Biomedical subjects
Publications and source records attributed to M J Keir.
Moderate antenatal renal pelvic dilation (5-15 mm) may suggest vesicoureteric reflux, but it is not known to predict renal scarring. Dimercaptosuccinic acid scans on such children aged over 4 years showed a scarring rate (0/133 boys, 1/56 girls) similar to our local population. Investigation and treatment of moderate dilation may not be required.
Estimation of glomerular filtration rate (GFR) using the clearance of chromium 51 EDTA ((51)Cr-EDTA) (or other radiolabelled isotopes) is reliable, but invasive and not always practicable. Mathematical models have been devised for estimating GFR using readily obtainable patient characteristics. Unfortunately, these models were developed using various patient populations and may not provide the optimal prediction of GFR in children with cancer. The current study uses population pharmacokinetics to determine the relationship between (51)Cr-EDTA clearance, and patient covariates in 50 paediatric cancer patients. These models were validated using a separate group of 43 children and were compared with previously published models of renal function. Body size was the major determinant of (51)Cr-EDTA clearance and inclusion of weight or surface area reduced the residual variability between individuals (coefficient of variation) from 61 to 32%. Serum creatinine was the only other parameter that significantly improved the model. Mean percentage error values of -5.0 and -1.1% were observed for models including weight alone or weight and creatinine, respectively, with precision estimates of 21.7 and 20.0%. These simple additive models provide a more rationale approach than the use of complex formulae, involving additional parameters, to predict renal function.
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The aim of this study was to assess the value of prone computed tomography compared with the traditional supine position, in the assessment of invasion of adjacent mediastinal structures by oesophageal cancer. A prospective, single blind case-case comparative study of signs of local tumour invasion was conducted. Sixty nine consecutive patients undergoing computed tomography for preoperative staging of oesophageal carcinoma were studied. Computed tomography scanning of the thorax was performed in the standard supine followed by prone position; in 39 patients the computed tomography findings were correlated with the surgical findings. Four established radiological signs used to assess mediastinal invasion were scored in each case. Based on the radiological scoring system, there was a significant down staging in the probability of aortic invasion in 12 of the 69 cases (p<0.05). A similar improvement in accuracy was seen in the cases undergoing surgery; of the 38 cases who did not have aortic invasion at operation, 10 cases were scored as high for aortic invasion on the supine scans compared with only three on the prone position (p<0.05). Prone scanning was not of significant additional value in the assessment of major airway or pericardial invasion. Modification of the computed tomography protocol to include scanning in the prone position will improve the accuracy of the preoperative staging of patients with oesophageal malignancy and reduce the chance of overstaging disease. Especially in centres where endoscopic ultrasound is not available, our modification may reduce the chance of denying patients potentially curative operations.
The novel GABA(B) receptor antagonist [3H]CGP 62349 binds rat cerebellar synaptosomal membranes with high affinity at a single population of sites (K(d) = 0.9 nM, B(max) = 760 fmol/mg protein). Solubilisation with 1% Triton X-100/0.5 M NaCl/10% glycerol resulted in a marked increase in [3H]CGP 62349 binding (K(d) = 0.5 nM, B(max) = 1285 fmol/mg protein). Competition of [3HCGP 35348 = CGP 36742. The GABA(A) ligand isoguvacine did not displace [3H]CGP 62349 binding. Partial purification of [3H]CGP 62349 binding sites was obtained by sucrose density centrifugation and a predominant protein in the peak binding fraction was recognised by an anti-GABA(B) receptor antibody and had a molecular weight similar to the recombinant expressed GABA(B)R1a. These results demonstrate that [3H]CGP 62349 provides a useful additional tool for further characterisation of the pharmacology and biochemistry of the native GABA(B) receptor.
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OBJECTIVE: The study set out to evaluate the relationship between the efficiency of pulmonary oxygenation and the extent of the reimplantation response as revealed on chest radiography after bilateral lung transplantation. MATERIALS AND METHODS: Postoperative chest radiographs of 31 patients who had undergone bilateral lung transplantation were evaluated for the extent of the reimplantation response. For each patient, the contemporaneous oxygenation indexes (partial pressure of oxygen in arterial blood divided by fraction of inspired oxygen) were calculated and correlated with a radiographic score produced from the evaluation of chest radiographs. RESULTS: The method of evaluating chest radiographs for the extent of the reimplantation response was shown to be reproducible. Although mean oxygenation indexes were found to decrease with increasing radiographic scores, this trend was not statistically significant. CONCLUSION: Although the extent of the reimplantation response on the early postoperative chest radiography inversely correlated with the oxygenation efficiency of the transplanted lungs, this finding was not statistically significant.
