Shaken babies.
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Battered Child Syndrome↗
Biomedical subjects
M A Green
Publications and source records attributed to M A Green.
Synthesis and evaluation of a monocationic copper(II) radiopharmaceutical derived from N-(2-pyridylmethyl)-N'-(salicylaldimino)-1,3-propanediamine.
The monocationic 67Cu complex of N-(2-pyridylmethyl)-N'-(salicylaldimino)-1,3-propanediamine was obtained in high radiochemical purity by reaction of 67Cu2+ with the ligand in ethanol solution. Although this compound exhibited low heart uptake, the desired myocardial retention was observed over the 30 min time period studied in a rat model. Since the octanol/water partition coefficient of [67Cu]Cu(II)-N-(2-pyridylmethyl)-N'-(salicylaldiminato)-1,3- propanediamine] is lower than a value believed to be the optimal myocardial uptake, it is likely that derivatives of this compound with a higher lipophilicity merit further investigation for use in myocardial imaging with copper radioisotopes.
Animals↗
A kit formulation for preparation of [(111)In]In-DTPA-folate, a folate-receptor-targeted radiopharmaceutical.
A kit formulation has been developed for convenient, routine compounding of (111)In-labeled In(III)-DTPA-Folate, an investigational radiopharmaceutical for targeting tumor-associated folate receptors. The kit consists of the DTPA-Folate conjugate in sodium citrate solution, from which [(111)In]In-DTPA-Folate can be rapidly and reliably compounded by the addition of aqueous [(111)In]In(III)-chloride.
Carrier Proteins↗
Simultaneous death of twins: an environmental hazard or SIDS?
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Accidents↗
Problems in the interpretation of hemorrhage into neck musculature in cases of drowning.
To investigate the possible causes of unexplained hemorrhage into the neck musculature in deaths due to drowning, all cases of drowning between the years 1985 and 1995 examined by members of the Department of Forensic Pathology, University of Sheffield were reviewed. Cases were selected in which hemorrhage was found within the neck musculature but in which no apparent explanation for the hemorrhage, such as compression of the neck or trauma, was present. Eight cases were identified from a total of 99 deaths from drowning. Postmortem hypostasis was distributed in the back or diffusely in 6 cases and in the face in 3 cases. The degree of decomposition varied but was severe in only 1 case. A raised blood alcohol level was detected in 3 cases. Anterior neck compartment hemorrhage is probably due to hypostasis in a high proportion of cases. The Prinsloo and Gordon artifact may be an operative factor in at least some cases. Hemorrhage may result from violent neck movements during the process of drowning. Apparent "bruising" of the neck musculature does not always indicate compression of or trauma to the neck.
Adult↗
A practical approach to suspicious death in infancy--a personal view.
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Autopsy↗
Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical.
UNLABELLED: Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors. METHODS: Athymic mice were subcutaneously inoculated with approximately 1.8 x 10(6) folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time (111)In-DTPA-folate, (111)In-DTPA or (111)In-citrate was administered by intravenous injection. RESULTS: The (111)In-DTPA-folate conjugate afforded marked tumor-specific (111)In deposition in vivo using this mouse model. The involvement of the folate receptor in mediating tumor uptake of (111)In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free folic acid (intravenous). The (111)In-DTPA-folate also shows folate receptor-mediated uptake and retention in the kidneys, presumably reflecting radiotracer binding to folate receptors of the proximal tubules. In control experiments, the (111)In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of (111)In, but with much poorer tumor-to-background tissue contrast than that obtained with (111)In-DTPA-folate. Unconjugated (111)In-DTPA showed no tumor affinity. CONCLUSION: Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.
Animals↗
Human biodistribution and dosimetry of the PET perfusion agent copper-62-PTSM.
