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PubMed2003

An economic assessment of inhaled formoterol dry powder versus ipratropium bromide pressurized metered dose inhaler in the treatment of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is debilitating and costly to manage. A recent clinical trial concluded that formoterol, a long-acting beta(2)-adrenoceptor agonist, was more clinically effective than inpratropium bromide in the management of COPD. OBJECTIVE: The aim of this study was to perform an economic assessment of the management of COPD with formeterol versus ipratropium bromide. METHODS: Assessment were based on the results of a previously published 12-week, multicenter, double-masked, randomized, parallel-group, placebo-controlled clinical trial comparing inhaled formoterol dry powder 12 and 24 microg BID with ipratropium bromide 40 microg QID pressurized metered dose inhaler and with placebo in 780 COPD patients. Treatment costs for study drugs and rescue medications were estimated from resource utilization and average wholesale prices. Costs were assessed with respect to forced expiratory lung volume in 1 second (FEV(1)) and patient-reported quality of life (QOL) as assessed via the St. George's Respiratory Questionnaire. Cost-effectiveness ratios were calculated for each treatment arm and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment relative to the next best alternative. Economic efficiency frontiers were identified. Sensitivity analysis was conducted. RESULTS: Cost analysis with respect to FEV(1) revealed an economic efficiency frontier formed by placebo, ipratropium bromide 40 microg, and formoterol 12 microg at their respective FEV(1) levels, with cost-effectiveness ratios of $30.18, $53.50, and $142.04, respectively, per FEV(1). The ICER for ipratropium over placebo was $273.03; for formoterol 12 microg over ipratropium, $1611.32. Cost analysis with respect to QOL showed an economic efficiency frontier formed by placebo and formoterol 12 microg at their respective QOL outcomes, with cost-effectiveness ratios of $25.96 and $32.56, respectively, per QOL score change. The cost-effectiveness ratio for ipratropium was $69.40,which was not on the QOL economic efficiency frontier. The ICER for formoterol 12 microg over placebo was $34.51 per QOL score point. CONCLUSIONS: Formoterol 12 microg provided greater QOL outcome than ipratropium bromide at an additional cost of $554.28 per year. Further research would be necessary to assess whether the differences in outcomes, particularly QOL, observed in the short term with formoterol would lead to favorable long-term health and economic outcomes.

Administration, Inhalation↗
PubMed1994

Influence of lung function and postnatal age on the response to nebulized ipratropium bromide in children born prematurely.

Nebulized ipratropium bromide reduces airways resistance in young children born prematurely, but that response is not invariable. We have assessed whether postnatal age or baseline lung function influences the effect of ipratropium bromide. Forty-five children, median gestational age 28 weeks (range 23-34) were studied at a postnatal age of 10 months (range 6-18). Twenty-four were symptomatic at follow-up. Airways resistance (Raw) was measured using a whole body plethysmograph before (baseline) and 20 min after nebulized ipratropium bromide. Sixteen patients had a significant improvement in Raw (a reduction in Raw greater than twice the coefficient of variation of the measurement). The baseline Raw of those 16 infants was significantly higher than the baseline Raw of the other 29 infants (P < 0.01). Multiple regression analysis, after taking into account baseline lung function and symptom status, demonstrated there was a significant relationship between the change in Raw following ipratropium bromide and postnatal age (P < 0.01). We conclude that both baseline lung function and postnatal age influence the response to nebulized ipratropium bromide in young children born prematurely.

Age Factors↗
PubMed2003

(-)-9-Dehydrogalanthaminium bromide, a new cholinesterase inhibitor, enhances place and object recognition memory in young and old rats.

