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Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

At least 91 records · Page 5Linked to original sources

Daily salivary progesterone levels in cyclical mastalgia patients and their controls.

Progesterone levels were measured in samples of saliva collected daily throughout the menstrual cycle in patients with pronounced cyclical mastalgia and breast nodularity. A control group matched for age, length of menstrual cycle and parity was also studied. No significant differences in progesterone levels were detected between the two groups for the luteal phase of the cycle. These data indicate that cyclical mastalgia is not associated with significant luteal phase progesterone insufficiency, as demonstrated by salivary levels and, by implication, serum levels of progesterone.

Adult

Survival patterns in hormone treated advanced breast cancer.

This study investigates a series of factors, all recordable by the time of presentation of distant metastases from primary breast cancer and relates these to survival after the initiation of endocrine therapies. One hundred and ninety-one patients have received endocrine therapy as initial treatment for distant metastases. In all patients both the histological grade and oestrogen receptor (ER) status of primary tumour tissue; the lymph node stage and menopausal status at mastectomy and the disease-free interval and sites of initial metastases are available for analysis. Four of these factors have been found to contribute independently towards prolonged survival after the initiation of treatment: tumour grade, ER status, disease-free interval and sites of metastases. Employing a multivariate analysis incorporating these four factors, three groups of patients have been identified with survivals of 67, 37 and 0 per cent at 18 months on therapy. These three groups of patients contain 37, 41 and 22 per cent of the patient population respectively.

Breast Neoplasms

Therapeutic traditions in Northern Ireland, Norway and Sweden: I. Diabetes. WHO Drug Utilization Research Group (DURG).

A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sample of 400 physicians in each country was asked to give their opinions on the choice of therapy for three model cases designed to cover the spectrum of treatment - from diet alone to insulin. Significantly more Swedish (65%) than Northern Irish (51%) and Norwegian (52%) doctors suggested diet alone for uncomplicated diabetes recently discovered in a middle aged, overweight man. For symptomatic diabetes in a 76 year old over-weight woman with few retinal microaneurysms, the majority of physicians in all three countries suggested treatment with sulphonylureas. Biguanides were here a more common alternative in Northern Ireland than in Scandinavia. For suspected secondary treatment failure in a 63 year old woman with no signs of complications, insulin was suggested by 71% of the Norwegian doctors but only by 44 and 49% of those in Northern Ireland and Sweden, respectively. General practitioners tended to suggest oral treatment earlier and to maintain it longer than hospital physicians. The study has demonstrated significant differences in the approach to treatment of Type II diabetes mellitus between physicians in the three countries. However, the differences were more prominent in the choice of drugs than in the threshold of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus

Therapeutic traditions in Northern Ireland, Norway and Sweden: II. Hypertension. WHO Drug Utilization Research Group (DURG).

A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension. Yet the utilization of antihypertensive drugs in Sweden is about 60% higher than in Northern Ireland and 30% higher than in Norway. Swedish physicians preferred beta-blockers as their first choice to a greater extent than physicians in Northern Ireland and Norway who selected thiazides more often. In general, the choice of drugs agreed with the sales and prescribing patterns in the three countries. Besides providing more insight in therapeutic traditions the study indicates that the lower prescribing of antihypertensive drugs in Northern Ireland, and to some extent in Norway, compared to Sweden, might be due to differences in true or apparent morbidity.

Antihypertensive Agents

Endogenous C19-steroids and oestradiol levels in human primary breast tumour tissues and their correlation with androgen and oestrogen receptors.

