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This study examines whether perception of family environment, attitudes toward life and death, and depression predict suicidality in elementary-school children. Seventy-eight participants ages 8 to 13 recruited through an elementary school and a university were assessed for attitudes toward life and death, depression suicidality, and family environment. A regression equation indicated that depression and attraction to life were the only variables accounting for variance in suicidality (49%). Family environment variables were moderately correlated with depression, indicating that family environment may play a role in the development and maintenance of depression of which suicidality is a symptom. Concurrent treatment of family issues may not only ameliorate children's symptoms, but also provide a critical sense of support that may decrease the likelihood that these children will become suicidal in the future. [ABSTRACT FROM AUTHOR]

Sow immunity plays an important role in preventing viral infection and disease in newborn piglets. Vertical transmission of porcine circovirus type 2 (PCV2) may perpetuate porcine circovirus associated disease (PCVAD) in newborn and growing pigs. Hence, the immunological effects of maternal immunoglobulin transfer of PCV2-specific antibodies on PCV2 viremia and immune response in piglets in commercial swine herds were evaluated. Sow vaccination has been shown to reduce viral shedding and viremia, and increases the neutralizing antibody (NA) titers. Since NAs are important for control of PCVAD and mammary secretions may contain high anti-PCV2 NA levels, we examined the PCV2 NA levels in colostrum, milk, sow serum, and piglet serum over time to investigate an association between NA levels and protection against infection. NA titers were remarkably high (up to 10 -6 50% neutralizing titer) in sow serum and colostrum on all farms regardless of viremia levels. In piglets vaccinated at 3 weeks of age, NA titers peaked at 10 weeks of age and continued to maintain high viral neutralizing titers to slaughter. The impact of maternally derived neutralizing activity was most evident during the suckling period. Although PCV2 was transmitted from sows to piglets in colostrum, piglets were largely nonviremic at weaning. Thus, NAs appear to control or suppress initial infection even though they are unable to clear or prevent infection later in life.

Mice deficient in TMEM218 (Tmem218(-/-) ) were generated as part of an effort to identify and validate pharmaceutically tractable targets for drug development through large-scale phenotypic screening of knockout mice. Routine diagnostics, expression analysis, histopathology, and electroretinogram analyses completed on Tmem218(-/-) mice identified a previously unknown role for TMEM218 in the development and function of the kidney and eye. The major observed phenotypes in Tmem218(-/-) mice were progressive cystic kidney disease and retinal degeneration. The renal lesions were characterized by diffuse renal cyst development with tubulointerstitial nephropathy and disruption of tubular basement membranes in essentially normal-sized kidneys. The retinal lesions were characterized by slow-onset loss of photoreceptors, which resulted in reduced electroretinogram responses. These renal and retinal lesions are most similar to those associated with nephronophthisis (NPHP) and retinitis pigmentosa in humans. At least 10% of NPHP cases present with extrarenal conditions, which most often include retinal degeneration. Senior-Løken syndrome is characterized by the concurrent development of autosomal recessive NPHP and retinitis pigmentosa. Since mutations in the known NPHP genes collectively account for only about 30% of NPHP cases, it is possible that TMEM218 could be involved in the development of similar ciliopathies in humans. In reviewing all other reported mouse models of NPHP, we suggest that Tmem218(-/-) mice could provide a useful model for elucidating the pathogenesis of cilia-associated disease in both the kidney and the retina, as well as in developing and testing novel therapeutic strategies for Senior-Løken syndrome., (© The Author(s) 2014.)

