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E L Bradley

Publications and source records attributed to E L Bradley.

At least 19 recordsLinked to original sources

Feasibility study for the development of certified reference materials for specific migration testing. Part 2: estimation of diffusion parameters and comparison of experimental and predicted data.

This paper describes the second part of a project whose main objective was to develop the know-how to produce certified reference materials (CRMs) for specific migration testing. Certification parameters discussed are the diffusion coefficient, D(P), the respective polymer-specific coefficient, A(P), of the migrant polymer combinations and the partitioning coefficient, K(P,F), describing the partitioning of the migrant between the polymer and a food simulant. The parameters were determined for 16 preliminary candidate CRMs. Each parameter was determined by one laboratory. The six materials most suitable as reference materials were selected and the parameters then determined by four laboratories. The coefficients resulting from this small-scale interlaboratory comparison study can be regarded as the most reliable values available to date. These coefficients were applied for a comparison of experimental and predicted migration data. The experimental migration data arose from the same project and were determined by one laboratory for the first 16 materials and subsequently by four laboratories for the six materials selected in the second phase. Overall, experimental and predicted migration data fit together quite well. Roughly half of the predicted data were within +/-10%; almost all predicted data were within +/-40% compared with the experimental data.

Benzophenones↗

Test method for measuring non-visible set-off from inks and lacquers on the food-contact surface of printed packaging materials.

The main objective was to develop a technique to expose spots of invisible set-off of inks and lacquers on the food-contact surface of food-packaging materials. Set-off is the unintentional transfer of components of printing inks from the outer printed surface onto the food-contact surfaces. The target sensitivity was 20 microg cm(-2) and the technique should be capable of examining large areas of printed substrate for no more than 4% coverage by set-off. These requirements equate to an ability to detect a worst-case migration potential of less than 50 microg kg(-1). Other objectives were the industrial requirements that the equipment should be inexpensive, should be easy to use by existing personnel and should preferably be non-destructive with a clear criterion for pass or fail. The approaches investigated included chemical analysis of solvent extracts, Fourier-transform infrared spectroscopy and microbeam analytical techniques, but these were found to be cumbersome and had only limited success. The objectives were achieved using an optical approach to excite and observe luminescence from invisible set-off. In model experiments, resins were applied to different substrates (plastic, paper and cartonboard). For a given resin on a given material, the key to success was to maximize the discrimination between the luminescence from the resin and that from the substrate by selecting the optimal combination of exciting wavelength and viewing goggles with selective wavelength filters. The required level of detection (20 microg cm(-2)) was achieved or exceeded for all ten resins tested on three different plastics. It was also achieved for two different papers and in all but four cases of the resins on three different cartonboards. Quantitation was achieved by the use of a calibration palette prepared using different quantities of resin spotted onto the relevant blank packaging material.

Electron Probe Microanalysis↗

Survey of the migration of melamine and formaldehyde from melamine food contact articles available on the UK market.

The migration of melamine and formaldehyde, monomers used in the production of melamine-ware food contact articles, has been determined from 50 retail articles purchased in the UK. The food simulant 3% aqueous acetic acid was used as this is the most aggressive simulant towards melamine plastics. The test conditions used were repeated exposure to the simulant for 2 hours at 70 degrees C, since the articles were all intended for general use including contact with hot foods and beverages. Melamine migrated from 43 of the 50 samples tested and formaldehyde migrated from all 50 samples. Directive 2002/72/EC specifies migration limits for both of these monomers in foods and food simulants. Melamine is restricted by a specific migration limit (SML) of 30 mg/kg (equivalent to 5 mg/dm(2)) and formaldehyde, along with hexamethylenetetramine expressed as formaldehyde, is restricted by a total (T) SML(T) of 15 mg/kg (equivalent to 2.5 mg/dm(2)). In all cases the migration of melamine was much lower than the SML for this monomer. The migration of formaldehyde exceeded the SML(T) for 5 of the 50 samples tested. The failure to comply with the SML(T) was accompanied by a number of visible surface effects including discolouration and/or pitting of the simulant contact surface and cracking of the articles. Similar surface effects were observed when one of the samples was exposed to fruit juice which confirmed the suitability of the exposure conditions and 3% acetic acid as a simulant for the articles tested. The ratio of specific migration to overall migration was consistent with, but did not prove, the hypothesis that high formaldehyde migration could be due to the use of excessive hexamethylenetetramine in the polymer formulation. All illegal products were voluntarily removed from the market by the product suppliers.

