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M Rutland

Publications and source records attributed to M Rutland.

15 recordsLinked to original sources
PubMed2003

Database deconvolution.

A new deconvolution technique is described. It regards the Rutland-Patlak plot as the integral of the retention function, and performs deconvolution by creating and then differentiating the Rutland-Patlak plot. The reasoning behind this approach is that in producing the Rutland-Patlak plot, both the content function and the integral of the input function are divided by the input function (i.e. the blood curve), and that this has the effect of producing data equivalent to that which would be produced if the input function did not vary (i.e. if there were a constant blood level of tracer). The concept was tested against data created by modelling techniques. It was able to reproduce retention functions with a variety of different shapes that were used to produce the artificial renogram data. The new deconvolution method is sufficiently simple to be used in either a database or a spreadsheet and does not require any special program units to be written. It does not appear to make any assumptions about the data nor the shape of the retention function, and does not appear to be vulnerable to the oscillating errors that sometimes occur in iterative deconvolution.

Algorithms↗
PubMed2002

Mean transit times without deconvolution...reconsidered.

A new deconvolution technique is described. It is based on an earlier method which used a graphical technique to analyse the early stages of organ data and blood curves to obtain the background subtraction factor and the uptake constant for tracer uptake by the organ. In that initial application, those variables were then applied to a later point on the organ and blood curves to calculate a mean transit time without first producing a retention function. This new deconvolution technique performs that later step on all points of the organ data curve to produce a function showing how the mean transit time varies with time. This considered to be the area under the retention function (i.e. the integral of the retention function), and the retention function itself is then obtained by differentiation. Modelling techniques were used to create renogram shapes by convoluting known (input) retention functions with a calculated blood curve. The new deconvolution method was then used to recover the retention function from each artificial data curve. The recovery of that input data implies that the new deconvolution technique is sufficiently successful to justify further consideration. In addition, as a demonstration, iterative deconvolution and the new method were both used on renograms from an obstructed kidney and a kidney with normal outflow. Both methods produced similar shaped retention functions.

Child, Preschool↗
PubMed2001

Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.

It has been claimed that the bisphosphonate space, a scintigraphic technique which simultaneously estimates bone uptake and renal clearance of bisphosphonate, can be used to predict the dose of bisphosphonate required to induce biochemical remission in Paget's disease. In a prospective study of 15 newly diagnosed patients with Paget's disease, bisphosphonate space measurements were made prior to treatment with intravenous clodronate. Treatment with clodronate 0.6 g was given four times weekly until the alkaline phosphatase (ALP) suppressed below the upper level of the reference range (120 u/l) or reached a plateau, and the cumulative dose required (1.8-7.8 g) was calculated. Overall, the bisphosphonate space correlated poorly with the total dose requirement (r = 0.441, P = 0.100), but the relationship was weakened by an outlier, who had the poorest renal function. Excluding this subject improved the correlation coefficient (r = 0.852, P <0.0001). The relationship between dose requirement and log10 initial ALP was not as strong (r = 0.672, P <0.01). However, for both ALP and the bisphosphonate space the 95% prediction intervals were wide. We conclude that the bisphosphonate space does relate to dose requirements for intravenous bisphosphonates, but that it is unreliable when renal function is poor, and may not offer much gain over the pretreatment ALP levels. Both ALP and the bisphosphonate space have wide prediction intervals, and are therefore poor guides to dose requirement.

Aged↗
PubMed2000

Application of the JKR Method to the Measurement of Adhesion to Langmuir-Blodgett Cellulose Surfaces.

The JKR method has been applied for studying adhesion between poly(dimethylsiloxane) (PDMS) caps and Langmuir-Blodgett cellulose surfaces including the substrate, hydrophobized mica, and two flat mineral surfaces, bare mica and glass. The self-adhesion of PDMS caps and oxidized PDMS caps are included as a reference to compare with literature data. The results of the measurements have been compared with previous studies using the surface force apparatus and similar systems. A satisfactory agreement is obtained for simple systems showing no, or very limited, hysteresis between loading and unloading curves. In several cases, however, a large hysteresis is found between loading and unloading curves, with a larger adhesion measured from the pull-off force than from the JKR-curve determined on loading. This is, for instance, the case for PDMS against cellulose. The situation is analogous to that found in wetting studies showing a large hysteresis between advancing and receding contact angles. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

"FUR"--one size suits all.

