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Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

At least 181 records · Page 10Linked to original sources

Oestrogen-receptor status and sites of metastasis in breast cancer.

The oestrogen receptor (RE) status of the primary tumour has been assessed in 466 of a consecutive series of 550 patients with primary operable breast cancer. All patients were followed up (without treatment) until the development of recurrence or metastases. Distant metastases have so far occurred in 124 patients and 82 have had symptomatic local or regional recurrence. A significant correlation exists between the RE status of the primary tumour and subsequent patterns of metastasis. Symptomatic metastases to regional lymph nodes are more common with RE- cancers. There is no significant difference in either time of onset or total incidence of distant metastases between patients with RE+ and RE- tumours. Distribution of distant metastases is influenced by RE status: RE+ tumours tend to recur in bone, RE- tumours show affinity for viscera.

Adult↗

Estrogen receptors and breast cancer.

Estrogen receptors have been assayed in a series of primary breast cancers from postmenopausal women; 59% of which were estrogen-receptor positive. These patients survived for a significantly longer period of time than those whose tumors were estrogen-receptor negative. The effect of estrogen-receptor status was only seen (and then markedly accentuated) in patients who had lymph-node invasion at the time of mastectomy. Such determinations also appear to be of value in preselecting those patients who, on recurrence, will benefit from tamoxifen therapy.

Adult↗

Characterisation of breast skin temperature rhythms of women in relation to menstrual status.

Circadian breast skin temperature rhythms were characterised throughout the menstrual cycle, for various locations on the left breast of ambulatory women. All subjects exhibited highly significant circadian rhythms (P less than 0.001). Changes in rhythm parameters, such as the mesor, amplitude and acrophase, were observed during the menstrual cycle. No consistent trend in these rhythm parameters was observed between subjects in relation to menstrual cycle stage. Experimental and statistical techniques used to characterise circadian rhythms in pre-menopausal women were applied to a post-menopausal woman with primary breast cancer. Comparison of rhythm parameters associated with the tumour area and corresponding site on the contralateral breast showed abnormal thermal characteristics such as elevated mesor values, decreased amplitude as well as changes in the timing of the acrophase. These properties may be exploited for the early detection of breast cancer. The project also involved the design and testing of an ambulatory device, known as the 'chronobra', for the measurement of breast skin temperature. The performance of the chronobra was in close agreement with reliable, conventional equipment. The chronobra now allows studies of breast skin temperature rhythms associated with breast disease to be extended.

Adolescent↗

Androgen and oestrogen binding in cytosols of human ovarian tumours.

The specific retention of androgens and oestrogens by cytoplasmic components of human ovarian tumours was investigated. High-affinity, low-capacity binding of androgens was observed in 88% of tumour specimens and oestrogen binding in 32%. Retention of oestrogens did not occur in the absence of androgen binding. The androgen-binding component, of sedimentation coefficient 7.5-8.5S, showed specificity for 5 alpha-dihydrotestosterone and 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881). In some instances, competition for R1881-binding sites indicated the presence of progesterone receptor-like binding. The data presented suggest strongly the existence of androgen and oestrogen receptors in some ovarian tumours and may be relevant to histopathological classification and therapeutic rationales.

Androgens↗

Measurement of diethylstilbestrol in plasma from patients with cancer of the prostate.

A specific radioimmunoassay has been developed for diethylstilbestrol (DES), using an antiserum raised against DES monocarboxymethyl ether and a tritium-labeled radioligand. Prior to radioimmunoassay, a fraction enriched in DES is obtained from a dichloroethane extract of plasma using Sephadex LH-20. The specificity of the assay is good, and the sensitivity (130 pg/ml) is adequate for accurate determination of DES in plasma from prostatic cancer patients treated with the drug. The precision is satisfactory, with an interassay coefficient of variation of approximately 10% at concentrations of approximately 1 ng/ml, and the blank values are negligible. Excellent agreement (r = 0.96) is observed between data obtained by radioimmunoassay and those obtained by a procedure using gas chromatography-high-resolution mass spectrometry. DES concentrations in the plasma of six treated (1 mg DES three times daily) patients were in the range 0.15 to 6.0 ng/ml. Increases in plasma concentration were observed within 2 hr of administration, with secondary rises occurring 5 to 6 hr later. Plasma testosterone concentrations were low in four of the patients; in a single subject, relatively high levels of testosterone were further elevated following administration of luteinizing hormone-releasing hormone.

Circadian Rhythm↗

Advantages of CUSUM techniques for quality control in clinical chemistry.

The performance of routine analytical laboratories is assessed, inter alia, by the use of appropriate internal quality control techniques. Despite evidence that the cumulative sum technique is generally superior to Shewhart-type control charts and many others, its use has been limited by the popular misconception that it is inferior to Shewhart's in detecting large variations and/or outliers in quality control data. The application of computer simulation methods has enabled us to answer this criticism and has provided the basis for further improvements in the design of the appropriate control scheme for general use in clinical chemistry.

Chemistry, Clinical↗

Relationship between primary breast tumor receptor status and patient survival.

For a minimum of 3- months, 250 women who underwent mastectomy for primary breast cancer have been followed up. ER status has had a pronounced effect upon disease-free interval and survival: in patients with node involvement ER-positive (ER+) tumors carry a better prognosis. Of patients with ER-positive primary tumors, 43% underwent objective response to their secondaries for a minimum period of six months. This compares with a response of only 18% for ER-negative (ER-) tumors. In patients who had previously received endocrine therapy and on relapse were treated with cytotoxic chemotherapy, objective response rate to chemotherapy was better in patients in whom the primary tumor had been ER-, but not significantly so.

