Aciclovir or ganciclovir universal prophylaxis of cytomegalovirus infection in liver transplantation: an economic analysis.

BACKGROUND: Cytomegalovirus (CMV) following orthotopic liver transplantation can result in significant morbidity and mortality. Prophylaxis with oral aciclovir (ACV) or ganciclovir (GCV) for all transplant recipients (universal prophylaxis) may be beneficial, but which agent is more cost-effective is unknown. METHODS: A single centre, retrospective study of all patients who had OLT at the Western Australian Liver Transplantation Service was performed. Patients received ACV from 1992 to 1998, and GCV from 1999 to 2001. A comparative cost-effectiveness analysis for the two groups was performed based on the mean total cost of the number of cases of CMV infection and disease as the clinical end-point. RESULTS: The ACV group comprised of 55 patients and there were 24 in the GCV group. The incidence of CMV disease was 7% and 4% for the ACV and GCV groups, respectively (P > 0.05). For CMV infection it was 16% and 8%, respectively (P > 0.05). GCV prevented more cases of CMV infection and disease than ACV but at an incremental cost of dollars A20,000 (dollars US10,172) per case prevented. Overall, ACV was more cost-effective than GCV by dollars A2200 (dollars US1119) per person. The cost benefit of ACV was derived principally through a reduced pharmaceutical cost. Both agents were well tolerated without development of antiviral resistance. CONCLUSIONS: Universal prophylaxis of CMV infection-following liver transplantation with aciclovir is more cost-effective than with ganciclovir.

Second trimester screening for Down's syndrome: 7 years experience.

OBJECTIVES: To evaluate the effectiveness of the first 7 years of a programme for second trimester antenatal screening for Down's syndrome, using alpha-fetoprotein (alphaFP) and total human chorionic gonadotropin (hCG) as maternal serum markers. METHODS: A clinical biochemistry laboratory providing a screening service for four obstetric units. Women attending for antenatal care who accepted an offer of serum screening for Down's syndrome were tested between 15 and 20 weeks gestation. Down's risk estimates were calculated using maternal serum alphaFP and total hCG results as modifiers of the maternal age related risk. Outcome was determined in collaboration with the regional cytogenetics unit. RESULTS: In 7 years 66,631 women were screened, in whom 108 Down's syndrome pregnancies were identified. Risks for Down's syndrome were reported without a specified cut off recommendation; however, at a cut off of 1 in 250, 72 (66.7%) of the affected pregnancies were screen positive, the false positive rate was 5.8%, and the uptake of amniocentesis 71.2%. The detection rate was higher in women screened before 17 weeks (70.5%) than in those screened at 17 weeks or later (56.7% overall and 20.0% in those under 30 years). The uptake of screening declined gradually from 84% in 1992 to 59.5% in 1998. CONCLUSIONS: Two marker screening using aFP and total hCG is an effective way of screening for Down's syndrome and is widely accepted in the local community. Detection rates were comparable with other second trimester studies using two markers including both total and free beta hCG.

Chronic toxicity of chloroform to Japanese medaka fish.

Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured chloroform concentrations of 0.017, 0.151, or 1.463 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic chloroform concentration. Histopathology was evaluated at 6 and 9 months. Chloroform was not hepatocarcinogenic to the medaka at the concentrations tested. Chronic toxicity was evidenced at these time points by statistically significant ([alpha] = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.463 mg/L chloroform. We assessed hepatocellular proliferation by exposing test fish to 5-bromo-2'-deoxyuridine in the aquarium water for 72 hr after 4 and 20 days of chloroform exposure; we then quantified area-labeling indices of the livers using computer-assisted image analysis. We observed no treatment-related increases in cellular proliferation. We analyzed cells in circulating blood in medaka after 6 months of chloroform exposure. Hematocrit, leukocrit, cell viability, and cell counts of treated fish were not significantly different from those of control fish. Using gas chromatography (GC), we evaluated intrahepatic concentrations of chloroform in fish after 9 months of exposure. Livers from the 0.151 and 1.463 mg/L chloroform-treated fish had detectable amounts of chloroform, but these levels were always lower than the aquaria concentrations of chloroform. Thus, it appeared that chloroform did not bioaccumulate in the liver. Unidentified presumptive metabolite peaks were found in the GC tracings of these fish livers.

Chronic toxicity of bromodichloromethane to the Japanese medaka (Oryzias latipes).

Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured bromodichloromethane (BDCM) concentrations of 0.018, 0.143, or 1.424 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic BDCM concentration. BDCM was not hepatocarcinogenic to medaka at the concentrations tested. Chronic toxicity was evidenced at 6 and 9 months by statistically significant (alpha = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.424 mg/L BDCM. Hepatocellular proliferation was assessed after 1, 4, and 20 days of BDCM exposure. Treatment-related increases or decreases in cellular proliferation were not observed at any time point. Hematocrit, leukocrit, cell viability, and cell counts of treated fish after 9 months of BDCM exposure were not significantly different from control fish. Intrahepatic concentrations were evaluated by gas chromatography after 9 months of BDCM exposure. Fish livers from all three BDCM treatments had detectable amounts of BDCM, with median intrahepatic concentrations of 1.02, 2.89, and 21.25 mg BDCM/kg fish liver in the low, middle, and high concentrations, respectively. Medaka chronic toxicity effects of statistically significant gallbladder and bile duct abnormalities occurred at 1.424 mg/L BDCM, well above median drinking water levels.

Biomarkers of immunotoxicity in fish: from the lab to the ocean.

Historically, host immunocompetence has been monitored using a battery of immune parameters. Recently, many of these same assays have been employed as biomarkers for predicting chemical-induced immunotoxicity in wildlife species. In this laboratory, assays measuring immunopathology, immune cell function, and host resistance against bacteria have been used successfully to assess immunotoxicity in laboratory-reared Japanese medaka (Oryzias latipes) and in feral fish populations. As an example of the latter, smallmouth bass collected from a PCB-contaminated site demonstrated significantly reduced phagocyte function and antioxidant activity compared to reference site fish. Taken together, these studies along with those from other investigators demonstrate the usefulness of immune assays as indicators to predict the toxicological risk associated with 'real-world' polluted aquatic environments.

Mammalian immunoassays for predicting the toxicity of malathion in a laboratory fish model.

This study describes the use of a panel of immune assays, originally developed by the National Toxicology Program for assessing xenobiotic-induced immunotoxicity in mice, to quantify the effects of sublethal malathion exposure on the immune responses of fish. For this study, Japanese medaka (Oryzias latipes) were exposed subchronically to the organophosphate pesticide malathion in a series of two experiments. In the first set of studies, fish were exposed for 7 or 14 d to untreated well water (i.e., controls) or to waterborne malathion at 0.2 or 0.8 mg/L. Following exposure, fish from each group were sacrificed and their kidneys (primary organ of leukopoiesis in fish and equivalent to mammalian bone marrow) were used to provide cells for assessing any malathion-induced effects upon nonspecific and acquired immune defense mechanisms. Effects upon humoral-mediated immunity were determined by enumerating antibody plaque-forming cell (PFC) numbers from a subset of fish exposed to malathion for 14 d and then injected intraperitoneally (ip) with sheep erythrocytes (sRBC). Results of these studies demonstrated that while malathion exposure had no significant effect upon hematocrit/leukocrit values or upon mitogen-stimulated T-cell lymphoproliferation, PFC numbers in the kidney of exposed fish were significantly reduced (compared to control fish) in a dose-dependent manner. In addition, total recoverable kidney cell numbers and viability, as well as superoxide anion production by kidney phagocytes, were reduced slightly (compared to control values) in fish exposed for 14 d to the highest malathion concentration tested. In the second set of experiments, medaka exposed for up to 21 d to either 0.1 or 0.3 mg malathion/L were challenged ip with an LD50 dose of the bacterial fish pathogen Yersinia ruckeri. Results from these infectivity studies demonstrated that exposure to either malathion concentration, for 14 or 21 d reduced host resistance against Yersinia infection. Taken together, these findings demonstrate the applicability of mammalian immune assays for predicting malathion-induced immunosuppression in a teleost fish, as well as the potential utility of a small laboratory fish to serve as an alternate model for mammals in immunotoxicological studies.

HICLAS: a taxonomic database system for displaying and comparing biological classification and phylogenetic trees.

MOTIVATION: Numerous database management systems have been developed for processing various taxonomic data bases on biological classification or phylogenetic information. In this paper, we present an integrated system to deal with interacting classifications and phylogenies concerning particular taxonomic groups. RESULTS: An information-theoretic view (taxon view) has been applied to capture taxonomic concepts as taxonomic data entities. A data model which is suitable for supporting semantically interacting dynamic views of hierarchic classifications and a query method for interacting classifications have been developed. The concept of taxonomic view and the data model can also be expanded to carry phylogenetic information in phylogenetic trees. We have designed a prototype taxonomic database system called HICLAS (HIerarchical CLAssification System) based on the concept of taxon view, and the data models and query methods have been designed and implemented. This system can be effectively used in the taxonomic revisionary process, especially when databases are being constructed by specialists in particular groups, and the system can be used to compare classifications and phylogenetic trees. AVAILABILITY: Freely available at the WWW URL: http://aims.cps.msu.edu/hiclas/ CONTACT: pramanik@cps.msu.edu; lotus@wipm.whcnc.ac.cn

First report of oil cavities in Scrophulariaceae and reinvestigation of air spaces in leaves of Leucophyllum frutescens.

