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Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

At least 127 records · Page 7Linked to original sources

Mammographic parenchymal patterns: value as a predictor of hormone dependency and survival in breast cancer.

The relation between the parenchymal pattern of the breasts as demonstrated on a mammogram and the estrogen-receptor status of the primary tumor in 337 patients with operable invasive breast cancer has been studied. These factors have also been correlated with the response to endocrine therapy in 92 patients who subsequently developed secondary disease. It has been shown that patients with a DY pattern are more likely to develop tumors that are estrogen-receptor (ER) positive (p = 0.01). Patients with secondary disease who have a DY pattern are more likely to respond to endocrine therapy (p = 0.001). The DY pattern has been shown to be at least as good an indicator of the probability of response to endocrine therapy as the estrogen-receptor status, and a combination of the two factors better than either taken singly. In a series of 141 postmenopausal women, the DY pattern, as determined at the time of mastectomy, was associated with significantly improved survival (p = 0.001). Mammographic parenchymal pattern could form the basis for selecting patients for endocrine therapy where no estrogen-receptor assay is available.

Breast Neoplasms

The use of salivary steroids to monitor circadian rhythmicity on expeditions in the arctic.

The circadian variation in salivary cortisol concentration was investigated in four men during a traverse on foot, of the Greenland ice cap and of salivary cortisol and testosterone on a summer expedition to Spitzbergen. In both instances circadian rhythmicity was demonstrated both before leaving the U.K. and throughout the expedition. The acrophase of the rhythms followed the changes in activity patterns on both expeditions although there was a dissociation between the cortisol and testosterone following an acute 8 hr phase shift in Spitzbergen. The mesor of cortisol in both instances tended to be higher than in the U.K. but the difference was never statistically significant. This work demonstrates the feasibility of using salivary steroid concentrations to investigate their circadian rhythmicity in circumstances where frequent blood sampling would be precluded.

Adult

The relationship of background mammographic pattern to hormone dependency in breast cancer.

We have studied the relationship between mammographic parenchymal pattern of the breast and oestrogen receptor (ER) status in the primary tumour in 337 patients with operable invasive breast cancer, and the response to endocrine therapy in patients subsequently developing secondary disease. Patients with dysplastic (DY) parenchymal pattern are significantly more likely to develop tumours which are ER-positive. In 92 patients who subsequently developed secondary disease, those whose primary tumour arose in a DY pattern breast were significantly more likely to respond to endocrine therapy irrespective of their ER status.

Breast

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

Carcinoma of the prostate: relationship of pretreatment hormone levels to survival.

Pretreatment hormone levels were determined in 222 patients with prostatic cancer and their prognostic value assessed. The patients were grouped into yearly survival categories and only those whose cause of death was due to the disease were included in the study. Low concentrations of testosterone in plasma at the time of diagnosis related to a poor prognosis. Patients who died within 1 yr of diagnosis had the lowest mean plasma levels of this steroid. The pretreatment mean plasma testosterone concentrations were found to be higher as the survival period of the various groups lengthened. This relationship was observed both when the total data were analysed and also when the patients were subgrouped depending on clinical evidence of spread of the tumour beyond the prostatic capsule (T3) or on the presence of metastases (M1). High pretreatment plasma concentrations of luteinizing hormone were also associated with poor survival. Follicle-stimulating hormone, prolactin and growth hormone concentrations did not correlate with survival time. The indications from this study are that poor testicular function is associated with early death from prostatic carcinoma and that the measurement of blood levels of testosterone at diagnosis could provide a prognosis of subsequent life-span.

Aged

Quantitative aspects of the E2 receptor assay for human breast tumour cytosol using dextran-coated charcoal.

Misclassification of the oestrogen status of a human breast tumour cytosol, arising from different sources and magnitudes of error in the dextran-coated charcoal (DCC) method, have been investigated using both practical and computer simulated data analysed by Scatchard and Mass Action models. The minimum detectable receptor site concentration, relative or absolute numerical bias and imprecision which are complex and integral functions of misclassification, have been calculated from practical data and for a range of experimental conditions likely to be encountered in practice. The Mass Action model was found to be superior and the computer program, designed to investigate the effects of methodological errors on quantitative aspects of the assay, may be a useful aid for analytical design and internal quality control of the receptor assay.