The objective of this study was to identify intra-farm risk factors that affected the colonization with Mycoplasma hyopneumoniae at weaning age. Three farrow-to-wean farms were visited at least 5 times each. An average of 54 piglets were sampled at each visit and assayed by means of real-time PCR in nasal swabs. The proportion of PCR positive piglets was evaluated as a response to several variables including dam's PCR status, piglet serological status, and local climatic conditions during the lactation period, as well as other factors. All piglets at weaning age were negative to M. hyopneumoniae in 2 of the 3 farms. M. hyopneumoniae positive piglets were demonstrated in 5 of 7 weaning groups in 1 farm. The proportion of M. hyopneumoniae positive piglets in each weaning group at the positive farm was correlated with the proportion of positive dams in the group. The prevalence of M. hyopneumoniae at weaning increased with the piglet's age in the groups where at least one dam was positive. These results highlight the influence of the sow in the sow-to-piglet colonization process, as previously reported, and contribute to a more comprehensive understanding of the epidemiology of M. hyopneumoniae infections., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The absence of commercialized vaccines and antiviral agents against dengue has made the disease a major health concern around the world. With the current dengue virus transmission rate and incidences, the development of antiviral drugs is of vital need. The aim of this project was to evaluate the possibility of developing a local medicinal plant, Phyllanthus as an anti-dengue agent., Methods: Cocktail (aqueous and methanolic) extracts were prepared from four species of Phyllanthus (P.amarus, P.niruri, P.urinaria, and P.watsonii) and their polyphenolic compounds were identified via HPLC and LC-MS/MS analysis. MTS assay was then carried out to determine the maximal non-toxic dose (MNTD) of the extracts, followed by screening of the in vitro antiviral activity of aqueous cocktail extracts against DENV2 by means of time-of-addition (pre-, simultaneous and post-) using RT-qPCR. The differentially expressed proteins in the treated and infected cells were analysed with two dimensional gel electrophoresis experiments., Results: Several active compounds including gallic acid, geraniin, syringin, and corilagen have been identified. The MNTD of both aqueous and methanolic extracts on Vero cells were 250.0 μg/ml and 15.63 μg/ml respectively. Phyllanthus showed strongest inhibitory activity against DENV2 with more than 90% of virus reduction in simultaneous treatment. Two-dimensional analysis revealed significantly altered levels of thirteen proteins, which were successfully identified by tandem MS (MS/MS). These altered proteins were involved in several biological processes, including viral entry, viral transcription and translation regulations, cytoskeletal assembly, and cellular metabolisms., Conclusions: Phyllanthus could be potentially developed as an anti-DENV agent.

There is evidence that genetic factors play a role in the complex multifactorial pathogenesis of hydrocephalus. Identification of the genes involved in the development of this neurologic disorder in animal models may elucidate factors responsible for the excessive accumulation of cerebrospinal fluid in hydrocephalic humans. The authors report here a brief summary of findings from 12 lines of genetically engineered mice that presented with autosomal recessive congenital hydrocephalus. This study illustrates the value of knockout mice in identifying genetic factors involved in the development of congenital hydrocephalus. Findings suggest that dysfunctional motile cilia represent the underlying pathogenetic mechanism in 8 of the 12 lines (Ulk4, Nme5, Nme7, Kif27, Stk36, Dpcd, Ak7, and Ak8). The likely underlying cause in the remaining 4 lines (RIKEN 4930444A02, Celsr2, Mboat7, and transgenic FZD3) was not determined, but it is possible that some of these could also have ciliary defects. For example, the cerebellar malformations observed in RIKEN 4930444A02 knockout mice show similarities to a number of developmental disorders, such as Joubert, Meckel-Gruber, and Bardet-Biedl syndromes, which involve mutations in cilia-related genes. Even though the direct relevance of mouse models to hydrocephalus in humans remains uncertain, the high prevalence of familial patterns of inheritance for congenital hydrocephalus in humans suggests that identification of genes responsible for development of hydrocephalus in mice may lead to the identification of homologous modifier genes and susceptibility alleles in humans. Also, characterization of mouse models can enhance understanding of important cell signaling and developmental pathways involved in the pathogenesis of hydrocephalus.