In a previous study, we showed that (-)-9-dehydrogalanthaminium bromide, a synthetic galanthamine derivative, was more potent than galanthamine in inhibiting acetylcholinesterase. We studied here the action of this new compound on recognition memory in young and old rats, using a two-trial recognition task designed to test both place and object recognition. (-)-9-dehydrogalanthaminium bromide was injected (0.3, 1, and 3 mg/kg, i.p.) in young and old rats before the acquisition phase, immediately after it, or before the retrieval phase of the task, in order to determine the stage of information processing affected by the compound. (-)-9-dehydrogalanthaminium bromide improved both place and object recognition in young rats, via an enhancement of acquisition (3 mg/kg: place recognition; 1 and 3 mg/kg: object recognition) and consolidation (1 and 3 mg/kg) information processing. In old rats, (-)-9-dehydrogalanthaminium bromide improved performance by acting on the acquisition processes of place (0.3, 1, and 3 mg/kg) and object (1 and 3 mg/kg) recognition. These results provide information on the profile of activity of (-)-9-dehydrogalanthaminium bromide on memory processes, and suggest that this new compound could have utility in the treatment of cognitive dysfunction occurring in Alzheimer's disease or in the normal course of aging.

Age Factors↗
PubMed1999

Comparison of SYBR Green I nucleic acid gel stain mutagenicity and ethidium bromide mutagenicity in the Salmonella/mammalian microsome reverse mutation assay (Ames test).

SYBR Green I nucleic acid gel stain is an unsymmetrical cyanine dye developed for sensitive detection of nucleic acids in electrophoretic gels. Its mechanism of nucleic acid binding is not known, whereas the most commonly used nucleic acid gel stain, ethidium bromide, is a well-characterized intercalator. We compared the mutagenicity of SYBR Green I stain with that of ethidium bromide in Salmonella/mammalian microsome reverse mutation assays (Ames tests). As expected [J. McCann, E. Choi, E. Yamasaki, B.N. Ames, Proc. Natl. Acad. Sci. USA, 72 (1975) 5135-5139], ethidium bromide showed high revertant frequencies in several frameshift indicator strains (averaging 68-fold higher than vehicle controls in TA98, 80-fold higher in TA1538, 15-fold higher in TA1537, and 4.4-fold higher in TA97a), only in the presence of rat liver extracts (S9). Small increases in revertant frequencies were observed for ethidium bromide in the base-substitution indicator strain TA102 both in the presence and absence of S9 (averaging 2.0- and 1.8-fold higher than vehicle controls, respectively) and in base-substitution indicator strain TA100 in the presence of S9 (averaging 1.6-fold higher than vehicle controls). A small mutagenic effect was detected for SYBR Green I stain in frameshift indicator strain TA98 (averaging 2. 2-fold higher than vehicle controls) only in the absence of S9 and in base-substitution indicator strain TA102, both in the presence and absence of S9 (averaging 2.2- and 2.7-fold higher than vehicle controls, respectively). Thus, SYBR Green I stain is a weak mutagen and appears to be much less mutagenic than ethidium bromide. These results suggest that SYBR Green I stain may not intercalate, and if it does, that its presence does not give rise to point mutations at a high frequency.

Animals↗
PubMed1977

The structure of chromatin: interaction of ethidium bromide with native and denatured chromatin.

The binding of ethidium bromide, as monitored by fluorescence enhancement, to chromatin prepared by nuclease digestion has been compared with the binding of the dye to sheared chromatin. The nuclease preparation (native chromatin) is characterized by a high affinity region of the Scatchard plot (r = 0-0.025, K1 = 1 X 10(6) M-1), a transition (r = 0.025-0.05), and a low affinity region (r = 0.05-0.12, K2 = 3 X 10(5) M-1). The final amount of ethidium bromide bound per base is 0.12 as compared with 0.20 for free DNA. Sheared chromatin has the two regions of high and low affinity (K1 = 2 X 10(6) M-1, K2 = 5 X 10(5) M-1) as originally shown by Angerer and Moudrianakis (1972), but the transition is much reduced or absent. Binding of the dye to native chromatin is independent of salt at concentrations ranging from 0.2 mM EDTA to 10 mM Tris-Cl, 10 mM NaCl, 0.2 mM EDTA, while sheared chromatin and DNA both bind ethidium bromide electrostatically as well as by intercalation at the low salt concentration, leading to extensive energy transfer. Thus the phosphate groups in native chromatin are unavailable to external cations even at very low salt. Polarization of fluorescence of ethidium bromide intercalated into native chromatin at low r is very high, indicating a highly rigid structure. As r approaches 0.02, there is a very rapid depolarization; at r = 0.03, the polarization is no greater than that of the dye intercalated into DNA. Depolarization is not due to energy transfer. The Scatchard plot derived for the bulk preparation of native chromatin is very similar to the one derived for the monomer nu body. These results indicate that the DNA in native chromatin is in a very rigid form, with its phosphate anions neutralized by structural components, not by free salt. Ethidium bromide intercalation appears partially to disrupt this structure, perhaps by unwinding, leading to slight changes in its properties.

