Nontyphoidal salmonella urinary tract infection in a case of hyperparathyroidism and nephrocalcinosis.

Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal Salmonella is usually associated with structural abnormalities of the urinary tract. Nephrocalcinosis and nephrolithiasis are the major risk factors. Although primary hyperparathyroidism has been reported to increase the risk of nephrocalcinosis and nephrolithiasis, little is known about the association between hyperparathyroidism and Salmonella urinary tract infection. We report the case of a 37-year old man who had a history of primary hyperparathyroidism and bilateral nephrocalcinosis and who developed urinary tract infection. Salmonella Group D was isolated from his urine specimen. Salmonella should be considered as a possible causality organism in patients with primary hyperparathyroidism and nephrocalcinosis who develop urinary tract infection. These patients need to be aware of the potential risks associated with salmonellosis.

Nontyphoidal Salmonella urinary tract infection in a case of hyperparathyroidism and nephrocalcinosis / Infección de las vías urinaria por Salmonella no tifoidea en un caso de hiperparatiroidismo y nefrocalcinosis

Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal Salmonella is usually associated with structural abnormalities of the urinary tract. Nephrocalcinosis and nephrolithiasis are the major risk factors. Although primary hyperparathyroidism has been reported to increase the risk of nephrocalcinosis and nephrolithiasis, little is known about the association between hyperparathyroidism and Salmonella urinary tract infection. We report the case of a 37-year old man who had a history of primary hyperparathyroidism and bilateral nephrocalcinosis and who developed urinary tract infection. Salmonella Group D was isolated from his urine specimen. Salmonella should be considered as a possible causality organism in patients with primary hyperparathyroidism and nephrocalcinosis who develop urinary tract infection. These patients need to be aware of the potential risks associated with salmonellosis.

Las infecciones por Salmonella no tifoidea se presentan a menudo con gastroenteritis auto-limitada. Las infecciones extra-intestinales focales son poco frecuentes, pero tienen una alta mortalidad y morbilidad. La infección de las vías urinarias causada por la Salmonella no tifoidea se asocia generalmente a anomalías estructurales de las vías urinarias. La nefrocalcinosis y la nefrolitiasis son los principales factores de riesgo. Aunque se ha reportado que el hiperparatiroidismo primario aumenta el riesgo de la nefrocalcinosis y la nefrolitiasis, poco se sabe sobre la asociación entre el hiperparatiroidismo y la infección de las vías urinarias por Salmonella. Damos a conocer aquí el caso de un hombre de 37 años con una historia de hiperparatiroidismo primario y nefrocalcinosis bilateral, que desarrolló una infección de las vías urinarias. La Salmonella del grupo D fue aislada de su muestra de orina. La Salmonella se debe considerar como un posible organismo de causalidad en pacientes con hiperparatiroidismo primario y nefrocalcinosis que desarrollan infección del tracto urinario. Estos pacientes necesitan tomar conciencia de los riesgos potenciales asociados con la salmonellosis.

Learning chronobiology by improving Wikipedia.

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.

The relationship between chronic hepatitis B infection and bone mineral, metabolism in peritoneal dialysis patients.

