Dermal absorption of permethrin following topical administration.

OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabies patients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.

Failure of surface ring mutant strains of Helicobacter mustelae to persistently infect the ferret stomach.

Helicobacter mustelae, the gastric pathogen of ferrets, produces an array of surface ring structures which have not been described for any other member of the genus Helicobacter, including H. pylori. The unique ring structures are composed of a protein named Hsr. To investigate whether the Hsr rings are important for colonization of the ferret stomach, ferrets specific pathogen free for H. mustelae were inoculated with an Hsr-deficient mutant strain or the wild-type H. mustelae strain. Quantitative cultures from antral biopsy specimens obtained at 3, 6, and 9 weeks postinoculation demonstrated no significant difference in the levels of bacteria in the ferrets that received the Hsr-negative strain and the ferrets infected with the parent strain. However, when the ferrets were biopsied at 12 and 15 weeks and necropsied at 18 weeks after infection, the levels of bacteria of the Hsr-negative strain in the stomach antrum were significantly reduced. This decline contrasted the robust antral colonization by the wild-type strain. The Hsr-negative strain did not efficiently colonize the gastric body of the study ferrets. Histological examination at 18 weeks postinoculation revealed minimal gastric inflammation in the animals that received the mutant H. mustelae strain, a finding consistent with its waning infection status, whereas lesions characteristic of helicobacter infection were present in ferrets infected with the wild-type strain. Scant colonization by the Hsr-negative H. mustelae strain at the end of the 18-week study, despite initial successful colonization, indicates an inability of the mutant to persist, perhaps due to a specific host response.

Mice lacking inducible nitric oxide synthase develop spontaneous hypercholesterolaemia and aortic atheromas.

Nitric oxide (NO) has been implicated in various aspects of the atherogenic process and has been shown to possess both protective and cytotoxic properties. Recently, increased expression of inducible nitric oxide synthase (iNOS) has been detected in atherosclerotic lesions, although there is no consensus as to its pathogenetic significance [1,2]. In this longitudinal study we show that iNOS plays an important protective role in the atherogenic process. Indirect systolic blood pressure was measured by photoplethysmography in unanesthetized mice fed either a basal or high salt diet, and found to be significantly higher in iNOS-deficient mice than in wild type controls at three months of age (P=0.038 (basal diet) and P=0.0005 (high salt diet)). In addition, relative to controls, the iNOS-deficient mice had significantly elevated serum cholesterol levels at 3, 9 and 12 months of age (P=0.0017, 0.0001 and 0.0002 for the respective ages) as well as a significantly higher incidence of atherosclerotic plaques. These findings suggest that iNOS targeted mutant mice, historically used as an animal model to investigate the role of nitric oxide in the inflammatory response [3,4], may also serve as a model for the study of cholesterol homeostasis and atherogenesis.

Hematologic and serum biochemical reference intervals for the chimpanzee (Pan troglodytes) categorized by age and sex.

Normal reference range intervals for hematologic and serum biochemical values in the chimpanzee (Pan troglodytes) have seldom been reported. The few studies that have been conducted either report values on the basis of a small number of animals, report values for all age groups or both sexes combined, or were designed specifically to document the effect of a particular condition on the normal range of hematologic and serum biochemical values. On the basis of data collected from 133 chimpanzees over a 17-year period, empirically based clinical reference ranges were derived to provide a guide for basic diagnostic and clinical care of chimpanzees. For either sex within each of four age groups, there is a table that summarizes serum biochemical and a table that summarizes hematologic values. These values are compared with prior values, and their importance in the care and well being of captive chimpanzee populations is discussed.

Differential susceptibility to hepatic inflammation and proliferation in AXB recombinant inbred mice chronically infected with Helicobacter hepaticus.

Helicobacter hepaticus is a naturally occurring pathogen of mice and has been used to develop models of chronic hepatitis, liver cancer, and, more recently, inflammatory bowel disease, in selected mouse strains. A/JCr mice are particularly susceptible to H. hepaticus-induced hepatitis and subsequent development of liver neoplasms, whereas C57BL/6 mice are resistant. In this study, we inoculated nine AXB recombinant inbred (RI) mouse strains, derived from A/J and C57BL/6 mice, with H. hepaticus to determine the genetic basis of resistance to Helicobacter-induced liver disease. Mice were surveyed 14 months after inoculation by culture and PCR for H. hepaticus colonization of the liver and cecum, and microscopic morphometric evaluations of the liver were performed to quantify and correlate the severity of inflammation, apoptosis, and proliferation. Analysis of variance of hepatic inflammation demonstrated significant variation among the RI strains (P < 0.0001), and the strain distribution pattern suggested a multigenic basis of disease resistance. Quantitative trait analysis using linear regression suggested possible linkage to loci on mouse chromosome 19. Hepatocellular and biliary epithelial apoptosis and proliferation indices, including proliferation of oval cells, were markedly increased and correlated with severity of inflammation. Prevalence of hepatic neoplasia was also increased in susceptible RI strains. These findings demonstrate a genetic basis for susceptibility to Helicobacter-induced disease and provide insight into its pathogenesis.