UNLABELLED: Copper-62-pyruvaldehyde bis(N4-methyl)thiosemicarbazone (PTSM) has been proposed as a generator-produced radiopharmaceutical for perfusion imaging using PET. Several clinical studies have demonstrated the ability of 62Cu-PTSM to quantitate myocardial and cerebral perfusion in humans. Because 62Cu-PTSM is generator-produced, it can be provided to clinical centers without cyclotron availability and, therefore, represents a cost-effective, practical PET perfusion tracer for clinical applications. To assess the safety, time-dependent biodistribution, and whole-body and organ-specific absorbed radiation dose estimates of this tracer, a Phase I study of 62Cu-PTSM was performed using whole-body imaging with PET in 10 healthy volunteers and with the radiopharmaceutical delivered by a compact modular generator unit. METHODS: Five male and five female subjects underwent a series of clinical tests and head-to-midthigh, whole-body PET scans at three time points over 1 hr after intravenous injection of 62Cu-PTSM. Before injection of the tracer, PET transmission scans were performed and used to correct the emission data for attenuation. Final image data were expressed in units of mCi/cc. Using standard organ weights, the percent injected dose per organ was calculated. Biodistribution data were obtained at three different time points and from these data biological half-lives in different organs were determined for calculation of radiation absorbed dose estimates. RESULTS: The liver was seen as the critical organ receiving a dose of 0.0886 rad/mCi. This organ defined the maximum single injected dose at 56 mCi using the limit of 5 rads to a critical organ per study per year. The whole-body dose is 0.0111 rad/mCi, resulting in a 0.622 rad exposure with a maximum single injection dose. Only trace levels of activity were found in the urine, which suggests low levels of urinary excretion and bladder exposure. No significant clinical, electrocardiographic or laboratory abnormalities were seen after the injection of 62Cu-PTSM. CONCLUSION: Copper-62-PTSM is a clinically safe radiopharmaceutical with favorable dosimetry for human studies at injected doses significantly above those projected for use in clinical studies.
Adult↗
A Messerer fracture.
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Accidents, Traffic↗
Cardiac muscarinic receptors. Cooperativity as the basis for multiple states of affinity.
Cooperativity has been investigated as the mechanistic basis for effects observed with cardiac muscarinic receptors in washed membranes from Syrian hamsters. Specifically, N-[3H]methylscopolamine labeled only 66-75% of the sites labeled by [3H]quinuclidinylbenzilate at apparently saturating concentrations of each radioligand. Also, receptors labeled by N-[3H]methylscopolamine revealed three states of affinity for agonists, both in native membranes and following irreversible blockade of about 80% of the sites by propylbenzilylcholine mustard; in both preparations, guanylylimidodiphosphate (GMP-PNP) effected an apparent interconversion of sites from higher to lower affinity for agonists and from lower to higher affinity for the antagonist. Excellent and mechanistically consistent descriptions of the data were obtained in terms of a model comprising cooperative and noncooperative forms of the receptor; the former was described by a variant of the Adair equation, and the latter was included to account for low-affinity sites that survived treatment with the mustard. If differences in apparent capacity derive from negative cooperativity in the binding of N-[3H]methylscopolamine, the cooperative form of the receptor was at least trivalent in native membranes; otherwise, constraints imposed by the effects of GMP-PNP at the concentrations of radioligand used in the assays dictate that the cooperative form of the receptor was at least tetravalent. In contrast, a divalent receptor is sufficient with the data from alkylated membranes, in accord with the reduced likelihood of interactions between functional sites within an oligomeric array. A model is presented wherein the receptor interconverts spontaneously between two or more states differing in their cooperative properties. The effects of GMP-PNP can be rationalized as a shift in the equilibrium between the different states.
Alkylation↗
Cardiac muscarinic receptors. Relationship between the G protein and multiple states of affinity.
An expanded version of the mobile receptor model has been assessed in studies on the binding of N-[3H]methylscopolamine and [35S]GTPgammaS to cardiac muscarinic receptors and their attendant G proteins in ventricular membranes from hamster. The model comprises two pools of receptor, one of which lacks G proteins, and a heterogeneous population of G proteins that compete for the receptor within the G protein-containing pool. To guide the formulation of the model itself and to define the various parameters, data were combined from assays performed under various conditions with native membranes and following irreversible blockade of about 80% of the receptors with propylbenzilylcholine mustard. Multiple G proteins are indicated primarily by multiple states of affinity evident in the dose-dependent effect of guanyl nucleotides on the binding of carbachol; G protein-free receptors are indicated by sites of low affinity for carbachol that survive treatment with the mustard. The expanded model generally succeeds where more frugal schemes have been inadequate, but it nevertheless fails to yield a mechanistically consistent description of the data. Guanyl nucleotides and partial alkylation do not affect the inhibitory potency of carbachol in a manner consistent with their supposed effect on the equilibrium between uncoupled and G protein-coupled receptors. As inferred from the model, G proteins are lost upon alkylation of the receptor, and their numbers are regulated by guanyl nucleotides. Parameters estimated via N-[3H]methylscopolamine are wholly inconsistent with the same parameters estimated via [35S]GTPgammaS. The failure of the model suggests that multiple states of affinity may not arise from a ligand-regulated equilibrium between free receptors and G proteins on the one hand and one or more RG complexes on the other.