Conspicuous air spaces in Leucophyllum (Scrophulariaceae; Leucophylleae) leaves have been suggested to be developmentally transformed secretory cavities. We reinvestigated air space development in Leucophyllum frutescens, using freehand sections of mature fresh leaves and paraffin sections of several leaf stages. Each of the numerous air spaces per leaf forms because greater separation occurs within a local group of spongy mesophyll cells than in the developing spongy mesophyll elsewhere. We found no anatomical evidence of transitory epithelial cells or lysis of cells in developing air spaces, thus the hypothesis that air spaces are transformed secretory cavities is not supported. However, an important finding was that all leaves had one pair of conspicuous true secretory cavities flanking the midvein at the apex, each lined by an epithelium and filled with oil. We also found conspicuous apical cavities in freehand sections of herbarium specimens of this and three other Leucophyllum species. Cavities were not seen in L. revolutum or in the related Eremogeton grandiflorus. This is the first report and description of a true internal secretory cavity in Scrophulariaceae. In the related family Myoporaceae, we found epithelium-lined cavities scattered abundantly in leaves of cleared samples of three genera.

Bioavailability of TNT residues in composts of TNT-contaminated soil.

Composting is being explored as a means to remediate 2,4,6-trinitrotoluene (TNT) contaminated soils. This process appears to modify TNT and to bind it to organic matter. The health hazards associated with dusts generated from such materials cannot be predicted without knowing if the association between TNT residues and compost particulate is stable in biological systems. To address this question, single doses of [14C]-TNT, soil spiked with [14C]-TNT, or compost generated with [14C]-TNT-spiked soils were administered to rats by intratracheal instillation. The appearance of 14C in urine and tissues was taken as an indication of the bioavailability of TNT residues from compost particles. In rats instilled with neat [14C]-TNT, about 35% of the 14C dose appeared in urine within 3 d. The 14C excreted in urine by these rats decreased rapidly thereafter, and was undetectable by 4 wk after treatment. Similar results were obtained with soil-treated rats. In contrast, after treatment with [14C]-TNT-labeled compost, only 2.3% of the total 14C dose appeared in urine during the first 3 d. Low levels of 14C continued to be excreted in urine from compost-treated rats for more than 6 mo, and the total amount of 14C in urine was comparable to that in TNT-treated animals. Determination of the radiolabel in tissues showed that 14C accumulated in the kidneys of rats treated with labeled compost but not in rats treated with [14C]-TNT or [14C]-TNT-spiked soil. These results indicate that the association between TNT and particulate matter in compost is not stable when introduced into the lungs. Accumulation of 14C in kidneys suggests the presence of a unique TNT residue in compost-treated rats. The rate of excretion and tissue disposition of 14C in rats treated with TNT-spiked soil indicate that TNT in soil is freely available in the lungs.

Down's syndrome screening using free beta hCG: instability can significantly increase the Down's risk estimate.

The stability of free beta hCG (human chorionic gonadotrophin) was assessed using a dual alpha-fetoprotein and free beta hCG assay. A significant increase in free beta hCG concentration was observed in heparinized samples left unseparated for 24 h or more, the mean increase in 21 samples being 10.2% after 24 h (P = < 0.001), increasing to 45.7% after 96 h. Similar results were also obtained in clotted samples. The effect of the increase in free beta hCG on the Down's risk estimate was calculated to assess the impact of delayed sample transport and separation. The Down's risk increased in all samples with increasing separation time, but this was most significant in two samples where, using a cut off of one in 250, the risk classification changed from low risk to high risk. These results suggest that delayed sample separation can have a significant effect on screening programmes using free beta hCG, particularly with respect to those patients whose risk classification is changed.

Parents and peer group as mediators of the effect of community structure on adolescent problem behavior.

Used a sample of 207 single-parent families residing in 104 small, Midwestern communities to test hypotheses regarding the link between community context and adolescent conduct problems and psychological distress. For boys, community disadvantage had a direct affect on psychological distress, while it indirectly boosted the probability of conduct problems by disrupting parenting and increasing affiliation with deviant peers. Community disadvantage was unrelated to the deviant behavior or emotional well-being of girls. Proportion of single-parent households in the community had a direct effect on girls' conduct problems. It also contributed indirectly to girls' conduct problems by increasing the probability of involvement with deviant peers. Possible explanations for these gender differences are provided.

Filter paper cortisol profiles in secondary adrenocortical insufficiency.