Breast Neoplasms

Patterns in drug utilization--national and international aspects: psychoactive drugs 1966-80.

Although the press claimed there were dramatic increases in the use of tranquillizers in Northern Ireland after the outbreak of civil unrest in 1969, our data, based on the computerised pricing system for drugs prescribed in the province, showed average annual increases of about 20% from 1966 to 1969, and 10% from 1970 to 1975, thereafter tranquillizer prescribing levels reached a plateau and declined between 1979 and 1980. Total psychotropic drug use also reached a peak in 1975, when about 12.5% of the adult population were estimated to have been receiving such a drug, and declined in the following 5 years. Benzodiazepines accounted for three-quarters of all psychotropic drugs and 98% of tranquillizers prescribed in 1980. Benzodiazepine tranquillizer prescribing has consistently been 20-30% higher than the rest of the United Kingdom, in contrast to hypnotic and antidepressant prescribing which has been consistently lower. The rate of increase in benzodiazepine tranquillizer prescribing over the decade from 1966 was greater than in other European countries, overtaking the level in Norway in 1972 and has since remained third to Iceland and Denmark. Some possible demographic and socioeconomic determinants of these trends are discussed. The prescribing of benzodiazepine hypnotics was almost entirely explained by these variables.

Anti-Anxiety Agents

The use of salivary progesterone assays in the assessment of ovarian function in postmenarcheal girls.

Menstrual cycle profiles of salivary progesterone were derived from daily samples obtained from 75 postmenarcheal girls aged between 12 and 17 years. Data were analysed to establish the proportion of girls exhibiting ovulatory cycles in each of several age groups following menarche or in groups based solely on chronological age. 'Luteal'-phase profiles of salivary progesterone, which were similar in shape to those characteristic of mature premenopausal women, were taken to indicate the probable occurrence of ovulation. The percentage of cycles in those subjects judged to be ovulatory, grouped according to gynaecological age, rose from 14% in the first year to 56% in the fourth year. Those classified according to chronological age, and where sufficient data permitted reliable estimates of the percentage of subjects ovulating, rose from 11% at 12 years of age to 64% for girls aged 16. These data are in reasonable concordance with published data using plasma progesterone and urinary methods for establishing ovulatory incidence, and indicate the value of salivary progesterone measurements in studies of ovarian function in adolescence.

Adolescent

Growth hormone and prostatic tumours: localization using a monoclonal human growth hormone antibody.

The immunocytochemical detection of endogenous human GH and the binding of exogenously applied human GH in tumour tissue from patients with benign prostatic hyperplasia or prostatic carcinoma is reported. Monoclonal human GH antibody binding was exclusively to the connective tissue in both benign and carcinomatous specimens. Specificity control experiments indicated that the antibody could be absorbed with human GH but not with human prolactin. Preincubating the sections with human GH considerably altered the immunocytochemical staining, reducing the reaction product within the connective tissue in a concentration-dependent manner and revealing a binding site for GH within the cytoplasm of epithelial cells.

Antibodies, Monoclonal

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

Hormone rhythms and breast cancer chronoepidemiology: salivary progesterone concentrations in pre- and post-menarchal girls and in normal premenopausal women.

Circadian and circatrigintan time series of salivary progesterone levels in premenarchal and adolescent girls and healthy mature premenopausal women have been investigated as a possible determinant for breast cancer risk. Circadian variations in progesterone appear to be more random than systematic and estimates of total daily progesterone output are better represented by samples pooled from several 2-hr specimens. Different patterns of circatrigintan progesterone secretion in girls are recognised and relate to those experienced in infertile and fertile women, though their relation to chronological or menarchal age is as yet uncertain. These data suggest that the measurement of salivary progesterone at premenarche, adolescence and maturity is a feasible, though statistically difficult, study for prospective identification of individuals at risk for breast cancer.

Adolescent

Circadian breast skin temperature rhythms: overt and occult benign and occult primary malignant breast disease.