The Hedgehog (Hh) pathway is a conserved signalling system essential for embryonic development and for the maintenance of self-renewal pathways in progenitor cells. Mutations that deregulate Hh signalling are directly implicated in basal cell carcinoma and medulloblastoma. The mechanisms of Hh pathway activation in cancers in which no pathway mutations have been identified are less clear, but of great translational significance. Small molecule inhibitors of the pathway, many of which are in early phase clinical trials, may shed further light on this question. Canonical Hh signalling promotes the expression of target genes through the Glioma-associated oncogene (GLI) transcription factors. There is now increasing evidence suggesting that 'non-canonical' Hh signalling mechanisms, some of which are independent of GLI-mediated transcription, may be important in cancer and development. The focus of this review is to summarise some of the known mechanisms of Hh signalling as well as its emerging role in cancer.

In later life, optimistic health appraisals promote well-being and survival, whereas pessimistic appraisals can be harmful. This study contrasted subjective health (SH) appraisals with objective health (OH) to identify realists, whose ratings were congruent (SH = OH), distinguishing them from health pessimists (SH < OH) and health optimists (SH > OH) with incongruent ratings. Health congruence and functional well-being of 757 older adults were assessed via two interviews conducted 5 years apart. We examined consistency in health congruence, and among those with persistent OH, we examined 5-year functional well-being changes that corresponded with SH shifts and determined whether SH shifts predicted 30-month survival. Most realists remained realists; health optimists and pessimists tended to become realists. Increased health optimism corresponded with enhanced functioning; increased pessimism corresponded with decreased functioning. Among realists, increasingly positive SH predicted survival. Findings have implications for quality and length of life among older adults with chronic health conditions.

The rat has been the preferred rodent toxicology species since before regulatory requirements have been in place, and there exists in the pharmaceutical industry and the regulatory agencies a significant amount of historical data for the rat. The resulting experience base with the rat makes the possibility of replacing it with the mouse for regulated toxicology studies untenable for all but the most extreme circumstances. However, toxicologists are very familiar with the mouse as a model for chronic carcinogenicity studies, and there exist multiple preclinical mouse models of disease. The authors evaluated the use of the mouse for early in vivo toxicology signal generation and prioritization of small molecule lead compounds prior to nomination of a development candidate. In five-day oral gavage studies with three test agents in the mouse, the authors were able to identify the same dose-limiting toxicities as those identified in the rat, including examples of compound-mediated hemolysis as well as microscopic lesions in the alimentary canal, kidney, and pancreas. Performing early signal generation studies in the mouse allows for earlier assessment of the safety liabilities of small molecules, requires significantly less compound, and allows evaluation of more compounds earlier in the project's life cycle.

ABSTRACTIn the absence of a universally agreed-upon definition of successful aging, researchers increasingly look to older adults for layperson views of aging and definitions of successful aging. To use lay definitions in studies of aging, however, researchers must address the definitions' consistency. In 2004, surviving members of the Manitoba Follow-up Study male cohort (mean age: 83 years) were asked twice for their definition of successful aging. A consistency category was assigned based on the similarity of themes in each of 654 pairs of definitions. At least half of the main themes were similar in 70 per cent of the definition pairs; 80 per cent of respondents repeated at least one theme. Positive or negative health events in the four-week interval between definitions and specific respondents' characteristics did not vary across consistency categories. This evidence for consistency supports our continued reliance on lay definitions of successful aging.