Binding Sites↗
PubMed2002

Flash photolytic generation and study of p-quinone methide in aqueous solution. An estimate of rate and equilibrium constants for heterolysis of the carbon-bromine bond in p-hydroxybenzyl bromide.

Flash photolysis of p-hydroxybenzyl acetate in aqueous perchloric acid solution and formic acid, acetic acid, biphosphate ion, and tris(hydroxymethyl)methylammonium ion buffers produced p-quinone methide as a short-lived species that underwent hydration to p-hydroxybenzyl alcohol in hydronium ion catalyzed (k(H(+)) = 5.28 x 10(4) M(-1) s(-1)) and uncatalyzed (k(uc) = 3.33 s(-1)) processes. The inverse nature of the solvent isotope effect on the hydronium ion-catalyzed reaction, k(H(+))/k(D(+)) = 0.41, indicates that this process occurs by rapid and reversible protonation of the quinone methide on its carbonyl carbon atom, followed by rate-determining capture of the p-hydroxybenzyl carbocation so produced by water, while the magnitude of the rate constant on the uncatalyzed process indicates that this reaction occurs by simple nucleophilic addition of water to the methylene group of the quinone methide. p-Quinone methide also underwent hydronium ion-catalyzed and uncatalyzed nucleophilic addition reactions with chloride ion, bromide ion, thiocyanate ion, and thiourea. The solvent isotope effects on the hydronium ion-catalyzed processes again indicate that these reactions occurred by preequilibrium mechanisms involving a p-hydroxybenzyl carbocation intermediate, and assignment of a diffusion-controlled value to the rate constant for reaction of this cation with thiocyanate ion led to K(SH) = 110 M as the acidity constant of oxygen-protonated p-quinone methide. In a certain perchloric acid concentration range, the bromide ion reaction became biphasic, and least-squares analysis of the kinetic data using a double-exponential function provided k(Br(-)) = 3.8 x 10(8) M(-1) s(-1) as the rate constant for nucleophilic capture of the p-hydroxybenzyl carbocation by bromide ion, k(ionz) = 8.5 x 10(2) s(-1) for ionization of the carbon-bromine bond of p-hydroxybenzyl bromide, and K = 4.5 x 10(5) M(-1) as the equilibrium constant for the carbocation-bromide ion combination reaction, all in aqueous solution at 25 degrees C. Comparisons are made of the reactivity of p-quinone methide with p-quinone alpha,alpha-bis(trifluoromethyl)methide as well as p-quinone methide with o-quinone methide.

Hydrocarbons, Brominated↗
PubMed2006

Reactions of cyclohexenyl iodonium tetrafluoroborate with bromide ion: retardation due to the formation of lambda3-bromoiodane.

The reaction of 4-tert-butylcyclohex-1-enyl(phenyl)iodonium tetrafluoroborate (1a) and the 4-chlorophenyl derivative (1b) with bromide ion was examined in methanol, acetonitrile, and chloroform. Products include those derived from the intermediate cyclohexenyl cation as well as 1-bromocyclohexene. Kinetic measurements show that the reaction of 1 is strongly retarded by the added bromide. The curved dependence of the observed rate constant on the bromide concentration is typical of a pre-equilibrium formation of the intermediate adduct with a fast bromide-independent reaction (solvolysis of the iodonium ion). The formation of the adduct, lambda3-bromoiodane, was also confirmed by the UV spectral change. The relative reactivity of the iodonium ion and lambda3-bromoiodane is evaluated to be on the order of 10(2). The bromide substitution product forms both via the S(N)1 reaction of the free iodonium ion and via the ligand coupling of the iodane.

