2013 multistate outbreaks of Cyclospora cayetanensis infections associated with fresh produce: focus on the Texas investigations.

The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0-∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.

The 2008 ACVP role delineation survey and initial data analysis: from the Role Delineation Task Force.

The American College of Veterinary Pathologists commissioned a role delineation survey to define the specialized tasks, knowledge, and tools that define the current practice of veterinary clinical pathology and veterinary anatomic pathology. The survey also identified when competence was acquired for each task (i.e., before certification or after certification). The response rate by diplomates was high, with approximately 50% of practicing pathologists within each specialty responding to each survey. Using the survey results, all tasks for each specialty were classified as either appropriate or unsuitable for testing in the certifying examinations. The role delineation survey data will facilitate the creation of test plans that objectively define the content in each certifying examination, the evaluation and enhancement of training curricula, and the optimization of continuing education opportunities for practicing veterinary pathologists.

Sodium chloride increases the ciliary transportability of cystic fibrosis and bronchiectasis sputum on the mucus-depleted bovine trachea.

Mucus retention in the lungs is an important feature of several respiratory diseases (Regnis, J.A., M. Robinson, D.L. Bailey, P. Cook, P. Hooper, H.K. Chan, I. Gonda, G. Bautovich, and P.T.P. Bye. 1994. Am. J. Respir. Crit. Care Med. 150:66-71 and Currie, D.C., D. Pavia, J.E. Agnew, M.T. Lopez-Vidriero, P.D. Diamond, P.J. Cole, and S.W. Clarke. 1987. Thorax. 42:126-130). On the mucus-depleted bovine trachea, the ciliary transport rate of sputum from patients with cystic fibrosis and bronchiectasis of other causes was slow, but the rate was doubled by increasing the sodium chloride content by 90 mM. Increasing the sputum osmolality by inspissation or by the addition of nonelectrolytes had a similar effect. The viscoelasticity of sputum, but not the bovine ciliary beat frequency, was markedly saline dependent over the pathophysiological range. This suggests that low mucus salinity, not (as is generally assumed) its under-hydration, contributes to its retention in bronchiectasis due to cystic fibrosis and other causes, probably by affecting its rheology. It also indicates how the genetic defect in cystic fibrosis might lead to impaired mucus clearance. Therapies that increase the osmolality of lung mucus might benefit patients with mucus retention.

Mucus-glycoproteins (mucins) of the cat trachea: characterisation and control of secretion.

Glycoproteins produced by the tracheae of anaesthetized cats were radiolabelled biosynthetically by a pulse administration of Na2 35SO4 and [3H]glucose into the tracheal lumen. Subsequently, radiolabelled secretions were washed from the tracheal lumen. Repeated doses of pilocarpine and then ammonia vapour were given to stimulate secretion. Pilocarpine-stimulated glycoproteins, which came mainly from the submucosal glands, were particularly enriched with 35S. Ammonia-stimulated secretions, which probably came mostly from the microvillous border of the surface epithelium, contained mainly 3H radioactivity but little 35S. Two negatively-charged glycoproteins of different molecular size were identified in the secretions: the larger component was excluded on Sepharose CL-4B and it had a higher 3H 35S ratio than the smaller component which was retarded on Sepharose CL-4B. The relative amount of the smaller component decreased progressively with repeated pilocarpine stimulation and it was not detected in secretions induced by ammonia. Pilocarpine stimulation caused little alteration in carbohydrate composition of the secreted glycoproteins. In response to ammonia, glycoproteins were secreted with a high sialic acid content but quantitatively they represented a small amount of material compared with that induced by pilocarpine. These findings suggest that tracheal glycoproteins from different epithelial-cell sources have distinctive chemical compositions and that their secretions may be independently regulated. The 35S-rich high-molecular-weight glycoproteins from the submucosal glands were of the mucin-type but those derived from the microvillus border may represent a different class of airway glycoproteins from typical epithelial mucins.

A procedure for the safety evaluation of natural flavor complexes used as ingredients in food: essential oils.

