Hantavirus infections in rodents
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Biomedical subjects
Publications and source records attributed to S Bennett.
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Previous work in the area of vulnerary agents is extensive. One material of focus has been positively charged ion exchange beads, which have been shown to promote a variety of wound-healing responses in several models. The goal of this work was to improve upon the clinical utility of positively charged dextran beads by creating a biodegradable version that maintains the material's inherent efficacy. A chemical method consisting of a sodium periodate oxidation was used to create a degradable diethylaminoethanol crosslinked dextran bead. The ability of this process to create a degradable bead was verified in vitro and in vivo. Furthermore, efficacy was shown in a rat linear incision model for a variety of beads exhibiting different degradation rates. The results show that efficacy is maintained by a degradable bead, but there is a diminution of the magnitude of the response as the mass loss rate is increased. Efficacy also was investigated for a moderate but completely degrading bead material over time and dose. Wound breaking strength was evaluated at days 7, 10, 14, 21, and 28 for degradable beads at doses of 10 mg/mL and 50 mg/mL. Although little difference in efficacy was noted for the increased dose, statistically significant increases over control were seen at days 7, 10, and 14 for the 10 mg/mL dose and at days 10 and 14 for the 50 mg/mL dose. At days 21 and 28 there were no differences between treated and control wounds.
The study reported describes an experimental biodegradable polymer ceramic composite with wax-like handling properties that was combined with 2.0 micrograms of recombinant human transforming growth factor beta (rhTGF-beta(1)). The polymer/rhTGF-beta(1) combination was introduced into standard-sized calvarial defects in rabbits to evaluate biodegradability, biocompatibility, hemostasis control, and bone promotion. The experimental wound model was a standard-size circular calvarial defect 8 mm in diameter. The experimental design included 24 skeletally mature New Zealand white rabbits divided evenly between two time periods (6 and 12 weeks) and among three experimental treatments (untreated defects and defects treated with polymer with or without rhTGF-beta(1)). Evaluations consisted of clinical examinations, standarized radiography, radiomorphometry, as well as histology and histomorphometry. Data were analyzed by an Analysis of Variance (ANOVA) and Fisher's Protected Least Significant Difference test at each time period (level of significance p < or = 0.05). Radiomorphometry data indicated that standard-sized defects treated with the wax-like polymer alone and the polymer plus 2.0 micrograms of TGF-beta(1) were significantly more radiopaque than control sites at both 6 and 12 weeks. Histomorphometric data revealed the amount of new bone was significantly greater at 6 weeks in the polymer plus 2.0 micrograms of TGF-beta(1) and in the control group than in the polymer alone. Moreover, at 12 weeks, there was significantly more new bone in the control than in either the polymer alone or the polymer plus 2.0 micrograms of TGF-beta(1). We speculate the incomplete biodegradation of the polymer ceramic composite contributed to the radiopacity and may have retarded osseous regeneration. It is important that the bone wax-like polymer material was biocompatible and acted as a hemostatic agent.
In 1994, 630 Gambian infants were immunized with three doses of the synthetic polypeptide malaria vaccine SPf66 or with a control vaccine. No significant protection against first or total attacks of malaria was observed among the children who received SPf66. However, the period of follow-up was short. Thus, 532 children were followed for a second malaria transmission season during which 291 episodes of malaria were detected. Protective efficacies of SPf66 against first attacks of malaria and against all attacks of malaria were 8% [95% CI-20%, 30%] and 2% [95% CI-26% 24%] respectively. SPf66 did not provide any significant degree of protection to Gambian infants during a second year of follow-up.
Clinical trials have indicated that treating mosquito nets with insecticide could be a potentially cost-effective method of preventing malaria. As malaria is one of the most common causes of death in children under five in developing countries, there has been substantial interest in whether such findings can be replicated for a country's control programme in practice. The cost-effectiveness of the Gambian National Insecticide-impregnated Bednet Programme (NIBP), from the viewpoint of providers (government and non-governmental agencies) and the community, has been calculated. Information was collected from existing records, interviews with NIBP personnel, observation and household surveys. Information is provided on the resource use consequences of the NIBP in terms of reduced expenditure on anti-malaria preventive measures, treatment in government health services, household financed treatment and "charity" (burial, funeral and mourning activities), as well as cash income lost as a result of child death. The annual implementation cost of the NIBP was D757,875 (US$91,864), of which 86% was recurrent cost. The estimated number of death averted was 40.56. The net implementation cost-effectiveness ratio per death averted and discounted life years gained were D3884 (US$471) and D260 (US$31.5), respectively. Adding the cost of all mosquito nets would increase the cost-effectiveness ratios by over five times, which is an important consideration for countries with a lower coverage of mosquito nets per capita. It is concluded that insecticide-impregnated mosquito nets are one of the more efficient ways of reducing deaths in children under 10 years in rural Gambia.