This work used amalgamated data from previous projects in order to test the concept that when organ function is expressed in terms of tracer kinetics, the results are independent of patient size or gender. Dynamic gamma camera studies were analysed by measuring the rate of movement of tracers from the blood into various organs. These rates were expressed as a "fractional uptake rate" (FUR), which is the fraction of tracer in the blood taken up by the organ per unit time. As these values were small, it was convenient to express the FUR per million seconds. The FUR was calculated using the expression FUR = SLOPE (of Rutland-Patlak plot), multiplied by B(0) (the blood curve value back-extrapolated to time zero), and divided by the TOTAL amount of tracer injected. Data were used from adult patients between the ages of 20 and 49 years who had normal organ function. Organ/tracer groups studied were the skeletal uptake of 99mTc-MDP, the renal uptake of 99mTc-MAG3, the renal uptake of 99mTc-MDP, the renal uptake of 99mTc-DTPA, the hepatic uptake of 99mTc-colloid, the splenic uptake of 99mTc-colloid, and the hepatic uptake of 99mTc-DISIDA. Each organ/tracer group was divided into three subgroups according to patient size (smallest, middle and largest), and also into subgroups according to gender. Comparison of these subgroups did not show any significant size- or gender-related differences in FUR values. It is concluded that for patients with normally functioning organs the FUR is independent of patient size or gender. Thus, the FUR is a valuable way of expressing organ function, particularly in patients with unusual or rapidly changing body size, such as children.

Adult↗
PubMed1999

Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.

Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.

Adult↗
PubMed1999

Report of the Radionuclides in Nephrourology Committee for evaluation of transplanted kidney (review of techniques).

Comprehensive evaluation of renal transplants has been important in differential diagnosis of medical and surgical complications in the early post-transplantation period and in the long-term follow-up. If performed well, it yields excellent functional and good anatomic information about the graft that can be effectively used in the patient. That includes selection of patients for biopsy and for various drug regimens. This is true especially in patients with anuric acute tubular necrosis (ATN) and in patients with developing chronic rejection. Improving indices of renal function (effective renal plasma flow, uptake of tubular tracers) can indicate resolution of tubular injury (ATN) while there is still no improvement in plasma creatinine. In patients with chronic rejection, plasma creatinine increases only after approximately 30% of renal function is lost due to graft fibrosis. Early recognition of this condition could permit treatment and delay of retransplantation. The protocol recommended at the Copenhagen meeting includes a flow study, scintigram of the kidneys, prevoid and postvoid bladder image, injection site image (quality control), time/activity curves of the graft and bladder, and quantitative data of perfusion, function, and tracer transit. The flow study obtained during the initial transit of the bolus through the graft could be performed either with 99mTc mercaptoacetyltriglycine, or 99mTc diethylenetriaminepentaacetate (DTPA). Quantitative analysis of perfusion facilitates interpretation of the study during the early post-transplantation period. ATN, common in cadaver transplants, typically shows adequate perfusion. The function phase should include images and time/activity curves. Images alone are insufficient. Quantitative data such as clearance or other indices of function and indices of tracer transit are essential for correct interpretation of the results. Normal images and normal graft function reliably exclude clinically important complications. A single scintigram demonstrating prolonged tracer transit with decreased function cannot separate acute rejection and ATN. On serial studies, decline in function and poor perfusion are indicative of acute rejection. A normally appearing scintigram without cortical retention, but with low function, is consistent with chronic rejection. Pharmacological intervention to exclude obstruction (diuretic renogram) or hemodynamically significant renal artery stenosis (angiotensin converting enzyme challenge) should be used whenever indicated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Enhancement of the anti-tumour effects of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by combination with 5-hydroxytryptamine and bioreductive drugs.