A scientifically based guide has been developed to evaluate the safety of naturally occurring mixtures, particularly essential oils, for their intended use as flavor ingredients. The approach relies on the complete chemical characterization of the essential oil and the variability of the composition of the oil in the product intended for commerce. Being products of common plant biochemical pathways, the chemically identified constituents are organized according to a limited number of well-established chemical groups called congeneric groups. The safety of the intake of the each congeneric group from consumption of the essential oil is evaluated in the context of data on absorption, metabolism, and toxicology of members of the congeneric group. The intake of the group of unidentified constituents is evaluated in the context of the consumption of the essential oil as a food, a highly conservative toxicologic threshold, and toxicity data on the essential oil or an essential oil of similar chemotaxonomy. The flexibility of the guide is reflected in the fact that high intake of major congeneric groups of low toxicologic concern will be evaluated along with low intake of minor congeneric groups of significant toxicological concern (i.e., higher structural class). The guide also provides a comprehensive evaluation of all congeneric groups and constituents that account for the majority of the composition of the essential oil. The overall objective of the guide is to organize and prioritize the chemical constituents of an essential oil in order that no reasonably possible significant risk associated with the intake of essential oil goes unevaluated. The guide is, however, not intended to be a rigid checklist. The Flavor and Extract Manufacturers Association (FEMA) Expert Panel will continue to evaluate each essential oil on a case by case basis applying their scientific judgment to insure that each natural flavor complex is exhaustively evaluated.

Expression of TRPM-2 during involution and regeneration of the rat liver.

Increased message levels of testosterone-repressed prostate message-2 (TRPM-2) have been associated with programmed cell death in many tissues. To study its involvement in the apoptotic elimination of hepatocytes during liver involution and regeneration, levels of TRPM-2 message were evaluated in situ and by the ribonuclease protection assay. Although significant increases in apoptotic bodies were observed in rats 96 h following treatment with lead nitrate and ethylene dibromide, an increase in TRPM-2 message was not detected. Therefore, the expression of TRPM-2 mRNA may be a poor indicator of the extent to which apoptosis occurs during liver involution.

The de-endothelialized rat carotid arterial graft: a versatile experimental model for the investigation of arterial thrombosis.

A novel model of arterial thrombosis was developed. A mechanical endothelium-denuding injury was created (using a scalpel blade) on harvested, freezer-stored rat carotid arteries. Vessel length of 5 mm. were grafted into the femoral arteries of recipient Sprague-Dawley rats using microvascular anastomotic technique. Patency rates in untreated animals were compared with those in animals receiving systemic aspirin or heparin. The control group patency after 2 hours of flow was 15%, while grafts in aspirin- and heparin-treated animals achieved 35% and 95% patency rates, respectively. Uninjured non-frozen carotid grafts in untreated animals yielded a 95% patency rate, while frozen grafts achieved an 80% patency. Therapeutic levels of aspirin, heparin, and urokinase were confirmed through tail bleeding and whole blood clotting tests, as well as platelet aggregation studies and scanning electron microscopy of the graft lumenal surfaces. A long-term series using syngeneic grafts placed in recipients (Lewis-to-Lewis) and employing systemic heparinization demonstrated maintenance of patency for 4 weeks. Scanning electron microscopy revealed good re-endothelialization, well advanced by one week. Histology confirmed the regrowth of endothelial cells, but showed sparse cellular repopulation of medial and adventitial layers. The mechanical injury model was compared to enzymatic de-endothelialization (using trypsin or collagenase), for which patency rates were similar (10% and 0%, respectively). Trypsin de-endothelialized vessels were tested in vitro for the amount of active trypsin remaining bound to the lumenal surface; no detectable activity was found when trypsin inhibitor was applied following trypsin treatment. The versatility of allowing both in vitro evaluation and in vivo patency assessment demonstrates the uniqueness and value of this new model, offering an avenue toward more direct investigations of surface-mediated thrombotic processes.

Haematological safety of antipsychotic drugs.

Haematological abnormalities are frequently encountered during treatment with antipsychotic drugs. Most of these are mild and of no clinical significance. In the case of many, there is often difficulty in establishing a cause-and-effect relationship between the drug and the abnormality. However, in a small minority of patients, hazardous, potentially life-threatening haematological effects can occur due to a combination of pharmacological and host factors. These include leucopenia and agranulocytosis. Although such effects are rare, it is essential that they are diagnosed and managed promptly. In this paper, the authors review the haematological adverse effects and safety of antipsychotic drugs and present a strategy for prevention.

Pyomyositis in a temperate climate. Presentation, diagnosis, and treatment.

The cases of eighteen patients who were treated for pyomyositis between 1970 and 1988 were evaluated. The diagnosis was often delayed because other primary diagnoses were considered, including muscle strain, synovitis, thrombophlebitis, and neoplasm, and because the symptoms were vague and prolonged (maximum duration, one year). The muscles around the hip and thigh were most commonly involved (twelve patients), and Staphylococcus aureus most commonly grew on culture (twelve patients). Computed tomography aided in the accurate diagnosis of the infection and of the extent of involvement. Incision, drainage, and antibiotic therapy eradicated the infection in all patients, and they had no residual functional limitations and minimum residual symptoms.