Data for planning disease control programs in most developing countries is often not available because they are usually expensive to gather. This study explored the potential use of peripheral health staff and community key informants in gathering community-level data about lymphatic filariasis. Agreement between findings of health workers and those of physicians was very high (kappa 0.66-0.87) for the clinical conditions examined. The prevalence of hydrocele was found to be a good predictor of communities at risk of filariasis. Community key informants provided very useful qualitative and quantitative data on the prevalence of clinical filariasis. The need to use nontraditional health professionals in gathering data for planing control programs is discussed.
A 6-y retrospective case note review was performed to determine the causes of ketoacidosis. 135 patients and 463 diabetic years were involved. Fifty-two ketoacidosis episodes occurred: 19 episodes in new patients and 33 episodes in 19 patients with established diabetes. 27% of newly diagnosed patients presented in ketoacidosis. They were similar in terms of age, sex and proportion living in single parent families to those presenting without ketoacidosis. The 33 ketoacidosis episodes occurring in established patients included 12 episodes in 3 children who were transferred to our care because of uncontrolled diabetes. Insulin omission was the cause of ketoacidosis in 9/19 (47%) patients, and was suspected in a further 5/19 (26%). Family and school problems were common and 14/19 patients came from single parent families. Established patients aged > or = 11 y were predominantly female (10F, 2M), whereas patients aged < or = 10 y were predominantly male (6M, 1F). 7 patients with multiple ketoacidosis episodes were all > or = 11 y and 6 were female. Families with > or = 2 diabetic children appeared vulnerable, 4 cases coming from 3/7 such families.
Preschool children with attention-deficit/hyperactivity disorder (ADHD) (27 boys, 5 girls, mean age 4 years 10 months) participated in a double-blind placebo-controlled crossover drug study to assess the side effects of methylphenidate. Children received twice daily, for at least 1 week each, placebo, 0.3 mg/kg methylphenidate, and 0.5 mg/kg methylphenidate. Side effects were monitored by a parent rating scale designed for medication studies. In general, methylphenidate was tolerated relatively well, with no children withdrawing because of adverse effects. Of 17 childhood behaviors usually associated with side effects, 8 behaviors showed significant changes, generally at the higher dose of methylphenidate. Interestingly, 3 of the side effects were associated with improved behavior. The number of side effects appeared higher than what is usually reported in a population of school-age children, but few parents reported them as being severe. Severe side effects were reported in less than 10% of the sample, with approximately as many reports of severe effects on placebo as on low and high doses of the medication. The results indicate that methylphenidate has a relatively low toxicity in preschool children (over the first 7-10 days), that some behavioral changes that might be viewed as side effects of methylphenidate are actually normal behaviors or ADHD behaviors in preschool children (e.g., sociability), that these "side-effect" behaviors are more common in preschool than school-age children, that some "side effects" of methylphenidate are associated with improvements in behavior, and that preschool and school-age children may have different side effects of methylphenidate (e.g., mood changes and anxiety).
Enhanced cutaneous wound healing by positively charged cross-linked diethylaminoethyl dextran beads (CLDD) was studied in a standardized incisional wound model in 20 adult and 20 geriatric Macaca mulatta (rhesus) partitioned equally over five time periods. Physiologic saline served as a control. Soft-tissue linear incisions were prepared between and 1 cm inferior to the scapulae. There were four incisions per rhesus; each incision was 1.5 cm long with 1 cm of undisturbed tissue between incisions, and both the experimental CLDD and physiologic saline treatments were administered to each rhesus. The incision treatments were either CLDD and soft-tissue closure with 4-0 BioSyn sutures or sterile physiologic saline and closure with 4-0 BioSyn sutures. The hypothesis was CLDD would enhance cutaneous wound repair. Verification of the hypothesis consisted of clinical examinations and histologic and tensiometric evaluations on biopsy specimens at 10 and 15 days, whereas 5-day and 2- and 4-month groups were assessed clinically and biopsy specimens were assessed histologically. The clinical course of healing for all groups was unremarkable. At 10 days, incisions in adult rhesus treated with CLDD had a 30-percent greater tensile strength compared with the physiologic saline-treated incisions (p = 0.01), whereas for geriatric rhesus, the CLDD treatment proved to be 15 percent greater in tensile strength compared with the physiologic saline cohort (p = 0.11). By day 15, incisions in adult rhesus were 26 percent stronger than the saline treatment group (p = 0.07), and the difference was 36 percent (p = 0.02) for the geriatric rhesus. From 5 through 15 days, histologic observations revealed a gradual decrease in quantity and integrity of CLDD, with no remnants of CLDD at either 2 or 4 months. Macrophages and multinucleated giant cells were localized in the dermis and were associated with the CLDD. These cells decreased commensurately with the decrease of CLDD beads. The data suggest that CLDD can enhance significantly the tensile properties of healing cutaneous wounds in both adult and geriatric rhesus. Moreover, if the wound healing is enhanced in geriatric patients, this finding may be clinically germane to conditions where wound healing is compromised, such as in diabetics and patients on steroids.
