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Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

338 records · Page 19Linked to original sources
PubMedDate not supplied

Endocrine treatment in prostate cancer.

Over its natural course, prostate cancer is a heterogeneous tumour with a generally slow but constant rate of growth. The androgen dependence of the prostate gland was demonstrated more than half a century ago by the landmark studies of Professor C. Huggins and colleagues. They established that androgens are implicated not only in growth regulation of the normal gland but also in the pathogenesis of prostate cancer, and that this malignant tissue retains some degree of androgen dependence. This concept was supported by studies of symptomatic clinical cancer, with androgen ablative therapy bringing relief to the patient in more than 80% of the cases. The classical treatment consisted of either bilateral orchiectomy, or administration of diethylstilbestrol (DES). Other forms of therapy followed, involving successive waves of new compounds that either withdrew androgen support from the cancer or blocked the androgens from their receptors in the prostate cancer cells. Chronologically, the progestagens can be well recognised, with one in particular: The successful derivative, cyproterone acetate (CPA). There also have been a number of oral vs. parenteral estrogens, the development of the luteinizing hormone-releasing hormone agonists (LH-RHA), the introduction of the non-steroidal anti-androgens characterised by flutamide and casodex, and more recently, the introduction of the LH-RHA. Moreover, there have been multiple possible forms of combination treatment to obtain maximal androgen blockade (MAB). However, no major differences in treatment outcome have been reported during the last 5 decades and most treatment choices have been based on tradition, associated side effects, the preferences of a particular doctor and patient, together with economic considerations. Furthermore, endocrine treatment has never been shown to cure clinical prostate cancer, which consequently has led to initiatives to defer endocrine treatment or to use it intermittently or use it as a form of neo-adjuvant or adjuvant treatment with surgery or radiotherapy. The history of endocrine therapy is replete with clinical trials that do not represent the patient population in general, and these trials share the clinical fact that they ignore the 20% to 30% of all patients who lack an initial response to a given endocrine treatment. Thus, it is no wonder that prognostic factors determine the outcome more than the treatment itself. Important to current endocrine treatment, however, is the shift to earlier stages of prostate cancer at initial diagnosis. Integration of endocrine treatment at this earlier phase in the pathogenesis of prostate cancer will substantially alter the treatment strategy in relation to long-term benefit with regard to survival, associated side effects, and costs. This complex adjustment is enhanced by recent discoveries in the molecular biology of the prostate which show, on the one hand, that the dihydrotestosterone-androgen receptor (DHT-AR) complex is important in the regulation of gene expression, but also that a number of intrinsic factors (e.g., peptide growth regulatory factors) can, through various paracrine, autocrine or intracrine interactions, exercise a major influence on cellular homeostasis and the regulation of prostatic growth.

Androgen Antagonists↗
PubMedDate not supplied

The importance of internal quality control data in National External Quality Assessment schemes. Plasma progesterone assays.

Co-ordinators of external quality assessment schemes in the U.K. despatch samples of quality control material to participant laboratories at frequent intervals to assess laboratory performance. We show, via a controlled experiment on the plasma progesterone assay, that the current analysis performed by the external assessors is inadequate and often leads to erroneous conclusions about a laboratory's performance. It is concluded that for a proper assessment of a laboratory's performance, the external assessor should prepare large pools of plasma and distribute them to all participants in the scheme to use as internal quality control material.

Chemistry Techniques, Analytical↗
PubMedDate not supplied

Application of Cusum techniques to the routine monitoring of analytical performance in clinical laboratories.

Quality control data from a radioimmunoassay of progesterone are analysed. The measurements are found to have a lognormal distribution. A likelihood analysis of the change-point is described. Some rival continuous inspection schemes are compared and it is pointed out that more efficient schemes than Shewhart's can be implemented in clinical laboratories with the aid of a computer.

Chemistry, Clinical↗
PubMedDate not supplied

Dose-interpolation of immunoassay data: uncertainties associated with curve-fitting.

Estimates of analyte concentrations, obtained by immunoassay, have error distributions which are generally underestimated. Better estimates, which take into account the distribution of the response metameter of the calibration curve and uncertainties associated with the location of the fitted curve, have been obtained by computer simulation using practical immunoassay data. The increased use of curve-fitting software in automated immunoassay equipment has prompted the investigation of reported analyte concentration distributions for three commonly used functions, namely the logit-log, the 4-parameter logistic and the four-parameter Amersham models. The stimulation model is of potential value for a variety of situations.

Biometry↗
PubMedDate not supplied

Influence of steroid-receptor complexes on transcription by human hypertrophied prostatic RNA polymerases.