The use of filter paper four point 24 hour cortisol profiles in the diagnosis and management of secondary adrenocortical deficiency was examined. Eighteen children with familial short stature and isolated growth hormone deficiency had normal 24 hour and morning plasma cortisol concentrations measured. Eight of 11 children with multiple pituitary hormone deficiencies had evidence of hypocorticalism despite previously normal baseline cortisols or responses to insulin hypoglycaemia or tetracosactrin. Nine of 11 children with hypopituitarism on replacement treatment (4.9-12.5 mg/m2/day) had satisfactory concentrations of cortisol, though morning cortisols were often low. Filter paper profiles are a simple, inexpensive, and relatively non-invasive way of managing children with suspected hypocorticalism and of monitoring their treatment.

A new data model for biological classification.

In the domain of biological classification, classifications are performed hierarchically. There are no standard classifications which are unanimously accepted by the community of each domain; many different interacting views of classification exist about the same data, and the discovery of new data results in changes to the existing classification. Even a single individual may change his or her own classification of a particular group. Since multiple classification views interact, they are semantically related. It is difficult to model this kind of dynamically evolving and semantically interacting classification system using traditional data models, which lack the structural flexibility necessary to support dynamic views of hierarchic classifications, and cannot properly capture the history of these complex interactions. We have developed a new data model which is suitable for supporting semantically interacting dynamic views of hierarchic biological classifications. On the basis of our new data model we have developed a prototype database system called HICLAS (HIerarchical CLAssification System); its domain is plant taxonomy. HICLAS is available through the Internet and an X-window interface has been implemented to support queries to classification data.

Screening for Down's syndrome: the first two years experience in Bristol.

OBJECTIVES: To evaluate the effectiveness of a programme for antenatal screening for Down's syndrome using alpha fetoprotein and total human chorionic gonadotrophin as maternal serum markers. SETTING: A district general hospital providing a screening service to a local purchasing authority and (under contract) to another purchasing authority in the same region. METHODS: Patients were counselled and screened between 15 and 20 weeks gestation and Down's risk estimates calculated using the maternal serum marker results as modifiers of the age related risk. Outcome was determined in collaboration with the Regional Cytogenetics Unit. OUTCOME MEASURES: Detection rate for Down's syndrome, false positive rate, uptake of screening, and uptake of amniocentesis. RESULTS: In two years 22816 women were screened (approximately 84% of population); 32 Down's pregnancies were identified, 19 (59.4%) had a reported risk of > or = 1:250 and 20 (62.5%) a reported risk of > or = 1:300. Of those screened before 17 weeks, 16/20 (80%) had a reported risk of > or = 1: 300 compared with 4/12 (33%) of those screened later (P = 0.008); 4.64% of patients screened had reported risks > or = 1: 250 and 5.87% reported risks of > or = 1:300. Amniocentesis uptake was 70% in patients with reported risks of > or = 1:300. CONCLUSIONS: Overall the screening programme was effective but screening before 17 weeks was very much more effective than screening later.

An analysis of coupled multicomponent diffusion in interstitial tissue.

A one-dimensional multicomponent kinetic model was developed to simulate the interstitial diffusion of macromolecules in a three component system, consisting of water, the macromolecule and the interstitial matrix. Movement of the individual components was modeled as occurring in finite jumps between discrete low energy wells along paths defined in terms of species occupation. The flow rate was expressed as a function of the local species concentration, the jump distance, and a kinetic frequency parameter. The model, implemented in pseudo-bond graph form, was examined by fitting it to data obtained for the transport of fluorescein tagged dextran to determine the kinetic constants for that specific system.

Experimental transmission of eastern equine encephalitis virus by strains of Aedes albopictus and A. taeniorhynchus (Diptera: Culicidae).

The vector competence of Aedes taeniorhynchus (Wiedemann) and four strains of Aedes albopictus (Skuse) was assessed for eastern equine encephalitis (EEE) virus isolated from Ae. albopictus collected in Polk County, Florida. Both species became infected with and transmitted EEE virus by bite after feeding on 1-d-old chicks that had been inoculated with EEE virus (viremia = 10(10.1) plaque-forming units [PFU] per ml of blood). However, when fed on an older chick with a lower viremia (viremia = 10(6.1) PFU per ml of blood), Ae. albopictus was significantly more susceptible to infection (90%, n = 61) than was Ae. taeniorhynchus (15%, n = 40). Transmission was also significantly more efficient by Ae. albopictus (36%, n = 44), than by Ae. taeniorhynchus (0%, n = 14). These data, combined with the recent isolation of EEE virus from Ae. albopictus and its opportunistic feeding behavior, indicate that Ae. albopictus could function as a bridge vector between the enzootic Culiseta melanura (Coq.)-avian cycle and susceptible mammalian hosts.