The tumour blood flow inhibitor 5,6-dimethylxanthenone-4-acetic acid (DMXAA) causes dramatic haemorrhagic necrosis in murine tumours, but activity is seen only at doses close to the toxic limit. This study investigates two approaches for increasing the therapeutic ratio of DMXAA. The first approach combines DMXAA with a second tumour blood flow inhibitor, 5-hydroxytryptamine (5-HT). Co-administration of 5-HT (700 micromol kg(-1)) to C3H mice caused marked enhancement of DMXAA effects against MDAH-MCa-4 tumours, with dose-modifying factors (DMFs) of >3 for blood flow inhibition (at 4 h), 2.3 for necrosis (at 12 h) and 2.0 for growth delay, without compromising the maximum tolerated dose of DMXAA (90 micromol kg(-1)). The data are consistent with ischaemic injury to the tumour being the major mechanism of anti-tumour activity. The second approach combines DMXAA (+/- 5-HT) with hypoxia-selective bioreductive drugs. Anti-tumour activity of all three bioreductive drugs tested (tirapazamine, CI-1010, SN 23816) was strongly potentiated by DMXAA, suggesting that there is a population of reversibly hypoxic tumour cells after DMXAA treatment. Co-administration of 5-HT further potentiated anti-tumour activity, but also increased host toxicity of tirapazamine and CI-1010 so that little therapeutic benefit was achieved. In contrast, the host toxicity of the dinitrobenzamide mustard SN 23816 was only slightly increased by DMXAA/5-HT, whereas the tumour growth delay at the maximum tolerated dose of SN 23816 was increased from 3.5 to 26.5 days. This study demonstrates that 5-HT and/or bioreductive drugs can improve the therapeutic activity of DMXAA in mice, and that with SN 23816 both approaches can be used together to provide considerably enhanced anti-tumour activity.

Animals↗
PubMed1997

Evidence for secular change in Paget's disease.

Death certification data has shown that death rates due to Paget's disease of bone and osteosarcoma in older people (assumed to be attributable to Paget's) declined in the latter part of the 19th and in the early 20th century, suggesting that there may be a secular trend toward less severe disease. We have reviewed a 21 year experience in a clinic specializing in Paget's disease. Data from all 1041 patients attending the clinic in this period were reviewed. Despite an increase in the susceptible population and an increased rate of referral to the clinic over this time (p = 0.012), there was a fall in the absolute numbers of patients referred with severe disease, as judged by the initial plasma alkaline phosphatase activity at presentation. In the years 1973-1978 the initial plasma alkaline phosphatase was > 500 U/L in an average of 22 new patients per year and > 1000 U/L in 12 per year. In the years 1988-1993, the figures were 12 and 3 per year, respectively. During this period, there were no other facilities offering scintigraphy or intravenous treatment for Paget's disease in the Auckland region, making it unlikely that patients with severe disease were being seen and treated elsewhere. The average age of newly referred patients rose steadily from a mean 62 years, in 1971-1973 to 71 years in 1991-1993 (p < 0.001). 534 subjects had scintiscans (52%) from which the extent of skeletal involvement was calculated. Skeletal involvement showed a significant negative correlation with year of birth (p < 0.01) but not with age or year of presentation. The proportion of patients with > 20% skeletal involvement had fallen by a third in the cohort born after 1926, compared to the cohort born before 1915. Our data demonstrate that, on average, newly referred patients with Paget's disease have less severe disease and are significantly older at diagnosis than was the case two decades ago.

Aged↗
PubMed1994

Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid.

PURPOSE: To determine whether 5,6-dimethylxanthenone acetic acid (DMXAA), a potent analogue of flavone acetic acid (FAA) inhibits blood flow in mouse mammary tumors, and to assess whether DMXAA enhances the antitumor effects of Tirapazamine (SR 4233) and the novel bioreductive drug SN 23862 (a dinitrobenbenzene mustard). METHODS AND MATERIALS: MDAH-MCa-4 mouse mammary tumors were grown i.m. in the leg of C3H/HeN mice. Tumor blood flow was assessed by the pertechnetate clearance method and subsequent growth delay was determined in the same tumors. RESULTS: Administration of DMXAA (65-70 mumol/kg) resulted in inhibition of tumor blood flow to approximately 25% of control values, with no recovery observed up to 36 h post-treatment. Combination of DMXAA with SR 4233 provided a significant increase in tumor growth inhibition relative to either drug alone. In this effect, DMXAA was qualitatively similar to FAA, but was approximately 10 x more potent. The interaction between DMXAA (65 mumol/kg) and SR 4233 (200 mumol/kg) was maximal with SR 4233 given between 15 min before and 60 min after DMXAA. For SN 23862, a similar enhanced growth delay was observed in combination with DMXAA, with no obvious time dependence between 15 min before and 4 h after DMXAA. When mean values for groups treated with SR 4233 (200 mumole/kg) alone and in combination with DMXAA (65-90 mumole/kg) were compared, a correlation was observed between tumor blood flow inhibition and subsequent growth delay. CONCLUSION: DMXAA is a potent inhibitor of blood flow in MDAH-MCa-4 tumors. Combination of this vasoactive drug with bioreductive agents leads to an enhanced antitumor effect. For SR 4233 and DMXAA, this enhanced effect may be predictable by measurement of tumor blood flow inhibition shortly after drug administration.