Journal Article↗
PubMed1998

The Basicity of p-Substituted Phenolates and the Elimination-Substitution Ratio in p-Nitrophenethyl Bromide: A HSAB Theoretical Study.

The influence of basicity in a set of para-substituted phenolates on the elimination-substitution ratio obtained upon reaction with p-nitrophenethyl bromide has been studied. A correlation between experimental equilibrium data (pK(a)) and reactivity indices obtained from density functional theory (DFT) was looked for in order to show that the hard and soft acids and bases principle (HSAB) is well suited to describe the basicity properties of the para-substituted phenolates. When the basicity of para-substituted phenolates increases, their global hardness and their condensed softness at the oxygen atom increase; the negative net charge, condensed nucleophilic fukui function, and condensed nucleophilic softness of the oxygen atom increase. The proposal that the alkyl halide substrate possesses a hard beta-hydrogen atom and a soft alpha-carbon was studied for p-nitrophenethyl bromide; it turns out that the beta-hydrogen atom is soft, even softer than the carbon atom. The experimental results for the elimination-substitution ratio for p-nitrophenethyl bromide can be explained from a local-local HSAB viewpoint for the para-substituted phenolates and p-nitrophenethyl bromide and not from a global-local level viewpoint as suggested before. The results suggest that para-substituted phenolates with higher basicity (harder), less delocalized negative charge into the fragment R-C(6)H(4), and a more polarizable oxygen atom (softer) do have a lower (relative) attraction toward an alkyl carbon atom (soft) than toward a hydrogen atom (softer) from p-nitrophenethyl bromide. The beta-hydrogen and alpha-carbon atoms can be considered to act as a Lewis acid toward the para-substituted phenolate nucleophile considered as a base.

Journal Article↗
PubMed2005

Solvation dynamics in aqueous anionic and cationic micelle solutions: sodium alkyl sulfate and alkyltrimethylammonium bromide.

Solvation dynamics of the fluorescence probe, coumarin 102, in anionic surfactant, sodium alkyl sulfate (C(n)H(2n+1)SO(4)Na; n = 8, 10, 12, and 14), and cationic surfactant, alkyltrimethylammonium bromide (C(n)H(2n+1)N(CH(3))(3)Br; n = 10, 12, 14, and 16), micelle solutions have been investigated by a picosecond streak camera system. The solvation dynamics in the time range of 10(-10)-10(-8) s is characterized by a biexponential function. The faster solvation time constants are about 110-160 ps for both anionic and cationic micelle solutions, and the slower solvation time constants for sodium alkyl sulfate and alkyltrimethylammonium bromide micelle solutions are about 1.2-2.6 ns and 450-740 ps, respectively. Both the faster and the slower solvation times become slower with longer alkyl chain surfactant micelles. The alkyl-chain-length dependence of the solvation dynamics in both sodium alkyl sulfate and alkyltrimethylammonium bromide micelles can be attributed to the variation of the micellar surface density of the polar headgroup by the change of the alkyl chain length. The slower solvation time constants of sodium alkyl sulfate micelle solutions are about 3.5 times slower than those of alkyltrimethylammonium bromide micelle solutions for the same alkyl-chain-length surfactants. The interaction energies of the geometry optimized mimic clusters (H(2)O-C(2)H(5)SO(4)(-) and H(2)O-C(2)H(5)N(CH(3))(3)(+)) have been estimated by the density functional theory calculations to understand the interaction strengths between water and alkyl sulfate and alkyltrimethylammonium headgroups. The difference of the slower solvation time constants between sodium alkyl sulfate and alkyltrimethylammonium bromide micelle solutions arises likely from their different specific interactions.

Anions↗
PubMed2000

A simple and effective separation and purification procedure for DNA fragments using dodecyltrimethylammonium bromide.

