The Brown University School of Medicine Class of 1995.
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Biomedical subjects
Publications and source records attributed to S R Smith.
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Since last reviewing the field, controlled release products have made the jump from research to clinical practice. The potential to extend the efficacy of periodontal therapy with such products is exciting, but also needs careful evaluation. This review will look at recent developments and also will examine the eventual place for these products in periodontics.
Rats with either posterior parietal (PPC) or dorsal hippocampal (HIP) lesions were tested for open-field activity, acquisition of a multiple T water maze habit, and presence of a 'cognitive map' of the water maze arena. The performances of control and PPC-lesioned rats were similar on all behavioral measures. However, the HIP-damaged rats demonstrated higher levels of general activity, severe deficits in both working and reference memory in the multiple T water maze task, and failed to develop a cognitive map of the water maze arena.
A method is described for the detection of DNA hybrids formed on a solid support, based upon the pairing of oligonucleotide chemistry and the technologies of electronic microdevice design. Surface matrices have been created in which oligonucleotide probes are covalently linked to a thin SiO2 film. 32P labeled target nucleic acid is then hybridized to this probe matrix under conditions of high stringency. The salient feature of the method is that to achieve the highest possible collection efficiency, the hybridization matrix is placed directly on the surface of a charge coupled device (CCD), which is used to detect 32P decay from hybridized target molecules (1, Eggers, M.D., Hogan, M.E., Reich, R.K., Lamture, J.B., Beattie, K.L., Hollis, M.A., Ehrilich, D.J., Kosicki, B.B., Shumaker, J.M., Varma, R.S., Burke, B.E., Murphy, A., and Rathman, D.D., (1993), Advances in DNA Sequencing Technology, Proc. SPIE, 1891, 13-26). Two implementations of the technology have been employed. The first involves direct attachment of the matrix to the surface of a CCD. The second involves attachment of the matrix to a disposible SiO2 coated chip, which is then placed face to face upon the CCD surface. As can be predicted from this favorable collection geometry and the known characteristics of a CCD, it is found that as measured by the time required to obtain equivalent signal to noise ratios, 32P detection speed by the direct CCD approach is at least 10 fold greater than can be obtained with a commercial gas phase array detector, and at least 100 fold greater than when X-ray film is used for 32P detection. Thus, it is shown that excellent quality hybridization signals can be obtained from a standard hybridization reaction, after only 1 second of CCD data acquisition.
Plant systems can activate aromatic amines into mutagens. In the plant cell/microbe coincubation assay, we earlier demonstrated that 2-aminofluorene and m-phenylenediamine were activated by plant cells into mutagens with reversion at the hisD3052 allele in Salmonella typhimurium strain TA98 as the genetic endpoint. New derivatives have been developed which possess elevated levels of acetyl-CoA:N-hydroxyarylamine O-acetyltransferase which are very sensitive to N-hydroxylated amines [Watanabe et al., 1990: Mutat Res 234:337-348]. The objectives of this research were to examine Salmonella strains with different acetyltransferase activities in the plant cell/microbe coincubation assay with a series of structurally related aromatic amines. The hypothesis tested was whether and to what degree a plant-activated metabolite of these aromatic amines could serve as a substrate for bacterial O-acetyltransferase and induce mutation in Salmonella. Every aromatic amine examined was activated by plant cells with YG1024 (the strain with elevated O-acetyltransferase activity) as the genetic indicator organism. The rank order of the mutagenic responses of YG1024 to the plant-activated aromatic amines was 2-aminofluorene > benzidine > m-phenylenediamine > 4-aminobiphenyl > 2,4-diaminotoluene > 2-naphthylamine. This rank order was expressed by TA98 but to a much lower degree. There was a very slight mutagenic response observed in TA98/1,8-DNP6 (a strain lacking O-acetyltransferase activity) with the plant-activated metabolites of benzidine and 4-aminobiphenyl. We conclude that the plant-activated aromatic amines are substrates for bacterial O-acetyltransferases.
