An advanced approach to reactivity rating.

Reactive hazards remain a significant safety challenge in the chemical industry despite continual attention devoted to this problem. The application of various criteria, which are recommended by the guidelines for assessment of reactive hazards, often causes unsafe results to be obtained. The main origins of such failures are as follows: (a) reactivity of a compound is considered as an inherent property of a compound; (b) some appropriate criteria are determined by using too simple methods that cannot reveal potential hazards properly. Four well-known hazard indicators--time to certain conversion limit, TCL; adiabatic time to maximum rate, TMR; adiabatic temperature rise; and NFPA reactivity rating number, Nr--are analyzed in the paper. It was ascertained that they could be safely used for preliminary assessment of reactive hazards provided that: (a) the selected indicator is appropriate for the specific conditions of a process; (b) the indicators have been determined by using the pertinent methods. The applicability limits for every indicator were determined and the advanced kinetics-based simulation approach, which allows reliable determination of the indicators, is proposed. The technique of applying this approach is illustrated by two practical examples.

Analysis of immunoreactivity to a Streptococcus equi subsp. zooepidemicus M-like protein To confirm an outbreak of poststreptococcal glomerulonephritis, and sequences of M-like proteins from isolates obtained from different host species.

The etiologic agent of a large 1998 outbreak of poststreptococcal acute glomerulonephritis (PSGN) in Nova Serrana, Brazil, was found likely to be a specific strain of Streptococcus equi subsp. zooepidemicus from contaminated cheese (S. Balter et al., Lancet 355:1776-1780, 2000). In the present study, we used a serologic screen for a known surface-exposed virulence factor to confirm the epidemiologic findings. Using primers flanking a previously characterized M-like protein gene (J. F. Timoney et al., Infect. Immun. 63:1440-1445, 1995), we amplified and sequenced the M-like protein (designated Szp5058) gene and found it to be identical among four independent acute-phase PSGN patient isolates. Convalescent-phase sera from 33 of 44 patients in the PSGN outbreak were found to contain antibodies highly reactive to a purified Szp5058 fusion protein, compared with 1 of 17 control sera (P < 0. 0001), suggesting that Szp5058 was expressed during infection and further implicating this strain as the cause of the PSGN outbreak. The predicted signal sequence and cell wall association motif of Szp5058 were highly conserved with the corresponding sequence from S. equi subsp. zooepidemicus SzpW60, while the predicted surface-exposed portions differed markedly between these two proteins. The 5' end of the szp5058 gene, including its variable region, was identical to the szp gene from another strain associated with a previous PSGN outbreak in England (M. Barham et al., Lancet i:945-948, 1983), and the corresponding szp sequence found from the Lancefield group C type strain isolated from a guinea pig. In addition, the hypervariable (HV) portion of szp5058 was identical to a previously published HV sequence from a horse isolate (J. A. Walker and J. F. Timoney, Am. J. Vet. Res. 59:1129-1133, 1998). Three other strains of S. equi subsp. zooepidemicus, including another strain previously associated with a PSGN outbreak, were each found to contain a distinct szp gene. Two of these szp genes had HV regions identical to szp regions from isolates recovered from different host species.

Epidemic nephritis in Nova Serrana, Brazil.

BACKGROUND: Outbreaks of nephritis have been rare since the 1970s. From December, 1997, to July, 1998, 253 cases of acute nephritis were identified in Nova Serrana, Brazil. Seven patients required dialysis, and three patients died. We did a case-control study to investigate the cause of the outbreak. METHODS: Using a matched cluster design, we examined seven recent patients, their family members (n=23), and members of neighbourhood-matched control households (n=22). We subsequently interviewed 50 patients and 50 matched controls about exposure to various dairy products. We also cultured dairy foods and took udder-swab and milk samples from cows. FINDINGS: Throat cultures indicated that nephritis was associated with group C Streptococcus equi subspecies zooepidemicus, a cause of bovine mastitis. S. zooepidemicus was detected in four of seven case households (six of 30 people) and no control households (p=0.09). Patients were more likely than matched controls to have consumed a locally produced cheese called queijo fresco (matched odds ratio 2.1, p=0.05). The nephritis attack rate was 4.5 per 1000 in Nova Serrana but 18 per 1000 in the village Quilombo do Gaia (p=0.003). The largest supplier of unpasteurized queijo fresco was a farm in Quilombo do Gaia. S. zooepidemicus was not detected in food samples or in swabs collected from cows in August, 1998, although mastitis was evident among cows on the suspected farm. Throat cultures of the two women who prepared cheese on this farm yielded the outbreak strain of S. zooepidemicus. After the cheese was removed from the distribution system, no further cases were reported. INTERPRETATION: A large outbreak of glomerulonephritis was attributed to S. zooepidemicus in unpasteurised cheese. This outbreak highlights the dangers of consuming unpasteurized dairy products and need for global efforts to promote food safety.

High concentrations of heavy metals in neighborhoods near ore smelters in northern Mexico.

In developing countries, rapid industrialization without environmental controls has resulted in heavy metal contamination of communities. We hypothesized that residential neighborhoods located near ore industries in three northern Mexican cities would be heavily polluted with multiple contaminants (arsenic, cadmium, and lead) and that these sites would be point sources for the heavy metals. To evaluate these hypotheses, we obtained samples of roadside surface dust from residential neighborhoods within 2 m of metal smelters [Torreón (n = 19)] and Chihuahua (n = 19)] and a metal refinery [Monterrey (n = 23)]. Heavy metal concentrations in dust were mapped with respect to distance from the industrial sites. Correlation between dust metal concentration and distance was estimated with least-squares regression using log-transformed data. Median dust arsenic, cadmium, and lead concentrations were 32, 10, and 277 microg/g, respectively, in Chihuahua; 42, 2, and 467 microg/g, respectively, in Monterrey, and 113, 112, and 2,448 microg/g, respectively, in Torreón. Dust concentrations of all heavy metals were significantly higher around the active smelter in Torreón, where more than 90% of samples exceeded Superfund cleanup goals. At all sites, dust concentrations were inversely related to distance from the industrial source, implicating these industries as the likely source of the contamination. We concluded that residential neighborhoods around metal smelting and refining sites in these three cities are contaminated by heavy metals at concentrations likely to pose a health threat to people living nearby. Evaluations of human exposure near these sites should be conducted. Because multiple heavy metal pollutants may exist near smelter sites, researchers should avoid attributing toxicity to one heavy metal unless others have been measured and shown not to coexist.

Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction.

A patient with refractory Crohn's disease had two separate episodes of bone marrow suppression while receiving 50 to 75 mg 6-mercaptopurine a day and 1000 to 1750 mg olsalazine a day. This adverse reaction necessitated dose reduction of 6-mercaptopurine on the first occasion and withdrawal of 6-mercaptopurine and olsalazine on the second occasion. The patient's red blood cell thiopurine methyltransferase (TPMT) activity was 1.2 U per milliliter red blood cells (low normal range) and her TPMT genotype was wild-type sequence for all known alleles of TPMT that result in low TPMT enzyme activity. In vitro enzyme kinetic studies confirmed the hypothesis that olsalazine and olsalazine-O-sulfate are potent noncompetitive inhibitors of recombinant human TPMT. We suggest that the patient's relatively low baseline level of TPMT activity was inhibited by olsalazine and olsalazine-O-sulfate, leading to decreased clearance of 6-mercaptopurine and its accumulation. This ultimately increased intracellular 6-thiopurine nucleotide levels to toxic concentrations, which caused bone marrow suppression.