A hospital-based case-control study of stillbirths and environmental exposure to arsenic using an atmospheric dispersion model linked to a geographical information system.

Although adverse reproductive outcomes have been associated with arsenic exposure, the extent and severity of the effects of chronic inhalation of low levels of arsenic on reproduction are not known. We conducted a hospital-based case-control study of stillbirths in a central Texas community that included a facility with more than a 60-year history of producing primarily arsenic-based agricultural products. We collected data on 119 cases and 267 controls randomly selected from healthy live-births at the same hospital and matched for year of birth. We abstracted medical and demographic data for the period January 1, 1983, to December 31, 1993, from hospital records and estimated socioeconomic status by median income from the 1990 Population and Housing Census data. We estimated arsenic exposure levels from airborne emission estimates and an atmospheric dispersion model and linked the results to a geographical information system (GIS) database. Exposure was linked by GIS to residential address at time of delivery. A conditional logistic regression model was fitted including maternal age, race/ethnicity, parity, income group, exposure as a categorical variable, and exposure-race/ethnicity interaction. The prevalence odds ratio observed for Hispanics in the high-exposure group (>100 ng per m3 arsenic) was 8.4, with a 95% confidence interval of 1.4-50.1.

Increased bloodstream infection rates in surgical patients associated with variation from recommended use and care following implementation of a needleless device.

OBJECTIVE: To determine if an apparent increase in bloodstream infections (BSIs) in patients with central venous catheters (CVCs) was associated with the implementation of a needleless access device. DESIGN: Retrospective cohort study using a derived CVC-days factor for estimating appropriate denominator data. SETTING: A 350-bed urban, acute, tertiary-care hospital. METHODS: BSI surveillance data were obtained, and high-risk areas for BSIs were determined. A random 5% sample of medical records was used to estimate CVC days, and a cohort study was conducted to compare BSI rates before and during needleless device use. A survey was conducted of nursing needleless-device practices. RESULTS: The surgical intensive-care unit (SICU), the medical intensive-care unit, and the solid organ transplant unit (OTU) were identified as high-risk units. Using existing surveillance BSI data and the estimated CVC days, the catheter-related BSI rates in the high-risk surgical patients were significantly higher during the needleless-device period compared with the preneedleless-device period (SICU, 9.4 vs 5.0/1,000 CVC days; OTU, 13.6 vs 2.2/1,000 CVC days). A survey of the nurses revealed that 60% to 70% were maintaining the needleless devices correctly. CONCLUSION: We observed a significant increase in the BSI rate in two surgical units, SICU and OTU, associated with introduction of a needleless device. This increase occurred shortly after the needleless device was implemented and was associated with nurses' unfamiliarity with the device, and needless-device use and care practices different from the manufacturer's recommendations.

Use of an estimation method to derive an appropriate denominator to calculate central venous catheter-associated bloodstream infection rates.

An outbreak investigation was conducted to determine if an increase in bloodstream infections (BSIs) in patients with central venous catheters (CVC) had occurred. Because other methods of obtaining CVC days were not feasible, we used an estimation method based on a random 5% sample of medical records to determine the proportion of days that a CVC was present for each of three patient units. This calculated ratio was used to estimate the total CVC days for each unit. A cohort study was conducted in which the BSI rates before and during needleless device use were compared. This article describes the methods used to calculate this estimated denominator and discusses the need for such a denominator to be used by infection control practitioners when prospective collection of CVC days is not possible.

Evaluation of the acceptability of a needleless vascular-access system by nurses.

BACKGROUND: Needleless intravenous-access devices have been introduced in an effort to reduce needlestick injuries and possible transmission of blood-borne pathogens to health care workers. However, there are no data on the acceptance of these devices by nursing personnel. METHODS: A survey of nursing personnel was taken at Indiana University Medical Center after introduction of a needleless intravenous device to determine their opinion after use of the needleless device. RESULTS: The majority of the nurses (72 of 94, 70%) had a favorable overall opinion of the device. Among those with a favorable opinion, 76% (55/72) responded that reduced risk of needlestick injury was the most important reason. Among those who had a negative opinion about the needleless-device system, 32% (7/22) reported that contamination risk was their major concern. Those who were trained before device use were more likely to properly use and maintain the needleless intravenous-access system. Of 89 respondents, 75.3% (67/89) believed that the initial training was adequate; however, 43% (29/67) thought that additional training after using the device for some time would have been beneficial. CONCLUSIONS: Comprehensive education programs that include training before and after device use are necessary if new needleless intravenous-access systems are to be successfully introduced and accepted by nursing personnel.