In this work we describe a simple two step separation procedure for the separation and purification of short DNA fragments. The first step involves precipitating the DNA using the cationic surfactant dodecyltrimethylammonium bromide. Dodecyltrimethylammonium bromide, unlike cetyltrimethylammonium bromide will not precipitate DNA before complexation is complete thus providing a high purity DNA. The second step involves dissolution of the DNA-dodecyltrimethylammonium complex in 75% ethanol, followed by precipitation of the Sodium-DNA salt, by titrating in a salt solution. This method is particularly suited to purification of short fragments as it does not require high salt concentrations in the ethanol precipitation step, which can be damaging for short DNA. The ability of dodecyltrimethylammonium bromide to remove ethidium bromide from intercalation sites on the DNA is also discussed

Chemical Precipitation↗
PubMed2002

Efficacy and safety of oxitropium bromide, theophylline and their combination in COPD patients: a double-blind, randomized, multicentre study (BREATH Trial).

We compare the efficacy including spirometry, peak expiratory flow (PEFR) and quality of life and safety of an 8-week treatment with inhaled oxitropium, theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease (COPD). We conducted a multicentre, double-blind, double-dummy randomized, parallel-group study at 29 Italian outpatients clinics. A group of 236 patients with mild-to-severe COPD (baseline FEV1 < or = 70% of predicted value) were recruited. Treatments were as follows: Inhaled oxitropium bromide 200 microg (N=75), sustained-release oral theophylline 300 mg (N=81) or their combination (N=80), taken twice daily. Spirometry (FEV1 and FVC) was evaluated every 4 weeks, and morning and evening PEFR (before and 2-4 h after drug intake) was measured daily. Symptoms, cough and dysponea, were recorded daily. Health status was evaluated at baseline and week 8 using the disease specific St George' Respiratory Questionnaire (SGRQ). Any adverse event occurring during the treatment period was recorded on a diary card. FEV1 and FVC improved in all the groups at 4 and 8 weeks, but the difference between treatment groups did not reach statistically significant levels. Differences between groups in pre-dosing morning and evening PEFR were not significant. Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs. However, differences between groups was significant only for evening values (P=0.008). The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed. SGRQ total scores decreased in all treatment groups after 8 weeks, particularly in the oxitropium and combination groups. Clinically significant change (> or = 4 units) was only observed in patients treated with oxitropium bromide whether with or without theophylline. Adverse events related to treatments were higher in the group treated with theophylline alone (P < 0.02). We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1, PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs. Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR. Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophylline alone.

Aged↗
PubMed2006

Theoretical investigation of the dissociation dynamics of vibrationally excited vinyl bromide on an ab initio potential-energy surface obtained using modified novelty sampling and feed-forward neural networks.

The reaction dynamics of vibrationally excited vinyl bromide have been investigated using classical trajectory methods on a neural network potential surface that is fitted to an ab initio database of 12 122 configuration energies obtained from electronic structure calculations conducted at the MP4(SDQ) level of theory using a 6-31G(d,p) basis set for the carbon and hydrogen atoms and Huzinaga's (43334334) basis set augmented with split outer s and p orbitals (4332143214) and a polarization f orbital with an exponent of 0.5 for the bromine atom. The sampling of the 12-dimensional configuration hyperspace of vinyl bromide prior to execution of the electronic structure calculations is accomplished by combining novelty-sampling methods, chemical intuition, and trajectory sampling on empirical and neural network surfaces. The final potential is obtained using a two-layer feed-forward neural network comprising 38 and 1 neurons, respectively, with hyperbolic tangent sigmoid and linear transfer functions in the hidden and output layers, respectively. The fitting is accomplished using the Levenberg-Marquardt algorithm with early stopping and Bayesian regularization methods to avoid overfitting. The interpolated potentials have a standard deviation from the ab initio results of 0.0578 eV, which is within the range generally regarded as "chemical accuracy" for the purposes of electronic structure calculations. It is shown that the potential surface may be easily and conveniently transferred from one research group to another. The files required for transfer of the vinyl bromide surface can be obtained from the Electronic Physics Auxiliary Publication Service. Total dissociation rate coefficients for vinyl bromide are obtained at five different excitation energies between 4.50 and 6.44 eV. Branching ratios into each of the six open reaction channels are computed at 24 vibrational energies in the range between 4.00 and 6.44 eV. The distribution of vibrational energies in HBr formed via three-center dissociation from vinyl bromide is determined and compared with previous theoretical and experimental results. It is concluded that the combination of ab initio electronic structure calculations, novelty sampling with chemical intuition and trajectories on empirical analytic surfaces, and feed-forward neural networks provides a viable framework in which to execute purely ab initio molecular-dynamics studies on complex systems with multiple open reaction channels.

