Duty on child-abuse expert witnesses.
Explore the source record for details and available documents.
Child↗
Biomedical subjects
M A Green
Publications and source records attributed to M A Green.
Preparation and biodistribution of copper-67 complexes with tetradentate Schiff-base ligands.
Uncharged, lipophilic, low molecular weight copper complexes labeled with generator-produced copper-62 are of interest as potential radiopharmaceutials for imaging the brain with positron emission tomography (PET). We report here the synthesis and biodistribution of a series of [67Cu]copper(II) complexes with tetradentate N2O2(2-)Schiff-base ligands. The compounds studied varied in lipophilicity from log P = 1.7 to log P = 3.6, where P is the octanol/water partition coefficient. In rat biodistribution studies the tracers were generally found to penetrate the blood-brain barrier following intravenous injection, but some far better than others. For closely related compounds brain uptake at 1 min postinjection increased with increasing lipophilicity, although log P was clearly not the sole determinant of high brain uptake. Substantial variations were also observed in the rate at which these various compounds are cleared from brain, with a few exhibiting the prolonged cerebral retention of tracer that would be desired for imaging with 62Cu and PET.
Animals↗
Microproteinuria predicts the severity of systemic effects of reperfusion injury following infrarenal aortic aneurysm surgery.
Noncardiogenic pulmonary dysfunction can be demonstrated in all patients following elective aortic aneurysm repair and is a cause of postoperative morbidity. Aortic clamping and reperfusion initiate a systemic inflammatory response producing endothelial damage and increases in vascular permeability. In the lung this is manifest as pulmonary edema and in the kidney as detectable increases in urinary protein excretion (microproteinuria). Immunoassay of low-level protein excretion appears to provide an index of the systemic effects of local reperfusion injury and may allow early prediction of complications such as pulmonary edema. Hourly urinary albumin and IgG excretion was measured in 40 patients undergoing infrarenal aortic aneurysm repair and expressed as ratios to urinary creatinine (albumin/creatinine ratio [ACR] and IgG/creatinine ratio [IgGCR]). These were compared to clinical outcome. Pulmonary dysfunction was assessed according to PaO2:FiO2 ratios and chest radiography. Within 180 minutes of beginning surgery all patients had significant increases in ACR and IgGCR. Ten patients who manifested respiratory dysfunction had significantly higher ACRs at 4 hours (median 84.8, 95% confidence intervals, range 47.7 to 136) than patients who made uneventful recoveries (median 16.6, 95% confidence intervals, range 7.9 to 31.7). IgGCR increases paralleled that of ACRs. Differences persisted for 24 hours. Urinary protein excretion rises rapidly during aortic surgery. The degree of increase appears to predict development of pulmonary dysfunction. This simple test may provide a rational basis for evaluation of therapeutic modalities to limit reperfusion injury in these patients.
Aged↗
Investigation of [67Ga]dimethylgallium(III) acetylacetonate as a potential radiopharmaceutical.
Carrier-added [67Ga]dimethylgallium(III) acetylacetonate, a four coordinate Ga complex with two hydrolytically-stable Ga-C bonds, was prepared at a specific activity of 2.8 mCi/mmol. The biodistribution of this tracer was determined following intravenous injection into rats as a 5% ethanol: 19% propylene glycol solution in saline. Although the myocardial levels of 67Ga were fairly constant over a 2 h time period (%ID/heart = 0.80 +/- 0.19, 0.67 +/- 0.04 and 0.62 +/- 0.07 at 1.30 and 120 min post-injection, respectively), somewhat slow clearance of activity from the blood would preclude the use of this organometallic gallium complex as a myocardial imaging agent.
Animals↗
Evaluation of Cu-PTSM as a tracer of tumor perfusion: comparison with labeled microspheres in spontaneous canine neoplasms.
