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Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

At least 55 records · Page 3Linked to original sources

Steroid hormone concentrations in relation to patient prognosis and prostate tumour grade.

Survival of patients who received endocrine therapy as first-line treatment for their prostatic cancer was statistically analysed in relation to several parameters, primary tumour stage, metastatic status, age, pretreatment plasma hormone concentrations and Gleason grade. Prognostic indices were derived for both M0 and M1 patients in which Gleason grade and plasma testosterone concentrations were significant prognostic factors. In the M1 patients growth hormone values were also significant and to a lesser degree age. The relationship of Gleason grade to testosterone, growth hormone, prolactin, the gonadotrophins and age was also analysed. No significant differences in any of these hormones was noted with increasing Gleason grade but the age of patients with Grade 5 tumours was significantly lower.

Carcinoma

Treatment of patients with advanced cancer of the prostate: phase III trial, zoladex against castration; a study of the British Prostate Group.

The interim results of the randomised, Phase III trial of Zoladex against castration in the management of patients with metastatic carcinoma of the prostate is discussed. Trials commenced in October 1984 and incorporated 359 patients when recruitment ceased in January 1986. The preliminary report concerns the first 240 patients who had a minimum of 3 months follow-up. Entry criteria included patients who had no previous treatment with the exception of first-line localised radiotherapy and those who had distant bone or soft tissue metastases. Fourteen patients were excluded on the basis of protocol violations. The objective assessment of response was based on the British Prostate Group Criteria and was performed monthly for the first 3 months and 3-monthly thereafter. Pre-treatment disease characteristics of patients in both groups were similar at entry and there were no significant differences in the subjective response data of patients between the orchidectomy (n = 106) and the Zoladex group (n = 120). Objective response rates at 12 and 24 weeks of treatment were also identical for both treatment groups. Serum testosterone concentrations were below the 'castrate' level (less than 2 nmol/L) for Zoladex group as well as the orchidectomy group up to 48 weeks. The drug was well-tolerated with minimal side effects, those resulting from testosterone withdrawal were similar in both groups. The report therefore indicates clearly that this partical formulation of LH-RH analogue provides a valuable alternative to the surgical procedure in the treatment of carcinoma of the prostate.

Buserelin

Oestrogen receptors in primary and advanced breast cancer: an eight year review of 704 cases.

ER content of primary tumour tissue has been examined in 704 patients presenting with operable breast cancer. The median follow-up is now 84 months and no patient has received adjuvant therapy of any kind. ER status is related to histological grade, menopausal status, initial site of metastases and subsequent response to endocrine therapy. A significant advantage in terms of survival is found in ER positive patients which is confined to those lymph node positive at mastectomy. DFI is also significantly related to ER status in lymph node positive patients. Survival after the symptomatic presentation of metastases and the institution of endocrine therapy is prolonged in patients with ER positive tumours. The overall response rate to endocrine therapy in assessable patients with ER positive tumours is 32%. By combining the ER status and histological grade of tumour tissue, a group of patients comprising 28% of those assessable to endocrine therapy can be identified (ER positive, grade I and II) with a response rate of 46%.

Aged

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

Determination of ovarian steroid hormone levels in saliva. An overview.

Assessment of ovarian activity based on saliva samples has proven particularly useful in studies of women in well-developed countries and is potentially of even greater value in women of lower socioeconomic status in Third World countries. Assay techniques suitable for measuring low concentrations of steroids in saliva have become available only recently, so data derived from salivary sampling regimens are far less extensive than those based on plasma or urinary sampling procedures. Collecting saliva is an attractive alternative to the more conventional procedures because of the ease of frequent collection and freedom from religious and social constraints. Simple, direct assays for salivary progesterone have been established, but those for estradiol require considerably more research before becoming useful in routine practice. Predicting ovulation with data derived from saliva sampling awaits the development of more suitable assays for salivary estradiol.

Estradiol

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