Biomedical subjects

G M Blake

Publications and source records attributed to G M Blake.

At least 109 records · Page 6Linked to original sources

PubMed1991

Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid.

Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r = 0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.

Adult↗

PubMed1991

The effect of positioning on dual energy X-ray bone densitometry of the proximal femur.

The influence of subject repositioning on the precision of bone mineral densitometry of the proximal femur using dual energy X-ray absorptiometry was estimated by determining the variation in the bone mineral density (BMD) of subjects scanned with their foot and leg position varying from that routinely used in clinical scanning. The mean variations in BMD of the femoral neck, Ward's triangle and trochanter were 2.7, 4.1 and 1.7%, respectively, in eight subjects scanned with the foot internally rotated by 0, 13 and 27 degrees. The mean variations in BMD in four subjects scanned with the leg in the customary position and abducted +/- 6 degrees from the conventionally used scanning position were 3.6, 2.8 and 1.6% for the same respective regions of interest. For diagnostic applications, the orientation of the leg and foot during scanning is relatively unimportant since the variations in BMD introduced by the different foot and leg orientations likely to be encountered in routine clinical scanning are small compared to the intrapopulation variation in BMD. However, for monitoring changes in BMD longitudinally, careful repositioning of the foot and leg will be necessary to achieve precision in vivo of less than 1%.

Absorptiometry, Photon↗

PubMed1991

Intersite comparison of the Hologic QDR-1000 dual energy X-ray bone densitometer.

UNLABELLED: We have compared results from 13 Hologic QDR-1000 bone densitometers: (i) by performing spine and hip scans on two normal volunteers; (ii) by acquiring sets of 10 sequential scans on a Hologic anthropomorphic spine phantom. For each QDR-1000 site visited a set of spine phantom scans was also acquired on a QDR-1000 at Guy's Hospital to serve as a control study. All scans were analysed using the Hologic scan comparison software. Radiographers at each site were asked to perform their own independent analysis of the scans of the two volunteers. The precision of the bone mineral density (BMD), bone mineral content (BMC) and projected area (Area) results for a set of 10 phantom scans was 0.11%, 0.14% and 0.12% respectively. The coefficient of variation (CV) between sites for the sets of phantom scans was 0.58% for BMD, 0.71% for BMC and 0.35% for Area. In comparison, CVs for the phantom scans acquired on a single QDR-1000 were 0.23%, 0.23% and 0.09% respectively. The CV for the BMD results on the two volunteers obtained using the scan comparison software averaged 1.4% for the spine and 2.1% for the femoral neck. The CV for the results obtained by site radiographers averaged 2.2% for the spine and 3.7% for the femoral neck. Significant differences in the technique used for hip analysis were found. CONCLUSIONS: (i) differences in calibration between systems were generally less than 1%; (ii) variations in results resulting from differences in analytical technique were more significant than those resulting from differences in calibration.

Absorptiometry, Photon↗

PubMed1990

Pharmacokinetics, biodistribution and dosimetry of 99Tcm(V)DMSA in humans with squamous cell carcinoma.

Technetium-99m (99Tcm)(V) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to evaluate squamous carcinoma (SCC) of the head and neck. This study evaluated the pharmacokinetics and biodistribution of 99Tcm(V)DMSA in patients with SCC and calculated the bone mass of a New Zealand White (NZW) rabbit. This data was then used to calculate the effective dose equivalent in man. A total of 16 patients were studied (5 with no tumour, 11 with tumour). 99Tcm(V)DMSA had a fast bi-exponential blood clearance in patients with no tumour (30 and 401 min) and patients with tumour (30 and 387 min) with no significant difference (p greater than 0.05) between the two groups. 99Tcm(V)DMSA had a fast cumulative urine excretion with mean half-times in non-tumour and tumour patients of 183 min and 244 min respectively. There was no significant difference (p greater than 0.05) between these two latter groups. The effective dose equivalent of 99Tcm(V)DMSA in man is 5.1 microSv/MBq.

Aged↗

PubMed1989

89Sr therapy: strontium plasma clearance in disseminated prostatic carcinoma.