UDP-GlcNAc: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) is an alpha(2)beta(2)gamma(2) hexameric enzyme that catalyzes the first step in the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. In humans, mutations in the gene encoding the alpha/beta subunit precursor give rise to mucolipidosis II (MLII), whereas mutations in the gene encoding the gamma subunit cause the less severe mucolipidosis IIIC (MLIIIC). In this study we describe the phenotypic, histologic, and serum lysosomal enzyme abnormalities in knockout mice lacking the gamma subunit and compare these findings to those of mice lacking the alpha/beta subunits and humans with MLII and MLIIIC. We found that both lines of mutant mice had elevated levels of serum lysosomal enzymes and cytoplasmic alterations in secretory cells of several exocrine glands; however, lesions in gamma-subunit deficient (Gnptg(-/-)) mice were milder and more restricted in distribution than in alpha/beta-subunit deficient (Gnptab(-/-)) mice. We found that onset, extent, and severity of lesions that developed in these two different knockouts correlated with measured lysosomal enzyme activity; with a more rapid, widespread, and severe storage disease phenotype developing in Gnptab(-/-) mice. In contrast to mice deficient in the alpha/beta subunits, the mice lacking the gamma subunits were of normal size, lacked cartilage defects, and did not develop retinal degeneration. The milder disease in the gamma-subunit deficient mice correlated with residual synthesis of the mannose 6-phosphate recognition marker. Of significance, neither strain of mutant mice developed cytoplasmic vacuolar inclusions in fibrocytes or mesenchymal cells (I-cells), the characteristic lesion associated with the prominent skeletal and connective tissue abnormalities in humans with MLII and MLIII. Instead, the predominant lesions in both lines of mice were found in the secretory epithelial cells of several exocrine glands, including the pancreas, and the parotid, submandibular salivary, nasal, lacrimal, bulbourethral, and gastric glands. The absence of retinal and chondrocyte lesions in Gnptg(-/-) mice might be attributed to residual beta-glucuronidase activity. We conclude that mice lacking either alpha/beta or gamma subunits displayed clinical and pathologic features that differed substantially from those reported in humans having mutations in orthologous genes.

Incubation periods of Neotropical birds are often longer than those of related species at temperate latitudes. We conducted a common-garden experiment to test the hypothesis that longer tropical incubation periods result from longer embryo development times rather than from different patterns of parental incubation behavior. House wrens, one of few species whose geographic range includes tropical equatorial and temperate high latitudes, have incubation periods averaging 1.2 days longer at tropical latitudes. We incubated eggs of house wrens in Illinois and Panama under identical conditions in mechanical incubators. Even after factoring out differences in egg size, tropical house wrens still required 1.33 days longer, on average, to hatch. We conclude that parental attendance patterns do not account for latitudinal differences in incubation period but that some other as yet unmeasured factor intrinsic to the egg or embryo, or both, extends development time in the tropics.

UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on acid hydrolases. The transferase exists as an alpha(2)beta(2)gamma(2) hexameric complex with the alpha- and beta-subunits derived from a single precursor molecule. The catalytic function of the transferase is attributed to the alpha- and beta-subunits, whereas the gamma-subunit is believed to be involved in the recognition of a conformation-dependent protein determinant common to acid hydrolases. Using knock-out mice with mutations in either the alpha/beta gene or the gamma gene, we show that disruption of the alpha/beta gene completely abolishes phosphorylation of high mannose oligosaccharides on acid hydrolases whereas knock-out of the gamma gene results in only a partial loss of phosphorylation. These findings demonstrate that the alpha/beta-subunits, in addition to their catalytic function, have some ability to recognize acid hydrolases as specific substrates. This process is enhanced by the gamma-subunit.

Objectives: A 1993 large water-borne outbreak of Salmonella typhimurium infections in Gideon, Mo, a city of 1100 with an unchlorinated community water supply, was investigated to determine the source of contamination and the effectiveness of an order to boil water., Methods: A survey of household members in Gideon and the surrounding township produced information on diarrheal illness, water consumption, and compliance with the boil water order., Results: More than 650 persons were ill; 15 were hospitalized, and 7 died. Persons consuming city water were more likely to be ill (relative risk [RR] = 9.1, 95% confidence interval [CI] = 2.9, 28.4), and the attack rate increased with increased water consumption. S. typhimurium was recovered from samples taken from a city fire hydrant and a water storage tower. Persons in 31% (30/ 98) of city households had drunk unboiled water after being informed about the boil water order, including 14 individuals who subsequently became ill. Reasons for noncompliance included "not remembering" (44%) and "disbelieving" (25%) the order., Conclusions: Communities with deteriorating water systems risk widespread illness unless water supplies are properly operated and maintained. Effective education to improve compliance during boil water orders is needed.