Copper-62-labeled Cu-PTSM is a promising generator-produced PET tracer for myocardial, cerebral and renal perfusion. To evaluate whether [62Cu]Cu-PTSM could also serve as a blood flow tracer in PET studies of tumor tissue, the tumor uptake of [62Cu]Cu-PTSM was examined in dogs with spontaneously-occurring soft-tissue neoplasms. Copper-67-labeled Cu-PTSM was administered intravenously to four anesthetized dogs, followed c. 5 min later by a left ventricular injection of 85Sr-labeled microspheres (15 microns) to provide an independent measure of tumor perfusion. Forty-seven tumors (average weight = 2.5 +/- 3.7 g) were obtained and sectioned into 80 samples. The correlation of 67Cu-PTSM uptake with regional renal perfusion was also examined in data from 395 tissue samples ranging in flow from 0.02 to 9.39 mL min-1 g-1. Rates of tumor perfusion assessed with 85Sr-labeled microspheres ranged from 0.011 to 3.0 mL min-1 g-1. No correlation was found between tumor size and the rate of tumor perfusion. However, an excellent linear correlation exists between tumor perfusion calculated from [62Cu]Cu-PTSM data and tumor perfusion measured with 85Sr-microspheres (r = 0.94 for 80 samples), suggesting that [62Cu]Cu-PTSM may be useful as a radiopharmaceutical for PET studies of tumor perfusion.
Animals↗
Chronic muscle stimulation improves ischaemic muscle performance in patients with peripheral vascular disease.
There is currently no established treatment for intermittent claudication with proven long term benefit. Exercise classes have been shown to improve walking distance. Chronic electromyostimulation (CEMS) a method of stimulating skeletal muscle has effects on normal muscle which may also benefit claudicants. We investigated the effects of one month of CEMS on claudicants in a single blind placebo controlled study. Patients were randomised to either CEMS (treatment) or transcutaneous nerve stimulation (TENS) placebo. The effects of the two modalities were assessed using the conventional measures of claudicating distance (CD), maximum walking distance (MWD), ankle-brachial pressure index (ABPI) and pressure recovery time (PRT). Muscle performance was assessed by the fatigue index (FI) a technique determining the decrease in ischaemic muscle response to repeated contraction. After 4 weeks treatment the CEMS group showed significant improvements in their median CD (88 to 111) and MWD (118 to 158); this was not seen in the control group. Muscle performance also increased significantly during the 4 weeks of treatment in the CEMS group but not in the control group. These changes were not maintained after CEMS was stopped. This pilot study suggests that CEMS may well have a role to play in the treatment of intermittent claudication though a number of further studies need to be undertaken.
Aged↗
Characterization of the prejunctional adenosine receptors in the rat anococcygeus muscle.
Adenosine receptor agonists inhibited electrically-evoked contractions of the rat isolated anococcygeus muscle. The compounds tested were: N6-cyclopentyladenosine (CPA), N((S, trans)-2-hydroxycyclopentyl)adenosine (GR79236), the R- and S-isomers of phenylisopropyladenosine (PIA), 5'-N-ethylcarboxamidoadenosine (NECA), ((2-(4-(2-carboxyethyl)phenyl)ethyl)amino)-N-ethylcarbox-amidoa denosine (CGS 21680) and N-((2-methylphenyl)methyl)adenosine (metrifudil). The rank order of agonist potency was: CPA = R-PIA = GR79236 = NECA >> S-PIA > metrifudil > CGS 21680, which is consistent with an effect mediated by adenosine A1 receptors. A similar rank order of potency was obtained for inhibition of electrically-evoked contractions of the guinea-pig ileum. However, there may be a lower receptor reserve in rat anococcygeus compared with the guinea-pig ileum, since higher concentrations of agonists were necessary to produce effects in the anococcygeus than in the guinea-pig ileum and S-PIA behaved as a partial agonist. The effect of NECA was antagonized in rat anococcygeus and guinea-pig ileum by the mixed A1/A2 receptor antagonist, 8-phenyltheophylline (pA2 values of 6.8 and 6.9, respectively). The selective A1-receptor antagonist, 8-cyclopentyl-1,3- dipropylxanthine (DPCPX), also blocked the inhibitory response to NECA in both tissues. Here, however, the pA2 values (9.6 and 8.6, respectively) were slightly but significantly different. These values confirm that the prejunctional adenosine receptors of the rat anococcygeus are of the A1 type, and suggest that they are similar but not necessarily identical to those of the guinea-pig ileum. The differing potencies of DPCPX as an antagonist of NECA between the preparations may reflect a tissue-dependent variation in sensitivity to this antagonist.