Safety evaluation of natural flavour complexes.

Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources. Many NFCs are derived from foods. In the present paper, a 12-step procedure for the safety evaluation of NFCs, 'the naturals paradigm', is discussed. This procedure, which is not intended to be viewed as a rigid check list, begins with a description of the chemical composition of the commercial product, followed by a review of the data on the history of dietary use. Next, each constituent of an NFC is assigned to one of 33 congeneric groups of structurally related substances and to one of three classes of toxic potential, each with its own exposure threshold of toxicological concern. The group of substances of unknown structure is placed in the class of greatest toxic potential. In subsequent steps, for each congeneric group the procedure determines the per capita intake, considers metabolic pathways and explores the need and availability of toxicological data. Additional toxicological and analytical data may be required for a comprehensive safety evaluation. The procedure concludes with an evaluation of the NFC in its entirety, also considering combined exposure to congeneric groups. The first experiences with the use of this procedure are very promising. Future safety evaluations of larger numbers of NFCs will indicate the usefulness of the system, either in its present form or in a form modified on the basis of experience.

52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery.

Potential ubiquinone (CoQ10; a natural fermentation product) toxicity was assessed in rats administered CoQ(10) by oral gavage for 1 year at 100, 300, 600, and 1200 mg/(kg day). No adverse changes in mortality, clinical signs, body weight, food consumption, or clinical pathology results occurred. CoQ(10) had elimination half-lives ranging from 10.7 to 15.2 h. At 1200 mg/(kg day), a high incidence of orange, granular, lumenal exudate in nasal turbinates occurred; microscopically, findings similar to those in the turbinates were occasionally observed in small granulomas within lung alveoli. A dose-related increased incidence of vacuolated macrophages (mesenteric lymph nodes) and vacuolated hepatic periportal cells was noted. Neither were associated with tissue damage or organ dysfunction, so they were not considered to be adverse. The nasal turbinate and lung findings were probably secondary to incidental exposure to crystallized test material. Overall, CoQ(10) was well tolerated by male and female rats at dose levels up to 1200 mg/(kg day).

Reactivity of glutathione with alpha, beta-unsaturated ketone flavouring substances.

The relative reactivities of a number of alpha, beta-unsaturated ketones used as flavourings were determined using glutathione as the nucleophile. Monosubstitution at the beta-position of the alpha, beta-unsaturated system impeded nucleophilic addition by approximately 1000 times. Beta-Disubstitution reduced reactivity by more than 100,000 times. Endocyclic alpha, beta-unsaturated ketones were generally less reactive than alicyclic analogues. By way of comparison, the most reactive flavouring investigated, 2-octene-4-one, was consumed by glutathione about 700 times less rapidly than was methylvinyl ketone. Methylvinyl ketone was found to condense with guanylic acid 240,000 times more slowly than with glutathione. It is concluded that alpha, beta-unsaturated ketones used as flavourings generally possess low electrophilicity.

Oral toxicity and carcinogenicity studies of sucrose acetate isobutyrate (SAIB) in the Fischer 344 rat and B6C3F1 mouse.

Sucrose acetate isobutyrate (SAIB), a food additive used as a flavour emulsion stabilizer in citrus-based soft drinks, was evaluated for chronic toxicity in B6C3F1 mice and Fischer 344 rats. SAIB dissolved in acetone was blended into NIH07 rodent diet at concentrations that were adjusted weekly during the first 12 to 18 months of the studies so that ingested dose levels per kg body weight were constant. Groups of 20 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 1 yr, and groups of 50 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 2 yr. Mice were fed dose levels of 0.0, 0.0, 1.25, 2.5 and 5.0 g SAIB/kg body weight for 2 yr. The highest doses fed, equivalent to dietary concentrations of approximately 5%, were considered to be the maximum concentrations that could be fed without risk of nutritional deficiencies. Depressions in body weight gain were noted, particularly in female rats during the first 12 to 18 months of the studies. Recovery during the last quarter of the 2-yr study suggests that the reduced body weight gain was nutritional rather than SAIB-related. There were no differences in survival between SAIB-treated rats or mice and controls. Decreased body weight gains, primarily in females, but less consistent than those in the rat, were noted in the 2-yr mouse study. No signs of toxicity were observed in clinical chemistry, haematology, organ weights, gross necropsy findings or light microscopy studies in the 1- or 2-yr rat studies. Electron microscopic examinations of liver sections from high dose level rats from the 1-yr study also revealed no effects of SAIB treatment. There were no significant increases in benign or malignant tumours in the long-term rat or mouse carcinogenicity studies. The lowest no-observed-adverse-effect level (NOAEL) was 2 g SAIB/kg body weight derived from the 1- and 2-yr chronic toxicity studies in the rat.