Objectives: Because the promotion of healthier life styles has become a public health issue of increasing interest, a survey was conducted to compare levels of preventive oral and general health behaviors., Methods: A randomly selected population of voters aged 19 years and older living in a multicultural suburb of metropolitan Toronto, Canada, participated in a mail survey., Results: Dentate respondents (n = 976) reported high optimal levels for at least daily toothbrushing (96%); moderate levels of preventive yearly dental examination (69%); and low levels for flossing (22%), using an interdental device (25%), not snacking between meals (12%), and consuming fewer than two cariogenic foods on the previous day (26%). For the general health behaviors, the majority did not smoke (75%), had low alcohol intake (89%), used seat belts (69%), and exercised three times weekly (50%). Additive indices for the oral and general health behaviors were significantly, although weakly, correlated (r = 13; P < .001) and few respondents (31.3%) scored high on both indices. OLS regression on a combined index of oral and general health behaviors found that females, older respondents, and those with higher incomes were more likely to engage in a higher level of health behaviors., Conclusions: These results indicate the need to develop health promotion life style programs that incorporate both dental and general health components and to target these programs to younger age groups, males, and those with low incomes.

An artificial neural network model for the recognition of Escherichia coli O157:H7 restriction patterns was designed. In the training phase, images of two classes of E. coli isolates (O157:H7 and non-O157:H7) were digitized and transmitted to the neural network. The system was then tested for recognition of images not included in the training set. Promising results were achieved with the designed network configuration, providing a basis for further study. This application of a new generation of computation technology serves as an example of its usefulness in microbiology.

Comparative pharmacotoxicity studies in rats were performed to evaluate the response to r-metHuIL-2[ala-125] following 2 or 4 weeks of daily intravenous or subcutaneous administration, as well as to evaluate pharmacokinetic and pharmacodynamic responses. Pharmacokinetic analysis indicated that r-metHuIL-2[ala-125] showed high bioavailability and nonlinear concentration profiles. Pharmacodynamic responses to intravenous or subcutaneous dosing with r-metHuIL-2[ala-125], as measured by white blood cell counts, were comparable. Preclinical safety studies (6, 30, and 150 micrograms kg-1 day-1) indicated that r-metHuIL-2[ala-125], whether given intravenously or subcutaneously, was associated with increased circulating and infiltrating levels of lymphocytes and eosinophils. Bone marrow lymphoid hyperplasia and splenic extramedullary hematopoiesis were similarly observed in each study. This pattern of effects was considered an exaggerated pharmacodynamic response to r-metHuIL-2[ala-125]. Of further note was a histopathologic finding described as hepatocyte single cell necrosis which was observed following both intravenous and subcutaneous administration and was considered to be a toxic response to high doses of r-metHuIL-2[ala-125]. The no observable adverse effect level (NOAEL) for r-metHuIL-2[ala-125] via intravenous administration was 6 micrograms kg-1 day-1, while that for subcutaneous administration was 30 micrograms kg-1 day-1. Data herein present a form of rHuIL-2 with pharmacokinetic and pharmacodynamic profiles that are similar when given by these two systemic routes. Pharmacotoxic data, based on NOAELs, suggest that subcutaneous administration may be a preferred clinical route of administration.

