Biomedical subjects

Phillip Scott

Publications and source records attributed to Phillip Scott.

42 records · Page 3Linked to original sources

PubMed2002

Management of acute ischemic stroke.

Prior to 1995 no proven therapy existed for acute ischemic stroke. In 1996 the U.S. Food and Drug Administration approved the use of intravenous rt-PA in acute stroke based largely on the results of a two-part trial sponsored by the National Institutes of Health and National Institute of Neurological Disorders and Stroke (NIH/NINDS). Five years following approval, however, thrombolytic treatment remains underutilized, occurring in only 1 to 2% of all stroke patients. The medical community is now being called upon to organize systems capable of delivering acute stroke care in a time-urgent manner not previously contemplated. Critical care specialists may be called upon to treat stroke occurring in hospitalized patients or to continue care initiated in the emergency department. This article briefly reviews the pathogenesis of cellular injury in stroke and its initial evaluation and care and then focuses on the data involving thrombolytic reperfusion. Special attention is given to postthrombolytic critical care issues as these represent an important determinant in patient outcome. Secondary stroke prevention strategies and complication management are discussed along with general intensive care issues for the stroke patient.

Journal Article↗

PubMed2002

Combined treatment with interleukin-12 and indomethacin promotes increased resistance in BALB/c mice with established Leishmania major infections.

Following infection of susceptible BALB/c mice with Leishmania major, early production of interleukin-4 (IL-4) is associated with the development of a nonprotective Th2 response and the development of progressive disease. Treatment of mice with IL-12 at the time of infection can promote the activation of a protective Th1 response; however, IL-12 treatment of mice with established infections has little effect on the progress of lesion development. This may be due to a down-regulation of the IL-12 receptor beta2 chain (IL-12Rbeta2) that accompanies the expansion of IL-4-producing Th2 cells. We have examined whether prostaglandins function to regulate in vivo responsiveness to IL-12. Mice treated with indomethacin are responsive to treatment with exogenous IL-12 through at least the first 2 weeks of infection and, unlike control mice treated with IL-12, develop an enhanced Th1-type response associated with increased enhanced resistance to infection. Cells from indomethacin-treated mice also exhibit enhanced production of gamma interferon (IFN-gamma) following in vitro stimulation with IL-12. Although in vivo indomethacin treatment did not appear to influence IL-12 production in infected mice, cells from indomethacin-treated mice did express higher levels of IL-12Rbeta2, suggesting that prostaglandins may play a role in the loss of IL-12 responsiveness observed during nonhealing L. major infections.

Animals↗

PubMed2002

Influence of parasite load on the ability of type 1 T cells to control Leishmania major infection.

BALB/c mice infected with Leishmania major developed a type 2 immune response which failed to control parasite replication. We found that scid mice that received splenocytes from BALB/c mice that had been infected for 3 weeks with L. major (a type 2 cell population) and that were subsequently infected with L. major were protected when they were treated with interleukin 12 (IL-12). In contrast, IL-12 was ineffective at protecting BALB/c mice infected for 3 weeks, suggesting that a high parasite load regulates the development of protective immunity. To determine how this regulation operates, we performed a series of adoptive transfers of naïve, type 1 or type 2 splenocytes into scid mice. The recipient scid mice were infected either for 5 weeks prior to cell transfer (and thus had a high parasite load) or at the time of cell transfer. scid mice that were infected for 5 weeks and received a type 1 cell population were able to cure their lesions. However, when 5-week-infected scid mice received both type 1 and 2 cell populations, they were unable to control their infections. In contrast, the same type 1 and 2 cells transferred to naïve scid mice, which were subsequently infected, provided protection. In addition, we found that naïve cells mediated protection in scid mice with established lesions. These results show that high parasite numbers do not block type 1 protective responses or the development of type 1 responses. Instead, the influence of a high parasite load is dependent on the presence of a type 2 cell population.

Animals↗

PubMed2002

Early enhanced Th1 response after Leishmania amazonensis infection of C57BL/6 interleukin-10-deficient mice does not lead to resolution of infection.