Recent studies have demonstrated that interleukin-10 (IL-10) has the capacity to protect mice from the lethal effects of endotoxin. In this investigation, we have examined the ability of IL-10 to protect both normal mice and Corynebacterium parvum-primed mice against endotoxin lethality. In the overwhelming majority of experiments, recombinant murine IL-10 (rMuIL-10) and recombinant human IL-10 (rHuIL-10) did not protect normal BALB/cJ mice from lipopolysaccharide (LPS)-induced lethality at doses up to 10 micrograms/mouse. Despite their inability to protect, both IL-10 preparations were highly effective in preventing the increase in serum tumor necrosis factor alpha (TNF-alpha) that occurred in response to the lethal dose of LPS. Moreover, a neutralizing antibody against TNF-alpha gave only partial protection when administered alone to BALB/cJ mice. Treatment with a combination of neutralizing antibodies against TNF-alpha and interferon-gamma (IFN-gamma) resulted in complete protection. In contrast to BALB/cJ mice, normal BDF1 mice were protected from lethal endotoxemia by treatment with both rMuIL-10 and rHuIL-10. However, IL-10 did not protect C. parvum-primed BDF1 against LPS lethality even though it caused a reduction in the LPS-induced serum TNF-alpha response in C. parvum-primed mice as well as in normal BDF1 mice. Neutralizing antibodies against TNF-alpha and IFN-gamma were protective when administered alone to normal BDF1 mice, as previously demonstrated in C. parvum-primed mice. These findings suggest that lethal endotoxemia is a result of the cooperative activities of TNF-alpha and IFN-gamma in normal mice of the BALB/cJ and BDF1 strains as well as in C. parvum-primed BDF1 mice. IL-10 appears to be less effective in protecting mice from lethal endotoxemia when cooperation between IFN-gamma and TNF-alpha is facilitated by high-level production of the cytokines as in C. parvum-primed mice or when there is evidence of strong synergy between them as in normal BALB/cJ mice.
Appropriate pH-related permissible soil-limit concentrations for cadmium in sewage sludge-treated agricultural soils were estimated from the proportional changes in concentrations of cadmium in potatoes, oats and ryegrass grown on two sludge-amended soils and at different pH values. Implications for potential human dietary intake of cadmium were also assessed. Yields of crops increased with increasing soil pH, probably in response to decreasing uptake of zinc as soil pH value was raised. In general, cadmium concentrations in peeled potato tubers, potato peelings, oat straw and ryegrass decreased as simple linear functions of increasing soil pH over the range of pH values measured (pH 3.9-7.6). Cadmium concentrations in potato peel were particularly sensitive to changing pH conditions, whereas cadmium levels in oat grain were independent of soil pH. On the basis that a highly precautionary approach is adopted in setting soil standards for heavy metals, appropriate permissible concentrations of cadmium in sludge-treated agricultural soil which protect the human food chain were determined as 2.0 and 2.5 mg Cd Kg(-1) for banded pH ranges of 5.0-5.5 and 5.5-6.0, respectively.
The effect of soil pH value on concentrations of Ni, Cu and Zn in ryegrass grown on two sludge-treated soils was examined under field conditions and the maximum permissible soil limit values for these elements were determined which prevent phytotoxicity in crops where sewage sludge is applied to agricultural soils with pH <6.0. Concentrations of all the elements in ryegrass decreased as simple linear functions of increasing soil pH and this response was consistent across the range of pH values measured (pH 4.2-7.0). The response of individual elements tended to differ though, with Cu being less sensitive to changing pH conditions compared with Zn and Ni which responded in a similar manner. The yield of ryegrass also increased with increasing soil pH value probably due to the effects on Zn uptake as the crop content of Zn exceeded known upper critical tissue concentrations for this element at both sites. The proportional change in metal content of ryegrass at pH 5.0, 5.5 and 7.0 from tissue concentrations at pH 6.0 was calculated to determine the permissible soil concentration values on the basis of current maximum limits set by the Sludge Regulations in the UK for sludge-treated agricultural land at pH 6.0-7.0. The estimated permissible concentrations of Ni and Zn in soil corresponded with the regulatory values at the low pH ranges, but were substantially above the current soil limits at pH 7.0 indicating larger quantities of these elements could be safely applied under alkaline soil conditions. The estimated soil limits for Cu implied that the current Regulations were highly precautionary for this element.
Under the current tort-malpractice system, mental health malpractice claims often harm defendants' reputations, disrupt relationships among providers, and breach patient confidentiality. Common areas of malpractice, together with difficulties in defining the standard of care and proving causation, are examined. Reform proposals involving the options of interdisciplinary compensation panels or binding arbitration are designed to protect plaintiff privacy, reduce time and cost of litigation, and increase satisfaction with the dispute resolution process.