To examine the preventive oral health behavior levels of randomly-selected dentate and edentulous adults, age 18 and over, a mail survey was conducted in North York, Ontario, a multicultural suburb of Metropolitan Toronto (n = 1,050). High optimal levels of at least daily tooth brushing were reported by the majority of the dentate (96 per cent). Lower rates were evident for yearly preventive visiting (69 per cent), daily flossing (22 per cent), daily use of an interdental device (25 per cent), not snacking between meals (12 per cent) and eating one or no cariogenic foods on the previous day (36 per cent). Logistic regression results indicated higher levels on an additive index of oral preventive behaviors for females, those having a higher education and non-Italian respondents. Edentulous respondents reported high daily denture cleaning rates (87 per cent), but less frequent night removal (51 per cent), checking for oral lesions (68 per cent) and preventive visiting (12 per cent). Oral disease is one of the most common and costly chronic disorders affecting modern populations. However, unlike most other chronic diseases, it is largely preventable. These data indicate a clear need for determined oral health promotion efforts to inform and encourage increased levels of preventive behaviors in addition to tooth and denture brushing, particularly among specific sociodemographic and ethnic groups.

No diagnostic test for pertussis in routine use in the United States has both high sensitivity and high specificity. During a statewide increase in the incidence of pertussis in Missouri, we studied the clinical features of 153 patients with suspected pertussis in the Greater St. Louis area from whom a specimen for pertussis culture had been taken between 15 May and 19 September 1989. In this cross-sectional study, nasopharyngeal cultures were more likely to be positive for persons whose specimens were collected < 21 days after cough onset (adjusted rate ratio [RRa] and 95% confidence interval = 3.4; 1.5-8.0) and who were not receiving erythromycin/sulfamethoxazole prior to the culture [RRa = 5.8; 0.8-40.6], who had received fewer than three prior doses of pertussis vaccine [RRa = 1.8; 0.8-4.2], and whose specimen was in transit to the laboratory for < 4 days [RRa = 2.0; 0.8-5.5]. Among children < 5 years of age, spasmodic cough plus a lymphocytosis of > 10,000/mm3 was the acute symptom complex associated with the highest predictive value for a positive culture result (67%). Cough for > or = 14 days plus whoop was sensitive (81%) and specific (58%) for identifying children with culture-confirmed pertussis. Direct fluorescent antibody staining performed well as a screening test for pertussis but requires substantial commitment of personnel and resources. In the absence of a positive culture result, clinical case definitions should be used for decision making (e.g., initiation of antimicrobial therapy and routine case reporting).

The effects of equimolar doses of the triphenylethylene antiestrogens tamoxifen and toremifene on female Sprague-Dawley rat liver were studied in a 52-week toxicity study which included a 13-week recovery period. Liver tumors were found in four out of five rats at the highest dose level of tamoxifen (45 mg/kg per day) after 52 weeks of dosing, and these appeared to be hepatocellular carcinomas in three rats. After the 13-week recovery period all surviving rats in the highest tamoxifen dose group had large liver tumors (diameter up to 2 cm) which appeared to be hepatocellular carcinomas in five out of six rats. No tumor was observed in the toremifene-treated rats (48 mg/kg per day) either after 52 weeks of dosing or after the recovery period. Electron microscopic morphometric analysis after 52 weeks of dosing revealed that at the tamoxifen high dose level, the volume densities of the peroxisomes, mitochondria, and residual bodies were elevated in the nonneoplastic hepatocytes of the rats. In the neoplastic hepatocytes of the tamoxifen-treated rats the volume density of nuclei was slightly elevated. The slight proliferation of peroxisomes and mitochondria might be related to tumor development in the tamoxifen treated rats.

Defining oral self-care as activities undertaken by individuals to maintain or promote dental health, this paper examines the distribution of oral self-care behaviours in a sample of dentate adults, age 50 and over, living in Ontario, Canada (n = 713). Results are presented separately for two older cohorts, respondents ages 50-64 and those 65 and older, and for females and males. Six oral self-care behaviours were examined: toothbrushing, flossing, use of an interdental device, extra fluoride use, frequency of between meal snacks and ingestion of cariogenic foods. High rates of self-care occurred only for toothbrushing. Age groups differed significantly for use of interdental devices, consumption of cariogenic foods and snacking between meals while gender differences were found for toothbrushing, flossing and consuming sweet foods. The need to target older adults and especially older males for oral hygiene information and instruction in order to counteract possible misleading beliefs learned before the advent of current dental hygiene practices is apparent from these data.