Circadian variations of breast surface temperature have been measured in patients with overt or occult benign breast disease, or in those with occult breast cancer. Subjects were studied in a hospital ward environment well-controlled with respect to ambient temperature. Using manual techniques temperatures were recorded half-hourly for 96 hr from replicate sensors placed on quadrants of the left and right breasts inclusive of tumour areas and similar sites on the contralateral breast. Application of time series analysis failed to consistently demonstrate differences in values for the rhythm parameters for the tumour area and contralateral site. It was apparent, however, that the tumour area was generally associated with a reduced initial variance of the series in addition to a reduced percentage variance explained by a time series model with two rhythmic components when compared to the control site. These data suggest that efforts to identify early breast disease from signals of breast temperature should, at least, be directed to studies of temperature variance.

Adult

Effects of talc on the rat ovary.

Exposure of rat ovaries to talc was accomplished by intrabursal injection. As early as 1 and up to 18 months after treatment, the ovaries and associated tissue were cystic in appearance; these changes were the result of bursal distention. Histologically the ovarian tissue was decreased in amount and spread as a remnant on the inner wall of the bursa. In four to 10 treated animals but in no controls, focal areas of papillary change were noted in the surface epithelium of the ovary. Polarized light and electron microscope microanalysis confirmed the presence of talc in the surface epithelium, ovarian cortex, and connective tissue matrix of the bursa. Although the changes in the ovarian surface may be related to direct effects of talc exposure, it is postulated that these changes might also be related to constant exposure to the high concentrations of steroid hormones which have undoubtedly accumulated in the intrabursal space.

Animals

The management of locally advanced carcinoma of the breast by Nolvadex (tamoxifen): a pilot study.

Fifty-one postmenopausal women with locally advanced breast cancer were treated initially by Nolvadex (Tamoxifen, ICI) alone and followed prospectively between 1974 and 1982. Twenty-three patients (40%) showed an objective response to therapy of whom 17 (75%) remain in remission at median follow-up of 36 months. Patients who failed to respond to Nolvadex therapy were treated by radiotherapy which achieved local control in 64%, with 10 months median duration. Nolvadex therapy conveys a good quality lengthy remission to a sizeable minority of patients. The majority of those who fail to respond are satisfactorily managed by radiotherapy.

Aged

Therapeutic potential of the LHRH agonist, ICI 118630, in the treatment of advanced prostatic carcinoma.

8 patients with advanced prostatic carcinoma were treated with the luteinising-hormone releasing-hormone agonist, ICI 118630, for up to 3 months. Patients received subcutaneous injections of ICI 118630 (either 100 micrograms or 250 micrograms daily). At the higher dose level, plasma testosterone concentrations were significantly reduced by day 14 and approximated to those previously recorded in castrated or diethylstilboestrol-treated patients. Plasma concentrations of luteinising hormone and follicle-stimulating hormone were similarly reduced. Reduction in the dose, to 100 micrograms/day, similarly reduced plasma testosterone. ICI 118630 shows considerable potential for the management of patients with advanced carcinoma of the prostate.

Acid Phosphatase

Trends in peptic ulcer related diseases from 1972 to 1980. Hospital activity analysis data and general practice cimetidine prescribing levels.

Between 1972 and 1980 Hospital Activity Analysis from 5 Northern Ireland Hospitals demonstrated a gradual increase in the number of patients discharged for all diagnoses whilst there was a decline in discharges for peptic ulcer related disease, (duodenal ulcer, gastric ulcer, gastrojejunal ulcer, peptic ulcer site unspecified and hiatal hernia). The mean number of peptic ulcer related disease discharges per year for 1977-80, when cimetidine became generally available, was 10% lower than that of 1972-76, mainly due to a decline in male patient numbers. The mean annual number of male patients with a duodenal ulcer fell significantly by 18% (U = 1, p less than or equal to 0.025) during the 1977-80 period, whereas female discharges decreased by only 4%. Between 1972-76 and 1977-80 the mean annual number of duodenal ulcer perforations decreased significantly by 21% in males but only by 4% in females. Surgery for peptic ulcer related disease was 47% less in 1977-80 period, with significant decreases in duodenal ulcer, gastric ulcer and hiatal hernia procedures. From 1977 to 1980 there was considerable growth in Northern Ireland general practice cimetidine prescribing with 300,000 prescriptions being dispensed over the period. Apart from male duodenal ulcer cases, hospitalisation for peptic ulcer related diseases did not decrease substantially after the introduction of cimetidine but duodenal ulcer perforation and conditions warranting surgery did decline.

Cimetidine