Acetic Acid↗

Method of test and survey of caprolactam migration into foods packaged in nylon-6.

An analytical method for the determination of the nylon-6 monomer caprolactam in foods is described. The foodstuff was extracted with ethanol: water (1:2) containing capryllactam as internal standard and the extract was defatted using hexane. The extract was analysed by liquid chromatography coupled with mass spectrometry. The test method was calibrated down to 0.7 mg kg(-1). The repeatability of the method was good, with a relative standard deviation of 9% at the 15 mg kg(-1) level. The method was demonstrated to be accurate in an independent external check sample exercise. The new method was applied to the analysis of 50 retail foodstuffs packaged in nylon-6. Caprolactam was detected and confirmed in nine of the 50 food samples, in the range 2.8-13 mg kg(-1). The presence of caprolactam was indicated in a further 15 samples, in the range 0.8-11 mg kg(-1), but these samples did not meet all of the five confirmation criteria applied. All migration levels (both confirmed and unconfirmed) were below the European specific migration limit for caprolactam, which is 15 mg kg(-1). The average migration for all 50 samples, setting non-detectables at half the limit of detection, was 2.6 mg kg(-1) with a standard deviation of 3.1 mg kg(-1) (n = 50). All samples found to contain detectable levels of caprolactam migration were for applications involving heating the food in the packaging. They were packs of, for example, sausage meat for which the food would have been heat processed in the nylon casing, or they were nylon pouches for heating foods by boiling, microwaving or roasting.

Caprolactam↗

Feasibility study for the development of certified reference materials for specific migration testing. Part 1: initial migrant concentration and specific migration.

The paper describes a project with the main objective of developing the know how to produce certified reference materials (CRMs) for specific migration testing. Certification parameters discussed are the initial concentration of the migrant in the polymer (C(P),0) and the specific migration into a food simulant under certain temperature/time conditions. Sixteen preliminary candidate CRMs were defined and produced. The most important polymers (low- and high-density polyethylene (LDPE and HDPE), polypropylene (PP), polystyrene (PS), polyethylene terephtalate (PET), plasticized polyvinyl chloride (PVC), rigid PVC, polyamides (PA)) and additives as well as monomers representing different physicochemical properties as target substances for migration were chosen. The stability and homogeneity of the migrants in the materials were tested and methods for the determination of the certification parameters were developed and validated. > From the 16 materials produced, the six most suitable CRM candidates (LDPE//Irganox 1076/Irgafos 168, LDPE//1,4-diphenyl-1,3-butadiene (DPBD), HDPE//Chimassorb 81/Uvitex OB, PP homo//Irganox 1076/Irgafos 168, HIPS, 1% mineral oil//styrene, PA 6//caprolactam) were selected. The feasibility of CRM production for the six candidate materials was demonstrated and a trial certification exercise was performed with participation of all four partner laboratories. All six materials showed suitable properties for future production as certified reference materials.

Consumer Product Safety↗

Can inflammatory pain prevent the development of acute tolerance to alfentanil?

UNLABELLED: Constant pain could, in principle, counteract mobilization of antianalgesia systems and prevent the development of acute tolerance to the analgesic effects of opioids. We sought to determine whether a tonic nociceptive input caused by inflammation inhibits the development of acute tolerance to alfentanil. The inflammation was induced by injection of carrageenan into the rat hind paw. A threshold of motor response to increasing pressure on the paw was used to determine analgesia. Alfentanil was administered IV with an infusion algorithm designed to maintain a constant plasma level of opioid for 4 h. The degree of acute tolerance was determined on the basis of decline in the level of analgesia. The continuous decline of the analgesic effect from its peak at 30 min to the end of the 4-h infusion period was profound, despite the constant-rate infusion of alfentanil. The degrees of decline were very similar in rats with and without carrageenan-induced inflammation (from 242 +/- 31 to 154 +/- 20 g, P < 0.0001; and from 242 +/- 33 to 148 +/- 14 g, P < 0.0001, respectively). The results suggest that inflammatory nociceptive input does not prevent the development of acute tolerance to opioid-induced analgesia measured as an increased reaction threshold to painful pressure. We conclude that acute tolerance to the analgesic effect of opioids is profound and develops very rapidly, even in the presence of constant nociceptive input. IMPLICATIONS: We examined whether inflammatory pain can prevent the rapid decline in analgesic effectiveness (acute tolerance) of alfentanil during its IV infusion. We found that acute tolerance to the analgesic effect of alfentanil, in the presence of constant pain caused by inflammation, develops as rapidly as without it.