The effects of 5alpha-dihydrotestosterone-receptor complexes on transcription in human hypertrophied prostate tissue were studied in a cell-free system reconstituted from the various subcellular fractions prepared from specimens of the diseased gland. Two major RNA polymerase species were isolated from human hypertrophied prostate. These were designated A and B and were distinguishable by their preference for divalent cations and their sensitivity to salt and alpha-amanitin. Moreover, RNA polymerase B, but not RNA polymerase A, could effectively transcribe a prostate chromatin template. Any enzyme activity endogenous to some chromatin preparations was shown to be characteristic of RNA polymerase B. 5alpha-Dihydrotestoterone-receptor complexes were transferred into prostatic chromatin both steroid- and tissue-specifically. The association of steroid-receptor complexes with chromatin produced changes in template activity and increased the transcription of the chromatin by exogenous and endogenous RNA polymerase B. With a number of specimens, however, there was considerable variation in accessible cytoplasmic receptor sites, uptake of steroid-receptor complexes by chromatin preparations, the template activity of the chromatin and its response to steroid-receptor stimulation. Nevertheless, the transcription characteristics of human hypertrophied prostatic chromatin appear to be influenced by steroid-receptor complexes, and the extent of the response to added complexes would undoubtedly be governed by pre-existing complexes having had an earlier effect.

Aged↗
PubMedDate not supplied

Breast skin temperature rhythms in relation to ovulation.

Breast skin temperatures have been monitored at 30-min intervals throughout wake-span for the whole or part of the menstrual cycle of women aged 20-37 years using both manual and automatic (chronobra) methods of measurement. Circadian breast skin temperature rhythms have been mathematically characterized and rhythm parameters assessed in relation to the estimated time of ovulation. Data generally indicate that there is a peri-ovulatory rise in breast temperature. Computer simulation and practical experiments, based on changes in the residual sums of squares from target values obtained for days in the cycle prior to ovulation, have indicated that this peri-ovulatory increase in temperature is possibly detectable within 24 h. The use of the chronobra and associated statistics may be of value in signalling the onset of the infertile phase of the menstrual cycle.

Adult↗
PubMedDate not supplied

Prolactin and breast skin temperature rhythms in postmenopausal women with primary breast cancer.

Plasma prolactin and cortisol were determined and breast skin temperatures measured in 8 postmenopausal diurnally active-nocturnally resting women, 7 with primary breast cancer and 1 with benign breast disease. In all subjects, prolactin peaked during the early morning hours. Cortisol and oral temperature served as internal physiological markers of anticipated rhythmicity in adrenocortical function and metabolism. In all patients studied, the tumour site had an increased mesor (midline-estimating statistic of rhythm) and reduced amplitude of the circadian breast skin temperature rhythm when compared to a similar site on the contralateral breast. Thermal asymmetry was also observed between left and right breasts. A cancer, if in the left breast, may reinforce lower amplitude and perhaps a higher mesor (associated with the healthy left breast in these particular patients), whereas if it is located in the right breast, it tends to nullify inter-mammary differences in mesor and amplitude. Screening for breast cancer appears to require subjects being monitored on at least two occasions before thermal abnormalities due to tumour or preneoplasia become discernible.

Aged↗
PubMedDate not supplied

Circadian rhythms of testosterone and cortisol in saliva: effects of activity-phase shifts and continuous daylight.

The variations in concentrations of testosterone and cortisol in saliva samples collected by 4 healthy young men whilst on a scientific expedition from Britain to Spitzbergen are described. The rhythms observed in steroid concentrations in saliva were characterized mathematically by cosinor analysis of the levels of testosterone and cortisol determined in saliva samples collected before, during and after the expedition. Whilst in Spitzbergen, the subjects were maintained initially on the British sleep-wake schedule which was later subjected to an 8-h phase change. Variations in testosterone concentrations in saliva appeared to be largely related to subject activity rather than any photoperiodic effect with rapid resynchronization of the circadian acrophase in response to the phase shift of the sleep-wake schedule. In contrast, variation in salivary cortisol levels appeared to be less related to activity and more dependent on the slower resynchronization of an endogenous rhythm of cortisol secretion.

Adult↗
PubMedDate not supplied

Toward a chronopsy: Part III. Automatic monitoring of rectal, axillary and breast surface temperature and of wrist activity; effects of age and of ambulatory surgery followed by nosocomial infection.

Data of core and breast surface temperature and motor activity collected automatically with ambulatory devices, reveal circadian rhythms of different prominence in these various potential chronobiologic markers. Chronobiologic serial sections further allow the study of any alterations of the circadian rhythm parameters following ambulatory surgery. An approach using miniaturized instrumentation and methods of time series analysis may signal the danger of postoperative complications and, if it prompts timely preventive measures, may increase the safety of ambulatory surgery in particular.

Ambulatory Surgical Procedures↗