Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD)

BACKGROUND: ARPKD is associated with mutations in the PKHD1 gene on chromosome 6p12. Most cases manifest peri-/neonatally with a high mortality rate in the first month of life while the clinical spectrum of surviving patients is much more variable than generally perceived. METHODS: We examined the clinical course of 164 neonatal survivors (126 unrelated families) over a mean observation period of 6 years (range 0 to 35 years). PKHD1 mutation screening was done by denaturing high-performance liquid chromatography (DHPLC) for the 66 exons encoding the 4074 aa fibrocystin/polyductin protein. RESULTS AND CONCLUSION: This is the first study that reports the long-term outcome of ARPKD patients with defined PKHD1 mutations. The 1- and 10-year survival rates were 85% and 82%, respectively. Chronic renal failure was first detected at a mean age of 4 years. Actuarial renal survival rates [end point defined as start of dialysis/renal transplantation (RTX) or by death due to end-stage renal disease (ESRD)] were 86% at 5 years, 71% at 10 years, and 42% at 20 years. All but six patients (92%) had a kidney length above or on the 97th centile for age. About 75% of the study population developed systemic hypertension. Sequelae of congenital hepatic fibrosis and portal hypertension developed in 44% of patients and were related with age. Positive correlations could further be demonstrated between renal and hepatobiliary-related morbidity suggesting uniform disease progression rather than organ-specific patterns. PKHD1 mutation analysis revealed 193 mutations (70 novel ones; 77% nonconservative missense mutations). No patient carried two truncating mutations corroborating that one missense mutation is indispensable for survival of newborns. We attempted to set up genotype-phenotype correlations and to categorize missense mutations. In 96% of families we identified at least one mutated PKHD1 allele (overall detection rate 76.6%) indicating that PKHD1 mutation screening is a powerful diagnostic tool in patients suspected with ARPKD.     

Evaluation of microbial inoculation and vegetation to enhance the dissipation of atrazine and metolachlor in soil

Four greenhouse studies were conducted to evaluate the effects of native prairie grasses and two pesticide-degrading bacteria to remediate atrazine and metolachlor in soils from agricultural dealerships (Alpha site soil, northwest Iowa, USA; Bravo site soil, central Iowa, USA). The Alpha soil contained a low population of atrazine-degrading microorganisms relative to the Bravo soil. Each soil freshly treated with atrazine or metolachlor was aged for a short or long period of time, respectively. An atrazine-degrading bacterium, Agrobacterium radiobacter strain J14a; a metolachlor-degrading bacterium, Pseudomonas fluorescens strain UA5-40; and a mixture of three native prairie grasses-big bluestem (Andropogon gerardii Vitman), yellow Indian grass (Sorghastrum nutans [L.] Nash), and switchgrass (Panicum virgatum L.)-were added to the soils after the soils were aged for long periods of time. The soils aged for short periods of time were treated with J14a, the prairie grasses, or both after aging. The J14a and the grasses significantly reduced the concentration of atrazine in Alpha soil when the soil was aged for a short period of time. However, these treatments had no statistically significant effect when the soil was aged for a long period of time or on atrazine in Bravo soil. Inoculation with UA5-40 did not enhance metolachlor dissipation in either soil, but vegetation did increase metolachlor dissipation. Our results indicate that the dissipation of atrazine by J14a is affected by the presence of indigenous atrazine-mineralizing microorganisms and probably by the bioavailability of atrazine in the soil.     

The transformational power of IT: Experience from patient safety leaders

Late last year, David J. Brailer, M.D., Ph.D., National Health Information Technology Coordinator for the Department of Health and Human Services, visited Evanston (IL) Northwestern Hospital (ENH) to observe its electronic medical record system. ENH is the first in the nation to put such a system into an acute care setting, including all three of its hospitals and its 70 medical offices and ambulatory sites. "It's been truly transformational for our processes, our delivery of care, our communications, and our way of doing business," says Mark R. Neaman, FACHE, ENH's president and chief executive officer. What's more, ENH has demonstrated at least a 20 percent reduction in medication errors, and the remaining errors have shifted from wrong medication and wrong patient to errors of timing, which are almost always less severe.     