Alfentanil↗

Pancreaticoduodenectomy for metastatic renal cell carcinoma: report of a case.

Metastasis to the pancreas from a distant primary cancer is uncommon, most cases being detected in the advanced stages of disease, often multiple in number, and diffusely displayed beyond surgical salvage. A solitary metastasis in the head of the pancreas is rarely encountered and although potentially amenable to surgical resection, surgeons are hesitant to perform pancreaticoduodenectomy for metastatic disease. Renal cell carcinoma is one malignancy with a propensity to metastasize to the pancreas. We report herein the case of a solitary pancreatic metastasis from renal cell carcinoma successfully treated by pancreaticoduodenectomy in a middle-aged man. A discussion on the indications and effectiveness of performing pancreaticoduodenectomy for metastatic renal cell carcinoma is also presented.

Carcinoma, Renal Cell↗

Acute tolerance to continuously infused alfentanil: the role of cholecystokinin and N-methyl-D-aspartate-nitric oxide systems.

UNLABELLED: To test the role of cholecystokinin (CCK) and N-methyl-D-aspartate-nitric oxide (NMDA-NO) systems in the development of acute tolerance to analgesia during alfentanil IV infusion, we conducted experiments in rats with the use of an infusion algorithm designed to maintain a constant plasma level of the opioid for 4 h. The degree of acute tolerance was determined on the basis of decline in the level of analgesia measured with a tail compression test. CCK(B) receptor antagonists (proglumide, CI-988, and L-365,260) and NMDA-NO cascade inhibitors (dizocilpine and NO synthase inhibitor) were administered before the start of alfentanil infusion. Use of 30 mg/kg proglumide, 10 mg/kg CI-988, and 1 mg/kg L-365,260 attenuated acute tolerance at 1 h of alfentanil infusion by approximately 60%, 55%, and 70%, respectively, and by the end of 4-h infusion by 50%, 50%, and 25%, respectively. Use of 0.1 mg/kg dizocilpine and 10 mg/kg N(G)-nitro-L-arginine methyl ester attenuated acute tolerance at 1 h of alfentanil infusion by approximately 65% and 65% and by the end of 4-h infusion by 30% and 0%, respectively. Comparison of the results with CCK(B) receptor antagonists and inhibitors of NMDA-NO cascade demonstrates that both groups of drugs provide more or less similar degrees of attenuation of acute tolerance to the antinociceptive effect of alfentanil, and none of these drugs completely prevents tolerance development. IMPLICATIONS: The mechanism of acute tolerance to the analgesic effect of alfentanil depends on participation of multiple systems of adaptation that include cholecystokinin(B) receptors and N-methyl-D-aspartic acid-nitric oxide cascade. Drugs that inhibit function of these systems attenuate tolerance development.

Alfentanil↗

The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations?

UNLABELLED: Ketamine administered intraoperatively in very small doses reduces postoperative opioid consumption. We suggest that this effect is the result of attenuation of acute tolerance to the analgesic effect of opioids. We sought to demonstrate that acute tolerance induced by alfentanil infusion can be attenuated by a dose of ketamine that is too small to produce a direct antinociceptive effect. The experiments were conducted in rats with the use of an infusion algorithm designed to maintain a constant plasma level of the opioid for 4 h. The degree of acute tolerance was determined on the basis of decline in the level of analgesia measured with a tail compression test. Ketamine (10 mg/kg) did not change the baseline pain threshold and did not increase the peak of alfentanil-induced analgesia. At the same time, it attenuated the development of acute tolerance to analgesia during alfentanil infusion and suppressed rebound hyperalgesia observed the day after the infusion. These effects were similar to those observed with dizocilpine (0.1 mg/kg). The development of acute tolerance to analgesia induced by the infusion of an opioid can be attenuated by ketamine administered in doses that are not large enough to provide a direct antinociceptive effect. Therefore, ketamine has the potential to reduce opioid consumption even in subanalgesic doses. IMPLICATIONS: Ketamine attenuated the development of acute tolerance to analgesia during alfentanil infusion and suppressed rebound hyperalgesia observed the day after the infusion.

