Safety of using nitrous oxide for conscious sedation in asthmatic patients.
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Biomedical subjects
Publications and source records attributed to M Gillman.
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A monitoring program, carried out in 1996 and 1997, has confirmed that toxic compounds, other than the most frequently detected toxins okadaic acid (OA) and dinophysistoxin-1 (DTX-1), are involved in DSP phenomena in the Adriatic Sea. Toxicity was assessed by the mouse bioassay; the content and the nature of the toxic components were established through fluorometric HPLC analysis combined with mass spectrometry. A rare pectenotoxin-2 (PTX-2) derivative, 7-epi-pectenotoxin-2 seco acid (7-epi-PTX-2SA), was the exclusive contaminant of samples collected from the central Adriatic in 1996. Contrary to its marked oral toxicity, intraperitoneally 7-epi-PTX-2SA displayed no toxic effects, hampering its detection by the mouse bioassay. In 1997, its concentration and frequency of appearance were lower than in 1996, with concomitant occurrence of OA, DTX-2, and a new unidentified component related to the DSP toxic group of compounds. This is the first report on the occurrence of DTX-2 in Adriatic mussels. A survey of the phytoplankton community in the surrounding seawater has established the presence of Prorocentrum micans and several potentially toxic species from the Dinophysis genus. A case of unexplained toxicity, associated with the occurrence of Gonyaulax polyedra, suggested possible shellfish contamination with yessotoxin (YTX).
Amnesic shellfish poisoning is a potentially lethal human toxic syndrome which is caused by domoic acid (DA) that originates in marine phytoplankton belonging to the Pseudonitzschia genus. A new sensitive liquid chromatographic-mass spectrometry (LC-MS) method has been developed for the determination of DA in various marine biological samples. The characteristic fragmentation pathways for DA were established using multiple stage MS on selected daughter ions, which were sequentially trapped and fragmented. Chromatography was performed using a gradient of acetonitrile-water (5:95 to 40:60), containing trifluoroacetic acid (0.05%), over 25 min at 0.2 ml/min with a C18 column (Luna-2, 150 x 2.0 mm, 5 microm). Using electrospray ionisation, multiple tandem MS experiments were performed with an ion-trap mass spectrometer (Finnigan MAT LCQ). The protonated DA molecule was the precursor ion, m/z 312, and the relative collision energies were optimised for multiple MS (MS(n), n = 2-4) studies. LC-MS3 using the ions, m/z 266 and 220, from the loss of two HCOOH molecules, produced the best sensitivity data. Calibration data for various MS modes were: MS (0.05-10 microg DA/ml, r2 = 0.9973); MS2 (0.025-10 microg DA/ml, r2=0.9997); MS3 (0.025-10 microg DA/ml, 0.9994). The detection limits (3:1 signal:noise) were better than 0.02 microg DA/ml for LC-MS, 0.014 microg DA/ml for LC-MS2 and 0.008 microg DA/ml for LC-MS3. This method was applied to determine DA in scallop (Pecten maximus) tissues, which subsequently led to the closure of several shellfish harvesting sites on the west coast of Ireland.
Okadaic acid (OA) and 7-epi-pectenotoxin-2 seco acid (7-epi-PTX-2SA) were identified as the toxic determinants in mussels from the central Adriatic Sea. The nature of the pectenotoxin-2 derivative was confirmed by chromatographic comparison with toxins present in algae extracts of Dinophysis acuta from Ireland, and by mass spectrometric analysis. The origin of shellfish toxicity has been associated with the occurrence of the Dinophysis species. This is the first report on the incidence of 7-epi-PTX-2SA in the Adriatic region.
Chronic psychological stress may raise the risk of preterm delivery by raising levels of placental corticotropin-releasing hormone (CRH). Women who have been the targets of racism or personal violence may be at particularly high risk of preterm delivery. The aims of this study are to examine the extent to which: (1) maternal experiences of racism or violence in childhood, adulthood, or pregnancy are associated with the risk of preterm birth; (2) CRH levels are prospectively associated with risk of preterm birth; and (3) CRH levels are associated with past and current maternal experiences of racism or violence. We have begun to examine these questions among women enrolled in Project Viva, a Boston-based longitudinal study of 6000 pregnant women and their children.