Journal Article↗
PubMed2006

Observation of dihalide elimination upon electron attachment to oxalyl chloride and oxalyl bromide, 300-550 K.

Rate coefficients have been measured for electron attachment to oxalyl chloride [ClC(O)C(O)Cl] and oxalyl bromide [BrC(O)C(O)Br] in He gas at 133 Pa pressure over the temperature range of 300-550 K. With oxalyl chloride, the major ion product of attachment is Cl2(-) at all temperatures (66% at 300 K); its importance increases slightly as temperature increases. Two other product ions formed are Cl- (18% at 300 K) and the phosgene anion CCl2O- (16% at 300 K) and appear to arise from a common mechanism. With oxalyl bromide, the Br2(-) channel represents almost half of the ion product of attachment, independent of temperature. Br- accounts for the remainder. For oxalyl chloride, the attachment rate coefficient is small [(1.8 +/- 0.5) x 10(-8) cm3 s(-1) at 300 K], and increases with temperature. The attachment rate coefficient for oxalyl bromide [(1.3 +/- 0.4) x 10(-7) cm3 s(-1) at 300 K] is nearly collisional and increases only slightly with temperature. Stable parent anions C2Cl2O2(-) and C2Br2O2(-) and adduct anions Cl- (C2Cl2O2) and Br- (C2Br3O2) were observed but are not primary attachment products. G2 and G3 theories were applied to determine geometries of products and energetics of the electron attachment and ion-molecule reactions studied. Electron attachment to both oxalyl halide molecules leads to a shorter C-C bond and longer C-Cl bond in the anions formed. Trans and gauche conformers of the neutral and anionic oxalyl halide species have similar energies and are more stable than the cis conformer, which lies 100-200 meV higher in energy. For C2Cl2O2, C2Cl2O2(-), and C2Br2O2(-), the trans conformer is the most stable conformation. The calculations are ambiguous as to the oxalyl bromide geometry (trans or gauche), the result depending on the theoretical method and basis set. The cis conformers for C2Cl2O2 and C2Br2O2 are transition states. In contrast, the cis conformers of the anionic oxalyl halide molecules are stable, lying 131 meV above trans-C2Cl2O2(-) and 179 meV above trans-C2Br2O2(-). Chien et al. [J. Phys. Chem. A 103, 7918 (1999)] and Kim et al. [J. Chem. Phys. 122, 234313 (2005)] found that the potential energy surface for rotation about the C-C bond in C2Cl2O2 is "extremely flat." Our computational data indicate that the analogous torsional surfaces for C2Br2O2, C2Cl2O2(-), and C2Br2O2(-) are similarly flat. The electron affinity of oxalyl chloride, oxalyl bromide, and phosgene were calculated to be 1.91 eV (G3), and 2.00 eV (G2), and 1.17 eV (G3), respectively.

Journal Article↗
PubMed2000

Central nervous system toxicity and early peripheral neuropathy following dermal exposure to methyl bromide.

CASE REPORT: We describe a case of early peripheral neuropathy and central nervous system toxicity as a result of acute predominantly dermal exposure to methyl bromide. A 32-year-old male was admitted after an accidental predominantly dermal exposure to methyl bromide while fumigating soil for pest control. The patient suffered dermal burns and vesicles on the upper and lower limbs. One week following exposure, he developed progressive weakness of the lower limbs, ataxia, paresthesiae of both legs and the left arm, hyperactive tendon reflexes in the lower limbs, and left Babinski sign. Nerve conduction velocity testing was compatible with axonal neuropathy. The patient recovered gradually from his burns. Three months postexposure he showed no signs of central nervous system toxicity, but the peripheral neuropathy was still present. DISCUSSION: Neurological effects primarily referable to the central nervous system following severe inhalation of methyl bromide have frequently been reported. The patient described in this study developed an unusual early peripheral neuropathy following dermal exposure. Peripheral neuropathy can be an outcome of methyl bromide intoxication, but is usually a late sequela of acute central nervous system toxicity or an aftereffect of repetitively inhaled chronic exposure. In this case, exposure to methyl bromide through abraded skin caused early peripheral neuropathy and central nervous system toxicity.