OBJECTIVE: To determine up to what age children remain at risk of developing a new renal scar from a urinary tract infection. DESIGN: Follow up study. Families of children who had normal ultrasound scans and scanning with dimercaptosuccinic acid (DMSA) after referral with a urinary tract infection when aged 3 (209) or 4 (220) were invited to bring the children for repeat scans 2-11 years later. A history of infections since the original scan was obtained for children not having a repeat scan. SETTING: Teaching hospital. SUBJECTS: Children from three health districts in whom a normal scan had been obtained at age 3-4 years in 1985-1992 because of a urinary tract infection. MAIN OUTCOME MEASURE: Frequency of new renal scars in each age group. RESULTS: In each group, about 97% of children either had repeat scanning (over 80%) or were confidently believed by their general practitioner or parent not to have had another urinary infection. The rate of further infections since the original scan was similar in the 3 and 4 year old groups (48/176 (27%)) and 55/179 (31%)). Few children in either group known to have had further urinary infections did not have repeat scanning (3/209 (1.4%) and 4/220 (1.8%)). In the 3 year old group, 2.4% (5/209) had one or more new kidney scars at repeat scanning (one sided 95% confidence interval up to 5.0%), whereas none of the 4 year olds did (one sided 95% confidence interval up to 1.4%). The children who developed scars were all aged under 3.4 years when scanned originally. CONCLUSIONS: Children with a urinary tract infection but unscarred kidneys after the third birthday have about a 1 in 40 risk of developing a scar subsequently, but after the fourth birthday the risk is either very low or zero. Thus the need for urinary surveillance is much reduced in a large number of children.
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delta-opioid receptor agonists mobilize intracellular Ca2+([Ca2+]i) in SH-SY5Y cells when applied in the presence of muscarinic agonists. The putative delta 1 receptor agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE) elevated [Ca2+]i with an EC50 of 11 nM and the putative delta 2 agonist deltorphin II elevated [Ca2+]i, with an EC50 of 14 nM. The maximal elevations of [Ca2+]i caused by both agonists were not different, nor were maximally effective concentrations of DPDPE (1 microM) and deltorphin II (1 microM) applied together more effective than either agonist applied alone. The elevations of [Ca2+]i caused by DPDPE (1 microM) and deltorphin II (1 microM), in the presence of carbachol, desensitized rapidly with continued opioid exposure and the cross-desensitization between PDPDE and deltorphin II was complete. The putative delta 1 selective antagonist 7-benzylidenenaltrexone (BNTX) and the putative delta 2 selective antagonist naltriben both reduced the elevations of [Ca2+]i caused by DPDPE (30 nM) and deltorphin II (10 nM), by greater than 50% at concentrations of less than 10 nM. In SH-SY5Y cells delta-receptor mediated elevation of [Ca2+]i is mediated by a population of receptors, which does not discriminate between agonists and antagonists purportedly selective for delta 1 or delta 2 receptors.
Since 1977 the Canadian Department of Fisheries and Oceans (DFO) has maintained a specimen bank for retrospective chemical analyses. The Great Lakes Fisheries Specimen Bank (GLFSB) is a complementary activity to the department's ongoing Great Lakes Contaminants Surveillance Program that has annually, since 1977, monitored levels of metals and organochlorines in aquatic biota throughout the Canadian Great Lakes. Past activities have focused on defining the effects of long-term frozen storage on the integrity of organochlorine residues in archived biological tissues. Archived samples have been reanalyzed for total PCBs, PCB congeners including co-planar PCBs, dioxin and furan isomers, and 22 toxaphene congeners. More recently, archived samples of predatory fish have been analyzed for stable isotopes of nitrogen (delta 15N) and carbon (delta 13C), as indicators of historical changes in food web dynamics. A catalogue or user-guide has recently been completed describing all information associated with samples stored in the GLFSB.
A prospective, randomized, double-blind study was undertaken to evaluate Zamifenacin 30 mg (Pfizer Ltd), a novel, orally-administered, gut-specific muscarinic receptor antagonist, as an adjuvant to the double contrast barium enema examination (DCBE). Zamifenacin was compared with placebo in terms of side-effects and colonic tone. Analysis of colonic tone was carried out by two independent observers, using a subjective grading system and also by an objective method using computerized planimetry. Interobserver variability was also assessed. Zamifenacin is safe and well tolerated but at the prescribed dose is an ineffective antispasmodic for DCBE. Subjective assessment of colonic tone was shown to be of limited value whilst the objective analysis using computerized planimetry was reliable and highly reproducible.