Relationship of physical fitness to prevalence and incidence of overweight among schoolchildren

OBJECTIVES: We examined the relationship between comprehensive fitness tests and overweight using a school surveillance system in a racially diverse city in the United States. RESEARCH METHODS AND PROCEDURES: Trained physical education teachers measured weight, height, and fitness annually from 2001 to 2003. We compiled data for a cross-sectional analysis (11,845 measurements on 6297 students, 5 to 14 years of age) and a 1-year prospective analysis (4215 measurements on 2927 students not overweight at baseline, 5 to 13 years of age). Overweight was defined as a BMI > or =95th percentile (Centers for Disease Control and Prevention 2000 growth charts), and underfit was defined as failing at least one of five fitness tests: endurance run, abdominal strength, flexibility, upper body strength, and agility (Amateur Athletic Union and Fitnessgram). Associations between fitness and overweight were examined using multivariate logistic regression models, adjusting for sociodemographic status and repeated measurements over time. RESULTS: The mean number of fitness tests passed was lower among students with a BMI above the 80th percentile. Overweight incidence over 1 year was 7% and 2% for underfit and fit girls, respectively (odds ratio, 3.3; 95% confidence interval, 2.0 to 5.6). Not passing either the endurance run or upper body strength test was associated with overweight incidence in both boys and girls. After adjusting for baseline BMI, the endurance run remained a significant predictor of incident overweight among girls (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.5). DISCUSSION: Findings support a cross-sectional inverse relationship between physical fitness and overweight among school-aged children. The direction of causation between fitness and overweight is not clearly established and merits further study.     

The relation of occupational organic solvent exposure to symptom reporting in a sample of white and Chinese midlife women

OBJECTIVE: This study examined the relation of occupational solvent exposure to menopausal and other symptoms in midlife women. METHODS: We conducted a cross-sectional study of 480 Chinese and 494 white women, aged 40-55 years, in Northern California. Levels of exposure to organic solvents (none, low, medium, or high) were assigned to each current job using a job-exposure matrix. RESULTS: A lower proportion of women with low occupational organic solvent exposure reported hot flashes or night sweats than working women with no solvent exposure (adjusted prevalence odds ratio [APOR] = 0.48, 95% confidence interval [CI] = 0.19-1.21). A greater proportion of women with high solvent exposure reported forgetfulness than women with no exposure (APOR = 2.51, 95% CI = 1.12-5.63). CONCLUSIONS: Some symptom reporting in midlife women was related to their occupational organic solvent exposure.     

Norovirus and foodborne disease, United States, 1991-2000

Efforts to prevent foodborne illness target bacterial pathogens, yet noroviruses (NoV) are suspected to be the most common cause of gastroenteritis. New molecular assays allow for better estimation of the role of NoV in foodborne illness. We analyzed 8,271 foodborne outbreaks reported to the Centers for Disease Control and Prevention from 1991 to 2000 and additional data from 6 states. The proportion of NoV-confirmed outbreaks increased from 1% in 1991 to 12% in 2000. However, from 1998 to 2000, 76% of NoV outbreaks were reported by only 11 states. In 2000, an estimated 50% of foodborne outbreaks in 6 states were attributable to NoV. NoV outbreaks were larger than bacterial outbreaks (median persons affected: 25 versus 15), and 10% of affected persons sought medical care; 1% were hospitalized. More widespread use of molecular assays will permit better estimates of the role of NoV illness and help direct efforts to control foodborne illness.     

Laboratory exposures to brucellae and implications for bioterrorism

Brucellae are class 3 organisms and potential agents of bioterrorism. Because of effective public health measures, brucellosis has become a rare disease in industrialized countries, and clinical microbiology laboratories are frequently unfamiliar with the genus. A low index of suspicion by physicians or failure to notify the laboratory, equivocal Gram-stain results, misidentification of the organism by commercial systems, unsafe laboratory practices, and laboratory accidents have been responsible for numerous cases of exposure to the organism and laboratory-acquired disease in recent years. Discovery of a laboratory exposure to brucellae should prompt an exhaustive investigation of the event and its circumstances, definition of the population at risk, enforcement of safe laboratory practices, and antimicrobial drug prophylaxis for exposed persons. Inadvertent exposures to brucellae in the clinical laboratory indicate a widespread lack of preparedness to cope with eventual biologic threats involving use of the organism.