Alfentanil↗

Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical patients.

UNLABELLED: Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-thiopental synergy, as demonstrated with midazolam-thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical. IMPLICATIONS: The propofol-thiopental hypnotic interaction is additive.

Adolescent↗

Hyperalgesia caused by nerve transection: long-lasting block prevents early hyperalgesia in the receptive field of the surviving nerve.

UNLABELLED: The aim of our study was to test the hypothesis that a long-lasting N-butyl tetracaine nerve block (>2 wk) would be much more effective in the prevention of hyperalgesia caused by nerve transection than the short-lasting lidocaine block. The study was performed with the use of the saphenous nerve section model in rats. The saphenous nerve was exposed and injected with saline, lidocaine (37 mM), or N-butyl tetracaine (37 mM). Ten minutes later, the nerve was transected in some of the rats. The development of mechanical hyperalgesia (pressure threshold) of the hindpaw was assessed during a 5-wk period. In rats with saphenous nerve transection without nerve block (saline injection), 3 h after the transection, the pressure threshold decreased by approximately 30% (from 175+/-11 g to 122+/-23 g, P < 0.0001); the threshold increased somewhat the next day, then it remained stable for 2 wk, with a slow process of recovery afterward. N-butyl tetracaine block without nerve transection caused a slow-developing decrease in the pressure threshold with the first statistically significant change at the sixth day. The comparison of the preventive effects of lidocaine and N-butyl tetracaine blocks on early hyperalgesia caused by nerve transection demonstrated that both lidocaine and N-butyl tetracaine prevented hyperalgesia 3 h after the transection. However, the protective effect of lidocaine disappeared the next day. In contrast, N-butyl tetracaine prevented early hyperalgesia for almost a week. The slow-developing late hyperalgesia caused by long-lasting nerve block makes it impossible to study the protective effect of such a block on late hyperalgesia caused by axotomy. As far as early hyperalgesia is concerned, the preventive effect of the N-butyl tetracaine was much longer than that of lidocaine and continued for approximately 1 wk. IMPLICATIONS: A long-lasting nerve block can prevent early hyperalgesia caused by nerve transection.

Anesthetics, Local↗

Operative vs. Nonoperative therapy in necrotizing pancreatitis.

Anecdotal and uncontrolled recommendations for programmatic surgical intervention in necrotizing pancreatitis are gradually being replaced by nonoperative approaches as prospective natural history information becomes available. In patients with sterile pancreatic necrosis, nonoperative managements has now been shown to result in a mortality rate equal or better to surgical debridement. Moreover, since surgical debridement of sterile pancreatic necrosis has not been shown to prevent or ameliorate co-existing organ failure, and given that secondary infection of sterile necrosis occurs as a result of operative debridement in 25% of cases and results in a trebling of mortality risk, it is becoming increasingly clear that surgical debridement in sterile necrotizing pancreatitis will become the exception rather than the rule. However, surgical debridement and drainage remains the preferred approach for infected pancreatic necrosis despite occasional anecdotal reports of successful management by transcutaneous or endoscopic means. While the optimal post-surgical technique of drainage remains controversial, a selective approach is reasonable, with the choice between closed drainage, lesser sac lavage, or schedule re-explorations being based upon extent of the necrotic process.

Bacterial Infections↗

Acute pancreatitis as a complication of polyarteritis nodosa.