The measurement of renal parenchymal volume using a calibrated computed tomography image processing method has been evaluated clinically on a cohort of patients with chronic pyelonephritis. Comparison of renal volume with function as assessed by 99Tcm DTPA renography demonstrated a simple linear relationship in patients who were normotensive and aproteinuric. The implications of this result on the interpretation of prognostic factors determining declining renal function in chronic pyelonephritis are discussed.
Ultrasound assessment of patients with renal impairment commonly includes measurement of bipolar renal length. Reduction in length is considered to indicate chronic renal disease and is a factor in deciding whether to proceed to renal biopsy. To date, no published data are available on interobserver and intraobserver variation in sonographic renal length measurement in adults. Bilateral renal lengths were measured in 20 adult subjects, with no history of renal disease, by three experienced operators, on two separate occasions. Limits of agreement for replicate measurements by each ultrasonographer and for replicate measurements by each pair of ultrasonographers were determined. Values of repeatability (a measure of intraobserver variation) and reproducibility (a measure of interobserver variation) were calculated for all renal length measurements, and for right and left renal lengths separately. Results indicate that replicate renal length measurements differ by less than 1.85 cm in 95% of cases, and the magnitude of variations is similar when measurements are made by either single or different ultrasonographers, and are similar for right and left renal length measurements. This suggests that sonographic bipolar renal length measurements in normal adult kidneys are reasonably reliable. In diseased kidneys, however, in which identification of renal poles is difficult, interobserver and intraobserver variation may be much greater.
A randomized prospective trial was undertaken on 196 consecutive patients referred for double-contrast barium enema examination to assess the relative efficacy of three colon cleansing regimes: Citramag (2 sachets), Picolax and Picolax with a preliminary cleansing enema. Each of the regimes was preceded by a 5 day low residue diet. The radiographs from the examinations were assessed on a double-blind basis. The quality of bowel preparation was significantly poorer (P < 0.001) in the group receiving the preliminary cleansing enema, notably with respect to mucosal coating, compared with the other two groups. The quality of the preparation was slightly better in the group receiving Picolax alone than in the Citramag group (P < 0.01), the difference being most apparent in the proximal colon. The laxatives were equally well tolerated. The study has formed the basis of a departmental audit. As a result, the bowel preparation has been standardized to a 5 day period of dietary restriction followed by 2 Picolax sachets. This measure has improved efficiency within the department with no sacrifice in quality.
Use of a height/plasma creatinine formula to estimate glomerular filtration rate (GFR) is simpler and less invasive than renal or plasma clearance methods. The aim of this study was to determine whether these formulas enabled accurate prediction of GFR measured from the plasma clearance of 51Cr labelled ethylenediaminetetra-acetic acid (51Cr-EDTA). Thirty nine patients underwent GFR measurement at least six months after potentially nephrotoxic chemotherapy. Altman-Bland analysis was performed on the measured GFR and that estimated simultaneously using the original and a modified Counahan-Barratt formula and the Schwartz formula. The limits of agreement of the estimated GFR with the measured GFR were unacceptably wide in each case, despite highly significant correlation coefficients. The bias was smallest for the modified Counahan-Barratt formula. Use of these formulas to estimate GFR in children is insufficiently accurate for research purposes and has limitations in clinical practice. Furthermore, use of correlation coefficients to evaluate different methods of measuring GFR is inappropriate.
A method of measuring glomerular filtration rate is proposed, intended for use during gamma camera renography and involving the continuous monitoring of DTPA activity in blood, a single blood sample, and a urine collection. Data obtained from experiments using a CsI scintillation detector are presented and used to demonstrate the validity of the method. In a comparison with a direct measurement of renal clearance of DTPA the proposed method showed an average overestimate of 13% compared to an overestimate of 30% for an uncorrected single-compartment model calculation of filtration rate. Some limited data using a gamma camera to monitor the DTPA activity in blood are also presented.
In this study 6 commercially produced kinetic modeling packages utilizing a variable volume, single pool urea model, as well as formulae to determine the delivery of therapy, have been compared by applying to each the same set of rigorously collected data for a group of 12 patients. Comparison of the kinetically derived parameters (urea generation rate [G], urea distribution volume [V], delivery of therapy [Kt/V], and normalized protein catabolic rate [nPCR]) showed that the values obtained for both G and V differed between packages owing to the numerical methods and the clearance used in the solution of the differential equations. Although a broad agreement between the values established for Kt/V and nPCR was noted, the 95% limits of agreement indicated that it would be prudent to exercise caution when comparing results established by different modeling packages.