Strontium plasma clearance is an important factor determining the absorbed dose to metastases and bone marrow in patients receiving 89Sr radionuclide therapy for metastatic bone disease. Amongst male patients with disseminated prostatic carcinoma, the renal component of strontium clearance is frequently greatly reduced compared with values reported for healthy middle aged men. We report a study of renal and gut strontium plasma clearance, renal function, calcium urinary excretion, parathyroid function and extent of skeletal osteoblastic metastatic disease in patients referred for radiostrontium therapy for metastasised prostatic malignancy. The wide variation in net strontium clearance was principally due to variation in the renal component. Low values of strontium renal clearance were found to correlate with the elevation of serum PTH and nephrogenous cyclic AMP, which in turn correlated with extent of skeletal metastatic disease. This suggests that the osteosclerotic metastases characteristic of prostatic carcinoma induce secondary hyperparathyroidism due to the high avidity of the skeleton for calcium. The resulting reduction in strontium excretion may be beneficial to the objectives of radiostrontium therapy.

Bone Neoplasms↗

PubMed1989

Measurements of the strontium plasma clearance rate in patients receiving 89Sr radionuclide therapy.

The total strontium plasma clearance rate due to excretion through the kidneys and gut has an important influence on the absorbed does delivered to skeletal metastases and red bone marrow in patients receiving 89Sr radionuclide therapy for disseminated prostatic carcinoma. Although a measurement of the renal strontium plasma clearance rate may readily be obtained through a 24-h urine collection, little information is available on the correlation between renal and total clearances. We describe a method of determining total strontium plasma clearance rate from whole body counter measurements of total body strontium retention and measurements of plasma strontium concentration following administration of a 85Sr tracer dose at the time of 89Sr therapy. Amongst the 26 patients whom we studied, the total clearance rate varied from 1.2-15.0 l/day, renal clearance rate from 0.1-11.5 l/day, and the mean gut clearance rate was 2.0 l/day. A close correlation was found between total and renal clearance, with the renal component accounting for 96% of the variance in total strontium plasma clearance. A weak collection may exist between gut and renal clearance.

Humans↗

PubMed1989

Glomerular filtration rate and the kinetics of 123I-metaiodobenzylguanidine.

We have recently reported evidence that the calcium antagonist nifedipine can improve the tumour retention of 131I-metaidobenzylguanidine (131I-MIBG) in patients with malignant phaeochromocytoma. During studies of the pharmacological modification of tumour MIBG kinetics, it is important to distinguish clearly between a direct effect on MIBG cellular retention by a pharmaceutical, and secondary effects due, for example, to a change in glomerular filtration rate (GFR). In order to provide the fundamental kinetic data required for the numerical modelling of the effect of nifedipine on tumour MIBG kinetics, we have investigated the influence of GFR on MIBG plasma and renal kinetics. The 123I-MIBG plasma curve and MIBG renal plasma clearance rate were studied in ten patients, ranging from subjects without biochemical or scintigraphic evidence of phaeochromocytoma to individuals with widely disseminated metastatic disease. GFR was measured using the 99mTc-DTPA plasma clearance method. In four cases, the studies were repeated with the patients taking oral nifedipine. Statistically significant correlations were found between GFR and the MIBG plasma concentration. MIBG renal plasma clearance rate and the early (0 to 5 min) renal excretion of MIBG. The data permit the evaluation of the plasma integral during the first few min following bolus injection, a quantity important in the numerical modelling of tumour kinetics. GFR was found to have a major influence on whole-body MIBG kinetics, but there was also evidence of the effect of the metastatic tumour burden.

3-Iodobenzylguanidine↗

PubMed1989

Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone.

Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

Bone Neoplasms↗

PubMed1988

Modification by nifedipine of 131I-meta-iodobenzylguanidine kinetics in malignant phaeochromocytoma.

Following a case report that oral nifedipine can suppress the secretion of noradrenaline by phaeochromocytoma, we examined the effect of nifedipine on the tumour kinetics of tracer 131I-meta-iodobenzylguanidine (131I-mIBG) in five patients referred for mIBG radionuclide therapy for disseminated malignant phaeochromocytoma. In one subject a striking modification of mIBG kinetics was found that resulted in a doubling of the absorbed dose to tumour while the patient was taking nifedipine. At the same time, urinary excretion of noradrenaline was suppressed by a factor of three. The effect of nifedipine in this patient was confirmed when tracer studies were repeated nine months later. The changes in tumour kinetics were shown to be due to prolonged retention of mIBG rather than increased tumour blood flow or alteration of the curve of mIBG plasma concentration as a function of time.

