, glucagon, growth hormone, cortisol and prolactin responses to the two species of insulin. It has been suggested that these differences may represent different central nervous system sensitivities to the two types of insulin. The CR responses to an intravenous bolus of 0.1 U/kg of neutral soluble semi-synthetic (SSHI) and biosynthetic (BHI) human insulins, porcine insulin and diluting medium as control were compared in six fasted normal male subjects. The plasma glucose fell similarly with all three insulins reaching a mean nadir of 1.5 +/- 0.2 mmol/l at 25 min. Peak responses to porcine, SSHI and BHI, respectively were: adrenaline--523 +/- 101, 424 +/- 62, 379 +/- 76 pg/ml; glucagon--0.064 +/- 0.01, 0.063 +/- 0.01, 0.078 +/- 0.01 nmol/l; cortisol--507 +/- 42, 539 +/- 65, 507 +/- 42 nmol; growth hormone--76 +/- 10, 76 +/- 5, 64 +/- 15 mU/l; prolactin--507 +/- 72, 608 +/- 103, 523 +/- 118 mU/l. These differences in CR response were not statistically significant. The results do not support the suggestion of a different hormonal counterregulatory response or central nervous system sensitivity to human and porcine insulins when administered by intravenous bolus injections to normal subjects.

Adult↗
PubMed1988

The use of serum carcinoembryonic antigen to assess therapeutic response in locally advanced and metastatic breast cancer: a prospective study with external review.

Serum carcinoembryonic antigen (CEA) has been measured throughout initial systemic endocrine treatment in 87 patients with stage III and 179 patients with stage IV breast cancer. Clinical response has been assessed after six months according to UICC criteria with external review of clinical and radiological data. Pretreatment CEA concentrations have been compared with those found in 55 'disease free' women attending a diagnostic breast clinic. A strong correlation exists between therapeutic response and alterations in CEA concentration (above 6 ng/ml) in patients presenting with stage IV disease. More than 50% of such patients either present with or develop CEA concentration greater than 6 ng/ml during the first six months of treatment.

Adult↗
PubMed1987

The treatment of metastatic prostatic cancer with the slow release LH-RH analogue Zoladex ICI 118630.

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Acid Phosphatase↗
PubMed1986

The use of an LH-RH agonist (ICI 118630, Zoladex) in advanced premenopausal breast cancer.

Fifty-three premenopausal patients presenting with advanced breast cancer have been treated with a potent new luteinising hormone-releasing hormone agonist Zoladex (ICI 118630) in a phase I clinical trial. On progression of disease 26 patients have undergone therapeutic oophorectomy. We present the clinical and endocrinological responses to treatment in 45 assessable patients. The response rate to Zoladex in this series was 31% and the ER status of the primary tumour was predictive of a response to the luteinising hormone-releasing hormone.

Adult↗
PubMed1986

Preliminary endocrinological evaluation of a sustained-release formulation of the LH-releasing hormone agonist D-Ser(But)6Azgly10LHRH in premenopausal women with advanced breast cancer.

Twenty-four premenopausal women with advanced breast cancer were treated with a sustained-release (depot) formulation containing 3.6 mg of the LH-releasing hormone agonist D-Ser(But)6Azgly10 LHRH (ICI 118630), given s.c. every 4 weeks for periods of up to 5 months. Although ICI 118630 initially stimulated LH and FSH secretion, serum gonadotrophin concentrations were suppressed on continued treatment. Increased LH and FSH concentrations were associated with relatively normal ovarian activity during the first month of treatment, but low progesterone concentrations were found in all patients thereafter. In 22 out of 24 women, oestradiol concentrations fell during the second month to values equivalent to those observed in oophorectomized or postmenopausal women. In two patients, persistent but reduced oestradiol production was recorded throughout. No appreciable side-effect of the drug was observed.

Breast Neoplasms↗
PubMed1985

Endocrinological and clinical aspects of LHRH action (ICI 118630) in hormone dependent breast cancer.

The effect of an LHRH agonist, D-Ser (But)6Azgly10-LHRH (Zoladex, ICI 118630) on pituitary gland and ovarian function has been investigated in patients with advanced breast cancer. In both pre and postmenopausal women ICI 118630 produced a substantial rise in circulating concentrations of gonadotrophins within 2 h of the first injection. However, on continued exposure to the drug plasma LH and FSH levels decreased to below pre-treatment values (14-21 days). This was especially evident in postmenopausal women. In premenopausal patients plasma progesterone and estradiol levels were significantly reduced after 2 and 4-6 weeks of therapy respectively, reaching values observed in oophorectomized or postmenopausal patients. No substantial acute or long-term influence of the drug on these hormones was seen in postmenopausal women. Breast tumor remissions were recorded primarily in premenopausal patients with estrogen receptor positive tumors. No responses were seen in patients with estrogen receptor negative disease. Minimal side effects were recorded.

Adult↗
PubMed1984

Therapeutic significance and the mechanism of action of the LH-RH agonist ICI 118630 in breast and prostate cancer.

The influence of the LH-RH agonist ICI 118630 on circulating levels of the pituitary gonadotrophins LH and FSH and the gonadal steroids oestradiol, progesterone, 17-hydroxyprogesterone and testosterone has been studied in phase I clinical trials of the drug in patients with advanced breast or prostate cancer. ICI 118630 initially stimulated plasma levels of LH and FSH. On continued treatment however, the drug reversed this response and produced a rapid decline in plasma testosterone and progesterone in male and female patients respectively. Plasma oestradiol concentrations equivalent to those seen in oophorectomised or postmenopausal women were eventually produced in all 5 female patients treated with ICI 118630. In one patient however persistent follicular activity occurred until her third menstrual cycle. No appreciable side effects of the drug were observed. These data indicate that ICI 118630 initiates a castration-like endocrine response and has potential in the treatment of hormone dependent tumours of the breast and prostate.

Breast Neoplasms↗
PubMed1984

Treatment of patients with advanced cancer of the prostate using a slow-release (depot) formulation of the LHRH agonist ICI 118630 (Zoladex).

Twenty two patients with advanced carcinoma of the prostate have been treated for up to 3 months with the slow-release (depot) formulation of the luteinizing hormone-releasing hormone (LHRH) agonist ICI 118630. Patients were randomized to receive one of three different doses of ICI 118630 of 0.9, 1.8 or 3.6 mg. The depot preparation was injected subcutaneously every 4 weeks. At the highest dose, the concentration of testosterone in serum was significantly reduced to castrate values after 2-3 weeks of therapy. The smaller doses of ICI 118630 (1.8 or 0.9 mg every 4 weeks) similarly reduced serum testosterone concentrations although, at the lowest dose, testosterone values were not suppressed in all patients during the first month. Hormonal changes were accompanied by subjective clinical improvement in symptomatic patients and there were no significant side effects. The data clearly demonstrate the considerable therapeutic potential of ICI 118630 in the depot formulation for the treatment of advanced carcinoma of the prostate.

Buserelin↗