Endogenous levels of testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), androstenedione and oestradiol as well as levels of androgen (AR) and oestrogen (ER) receptors were measured in human primary breast tumour samples. The purification procedure developed allowed simultaneous quantitation of the four steroids, by radioimmunoassay, in small samples with adequate precision, sensitivity and accuracy. The majority of the tumours analysed contained detectable levels of the four steroids in the homogenate or cytosol fractions. There was no significant correlation between steroid content of the tissue and the age of the patient for any of the four steroids. A positive correlation (r = 0.71) was found between the levels of 5 alpha-DHT and testosterone in tumours. In general, tissue steroid concentrations decreased with an increase in dedifferentiation. Fifty-two per cent of the tumours analysed for receptor content were found to be ER positive, and a similar proportion were AR positive. No relationship was observed between AR status and age although receptor concentration was significantly (P = 0.004) higher in post-menopausal women when only receptor positive tumours were evaluated. The mean values for AR and ER were higher in tumours containing both receptors than in tumours showing either receptor alone; there was, however, no significant relationship between concentrations of the two receptors. No correlation was observed between tumour AR or ER status and any of the four steroids measured in either fraction. In addition, the ratio between the combined levels of 5 alpha-DHT and testosterone compared to oestradiol in the same tumour, only showed a maximum value of 40. Thus, in vivo these two androgens are unlikely to influence oestrogen action in human primary breast tumours by interfering with the association of oestradiol with its receptor.

Adult

Attribute processing in patients with graphical copying disability.

This study investigated whether defective copying of multiple-line figures in lesion patients is associated with a deficit in perceptually processing and copying elementary attributes. Lesion and Control patients were assessed on a copying test comprising multi-line figures, and on parallel perceptual and motor forms of single-attribute tasks for Size, Orientation, Angle, Position and Direction. Copying test performance was correlated with perceptual attribute performance for the Lesion but not the Control group. Mean attribute performance of the Lesion patients who showed a copying disability (defined as a copying performance below the minimum performance of the Control group) was inferior to that of the non-disabled and Control subjects. The non-disabled patients did not differ from the Controls on any of these tasks. Performance in the copying test for left- and right-hemisphere patients did not differ, but left-hemisphere patients showed less impairment in the simple attribute tasks. The results are discussed in terms of the role of elementary perceptual deficits in copying disability and hemispheric differences in the nature of this condition.

Adolescent

Evaluation of biopsy techniques for androgen receptor assay in human prostatic tissue.

Androgen receptors were assayed in nuclei prepared from human benign hypertrophic prostate tissue obtained at retropubic prostatectomy by transurethral resection (TURP) and by cold punch resection. Androgen receptor was not detected in 70% of the transurethrally resected samples, and in those cases where receptors were observed they showed no correlation with enucleated samples. However, androgen receptors were detected in all cold punch resected samples and enucleated tissue with similar concentrations evident in samples from the same gland. These results suggest that prostate specimens collected by TURP are not suitable for androgen receptor analysis, whereas the technique of cold punch resection yields prostate samples that are more reliable for a correct evaluation of androgen receptor content.

Aged

Immunocytochemical assay for estrogen receptors applied to human prostatic tumors.

An immunocytochemical assay using a monoclonal antibody to estrogen receptor was applied to frozen sections of 43 prostatic tumors. In addition, in 16 tumors the results of the immunocytochemical assay were compared with those obtained using an enzyme immunoassay for estrogen receptor, a tritiated ligand binding assay, and a histochemical procedure using fluorescein-labeled estradiol conjugates. Specimens from 14 patients with benign prostatic hyperplasia and 29 patients with prostatic carcinoma were analyzed in assays in which human breast carcinoma specimens of high, medium, low, or negative estrogen receptor content acted as controls. The intensity of nuclear staining and the percentage of stained cells in the breast sample controls correlated well with estrogen receptor content as determined by both the enzyme immunoassay and the tritiated ligand binding assay. None of the fixed, frozen sections from the 43 prostatic tumors exhibited nuclear staining of either the benign or the malignant epithelial cells or of the stromal components. Negative results were also obtained with the tritiated ligand binding assay. The majority of prostatic samples were negative when using the enzyme immunoassay but four specimens had a mean value of 6.2 fmol/mg protein which is just above the sensitivity of the assay. Using fluorescein-labeled estradiol conjugates both cytoplasmic and nuclear binding was observed in the prostatic samples which did not correlate with the results obtained by the other three procedures.

Histocytochemistry

Quantitative common carotid artery blood flow: prediction of internal carotid artery stenosis.