OBJECTIVE: Abnormality of bone mineral metabolism is a common complication in chronic liver disease and/or chronic renal disease patients. We designed this study to evaluate the relationship between chronic hepatitis B infection and bone mineral metabolism in peritoneal dialysis patients. PATIENTS AND METHODS: Serum calcium[adj], phosphorus, calcium and phosphorus product (Ca x P), along with intact parathyroid hormone (iPTH) levels were compared in peritoneal dialysis patients with and without chronic hepatitis B infection. RESULTS: A total of 220 patients (142 female, 78 male) with a mean age of 56.30 +/- 14.28 (range 19 - 86) years old were recruited, 23 showed chronic hepatitis B infection and 197 showed none. No statistically significant difference in serum calcium[adj] levels (9.90 +/- 0.85 mg/dl vs. 10.08 +/- 0.80 mg/dl, p = 0.354), phosphorus levels (5.26 +/- 1.58 mg/dl vs. 5.21 +/- 1.35 mg/dl, p = 0.879) and calcium and phosphorus product (Ca x P) (52.23 +/- 17.54 mg(2)/dl(2) vs. 52.42 +/- 14.16 mg(2)/dl(2), p = 0.960) between groups with and without chronic hepatitis B infection was observed. Serum iPTH levels were significantly lower in chronic hepatitis B patients (median 143 pg/ml, range 3.42 - 889) than in the control group (median 235 pg/ml, range 3 - 2381) (p = 0.035). As analyzed by multi-variable linear regression, chronic hepatitis B was a predictor of lower serum iPTH levels (beta = -0.271; p = 0.030) after adjustments for age, gender, serum calcium and phosphorus levels and diabetes. CONCLUSION: No significant difference in serum calcium[adj]), phosphorus and calcium and phosphorus product (Ca x P) levels appeared between peritoneal dialysis patients with and without chronic hepatitis B infection. Serum iPTH levels proved to be definitely lower in chronic hepatitis B infection patients.

Dissemination of multidrug-resistant, class 1 integron-carrying Acinetobacter baumannii isolates in Taiwan.

In this study, 283 multidrug-resistant Acinetobacter baumannii (MDR-AB) bloodstream isolates were collected between 1996 and 2004, from three teaching hospitals located in different regions of Taiwan. Susceptibility data showed that strains carrying class 1 integrons were significantly more resistant (p <0.01) to all tested antibiotics (except aztreonam and chloramphenicol) than strains lacking integrons, Seven types of gene cassette were identified among these strains, including two that have not been previously reported. The vast majority of the cassettes encoded aminoglycoside resistance genes, including aacA4, aacC1, aac(6')-II, aadA1, aadA2, aadA4 and aadDA1. Sixteen distinct ribotypes were identified in MDR-AB isolates carrying class 1 integrons. Only one strain was found to produce an extended-spectrum beta-lactamase, i.e. VEB-3. In the 18 imipenem-resistant strains, two carbapenenmase genes, bla(VIM-11) and bla(OXA-58), were found concomitantly in one isolate. An island-wide epidemic clone and an endemic clone from a hospital located in the northern region were identified by ribotyping. On the basis of the susceptibility data among the different ribogroups, the epidemic clone was associated more significantly with resistance to cefepime and ampicillin-sulbactam than was the endemic clone. In conclusion, the presence of class 1 integrons was significantly associated with resistance in MDR-AB, and the epidemic, class 1 integron-carrying MDR-AB clone was found to be widespread in Taiwan.

Selection of differentially expressed genes in microarray data analysis.

One common objective in microarray experiments is to identify a subset of genes that express differentially among different experimental conditions, for example, between drug treatment and no drug treatment. Often, the goal is to determine the underlying relationship between poor versus good gene signatures for identifying biological functions or predicting specific therapeutic outcomes. Because of the complexity in studying hundreds or thousands of genes in an experiment, selection of a subset of genes to enhance relationships among the underlying biological structures or to improve prediction accuracy of clinical outcomes has been an important issue in microarray data analysis. Selection of differentially expressed genes is a two-step process. The first step is to select an appropriate test statistic and compute the P-value. The genes are ranked according to their P-values as evidence of differential expression. The second step is to assign a significance level, that is, to determine a cutoff threshold from the P-values in accordance with the study objective. In this paper, we consider four commonly used statistics, t-, S- (SAM), U-(Mann-Whitney) and M-statistics to compute the P-values for gene ranking. We consider the family-wise error and false discovery rate false-positive error-controlled procedures to select a limited number of genes, and a receiver-operating characteristic (ROC) approach to select a larger number of genes for assigning the significance level. The ROC approach is particularly useful in genomic/genetic profiling studies. The well-known colon cancer data containing 22 normal and 40 tumor tissues are used to illustrate different gene ranking and significance level assignment methods for applications to genomic/genetic profiling studies. The P-values computed from the t-, U- and M-statistics are very similar. We discuss the common practice that uses the P-value, false-positive error probability, as the primary criterion, and then uses the fold-change as a surrogate measure of biological significance for gene selection. The P-value and the fold-change can be pictorially shown simultaneously in a volcano plot. We also address several issues on gene selection.