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Domoic acid (DA) is a neurotoxic amino acid that is responsible for the human toxic syndrome, amnesic shellfish poisoning (ASP). A new rapid, sensitive liquid chromatographic (LC) method has been developed for the determination of DA in various marine samples. DA in marine biological materials was derivatised with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) and analysed using isocratic reversed-phase LC with fluorimetric detection. The calibration, based on standard DA solutions, was linear in the range 0.04-2 microg/ml (r2=0.998) and the detection limit (3:1, signal/noise) was better than 1 ng/ml. Using the certified reference material (MUS-1B), recoveries of DA from shellfish tissue were >95% (n=5). When a strong anion exchange SPE cartridge was used for sample clean-up the detection limit was 6 ng DA/g mussel tissue. Good reproducibility was achieved with RSD values ranging from 3% for 8 microg DA/g (n=5), to 5% for 0.04 microg DA/g (n=5). This new method was successfully applied to the determination of DA in naturally contaminated shellfish and in marine phytoplankton cultures of Pseudonitzschia sp.
Adult height has been found to be inversely associated with mortality. Recently, it has been suggested that growth in utero is linked with adult risk of several chronic diseases. The authors examined possible associations between birth weight, birth length, and adult height in young Danish men. They conducted the study in the fifth conscription district of Denmark including all the men born after January 1, 1973 who were residents in the study area during the period August 1, 1993 to July 31, 1994. The Danish Medical Birth Register contains information on all births in Denmark since January 1, 1973. Data on height from the Conscription Register were linked to the Danish Medical Birth Register in 4,300 conscripts examined. Nearly all Danish men have to register with the draft board around age 18 years of age where they undergo a physical examination. There was a strong positive association between birth weight and adult height; for subjects with birth weight < or = 2,500 g, mean height was 175.7 cm, while for those with birth weight > or = 4,501 g, mean height was 184.1 cm. A positive association was also found between birth length and adult height. For subjects with birth length < 47 cm, mean adult height was 175.2 cm, increasing to 184.3 cm at birth length > 56 cm. The associations between birth length and adult height persisted after adjustment for birth weight, gestational age, and other confounders, while the associations between birth weight and adult height almost disappeared when adjusting for birth length and the same confounders. Genetic and/or environmental factors operating both during the pre- and postnatal period may be responsible for the association between birth length and adult height.
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A new toxin, dinophysistoxin-2B (DTX-2B) was isolated from Irish mussels using silica chromatography, gel permeation, octadecylsilane solid-phase extraction and repeated preparative high-performance liquid chromatography (HPLC). Dinophysistoxin-2 (DTX-2) was also isolated from shellfish using the same procedures. The separation of these toxins in chromatographic fractions was monitored using fluorimetric HPLC following derivatization with 9-anthrylmethyldiazomethane or 1-bromoacetylpyrene. Flow-injection analysis-mass spectrometry (FIA-MS) with an atmospheric pressure ionization (API) and an ionspray (ISP) interface showed a mass spectrum dominated by the protonated molecule, [M+H]+, at m/z 805 for DTX-2B, thus indicating that this new toxin has the same mol.wt as okadaic acid and DTX-2. The low-energy fragment ion spectrum, as produced in FIA-MS experiments by up-front collision-induced dissociation of the protonated molecule of DTX-2B, showed fragment ions corresponding to successive losses of water molecules from the [M+H]+ ion. This low collision energy fragmentation pattern is typical of marine polyether toxins such as okadaic acid, DTX-2 and DTX-1. These results provide strong evidence that DTX-2B is another okadaic acid isomer.