CONCLUSIONS: Polyarteritis nodosa (PAN) must be considered as one of the rare causes of "idiopathic" acute necrotizing pancreatitis. BACKGROUND: PAN is characterized by panmural inflammation of arterioles causing arteriolar ectasia, aneurysm formation, and thrombosis, resulting in organ ischemia. METHODS: We report a case of necrotizing pancreatitis associated with segmental necrosis of the liver and spleen due to polyarteritis nodosa. RESULTS: Five previously reported cases of documented acute pancreatitis secondary to PAN have been identified from the English literature. The mechanism through which pancreatic ischemia results in acute pancreatitis is unknown. Although limited pancreatic infarction is common in PAN, necrotizing pancreatitis is rare, and the poor overall prognosis of PAN is owing largely to other organ complications.

Adult↗

Role of the ovary in the adrenal androgen excess of hyperandrogenic women.

OBJECTIVE: To test the hypothesis that ovarian hormones in women with hyperandrogenism alter adrenocortical steroidogenesis. DESIGN: Combination of two prospective studies. SETTING: Academic medical centers. PATIENT(S): Eighteen hyperandrogenic patients demonstrating hirsutism with either hyperandrogenemia, oligomenorrhea, or both. Eighteen healthy nonhirsute eumenorrheic untreated women served as controls. INTERVENTIONS: Blood sampling basally and after acute adrenal stimulation with ACTH, before and after 20-24 weeks of leuprolide administration. Nine patients also received 0.625 mg/d of oral conjugated esterified estrogens and 10 mg of medroxyprogesterone acetate days 1-12 of the month (i.e., estrogen replacement therapy [ERT]), whereas the remaining nine did not. MAIN OUTCOME MEASURE(S): Before and after the administration of the GnRH agonist (GnRH-a), the basal concentrations of DHEAS; and the levels of androstenedione (A4), DHEA, androstenediol, 11 beta-hydroxyandrostenedione (11-OHA4), and cortisol before and 60 minutes after acute adrenal stimulation, were measured. RESULT(S): Levels of DHEAS, androstenediol, and 11-OHA4 decreased by 15%-30%, regardless of whether patients initially had or did not have DHEAS excess. However, only hyperandrogenic patients with elevated levels of DHEAS showed a significant decrease in basal DHEA levels. No statistically significant difference in the response of either androgen to ACTH (1-24) stimulation was noted with ovarian suppression, regardless of initial DHEAS level or use of ERT. CONCLUSION(S): We found no evidence that ovarian hormone secretion affected adrenal steroidogenesis, and those women with the highest adrenal androgen levels had the least response to GnRH-a suppression. These findings further support the concept of an intrinsic, and possibly primary, abnormality of adrenocortical steroidogenesis in a subset of hyperandrogenic women that is independent of ovarian abnormalities.

Adolescent↗

Oxygen consumption and carbon dioxide production in male prairie deermice (Peromyscus maniculatus bairdii) in different reproductive conditions and group densities.

Natural and laboratory populations of Peromyscus exhibit a profound but reversible reproductive inhibition related to population density. Our earlier studies described the endocrine physiology of inhibited animals which resembles a condition of delayed puberty, but they did not reveal a primary mechanism for the induction and maintenance of the inhibition. These studies indicated that reproductive inhibition could be associated with an overall change in general metabolism. To test this hypothesis, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in three groups of Peromyscus maniculatus males that were: 1) reproductively-proven, 2) reproductively-inhibited, or 3) recovered from inhibition. We found that the mean of the 2-hr period with the lowest VO2 (the Resting Metabolic Rate, or RMR) was significantly lower, and the mean Respiratory Exchange Ratio (RER) was significantly higher in reproductively-inhibited males compared with reproductively-proven males. In addition, previously inhibited males allowed to recover reproductive function had a significantly higher mean VO2, while the mean RER was not different from reproductively-proven males. Moreover, and contrary to some studies with other species, increasing the ambient carbon dioxide concentration or the caging densities to as high as six animals did not significantly affect oxygen consumption when compared with the corresponding values for individuals. Taken together, these findings indicate that the reproductive inhibition observed in P. maniculatus laboratory populations is causally associated with a significant reduction in general metabolism and that this metabolic reduction which is associated with reproductive-inhibition is not induced by a CO2 signal or induced by absolute density, per se.

Animals↗