Objective: To describe and determine the source of a large outbreak of Escherichia coli O157:H7 (ECO157) infections in Missouri., Design: A case-control study and a household survey., Setting: A small city in a rural Missouri township that had an unchlorinated water supply., Patients: Case patients were residents of or visitors to Burdine Township with bloody diarrhea or diarrhea and abdominal cramps occurring between 15 December 1989 and 20 January 1990., Measurements: Escherichia coli O157 was isolated from 21 stool specimens. All isolates were resistant to sulfisoxazole, tetracycline, and streptomycin; produced Shiga-like toxins I and II; and had one 60-megadalton plasmid., Results: Among the 243 case patients, 86 had bloody stools, 32 were hospitalized, 4 died, and 2 had the hemolytic uremic syndrome. In the case-control study, no food was associated with illness, but ill persons had drunk more municipal water than had controls (P = 0.04). The survey showed that, during the peak of the outbreak, bloody diarrhea was 18.2 times more likely to occur in persons living inside the city and using municipal water than in persons living outside the city and using private well water (P = 0.001). Shortly before the peak of the outbreak, 45 water meters were replaced, and two water mains ruptured. The number of new cases declined rapidly after residents were ordered to boil water and after chlorination of the water supply., Conclusions: This was the largest outbreak of ECO157 infections, the first due to a multiply resistant organism, and the first shown to be transmitted by water. System-wide chlorination as well as hyperchlorination during repairs might have prevented this outbreak. Both bloody and nonbloody diarrhea may be common manifestations of this infection, which is probably underdiagnosed because of the failure of routine stool cultures to identify the organism. Cities with deteriorating water systems using untreated water risk widespread illness from contaminated drinking water.

Heavy metal nephropathy is a pathologic entity of the renal tubular epithelium of rats, evoked by lead, gold, and other heavy metals. It is characterized acutely by coagulative necrosis, subacutely by cortical fibrosis, and chronically by cytomegaly and karyomegaly. Finally, adenomas develop, some of which become malignant.

Auranofin, a gold-containing compound, was administered to Charles River CD-1 mice for 18 months to assess its possible carcinogenicity. The mice were dosed orally with 1.0, 3.0, or 6.0 (increased to 9.0 on Day 294) mg/kg/day. Each dose group and each of two control groups contained 110 males and 110 females. Survival was greater than 70% at the end of the study. No effect of the treatment on neoplastic or nonneoplastic lesions was found. This is in contrast to the results reported in rats. Auranofin in rats produced a heavy metal nephropathy characterized by acute coagulative necrosis, subacute renal cortical fibrosis, chronic cytomegaly and karyomegaly, and finally renal cortical neoplasia (adenomas and adenocarcinomas). The lack of effect of auranofin on tumor incidence in mice suggests the findings in rats may be species specific.

In the summer of 1981, an outbreak of diarrhea occurred in students and staff at a school for mentally retarded adults and children in Columbia, Missouri. Forty-one (48%) of 86 students and 38 (28%) of 137 staff members in the two dormitories with the lowest functioning students were ill. Enteroinvasive Escherichia coli 0124:H30 was isolated from 20 persons including six staff members, 13 students, and the ill mother of one of the students. Contact with students was associated with illness. Thirty-eight (33%) of the 115 student-care staff members and none of the 22 nonstudent-care staff members who worked in the two dormitories were ill (p = 0.004, chi-square). In the dormitory with the most dependent students, illness in student-care staff was associated with the number of contacts with ill students and with having taken a student home during the outbreak. Control measures to interrupt transmission included separation of symptomatic or culture-positive students from those who were well, and emphasizing handwashing. The authors present these findings as the first report of person-to-person transmission in an outbreak of enteroinvasive E. coli.