Animals↗
Mixed bis(thiosemicarbazone) ligands for the preparation of copper radiopharmaceuticals: synthesis and evaluation of tetradentate ligands containing two dissimilar thiosemicarbazone functions.
A series of four "mixed" bis(thiosemicarbazone) keto aldehyde derivatives containing dissimilar thiosemicarbazone functions were synthesized and evaluated as ligands for preparation of radiocopper-labeled radiopharmaceuticals. The pyruvaldehyde-based mixed bis(thiosemicarbazone) ligands CH3C[=NNHC(S)NH2]CH[=NNHC(S)NHMe] (4a), CH3C[=NNHC(S)NHMe]-CH[=NNHC(S)NH2] (4b), CH3C[=NNHC(S)NH2]CH[=NNHC(S)NMe2] (4c), and CH3C[=NNHC-(S)NHMe]CH[=NNHC(S)NMe2] (4d) were obtained by reaction of thiosemicarbazide, N4-methylthiosemicarbazide, or N4,N4-dimethylthiosemicarbazide with pyruvaldehyde 2-thiosemicarbazones that had been generated by oxidative cleavage of the appropriate pyruvic aldehyde dimethyl acetal 2-thiosemicarbazone. The 67Cu-labeled complexes of ligands 4a-d were prepared and screened in a rat model to assess the potential of each chelate as a 62Cu radiopharmaceutical for imaging with positron emission tomography. In the rat model the 67Cu complexes of ligands 4a-d exhibit significant uptake into the brain and heart after intravenous injection, following trends similar to those previously reported for the related bis(thiosemicarbazone) complexes, Cu-PTS, Cu-PTSM, and Cu-PTSM2 (derived from pyruvaldehyde bis(thiosemicarbazone), pyruvaldehyde bis(N4-methylthiosemicarbazone), and pyruvaldehyde bis(N4,N4-dimethylthiosemicarbazone), respectively). Ultrafiltration studies using solutions of dog and human serum albumin reveal that the 67Cu complexes of ligands 4a-d, like the Cu(II) complex of pyruvaldehyde bis(N4-methylthiosemicarbazone), interact more strongly with human albumin than dog albumin.
Animals↗
Selective antagonism of the GABA(A) receptor by ciprofloxacin and biphenylacetic acid.
1. Previous studies have shown that ciprofloxacin and biphenylacetic acid (BPAA) synergistically inhibit y-aminobutyric acid (GABA)A receptors. In the present study, we have investigated the actions of these two drugs on other neuronal ligand-gated ion channels. 2. Agonist-evoked depolarizations were recorded from rat vagus and optic nerves in vitro by use of an extracellular recording technique. 3. GABA (50 microM)-evoked responses, in the vagus nerve in vitro, were inhibited by bicuculline (0.3-10 microM) and picrotoxin (0.3-10 microM), with IC50 values and 95% confidence intervals (CI) of 1.2 microM (1.1-1.4) and 3.6 microM (3.0-4.3), respectively, and were potentiated by sodium pentobarbitone (30 microM) and diazepam (1 microM) to (mean+/-s.e.mean) 168+/-18% and 117+/-4% of control, respectively. 5-Hydroxytryptamine (5-HT; 0.5 microM)-evoked responses were inhibited by MDL 72222 (1 microM) to 10+/-4% of control; DMPP (10 microM)-evoked responses were inhibited by hexamethonium (100 microM) to 12+/-5% of control, and alphabetaMeATP (30 microM)-evoked responses were inhibited by PPADS (10 microM) to 21+/-5% of control. Together, these data are consistent with activation of GABA(A), 5-HT3, nicotinic ACh and P2X receptors, respectively. 4 Ciprofloxacin (10-3000 microM) inhibited GABA(A)-mediated responses in the vagus nerve with an IC50 (and 95% CI) of 202 microM (148-275). BPAA (1-1000 microM) had little or no effect on the GABA(A)-mediated response but concentration-dependently potentiated the effects of ciprofloxacin by up to 33,000 times. 5. Responses mediated by 5-HT3, nicotinic ACh and P2X receptors in the vagus nerve and strychnine-sensitive glycine receptors in the optic nerve were little or unaffected by ciprofloxacin (100 microM), BPAA (100 microM) or the combination of these drugs (both at 100 microM). 6. GABA (1 mM)-evoked responses in the optic nerve were inhibited by bicuculline with an IC50 of 3.6 microM (2.8-4.5), a value not significantly different from that determined in the vagus nerve. Ciprofloxacin also inhibited the GABA-evoked response with an IC50 of 334 microM (256-437) and BPAA (100 microM) potentiated these antagonist effects. However, the magnitude of the synergy was 48 times less than that seen in the vagus nerve. 7. These data indicate that ciprofloxacin and BPAA are selective antagonists of GABA(A) receptors, an action that may contribute to their excitatory effects in vivo. Additionally, our data suggest that the molecular properties of GABA(A) receptors in different regions of the CNS influence the extent to which these drugs synergistically inhibit the GABA(A) receptor.