Aniline Mustard↗
PubMed1994

Glomerular hyperfiltration in young Polynesians with type 2 diabetes.

An increase in glomerular filtration rate (hyperfiltration) may be an important early event in the initiation of diabetic nephropathy but the prevalence of hyperfiltration appears to vary between different populations with type 2 diabetes. We have measured glomerular filtration rate using 51Cr EDTA clearance in 15 young Polynesians (mean age 32 years), 1-30 months after the initial diagnosis of type 2 diabetes and 15 control Polynesian subjects of comparable age and sex distribution. The mean glomerular filtration rate in the diabetic subjects (216 ml/min) was 57% greater than that of the controls (137.5 ml/min, P < 0.0001). About one-third of their excess in glomerular filtration rate could be accounted for by the marked obesity of the diabetic subjects, but even after correcting for body size the diabetic subjects still had a significantly higher mean glomerular filtration rate than controls (165.6 vs. 119.6 ml/min per 1.73 m2, P < 0.001); 73% of the diabetic subjects had hyperfiltration (> 140 ml/min per 1.73 m2). The diabetic subjects were normotensive but nonetheless had increased rates of albumin excretion (median 61 versus 9 mg/day, P < 0.001). We conclude that hyperfiltration is common in young Polynesians with recently diagnosed type 2 diabetes. Prospective studies are needed to determine whether this early abnormality of renal function heralds the later development of overt nephropathy.

Adult↗
PubMed1988

Treatment of metastatic prostate carcinoma with the depot LRH analog Zoladex.

A long-acting LRH agonist (ICI 118630, Zoladex) was given by monthly subcutaneous injection to 25 patients with previously untreated symptomatic advanced prostatic carcinoma. The medication was well tolerated with the only side effect being hot flushes in 15 patients. Subjective improvement occurred in 22 patients, and disease remission or stabilization judged by objective criteria was seen in 21 and 18 patients from the total group at 3 and 6 months of treatment, respectively. Twelve of 18 patients followed for 1 year were still in objective remission/stabilization. Prostate volume measured by ultrasound decreased by a mean value of 75% and urine flow increased significantly. There were significant falls in serum testosterone and gonadotrophin levels and significant although lesser reductions in serum androstenedione and dehydroepiandrosterone. These changes were accompanied by significant reductions in serum acid and alkaline phosphatase and a rise in serum osteocalcin. Four patients (16%) experienced an initial tumor flare. Although only a small number of patients were studied, Zoladex appeared to be a well-tolerated agent for treatment of prostatic carcinoma, with an initial clinical response similar to that seen with standard endocrine therapy.

Adult↗
PubMed1986

Evaluation of therapeutic decisions in patients with suspected pulmonary embolism and a low probability lung scan: application of Bayes' Theorem.

Three hundred and one consecutive lung scans were reviewed to determine the frequency of the different ventilation perfusion scan patterns and their use in the management of suspected pulmonary embolism. Based on the original report, an accurate diagnosis was possible in 99 patients (33%). Within this group pulmonary embolism was excluded by a normal lung scan in 35 (12%), and confirmed in 64 (21%) patients having a high probability pattern. There were 194 (64%) patients with a low probability scan, but in only 24 of these (12%) was venous thromboembolism objectively confirmed or excluded by additional investigations. Although the low probability scan is non-specific, the scan result was used as the sole objective test to determine therapy in 170 patients (56%). The clinical decision was to withhold anticoagulants in 143 patients and to treat 27 patients. Probability estimates using Bayes' Theorem have been applied to evaluate these management decisions.

Adolescent↗
PubMed1984

Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate); a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate).

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.

Aged↗