Administration, Cutaneous↗
PubMed2002

An unusual case of methyl bromide poisoning.

A nonlethal poisoning case by methyl bromide in a young woman due to leakage of old fire extinguishers is described. The patient developed major action and intention myoclonus the day following exposure. Inorganic bromide concentrations in plasma were determined by inductively coupled plasma mass spectrometry. The initial plasma bromide level was 202 mg/L, 40-fold in excess than the commonly accepted tolerance limit, and decreased slowly to normal levels within 2 months. Although plasma inorganic bromide concentration is known not to be directly correlated to the severity of organic bromide poisoning, its determination was, in the present case, particularly useful to confirm the diagnosis. One year post-exposure, the patient showed no sign of central nervous system toxicity. While such a case of poisoning is particularly rare today, it illustrates, however, that the danger still exists in France although the destruction

Anticonvulsants↗
PubMed1997

Localization of the major ethidium bromide binding site on tRNA.

Binding of ethidium bromide to Escherichia coli tRNAVal and an RNA minihelix based on the acceptor stem and T-arm of tRNAVal was investigated by 19F and 1H NMR spectroscopy of RNAs labeled with fluorine by incorporation of 5-fluorouracil. Ethidium bromide selectively intercalates into the acceptor stem of the tRNAVal. More than one ethidium bromide binding site is found in the acceptor stem, the strongest between base pairs A6:U67 and U7:A66. 19F and 1H spectra of the 5-fluorouracil-substituted minihelix RNA indicate that the molecule exists in solution as a 12 base-paired stem and a single-stranded loop. Ethidium bromide no longer intercalates between base pairs corresponding to the tRNAVal acceptor stem in this molecule. Instead, it intercalates between base pairs at the bottom of the long stem-loop structure. These observations suggest that ethidium bromide has a preferred intercalation site close to the base of an RNA helical stem.

Base Sequence↗
PubMed1996

Methyl bromide intoxication during grain store fumigation.

There have been over 300 cases of methyl bromide poisoning reported in the literature. The first objective of this case report was to bring out an experience with the false belief that work in a closed space is safe when accompanied by the use of a cartridge respirator with activated charcoal. The second objective of this article was to demonstrate the marked toxicity of methyl bromide with the potential to cause long-term neurological damage. Two experienced fumigation workers (equipped with rapidly saturable respiratory cartridges) entered a building where the concentration of methyl bromide was 17g x m-3 instead of the advised 20mg x m-3. They felt rapidly unwell and complained of nausea and shortness of breath, followed for one them by generalized convulsions. Five months later this last man was still bedridden. The other worker had almost no after-effects. The highest bromide level was found in the blood and also in the activated charcoal cartridge of the most injured worker. There was a relationship between methyl bromide level exposure and neurological damage importance.

Adult↗
PubMed1992

Inhibition of inhaled metabisulphite-induced bronchoconstriction by inhaled frusemide and ipratropium bromide.

1. The effect of inhaled frusemide and high dose inhaled ipratropium bromide on bronchoconstriction induced by inhaled metabisulphite was studied in 10 atopic volunteers. 2. Frusemide (40 mg), ipratropium bromide (0.5 mg) or saline placebo were administered by nebuliser in a double-blind fashion, prior to construction of a dose-response curve to metabisulphite (2.5-100 mg ml-1). 3. Geometric mean of the provocative dose of metabisulphite that caused a 35% fall in specific airways resistance (sGaw) after placebo was 13 (95% confidence intervals CI 4-36 mumol) compared with 36 (16-78) mumol after ipratropium bromide and 45 (22-94) mumol after frusemide. 4. Mean maximum fall in sGaw was 49 (40-57)% after placebo, 11 (0-22)% after frusemide and -1 (-25-22)% after ipratropium bromide. 5. Frusemide significantly protected against metabisulphite induced bronchoconstriction (P less than 0.005). The protection from high dose ipratropium bromide was also significant (P less than 0.05), but the response was more variable between subjects.

Administration, Inhalation↗