C3H and C57BL/6 mice are resistant to Leishmania major but develop chronic lesions with persistent parasite loads when they are infected with Leishmania amazonensis. These lesions develop in the absence of interleukin-4 (IL-4), indicating that susceptibility to this parasite is not a result of development of a Th2 response. Expression of the cytokine IL-10 during infection could account for the lack of IL-12 expression and poor cell-mediated immunity towards the parasite. Therefore, we tested the hypothesis that IL-10 plays a central role in downmodulating the Th1 response after L. amazonensis infection. Infection of C57BL/6 IL-10-deficient mice indicated that in the absence of IL-10 there was early enhancement of a Th1 response, which was downregulated during the more chronic stage of infection. In addition, although there were 1- to 2-log reductions in the parasite loads within the lesions, the parasites continued to persist, and they were associated with chronic lesions whose size was similar to that of the control lesions. These experiments indicated that L. amazonensis resistance to killing in vivo is only partially dependent on expression of host IL-10. However, IL-10-deficient mice had an enhanced delayed-type hypersensitivity response during the chronic phase of infection, indicating that there were Th1 type effector cells in vivo at this late stage of infection. These results indicate that although IL-10 plays a role in limiting the Th1 response during the acute infection phase, other immunomodulatory factors are responsible for limiting the Th1 response during the chronic phase.

Animals↗

PubMed2002

Activity of azithromycin against Leishmania major in vitro and in vivo.

Azithromycin, an azalide antibiotic of the macrolide family, concentrates in the tissues and especially in macrophages. Because Leishmania parasites reside in these cells, we tested this antibiotic for a possible antileishmanial activity in vitro and in vivo. Azithromycin decreased the Leishmania major promastigote count in cell-free cultures at log phase approximately 50-fold. In macrophage cultures infected with L. major amastigotes, azithromycin caused a significant decrease in parasite levels with an ED50 of 12 microg/ml. The activity in vivo was evaluated after infection of the footpads of susceptible BALB/cByJ mice and resistant C57BL/6J mice with L. major. Treatment of BALB/cByJ mice with azithromycin, 100 to 200 mg/kg/d, resulted in a significant decrease in lesion size and in the number of parasites per lesion, whereas no effect was seen in the treated C57BL/6J mice. Azithromycin has activity against L. major in vitro and in vivo. Given the severity of the disease and the limitations of the available therapeutic agents, azithromycin may have a significant role in the treatment of this group of diseases.

Animals↗

PubMedDate not supplied

Access to intra-arterial therapies for acute ischemic stroke: an analysis of the US population.

BACKGROUND AND PURPOSE: Intra-arterial therapies for ischemic stroke offer promise as a means to extend the time window for acute treatment. The purpose of this study was to identify the percentage of the US population with potential access to interventional neuroradiologic expertise within 6 hours of the onset of stroke symptoms. METHODS: Hospital locations of interventional neuroradiologists were identified from the 2002 roster of the American Society of Interventional and Therapeutic Neuroradiology. Data for populations in surrounding regions were extracted from US Census 2001 data by zip code. Standard transport speeds for emergency medical services were used in our estimates of the population living within a 5-hour transport time, which was a 6-hour treatment window less a 1-hour door-to-needle time, resulting in a 200-mile radius. A 2-hour transport time, or 3-hour treatment window, reflected a 65-mile radius. RESULTS: A total of 385 interventional neuroradiologists were identified, practicing in 45 states. With a 200-mile radius, 99% of the total US population had access to neurointerventional treatment within 6 hours of symptom onset. With a 65-mile radius, 82% of the population had access within 3 hours of symptom onset. Alaska and the Mid-Northwest region covering Idaho, Wyoming, North Dakota, and South Dakota had limited coverage. CONCLUSION: Most of the US population has access to interventional neuroradiologic expertise for acute stroke therapy. These data suggest that interventional therapies that extend the time window for treating acute ischemic stroke could have a major effect on public health and merit further research development and investment.

Brain Ischemia↗