Adult↗

Debendox and congenital malformations in Northern Ireland.

An investigation was carried out in Northern Ireland into the alleged association between fetal abnormalities and Debendox, an antiemetic drug used in pregnancy. During the period 1966-78 the total number of births each year and the overall incidence of congenital malformations per 10 000 births fell. The incidences of cleft lip, cleft palate, reduction deformities, and defects of the heart and great vessels fell from 1966 to 1976 but increased in 1977 and 1978. During the same period (1966-78) the number of prescriptions for Debendox issued by general practitioners increased more than fourfold. These observations suggest that there is no relation between congenital malformations and the use of Debendox. This conclusion, however, does not take into account other drug- or environmental-related factors that may have resulted in a reduction in the number of congenital malformations and would hence have masked an increase associated with greater usage of Debendox. In particular, the amount of Debendox sold direct to the public without a prescription and the use of the drug by patients who were not pregnant could not be established. The amount of drug used in these ways is probably small, and it is difficult to see how it might influence the conclusions reached.

Abnormalities, Drug-Induced↗

Plasma spermidine concentrations in patients with tumours of the breast or prostate or testis.

Plasma spermidine concentrations were measured by radioimmunoassay in normal subjects and in patients with various tumours of the breast, prostate or the testis. The sensitivity of the method was 0.45 pmol spermidine/20 microliter plasma and the cross reactivity was 13% with putrescine and 2% with spermine. Plasma spermidine concentrations were raised in 25% of the patients with prostatic cancer (mean concentration 316.7 +/- 240.69 nmol/l) and in 8% of the patients with benign prostatic hyperplasia (mean concentration 198.9 +/- 169.92 nmol/l). No correlation was found between elevated plasma levels of spermidine in the prostatic cancer patients and tumour stage or metastatic status of the patients. No correlation of plama spermidine concentrations and age was found in 61 normal male subjects (mean concentration 200.3 +/- 137.71 nmol/l plasma). Only 29% of the patients with breast carcinoma had elevated levels of spermidine compared to normal female subjects. Plasma spermidine concentrations did not correlate with clinical stage or oestrogen receptor status in these patients. Patients with testicular tumours had elevated mean concentrations of plasma spermidine. One out of five patients with seminoma of the testis and six out of 16 patients with teratoma of the testis had significantly elevated concentrations.

Adult↗

Possible test for selection of adjuvant systemic therapy in early cancer of the breast.

The estrogen receptor content and the thymidine labelling index have been correlated in a series of primary cancers of the breast. Receptor was assayed in tumours of 409 patients with operable breast cancer. Recurrence rates were significantly higher in patients whose tumours did not contain receptors than in those whose tumours did. Women without axillary node involvement whose tumours lacked oestrogen receptors showed the same high rate of recurrence as all women with axillary involvement. The oestrogen receptor status of metatases was similar to that of the primary tumours. The thymidine labelling of 83 tumours was inversely related to their receptor content. Tumours without receptors had the highest indices and therefore the highest potential tumour growth. These results have been discussed in relation to selection of systemic adjuvant therapy.

Breast Neoplasms↗

Analysis of testosterone and dehydroepiandrosterone in saliva by gas chromatography-mass spectrometry.

Testosterone and 3 beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) have been identified in human parotid fluid and saliva by gas chromatography-mass spectrometry/selected ion monitoring analyses of the t-butyldimethylsilyl ether and methyl oxime, t-butyldimethylsilyl ether derivatives. High specificity of analysis has been achieved by the use of high mass spectrometric resolution or by the monitoring of metastable peaks. Quantitative analyses indicate concentrations of both unconjugated testosterone and unconjugated dehydroepiandrosterone in the range 200-800 pmol/l in the saliva and parotid fluid of the normal males examined. These represent 1.5-7.5% of the concentrations of the steroids in blood plasma taken from the same subjects.

Dehydroepiandrosterone↗

Tissue androgen concentrations in golden hamsters with benign prostatic tumours.

Using gas chromatography-high resolution mass spectrometry with selected ion detection, the concentrations of testosterone, 5alpha-dihydrotestosterone, androsterone, 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17alpha-diol and 5alpha-androstane-3beta,17beta-diol were measured in the dorsal and ventral prostates of two strains of golden hamster (Mesocricetus auratus) at various ages from 60 to 250 days. The tissue concentrations from a control strain were compared with those of the BIO 87.2 strain of hamster, the latter developing benign hyperplasia of the prostate between 90 and 120 days of age. Marked increases in the concentration of total 5alpha-androstanediols in both prostatic lobes of the BIO 87.2 strain were detected, with the highest level of over 345 nmol/g protein being found at 200 days of age. In comparison, the control strain showed a less pronounced increase in concentration at 150 days. Increases in total 5alpha-androstanediols were mainly associated with increases in the concentration of 5alpha-androstane-3alpha,17beta-diol. Concentrations of testosterone in prostatic tissue were also found to increase in the BIO 87.2 animals with peak values being seen at 200 days. Increases in concentration of androsterone were observed by 150 days and these levels were maintained up to 250 days of age. Control animals showed no comparable increases in testosterone and androsterone during the time-course studied. Surprisingly, no significant variation in 5alpha-dihydrotestosterone concentration was detected in either strain from 60 to 250 days although levels were slightly but consistently higher in the BIO 87.2 strain. There were no significant fluctuations in any of the androgens assayed either before or during tumour development. The increases in 5alpha-androstane-3alpha,17beta-diol, testosterone and androsterone were detected only after tumours had become established.

Androgens↗