BACKGROUND: Previous studies of Danish young men showed a steep increase of obesity since the birth years of the early 1940s with a levelling off in the 1950s. OBJECTIVE: To study the current prevalence of obesity and its recent changes in Danish young men. DESIGN: Cross-sectional study based on weight and height measured at the military board for the birth cohorts 1955, 1965 and 1973-75. SUBJECTS: We obtained information from the old paper files comprising the two cohorts of men born in 1955 (6549 adults) and 1965 (6404 adults) and prospectively examined 4300 from the birth cohorts 1973-75 in a conscription district in Denmark during the period 1 August 1993 to 31 July 1994. RESULTS: The prevalence of obesity (defined as body mass index (BMI) > or = 30 kg/m2) was 1.5% in 1955, 2.1% in 1965 and 4.6% in 1973-75 birth cohorts. The median BMI has increased during the period from 21.7-22.8 kg/m2. CONCLUSION: Obesity is relatively common and has increased among Danish young men.
Hypotheses that dissolved organic carbon (DOC) and electrochemical charge affect the rate of methylmercury [CH3Hg(I)] synthesis by modulating the availability of ionic mercury [Hg(II)] to bacteria were tested by using a mer-lux bioindicator (O. Selifonova, R. Burlage, and T. Barkay, Appl. Environ. Microbiol. 59:3083-3090, 1993). A decline in Hg(II)-dependent light production was observed in the presence of increasing concentrations of DOC, and this decline was more pronounced at pH 7 than at pH 5, suggesting that DOC is a factor controlling the bioavailability of Hg(II). A thermodynamic model (MINTEQA2) was used to select assay conditions that clearly distinguished among various Hg(II) species. By using this approach, it was shown that negatively charged forms of mercuric chloride (HgCl3-/HgCl(4)2-) induced less light production than the electrochemically neutral form (HgCl2), and no difference was observed between the two neutral forms, HgCl2 and Hg(OH)2. These results suggest that the negative charge of Hg(II) species reduces their availability to bacteria and may be one reason why accumulation of CH3Hg(I) is more often reported to occur in freshwater than in estuarine and marine biota.
An experimental approach based on the assembly of genes of a catabolic pathway was used to detect transconjugants in aquatic communities. Resistance to phenylmercury acetate was established in transconjugants when wide-host-range conjugal plasmids containing merB, the gene encoding organomercurial lyase, were transferred to strains from aquatic communities that had been acclimated to inorganic mercury and thus enriched for populations containing merA, the gene encoding mercuric reductase (T. Barkay, Appl. Environ. Microbiol. 53:2725-2732, 1987). Conjugation was confirmed by using the plasmids' encoded antibiotic resistance patterns and by hybridization with a eukaryotic gene. Three merB-conjugal plasmids, belonging to incompatibility groups W (pGTE16), P1 (pGTE26), and N (pGTE25), were prepared. Transfers by filter matings of pGTE16 and pGTE26 from Pseudomonas aeruginosa PA01 to indigenous strains were at efficiencies of 4.5 x 10 and 4.8 x 10 transconjugant per potential recipient, respectively. These efficiencies were from 1 to 2 orders of magnitude below those observed for intraspecies matings with genetically marked recipients. The third plasmid, pGTE25, was not stably maintained in P. aeruginosa donors, and its transfer from Escherichia coli donors was below the level of detection. Characterized transconjugant strains were shown to be Pseudomonas spp. Potential applications of the described experimental approach in the creation of bacterial populations with new catabolic capabilities in hazardous waste sites and in the detection of transfer of recombinant DNA from engineered microorganisms to indigenous bacteria are discussed.
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An investigation of the Hg2+ resistance mechanism of four freshwater and four coastal marine bacteria that did not hybridize with a mer operonic probe was conducted (T. Barkay, C. Liebert, and M. Gillman, Appl. Environ. Microbiol. 55:1196-1202, 1989). Hybridization with a merA probe, the gene encoding the mercuric reductase polypeptide, at a stringency of hybridization permitting hybrid formation between evolutionarily distant merA genes (as exists between gram-positive and -negative bacteria), detected merA sequences in the genomes of all tested strains. Inducible Hg2+ volatilization was demonstrated for all eight organisms, and NADPH-dependent mercuric reductase activities were detected in crude cell extracts of six of the strains. Because these strains represented random selections of bacteria from three aquatic environments, it is concluded that merA encodes a common molecular mechanism for Hg2+ resistance and volatilization in aerobic heterotrophic aquatic communities.