Common carotid artery (CCA) blood flow was measured noninvasively with a pulsed Doppler duplex scanner modeled after the Octoson (Ultrasonics, Inc., No. Yonkers, N.Y.). The aim of the study was to determine normal values and to assess the accuracy of CCA flow as a predictor of internal carotid artery (ICA) stenosis. One hundred one people who did not have disease were studied; the overall mean flow rate was 395 +/- 79 ml/min (mean +/- S.D.). There was no significant correlation with age, height, or body surface area but there was with body weight (p less than 0.05). A statistically significant difference was evident between men (424 +/- 88 ml/min) and women (371 +/- 62 ml/min) (p less than 0.001). The intrasessional variation (S.D./mean) was 13% and the intersessional variation, 16%. No significant difference was seen between the sides. Ninety-two patients who had carotid angiography were studied and the flow rates compared with the degree of ICA stenosis on each side. The flow rate for mild ICA stenosis (1% to 39%) was 404 +/- 109 ml/min, for moderate stenoses (40% to 69%), 390 +/- 91 ml/min, and for severe stenoses (70% to 99%), 351 +/- 109 ml/min. There was a significant difference in flows only between mild and severe grades of stenosis of the ICA (p less than 0.01). With unilateral stenosis, comparison of flow values in the normal and affected sides showed the greatest discriminatory power when the absolute difference of flow values was taken (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Duplex scanning of the portal vein and portasystemic shunts.

This article describes the preliminary findings of a Duplex ultrasound technique that enables the patency of the portal circulation and portosystemic shunt patency to be determined. In addition, the equipment allows the noninvasive measurement of quantitative rates of blood flow in these vessels. Portal vein flow was 952 +/- 273 ml/min in 10 normal subjects after an overnight fast and increased by 50% at 30 minutes in response to a standard 660-calorie liquid meal. Thirteen portosystemic shunts were scanned, and hemodynamic information was obtained from 10. Three of the four patients who had a Warren shunt performed 3 to 4 years earlier had portal vein occlusion. There is evidence of an increase in flow through the Warren shunt on feeding, suggesting a hemodynamic connection to the mesenteric side of the circulation. The apparatus, technique of examination, and the characteristics and difficulties with particular types of shunts are described.

Adult

Evaluation of an enzyme immunoassay for estrogen receptors in human breast cancers.

An estrogen receptor enzyme immunoassay kit (ER-EIA) has been evaluated in 70 human breast carcinomas against a routine cytoplasmic [3H]estradiol binding assay (ERU). A linear correlation between the ER-EIA and the ERU was observed for binding values up to 400 fmol/mg of cytosol protein. Above this value, the ERU underestimates the concentration of receptor. The ERU gave a lower number of estrogen receptor-positive tumors (50 of 70) than did the ER-EIA assay (59 of 70). In the ERU-negative ER-EIA-positive tumors, receptor values as determined by the ER-EIA assay all fell below 50 fmol/mg of protein (mean, 19.9 +/- 4.2 fmol/mg of protein). Application of an exchange procedure which estimates the total steroid binding capacity of the cytosol gave positive results in 7 of 9 ERU-negative ER-EIA-positive tumors (mean, 16.9 +/- 2.95 fmol/mg of protein). Subdivision of the binding data according to the menopausal status of the patient indicates low receptor values in premenopausal women by each assay. A correlation between the ER-EIA assay and the histological grade of tumors was observed; Grade I well-differentiated tumors were all positive, while Grade II and III tumors were 86% and 75% positive, respectively. No correlation between the ER-EIA assay and tumor lymph node stage or tumor size was observed.

Adult

The effect of prolactin on human BPH epithelial cell proliferation.