Adenosine↗
Diagnostic features of transfusion associated graft versus host disease.
AIMS: To define the immunopathological profile of transfusion associated graft versus host disease (TA-GvHD) to elucidate its pathophysiology and to determine if any features are of diagnostic value. METHODS: Nine patients (age range 14-61 years) who developed histologically confirmed TA-GvHD between 1989 and 1992 were studied. Immunohistochemical analysis of frozen and formalin fixed skin biopsy tissue was performed. Sections were stained with antibodies to CD3, CD8, CD4 and HLA-DR, using a routine streptavidin-biotin technique with standard diaminobenzidine development. RESULTS: All biopsy specimens showed aberrant positive expression of HLA-DR by epidermal keratinocytes. In four patients, all of whom died, HLA-DR was diffusely expressed throughout the epidermis; in the other five cases keratinocyte expression of HLA-DR was more focal. In all biopsy specimens T cells had infiltrated the dermis and epidermis. In all nine cases CD4+ T helper/inducer cells were the predominant T cells. DISCUSSION: Immunohistochemical studies are of value in the diagnosis of TA-GvHD. Aberrant keratinocyte expression of HLA-DR and dermal and epidermal infiltration of CD4+ T cells are immunopathological features of TA-GvHD. Immunohistochemical analysis of skin biopsy tissue using antibodies to these markers is thus a useful investigation in pancytopenic patients presenting with unexplained rashes.
Adolescent↗
Surveillance policy for early detection of failing arteriovenous fistulae for haemodialysis.
We have developed a programme of surveillance for arteriovenous fistulae. Indications for investigation were a reduction of thrill or pulsation on the fistula, decreasing flow (< 200 ml/min) and/or increased venous return pressure (> 150 mmHg.) when on haemodialysis. Between March 1992 and February 1993 we performed intravenous digital subtraction fistulograms in 17 patients. These investigations demonstrated vein stenosis in 11 patients, nine with primary arteriovenous fistulae and in two with secondary access. There was disease of the arterial inflow in one, and no evidence of anatomical problems in the remaining five. As a result revision surgery was performed in 10 cases and percutaneous transluminal angioplasty in the remaining two cases. Five patients underwent dialysis the following day on the same site, avoiding temporary access. Sixteen patients (94%) are still using the same site for haemodialysis at mean follow-up time of 6.1 months (range 2-12 months) and one failed subsequently. Close surveillance of arteriovenous fistulae leads to detection of stenosis prior to occlusion and intervention increases patency, preserves alternative access sites, and prevents central venous cannulation for temporary access.
Adult↗
Development and validation of a solvent extraction technique for determination of Cu-PTSM in blood.
The partitioning of [67Cu]Cu-PTSM between plasma and red blood cells (RBC) was investigated in vitro with human, rat, pig and dog blood. Significant inter-species variability is observed in the plasma/RBC partitioning of tracer, ranging from c. 75% association with plasma in human blood to only c. 35% association with plasma in dog blood. This inter-species difference results from selective association of the [67Cu]Cu-PTSM tracer with human albumin. When [67Cu]Cu-PTSM is mixed with human blood in vitro at 37 degrees C the fraction of 67Cu-radioactivity that remains plasma-associated decreases with time, apparently due to the expected intracellular decomposition of the Cu-PTSM complex by RBC; however, this process is sufficiently slow that it should have limited influence on [62Cu]CU-PTSM biodistribution following intravenous injection. Octanol extraction of blood was found to be an effective technique for quantitating the amount of intact [67Cu]Cu-PTSM complex in blood samples. When imaging with [62Cu]Cu-PTSM, octanol extraction may be useful for determining the [62Cu]Cu-PTSM content of arterial blood samples to establish a true radiotracer input function.