3-Iodobenzylguanidine↗

PubMed1988

The pharmacokinetics of selenium in psoriasis and atopic dermatitis.

The pharmacokinetics of [75Se-L]-selenomethionine was studied in 10 patients with psoriasis, 10 with atopic dermatitis and 10 healthy subjects. Values for the gut absorption and the rate of endogenous excretion of [75Se-L]-selenomethionine, the exchangeable total-body selenium and plasma selenium concentration showed no significant differences between either patient group and the controls. The results suggest that there is no gross abnormality of selenium pharmacokinetics in either disease, and fail to explain why previous studies have found reduced selenium concentrations and selenium-dependent glutathione peroxidase activity in psoriasis and atopic dermatitis.

Adult↗

PubMed1988

Strontium-89 therapy: measurement of absorbed dose to skeletal metastases.

We report measurements of absorbed dose to vertebral metastases in ten patients referred for 89Sr therapy for disseminated prostatic carcinoma. Patients received a tracer dose of 85Sr at the time of 89Sr treatment and metastatic strontium retention was monitored scintigraphically for 6 mo. Metastatic 85Sr activity corrected for tissue attenuation was measured using the conjugate view principle, with special care taken to eliminate errors due to the selection of the metastatic region of interest. Metastatic volume was determined from high resolution CT images, and density inferred from Hounsfield number using the QCT bone mineral calibration of Genant and Cann. The mean absorbed dose was 850 rad/mCi (23 cGy/MBq) with a range from 220-2260 rad/mCi (6 to 61 cGy/MBq). The wide range found was consistent with the variation expected to arise due to differences in strontium renal plasma clearance (range 0.1-11.81/day) and extent of skeletal metastatic disease (varying from two small metastases to a superscan on [99mTc]MDP images) among the patients studied.

Humans↗

PubMed1987

89Sr radionuclide therapy: dosimetry and haematological toxicity in two patients with metastasising prostatic carcinoma.

We present dosimetry for spinal metastases and red bone marrow in two patients who received 89Sr therapy for disseminated prostatic carcinoma. Absorbed dose to metastases was estimated by combining 85Sr gamma camera studies with computed tomographic measurements of bone mass, and doses of 20 cGy/MBq and 24 cGy/MBq were found for vertebral metastases that uniformly involved the bodies of L3 and D12 respectively. Absorbed dose to red bone marrow was estimated from total body strontium retention studies using the ICRP model for bone dosimetry, and a ratio of metastatic to marrow dose of around 10 was found in each patient. Although they received comparable treatment activities of around 200 MBq, the patients showed markedly different haematological response, this difference being confirmed when each received a second 89Sr treatment 6 months after the first. As a result, clinically significant thrombocytopenia occurred in one patient which prevented further radiostrontium therapy being given.

Adenocarcinoma↗

PubMed1987

Strontium kinetics in metastasized prostatic carcinoma: a comparison with the predictions of impulse response function analysis.

Amongst patients referred for 89Sr palliation of disseminated prostatic carcinoma, we have found wide variations in extent of skeletal metastatic disease and in strontium renal plasma clearance. A numerical technique using impulse response function analysis is reviewed which enables the effect of such variations on the total body, plasma and metastatic strontium retention functions to be calculated. The prediction of the model are compared with kinetic data from patients presenting for radiostrontium therapy, and correlations that have important implications for 89Sr dosimetric studies are confirmed. The simplest kinetic data required to allow for these effects in studies of dose-response and haematological toxicity following radio-strontium treatment are discussed and attention is drawn to a small group of patients who may form a significant exception to the general model.

Bone Neoplasms↗

PubMed1987

Strontium-89 therapy: strontium kinetics and dosimetry in two patients treated for metastasising osteosarcoma.

We report a study of strontium kinetics in two patients who received 89Sr therapy for disseminated osteogenic sarcoma, together with estimates of absorbed dose to the principal metastases and to bone marrow. In neither patient did tumour uptake of strontium have a significant effect on whole-body retention. In one patient, whole-body strontium kinetics agreed closely with the ICRP standard model, while in the second, retention was extremely prolonged, probably due to hypertrophic osteoarthropathy. Strontium-85 scintigraphy, surface counting and high-resolution whole-body profiles agreed in showing that in both patients tumour turnover of strontium was very rapid, with a biological half-life of only a few days. Absorbed dose to tumour was found to be comparable in magnitude to the mean bone-marrow dose. We have no reason to believe that 89Sr therapy was of clinical benefit to either patient.