Adenosine Triphosphate↗
Research radionuclide availability in North America.
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Canada↗
Forensic three-dimensional facial reconstruction: historical review and contemporary developments.
Despite varied attempts to achieve standardization in traditional techniques and the promotion of some newly developed ones, facial reconstruction remains on the threshold between art and science. It is the point at which science ends and the medical illustrator takes over that has led to most reservations over this branch of forensic anthropology. The purpose of this paper is to demonstrate that many techniques of facial reconstruction are prima facie questionable and to illustrate some possible solutions to the problems which are currently being explored by the Facial Reconstruction Project at the University of Sheffield (UK). The review includes 15 responses to a questionnaire which was offered to facial reconstruction experts and related specialists. The use of 3D color laser scanning equipment, collection of tissue depth measurements from CT scans and the development of a computer system for 3D forensic facial reconstruction, are described.
Face↗
Research radionuclide availability in North America: part 2.
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Canada↗
Respiratory health in asbestos-exposed ironworkers.
This study aimed to determine the prevalence of respiratory morbidity among asbestos-exposed ironworkers and to determine the relationship between respiratory morbidity indices and length of exposure. A medical screening provided information on chest radiographic abnormalities, pulmonary function, rales, finger clubbing, and respiratory symptoms for 547 asbestos-exposed ironworkers. Union pension records furnished data on length of exposure. The study group exhibited on increased prevalence of small irregular opacities, pleural plaques, and pleural thickening on chest x-ray; reduced FEF 25-75; rales; and respiratory symptoms. After controlling for the effect of cigarette smoking and age, years since joining the ironworkers union were significantly associated with profusion, pleural thickening, pleural plaques, rales, percent predicted FVC, reduced FVC, reduced FEV1, reduced FEV1/FVC, and dyspnea grades I, II, III, and IV.
Female↗
Antioxidant depletion during aortic aneurysm repair.
Ischaemia-reperfusion injury generates oxygen-derived free radicals leading to local and distant damage. A simple method of following oxidative activity is to measure the consumption of endogenous scavenging antioxidants; an enhanced chemiluminescent assay was used to study this phenomenon in 21 patients undergoing surgery for abdominal aortic aneurysm (AAA). Samples of peripheral venous blood were taken before induction of anaesthesia and then from a central venous line and the inferior mesenteric vein before, during, and after clamping of the aorta. Further specimens were taken from the central line at 2, 6 and 24 h after operation. Antioxidant concentration in the peripheral, central and inferior mesenteric blood were similar, indicating that anaesthesia and surgical dissection had no effect. Levels decreased significantly in central and inferior mesenteric blood during and after clamping, but returned to normal by 24 h. These results confirm ischaemia-reperfusion phenomena in AAA repair.
Aged↗