Animals↗
The need for endoscopic biopsy in the diagnosis of upper gastrointestinal graft-versus-host disease.
Explore the source record for details and available documents.
Biopsy↗
Lithium modulation of phosphoinositide signaling system in rat cortex: selective effect on phorbol ester binding.
Recent work indicates that the therapeutic action of lithium may be mediated through perturbation of postreceptor second messenger systems. To elucidate further the postreceptor cellular sites of action(s) of lithium, the effect of chronic lithium treatment on various components of the receptor-activated phosphoinositide pathway was investigated. We found that chronic administration of lithium (0.2% LiCl, 21 days) to adult male rats did not significantly affect phosphoinositide hydrolysis in cerebral cortical slices induced by carbachol (1 mM) or NaF (10 mM). Nor did the same treatment alter the carbachol (1 mM) potentiation of guanosine 5'-(gamma-thio)triphosphate (30 microM) stimulation of phosphoinositide hydrolysis (an index of receptor/G protein coupling) in cortical membranes. Immunoblotting studies revealed no changes in the levels of G alpha q/11 immunoreactivity in the cortex after chronic lithium treatment. The levels of protein kinase C, as revealed by specific binding of [3H]phorbol dibutyrate ([3H]PDBu), were significantly reduced in the cytosolic fraction and increased in the particulate fraction of rat cortex after chronic lithium, whereas the KD of [3H]PDBu binding remained relatively constant. A small and insignificant decrease in the density of [3H]inositol 1,4,5-trisphosphate binding was also found in the cortex. The above data suggest that chronic lithium treatment affects neither the muscarinic cholinergic-linked phosphoinositide turnover nor the putative G protein alpha subunit (G alpha q/11) responsible for phospholipase C activation. However, a possible translocation and activation of protein kinase C activity may be significant in the therapeutic effect of this mood-stabilizing agent.
Animals↗
Quantification of regional myocardial perfusion with generator-produced 62Cu-PTSM and positron emission tomography.
BACKGROUND: Noninvasive assessment of regional myocardial perfusion at rest and after stress is important for the objective evaluation of the effects of coronary artery disease and its response to therapy. Centers that do not have cyclotrons rely on generator-produced radioisotopes for assessment of regional myocardial perfusion with positron emission tomography (PET). The aim of the present study was to develop and implement an approach to quantify regional myocardial perfusion using copper(II) pyruvaldehyde bis-(N4-thiosemicarbazone) (PTSM) labeled with the generator-produced, positron-emitting radionuclide 62Cu (t1/2 = 9.7 minutes). METHODS AND RESULTS: Regional perfusion was estimated from dynamic PET scans after intravenous administration of 62Cu-PTSM in 21 studies in 13 intact dogs evaluated over a wide range of myocardial flow values. In 15 interventions in nine dogs, regional perfusion was also estimated with H2(15)O. Regional perfusion with 62Cu-PTSM was estimated from dynamic blood and tissue time-activity curves, along with the model parameter k1 (forward rate of transport) and the PET parameter FBM (fraction of blood pool activity observed in tissue), using a two-compartment kinetic model. Arterial blood activity was corrected for red blood cell-associated 62Cu. In 44 comparisons, estimates of regional perfusion with 62Cu-PTSM correlated well with estimates obtained with concomitantly administered radiolabeled microspheres (y = 0.90x +/- 0.15, r = 0.95, p < 0.05) over a flow range from 0.23 to 6.14 ml/g per minute. In five healthy human volunteers evaluated at rest with H2(15)O and 62Cu-PTSM, regional perfusion estimated with 62Cu-PTSM was not significantly different from that obtained with H2(15)O (1.05 +/- 0.36 versus 0.96 +/- 0.28 ml/g per minute). 62Cu-PTSM provided high-quality images of the heart. CONCLUSIONS: The results of this study demonstrate that quantification of regional myocardial perfusion is feasible using generator-produced 62Cu-PTSM. Since 62Cu-PTSM can be used to estimate perfusion in the brain, kidney, and tumors as well as in the heart, it is an attractive tracer for centers that rely on generator-produced tracers for the evaluation of perfusion with PET.