Predictors of recidivism in DUIIs.

The prior driving records of 397 drivers arrested for drinking and driving in the year 1983 were examined with the purpose of comparing biographical factors and variables relating to driving history and arrest circumstance between recidivist and nonrecidivist drinking drivers. Of these drivers, 174 (44%) had more than one arrest within a 12-year study period, while 223 (56%) had only one. Significant differences were found among drivers with different numbers of drinking and driving offenses. Drivers with one or two DUII arrests had more non-moving traffic violations than drivers with three or more DUII arrests. Drinking and driving offenders with higher levels of arrests were more likely to be unemployed, to have a past criminal record, to be arrested for drinking and driving on a weekday during afternoon and early evening hours, to drive with a suspended or revoked license and to refuse a blood alcohol level determination test. In this study DUII offenders with four or more arrests fit the descriptive model of alcoholism.

Problems in deterrence: a comparison of the driving histories of DUII and non-DUII drivers.

Driving records of subjects arrested for driving under the influence of intoxicants (DUII), both recidivists and nonrecidivists, were compared with records of an age- and sex-matched random sample of non-DUII drivers. Major differences were found between DUII and non-DUII groups in the incidence of traffic violations but some differences also existed between nonrecidivist and recidivist DUII subjects. Rehabilitative diversion programs for first-time DUII offenders did not affect recidivism rates in the study population. Findings in this study suggest that general deterrence directed at the non-DUII population should receive emphasis equal to specific deterrence directed at DUII offenders.

Posterior labral tear as a block to reduction in an anterior hip dislocation.

The patient presented with an anterior dislocation of the hip that could not be centrically reduced by closed methods. Computed tomographic imaging after trial reduction revealed a posterior fragment that was limiting reduction. At the time of open reduction, a large posterior labral tear with a small avulsed posterior acetabular rim of bone was found to be blocking the reduction.

Effect of captopril on the progression of induced pyelonephritis in the rat.

The effect of captopril, an angiotensin-converting enzyme inhibitor, was studied in rats subjected to Escherichia coli pyelonephritis. Eight weeks after pyelonephritis was induced in male Sprague-Dawley rats, the rats were randomly assigned to treatment groups based on urinary protein excretion. In experiment 1, rats were given captopril, 50 mg/kg of body weight, or saline solution via daily intraperitoneal injection. To eliminate complications with captopril-induced peritonitis, experiment 2 was performed in which rats were given the same treatment by daily gavage. In both experiments, 24-hour urinary protein excretion in the saline-treated rats was significantly greater than that of the captopril-treated rats after 12 weeks of treatment (P less than 0.05). Plasma urea nitrogen, plasma creatinine, and endogenous creatinine clearance did not differ between treatment groups during the course of therapy in experiment 1. There were no differences in these values in experiment 2, except at week 8 of treatment when the captopril-treated rats had significantly lower plasma creatinine and higher endogenous creatinine clearance than did the saline-treated rats (P less than 0.05). There was also no difference between treatment groups in the degree of morphologic renal damage based on light microscopic evaluation of kidneys at the end of treatment.

Laboratory evaluation of liver disease.

With respect to liver disease, the primary function of the laboratory is to identify its presence. Tests are not available that permit a specific diagnosis and an accurate prognosis. Several tests should be present in a minimum data base that can help identify hepatobiliary disease. They are ALT, SAP, total serum bilirubin, urine bilirubin, cholesterol, albumin, BUN, glucose, red cell morphology, and urine sediment. It is sometimes possible to tentatively identify whether a disease is primarily hepatocellular or biliary from the pattern of changes that occur in these tests. In addition, an estimate of the severity is sometimes possible when abnormal values are extreme. The keys are to avoid overinterpretation, use serial evaluations, and rely on a liver biopsy when definitive answers are needed. If liver disease is suspected but there are only marginal changes in the routine tests, the more sensitive tests of function, BSP retention and ammonia tolerance, are warranted. In the future, as more knowledge is gained about the responses of ARG, GGT, and ICG retention to naturally occurring diseases, these tests may join or replace some of those currently used. Also, as the ability to accurately and economically measure the various bile acids improves, a sensitive, yet noninvasive, method to detect and define modest changes in hepatobiliary function may result.

Acute rupture of the extensor hallucis longus tendon.

A 40-year-old man with a history of previous cheilectomy and two steroid injections for first metatarsophalangeal degenerative joint disease sustained an acute rupture of the extensor hallucis longus tendon. He was treated successfully with delayed primary repair of the tendon.