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BACKGROUND: An assessment technique was developed to measure the abilities of medical students to deal with moral and ethical issues. METHOD: Assessments of ability in moral reasoning and ethical judgement were administered in July and August of 1991 and 1992 to 511 fourth-year students from five northeastern U.S. medical schools. Five behavioral parameters were measured during each student's encounter with a standardized patient (SP), who graded the student's performance. Immediately following the encounter, each student was asked to describe at least two moral conflicts in a short essay, which was graded by the authors of the study. Statistical analysis used chi-square, Fisher's exact test, and Spearman rank correlation. RESULTS: Poor performance on the interactive tasks with the SP was observed among 11% of the students; on the written (analytical) tasks, among 14.1%; and on both portions of the assessment, among 2.3%. Little relationship existed between performances on the interactive and written portions. CONCLUSION: That a low degree of relationship was found between the students' performances on the interactive and written portions of the assessment suggests that the two portions measure different skills. To address student differences, the authors formulated a model for categorizing students that would be useful in individualizing remedial strategies.
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The aim of this study was to determine whether the use of a pre-brushing mouthwash Plax reduced extrinsic tooth-staining in vivo and in vitro. Firstly, in a double-blind placebo controlled cross-over study, 20 subjects with tooth staining used Plax or a placebo for 14-day periods separated by a 1-month wash-out period. The area of stain was assessed before and after each mouthwash had been used from clinical photographs. Secondly, extracted 3rd molar teeth were stained with tea and chlorhexidine. After exposure to either Plax or placebo, the teeth were brushed in a standardized manner. The area and intensity of stain were assessed before and after rinsing and brushing. Results of the study in vivo showed that the mean % stained area for any of the surfaces studied changed very little throughout the study. No statistically significant changes were detected (Student t-test, p > 0.05). Results of the study in vitro showed that the mean area of stain fell by 19% after exposure to Plax and by 17% after exposure to placebo. No statistically significant changes were detected (Student t-test, p > 0.05). There were also no significant changes in intensity (Wilcoxon signed rank sum test p > 0.1).
SofScale is a pre-scaling gel, containing disodium EDTA and sodium lauryl sulphate, which is claimed to soften calculus and therefore facilitate its removal. 31 subjects were treated in a double blind randomised placebo controlled split mouth study to evaluate this product. Test or placebo gels were applied to the lingual surfaces of the mandibular teeth for 4 min and the time taken to complete the removal of supragingival calculus recorded. The operator recorded on which side the calculus was considered easier to remove and the patient indicated how comfortable the scaling had been. The mean calculus index was 1.99 for the SofScale group and 1.97 for the placebo. The mean time taken to complete scaling was 5.31 min for both groups. Using the Student t-test, there were no statistically significant differences (p > 0.7) between either the calculus index or time taken to complete the scaling between the groups. The operator did not consider SofScale to facilitate calculus removal and patients did not find calculus removal more comfortable when SofScale had been used. There was no increased sensitivity in the SofScale group following scaling. The results of this study do not support the use of SofScale as an adjunct to scaling.
OBJECTIVES: To determine how Medicaid prescription drug policies differ by state, and to assess how these policies affect pharmacies and the drug therapies available to Medicaid patients with HIV infection or tuberculosis. EVALUATION PROCESS: The state affiliates of the American Pharmaceutical Association (APhA) were surveyed to learn how state Medicaid policies impact the provision of prescription drugs to Medicaid patients within their state. The survey focused on Medicaid payment level incentives, Medicaid payments compared with private payments, Medicaid utilization policies, and incentives and disincentives in each state's Medicaid payment system. RESULTS: Approximately two-thirds of the APhA affiliates reported that the Medicaid payment levels in their states for drugs used to treat HIV-related illnesses were at least moderately below private payment levels; in 11 states these Medicaid payments were substantially below those of private payers. Many APhA affiliates responding to the survey stated that the Medicaid program in their state limited the number of reimbursed drugs that Medicaid patients can receive. Eight APhA affiliates reporting that these utilization limits created restrictions on the ability of Medicaid patients with AIDS and HIV-related infections to receive needed medications. CONCLUSIONS: With Medicaid programs becoming the major payers of AIDS-related healthcare, federal policies should standardize Medicaid coverage, payment, and utilization policies for prescription drugs needed by Medicaid recipients with HIV-related conditions. This would enable Medicaid patients to receive necessary and adequate drug therapies regardless of their state of residence. These federally mandated policies also would require an increased federal role in financing this expanded Medicaid drug coverage.
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