Animals↗
Physiological responses during simulated competition.
Laboratory studies with competitive athletes often use graded exercise protocols to elicit physiologic responses. This pattern of power output is different than ordinarily employed by athletes during competition. To understand the physiologic responses during competition, we studied 24 athletes (speed skaters, cyclists, triathletes) during simulated competition, a 5-km time trial on a racing bicycle attached to a windload simulator, and during cycle ergometer graded exercise testing (N = 8). During the time trial the velocity pattern was similar to real world competitions, and the subjects indicated that the time trial was perceptually similar to competition. Physiologic responses were of significantly greater magnitude vs graded exercise (VO2max: 3.46 +/- 0.73 vs 3.27 +/- 0.79 l.min-1; VEmax: 138 +/- 27 vs 119 +/- 22 l.min-1; HRmax 184 +/- 11 vs 175 +/- 11 beats x min-1; HLa 14.8 +/- 3.7 vs 11.9 +/- 2.1 mM). All physiologic measures increased steadily throughout the time trial (km 0, 1, 2, 3, 4, and 5: VO2 = 1.03, 2.95, 3.42, 3.69, 3.82, and 3.92 l.min-1; HR = 93, 175, 181, 185, 189, and 194 beats.min-1; VE = 31, 99, 120, 129, 145, and 156 l.min-1; HLa = 2.9, 5.6, 7.2, 9.2, 10.6, and 13.5 mM). In six subjects (speed skaters), the peak values observed during time trial for HR (188 +/- 6 vs 191 +/- 5 beats.min-1) and HLa (16.4 +/- 3.1 vs 17.0 +/- 4.2 mM) were not significantly different than observed during real world competition.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A gallium-68 radiopharmaceutical that is retained in myocardium: 68Ga[(4,6-MeO2sal)2BAPEN]+.
The cationic gallium(III) complex formed with the bis(4,6-dimethoxy)salicylaldimine of N,N'-bis(3-aminopropyl)ethylenediamine has been investigated as a potential 68Ga radiopharmaceutical for imaging the heart with PET. The 67Ga complex of this ligand was prepared by ligand exchange from 67Ga-acetylacetonate and its biodistribution determined in ether anesthetized rats following intravenous injection. At 1 min postinjection, 1% of the injected dose was found in the heart with heart-to-blood and heart-to-lung ratios of 2.3:1 and 1.9:1, respectively. No clearance of 67Ga radioactivity from the heart was observed over the 1-min to 2-hr time frame studied. The 68Ga complex of this ligand was also prepared and the tracer further evaluated in a PET imaging study with a normal dog. Beyond 20 min postinjection, the heart was clearly delineated in the 68Ga PET images with good heart-to-blood and heart-to-lung contrast. No clearance of myocardial 68Ga radioactivity was observed over the 90-min imaging period, which is consistent with the results obtained in the rat. Gallium-68 complexes of this type may be useful as radiopharmaceuticals for imaging the heart with PET.
Animals↗
Potential gallium-68 tracers for imaging the heart with PET: evaluation of four gallium complexes with functionalized tripodal tris(salicylaldimine) ligands.