Epithelial cell monolayers derived from specimens of human benign prostatic hyperplasia (BPH) tissue by an explant culture technique were cultured with prolactin in the presence and absence of androgens. Proliferation of the cells was measured by both autoradiographic assessment of [3H]-thymidine uptake and stathmokinetic procedures. Prolactin significantly stimulated the growth of these cells in the concentration range 0.5 mIU/ml to 10 mIU/ml but was inhibitory at a concentration of 100 mIU/ml. In the presence of testosterone (1 X 10(-7) M), prolactin at low concentrations (greater than 1 mIU/ml) but not at 10 mIU/ml, the concentration at which all other experiments were performed, produced a further stimulation in the proliferation. The increase in growth seen with cells cultured with 5 alpha-dihydrotestosterone (1 X 10(-7) M) was reduced with addition of prolactin at high concentrations (10-100 mIU). When the fetal calf serum used in the cultures was stripped of endogenous steroids, prolactin still increased cell proliferation, although to a reduced extent. This indicated that the effects of prolactin were not dependent on the presence of androgens.

Cells, Cultured

A prognostic index for the clinical management of patients with advanced prostatic cancer: a British Prostate Study Group investigation.

Patients with histologically proven carcinoma of the prostate (n = 186) were initially assessed and followed up according to the standardized protocol of the British Prostate Study Group, urologists from which contributed patients to this investigation. These patients were given either endocrine therapy or orchidectomy as first line treatment; the ratio of the number of patients receiving these two treatments was similar in each group of subjects compared for survival. Prognostic indices were derived for all patients and for those classified according to the presence (M1) or absence (M0) of metastases. The prognostic indices were derived from clinical and hormone data obtained at initial presentation. Whereas the degree of tumor differentiation and plasma testosterone concentrations were significant prognostic factors in both M0 and M1 disease, growth hormone was only significant in M1 patients, where age was also of borderline significance; elevated growth hormone, higher Gleason grade, younger age, and lower testosterone indicated a poorer prognosis in M1 patients. These findings indicated the feasibility of selecting a poor prognostic group of patients that may derive benefit from a more aggressive therapy.

Age Factors

Validation of observed differences in the utilization of antihypertensive and antidiabetic drugs in Northern Ireland, Norway and Sweden.

The amount of antihypertensive and antidiabetic drugs based of defined daily doses per 1000 inhabitants per day varies two to three fold between Northern Ireland, Norway, and Sweden. We explored whether variations based on the universally applied defined daily doses might be accounted for by national differences in the actual average prescribed daily doses. Use of prescribed daily doses for antihypertensive drugs resulted in Northern Irish and Norwegian consumption figures which were respectively 40 and 21% lower than the Swedish one, compared to 38 and 25% when defined daily doses were used. The effect of population age-sex differences on the gross defined daily doses per 1000 inhabitants per day figures was determined by applying the Northern Irish or Norwegian age-sex group proportions to Swedish age-sex specific sales data. Taking population differences into account would have resulted in antihypertensive drug use being 21 rather than 38% less in Northern Ireland and 18 rather than 25% less in Norway. Also adjustment for prescribed daily doses left an unexplained difference of 23% between Sweden and Northern Ireland and 14% between Sweden and Norway. For oral antidiabetics use of prescribed daily doses resulted in a Northern Irish - Swedish difference of 62% compared to 67% when defined daily doses were used. Simultaneous adjustment for population differences and prescribed to defined daily dose variations left a 52% difference.

Adolescent

Evaluation of luteal-phase salivary progesterone levels in women with benign breast disease or primary breast cancer.

Salivary progesterone concentrations were determined in premenopausal parous women with a mean age of ca. 40 yr who had a history of either benign breast disease (n = 15) or primary breast cancer (n = 15) and in a group of age-matched healthy women (n = 15). Saliva samples were collected at 09.00 and 21.00 hr daily for one complete menstrual cycle and progesterone concentration was measured by radioimmunoassay. Characteristic luteal-phase progesterone profiles were observed in all subjects in each of the three groups but no statistical intergroup differences could be demonstrated for age-matched subjects in each group. These studies indicated that ovarian dysfunction, as judged from salivary progesterone concentrations, was not apparent in older premenopausal women with a history of benign breast disease or primary breast cancer when compared with age-matched controls.

Adult