Adolescent↗

PubMed1987

Strontium-89 radionuclide therapy: a dosimetric study using impulse response function analysis.

In a series of patients receiving 89Sr palliation for metastasised prostatic carcinoma, strontium renal plasma clearance was found to vary from 0.14 to 11.81 day-1, and the extent of skeletal metastatic disease seen on 99Tcm-MDP images varied from a few small metastases to a superscan. Using a numerical technique based on impulse response function (IRF) analysis, we have investigated the effect of such variation between patients on 89Sr dosimetry. The whole-body IRF, HWB(t), is defined by the deconvolution of the whole-body strontium retention function, RWB(t), with the plasma retention function, P(t). For patients with minimal metastatic bone disease we assumed HWB(t) = HO(t), where HO is the IRF derived from the International Commission on Radiological Protection model for normal strontium metabolism. The strontium plasma clearance, k, was allowed to vary, and the resulting variation of RWB(t), P(t) and absorbed dose to bone marrow calculated. By convoluting P(t,k) with the IRF measured for a discrete metastasis, the effect of varying k on tumour dose was investigated. Tumour and bone marrow dose were shown to change by a factor of three as k varied over the range observed in patients. For patients with extensive metastatic bone disease we assumed HWB(t) = (1-beta)HO(t) + beta HS(t), where HS was the IRF measured for a superscan patient and beta was a parameter reflecting the extent of skeletal metastatic disease. The effect of varying beta on tumour and bone marrow dose was investigated, and dose shown to decrease by a factor of five as beta increased from zero to unity. Impulse response function analysis was found to be a powerful and useful aid in clarifying the relationship between strontium kinetics and 89Sr dosimetry.

Bone Marrow↗

PubMed1986

Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate.

Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t less than 6 days, and was an important secondary factor at later times. Over the interval 30 days less than t less than 90 days, R(t) was closely fitted by the power law function R(t) = R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗

PubMed1986

Thallium-pertechnetate subtraction scintigraphy: a quantitative comparison between adenomatous and hyperplastic parathyroid glands.

In a prospective study of 201Tl-99mTc subtraction scintigraphy, 61 hyperparathyroid patients were investigated prior to neck exploration. At surgery, 46 adenomatous and 28 hyperplastic parathyroid glands were excised. We examined the relationship between the pathological category of these glands, their mass, uptake of 201Tl thallous chloride, and the frequency of true-positive and false-negative scintigraphic findings. The variation of sensitivity with parathyroid mass was found to be similar for both adenomatous and hyperplastic glands, with a detection threshold that lay in the range 0.3-0.8 g. The higher overall sensitivity for the detection of adenomas (85%) compared with hyperplasias (44%) was due to the smaller mean weight of the latter. When the parathyroid uptake of thallium was quantified scintigraphically, the practical detection limit of subtraction scanning was found to be an uptake of 0.015%. For glands greater than 1.5 g in weight, uptake increased linearly with mass, and specific uptakes were within the range 0.01-0.04%/g. Below lg, certain small glands had much higher specific uptakes, up to 0.2%/g. The range of specific uptakes found was similar for both adenomatous and hyperplastic categories. Multinodular or diffuse goitre was a cause of failure in 10% of investigations. In a further 5%, a solitary thyroid nodule gave rise to a false-positive result.

Adenoma↗

PubMed1986

A simple objective method of recognizing goitre during parathyroid scintigraphy.

The presence of diffuse or multinodular goitre can lead to a false negative study of 10 to 20% of parathyroid investigations when the thallium-pertechnetate subtraction technique is used. A simple quantitative index is described that aids recognition of scintiscans whose diagnostic value may be limited by goitre. The index, referred to as the thallium thyroid index (TTI), is obtained from the ratio of thyroidal thallium counts above background to the mean background count density (expressed as counts cm-2) measured in regions just above and below the thyroid image. It correlates linearly with thyroid mass over the range 7 to 50 g, and goitre is likely to adversely affect the diagnostic quality of parathyroid scintiscans for values of TTI greater than 30 cm2 (corresponding to thyroid masses exceeding 35 g). TTI is insensitive to the time of commencement of image acquisition for times between 2 to 30 min following injection of the patient, and its correlation with thyroid mass has been confirmed by independent series of scans in two centres.

Adenoma↗