Gallium-67 and 68Ga complexes have been synthesized with tripodal hexadentate salicylaldimine ligands derived from 1,1,1-tris(salicylaldiminomethyl)ethane, sal3tame. The four ligands evaluated contained alkoxy substituents (n-BuO-, iso-BuO-, sec-BuO-, and n-PrO-) on the terminal ethane carbon of the ligand backbone. In the case of the n-PrO-derivative, the tris(salicylaldimine) ligand was additionally substituted with methoxy groups in the 5-position of the aromatic rings. The 67Ga and 68Ga-complexes of these ligands were prepared by ligand exchange from 67Ga- or 68Ga-acetylacetonate in ethanol. The nonradioactive Ga[(sal)3tame-O-iso-Bu] complex was similarly prepared and shown by x-ray crystallography to exhibit the expected pseudo-octahedral N3O3(3-) coordination sphere about the Ga3+ center. These Ga-radiotracers are highly lipophilic, as demonstrated by their octanol/water partition coefficients. Log P values of 3.1, 3.1, 2.6, and 2.5 were found for the [(sal)3tame-O-iso-Bu], [(sal)3tame-O-n-Bu], [(sal)3tame-O-sec-Bu], and [(5-MeOsal)3tame-O-n-Pr] complexes, respectively. Following intravenous injection into rats, these complexes are rapidly cleared from the blood and exhibit significant myocardial uptake. At 1 min postinjection, 2.4%, 2.0%, 2.1% and 1.1% of the injected dose was found in the heart for the iso-BuO, n-BuO, sec-BuO, and n-PrO complexes, respectively, dropping to 1.0%, 0.8%, 0.8%, and 0.7% at 5 min. The corresponding heart-to-blood ratios are quite high: 17 +/- 3, 14 +/- 2, 12 +/- 2 and 3.5 +/- 0.4 at 1 min and 14 +/- 4, 10 +/- 1, 10 +/- 1 and 3.2 +/- 0.1 at 5 min postinjection. High quality myocardial images were obtained with PET in a normal dog using data collected from 2 to 10 min following intravenous injection of 68Ga[(sal)3tame-O-iso-Bu].
Animals↗
Effect of pacing strategy on cycle time trial performance.
Despite interest in competitive strategy by coaches and athletes, there are no systematically collected data regarding the effect of differences in pacing strategy on the outcome of middle distance (2-4 min duration) events. In this study different pacing strategies were evaluated using a 2-km time trial on a bicycle attached to a wind load simulator. Well-trained subjects (N = 9) performed five separate time trials with the pace during the first 50% of the trial experimentally constrained within the usual real world range from very slow (approximately 55% of best time) to very fast (approximately 48% of best time). Serial VO2 was measured to estimate the oxidative contributions to the trial and accumulated O2 deficit and postexercise blood lactate measured to estimate the anaerobic contribution to the trial. The evenly paced trial (first 1 km = 50.9% final time) produced the fastest total time. The starting pace to final time relationship was described by a U shaped second order polynomial curve with the nadir for final time at a starting pace of 51% of best total time. There were no systematic differences in serial VO2, accumulated O2 deficit, or postexercise lactate that could account for the pacing related variations in performance. The data support the concept of relatively even pacing in middle distance events with negative consequences for even small variations in this strategy.
Analysis of Variance↗
Prognostic importance of histological and immunopathological assessment of skin and rectal biopsies in patients with GVHD.
Skin and rectal biopsies from patients with GVHD were examined histologically and immunopathologically before and after treatment for the disease. The patients were divided into two groups: those showing a good response to treatment and those showing a poor or no response. The aims of the study were to assess the possibility of predicting the response to treatment and to compare good and poor responders after treatment. The results show that there are no features on either skin or rectal biopsy that could identify those patients with early GVHD who would respond to treatment. Following treatment with steroids there was no change histologically in the grading of the skin biopsy whereas the rectal biopsy showed improvement in six of nine good responders and no improvement in the poor responders. There was an increase in infiltrating lymphocytes in both the skin and rectum of patients showing a poor response and this is most likely due to the ongoing immune reaction. The pre-treatment biopsy did not show any features that would predict this development and was therefore of no prognostic value. However, examination of skin and rectal biopsies may aid in determining whether patients are responding to the treatment given for GVHD.
Adolescent↗