Decision threshold adjustment in class prediction.

Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations.

Classification ensembles for unbalanced class sizes in predictive toxicology.

This paper investigates the effects of the ratio of positive-to-negative samples on the sensitivity, specificity, and concordance. When the class sizes in the training samples are not equal, the classification rule derived will favor the majority class and result in a low sensitivity on the minority class prediction. We propose an ensemble classification approach to adjust for differential class sizes in a binary classifier system. An ensemble classifier consists of a set of base classifiers; its prediction rule is based on a summary measure of individual classifications by the base classifiers. Two re-sampling methods, augmentation and abatement, are proposed to generate different bootstrap samples of equal class size to build the base classifiers. The augmentation method balances the two class sizes by bootstrapping additional samples from the minority class, whereas the abatement method balances the two class sizes by sampling only a subset of samples from the majority class. The proposed procedure is applied to a data set to predict estrogen receptor binding activity and to a data set to predict animal liver carcinogenicity using SAR (structure-activity relationship) models as base classifiers. The abatement method appears to perform well in balancing sensitivity and specificity.

Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells.

Microarray analysis is a powerful tool to identify the biological effects of drugs or chemicals on cellular gene expression. In this study, we compare the relationships between traditional measures of genetic toxicology and mutagen-induced alterations in gene expression profiles. TK6 cells were incubated with 0.01, 0.1, or 1.0 microM +/-anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) for 4 h and then cultured for an additional 20 h. Aliquots of the exposed cells were removed at 4 and 24 h in order to quantify DNA adduct levels by 32P post-labeling and measure cell viability by cloning efficiency and flow cytometry. Gene expression profiles were developed by extracting total RNA from the control and exposed cells at 4 and 24 h, labeling with Cy3 or Cy5 and hybridizing to a human 350 gene array. Mutant frequencies in the Thymidine Kinase and Hypoxanthine Phosphoribosyl Transferase genes were also determined. The 10alpha-(deoxyguanosin-N(2)-yl)-7alpha,8beta,9beta-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (dG-N(2)-BPDE) adduct increased as a function of dose and was the only adduct identified. A dose-related decrease in cell viability was evident at 24 h, but not at 4 h. Cell death occurred by apoptosis. At 4 h, analysis of the gene expression profiles revealed that Glutathione Peroxidase and Gadd45 were consistently upregulated (greater than 1.5-fold and significantly (P < 0.001) greater than the control in two experiments) in response to 1.0 microM BPDE exposure. Fifteen genes were consistently down-regulated (less than 0.67-fold and significantly (P < 0.001) lower than the control in two experiments) at 4 h in cultures exposed to 1.0 microM BPDE. Genes with altered expression at 4 h included genes important in the progression of the cell-cycle and those that inhibit apoptosis. At 24 h post-exposure, 16 genes, involved in cell-cycle control, detoxification, and apoptosis were consistently upregulated; 10 genes were repressed in cultures exposed to the high dose of BPDE. Real-time quantitative PCR confirmed the differential expression of selected genes. These data suggest that changes in gene expression will help to identify effects of drugs and chemicals on molecular pathways in cells, and will provide useful information about the molecular responses associated with DNA damage. Of the endpoints evaluated, DNA adduct formation was the most sensitive indicator of DNA damage. DNA adduct formation was clearly evident at low doses, but the number of genes with significantly altered expression (P < 0.001) was minimal. Alterations in gene expression were more robust at doses associated with cellular toxicity and induction of mutations.