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The incidence of Plasmodium falciparum infection has been followed in a birth cohort of 71 infants in southern Ghana, an area of perennial malaria transmission. Parasite DNA detection established the presence of a high rate of infection in newborns (13.6%), a low level of infection from two to 26 weeks (1.5-9.7%) and a steadily increasing parasite rate from 26 weeks of age. The median age to first infection was 42 weeks. Five cases of fever (temperature > or = 37.5 degrees C) and parasite density greater than 1,000 parasites/microl of blood, all in children more than 18 weeks of age, were considered possible cases of clinical malaria. The risk of infection was almost three times higher in the wet season than in the dry season and increased significantly from the age of 18 weeks. The level of malaria-specific IgG at birth was positively correlated with risk of infection in children 6-12 months of age, indicating that maternally derived anti-malarial IgG is correlated with exposure to malaria infection. There was no association between malaria-specific IgG at birth and risk of infection in children 0-6 months of age. However, infants do appear to possess mechanisms to limit parasite growth and a role for maternal antibody cannot be ruled out.
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Understanding how the regulation of growth factor pathways alters during prostate cancer (PC) progression may enable researchers to develop targeted therapeutic strategies for advanced disease. PC progression involves the shifting of cells from androgen-dependent growth to an androgen-independent state, sometimes with the loss or mutation of the androgen receptors in PC cells. Both autocrine and paracrine pathways are up-regulated in androgen-independent tumors and may replace androgens as primary growth stimulatory factors in cancer progression. Our discussion focuses on growth factor families that maintain homeostasis between epithelial and stromal cells in the normal prostate and that undergo changes as PC progresses, often making stromal cells redundant. These growth factors include fibroblast growth factor, insulin-like growth factors, epidermal growth factor, transforming growth factor alpha, retinoic acid, vitamin D3, and the transforming growth factor beta families. We review their role in normal prostate development and in cancer progression, using evidence from clinical specimens and models of PC cell growth.
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This paper considers methods of statistical analysis for highly skewed immune response data. Observations from population studies of immunological variables are rarely normally distributed between individuals; typically the distribution shows extreme levels of skewness. In some situations, skewness remains considerable even after transforming the data. Using resampling techniques, applied to several actual datasets of ELISA assay data, we consider the robustness of normal parametric methods, e.g. t tests and linear regression. Despite the skewness of the transformed data, we demonstrate that such methods are quite robust depending on the number of observations, type of analysis and severity of skewness. We also illustrate how bootstrap resampling can be used to provide a valid alternative method of analysis that can be used either for checking normal parametric analysis or as a direct method of analysis. We illustrate this combined approach by analysing real data to test for association between human serum antibodies to malaria merozoite surface proteins, MSP1 and MSP2, and resistance to clinical malaria, and confirm the protective effect of antibodies to MSP1 and demonstrated a similar protective effect for some antibodies to MSP2.
The study presented a theoretical and empirical approach to the adult drawing process. Four possible sources of drawing inaccuracies were described: misperception of the object, inability to make good representational decisions, deficient motor skills, and misperception of the drawing. In four studies the degree to which the latter three sources contributed to drawing inaccuracies was assessed. The results suggest that (a) motor coordination is a very minimal source of drawing inaccuracies, (b) the artist's decision-making process is a relatively minor source of drawing inaccuracies, and (c) the artist's misperception of his or her work is not a source of drawing inaccuracies. These results suggest that the artist's misperception of the object is the major source of drawing errors.