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Biomedical subjects

D Sacks

Publications and source records attributed to D Sacks.

At least 19 recordsLinked to original sources
PubMed2001

The potency and durability of DNA- and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge.

DNA- and protein- based vaccines against cutaneous leishmaniasis due to Leishmania major were evaluated using a challenge model that more closely reproduces the pathology and immunity associated with sand fly-transmitted infection. C57BL/6 mice were vaccinated s.c. with a mixture of plasmid DNAs encoding the Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or with autoclaved L. major promastigotes (ALM) plus rIL-12, and the mice were challenged by inoculation of 100 metacyclic promastigotes in the ear dermis. When challenged at 2 wk postvaccination, mice receiving AgDNA or ALM/rIL-12 were completely protected against the development of dermal lesions, and both groups had a 100-fold reduction in peak dermal parasite loads compared with controls. When challenged at 12 wk, mice vaccinated with ALM/rIL-12 maintained partial protection against dermal lesions and their parasite loads were no longer significantly reduced, whereas the mice vaccinated with AgDNA remained completely protected and had a 1000-fold reduction in dermal parasite loads. Mice vaccinated with AgDNA also harbored few, if any, parasites in the skin during the chronic phase, and their ability to transmit L. major to vector sand flies was completely abrogated. The durable protection in mice vaccinated with AgDNA was associated with the recruitment of both CD8(+) and CD4(+) T cells to the site of intradermal challenge and with IFN-gamma production by CD8(+) T cells in lymph nodes draining the challenge site. These data suggest that under conditions of natural challenge, DNA vaccination has the capacity to confer complete protection against cutaneous leishmaniasis and to prevent the establishment of infection reservoirs.

Animals↗
PubMed2001

CPT coding by interventional radiologists: accuracy and implications.

PURPOSE: To evaluate the accuracy of Current Procedural Terminology (CPT) coding for interventional radiology services when coding is performed by the operating physician. MATERIALS AND METHODS: Coding data for 1,174 interventional radiology encounters in 736 patients were analyzed for appropriate use of CPT codes. Physician operators initially assigned provisional codes. Formal coding for billing purposes was performed at a later date by one of two experienced interventional radiology physician coders. Initial operator coding errors and associated relative value unit (RVU) impact were analyzed. The coding patterns of experienced physician coders were compared with those of the other interventionalists. RESULTS: Only 82% of encounters were initially coded correctly, with a small net tendency toward undercoding. The overall net RVU impact of errors was only -1.2%, with the effects of undercoding outweighing those of overcoding. More complex cases (> or =4 CPT codes) were much more likely to be coded erroneously than less complex cases (24% vs 14%, P <.001). Experienced physician coders committed significantly fewer errors than other physicians (10% vs 25%, P <.001), but there was a similar minimal net RVU impact of errors (-1.1% vs -1.4%, P =.198). CONCLUSION: Although initial physician coding errors for interventional radiology procedures are common, the net RVU impact is minimal. The accuracy of experienced physician coders is significantly higher than that for other interventionalists. Because of the regulatory consequences of coding inaccuracies, practices should establish quality improvement systems to minimize errors and use the skills of experienced individuals in their coding processes.

Forms and Records Control↗
PubMed2001

Molecular aspects of parasite-vector and vector-host interactions in leishmaniasis.

Leishmania-sand fly interactions are reviewed in the context of the potential barriers to the complete development of the parasite that exist within the midgut environment of phlebotomine flies and the molecular adaptations that the parasite has evolved that permit the development of transmissible infections to proceed. Cell surface and secreted phosphoglycans protect the parasite from the proteolytic activities of the blood-fed midgut, mediate attachment to the gut wall in order to maintain infection during excretion of the bloodmeal, and contribute to the formation of a biological plug in the anterior gut that may promote transmission by bite. The importance of vector saliva in modulating the host response to transmitted parasites is also reviewed.

Animals↗
PubMed2001

Condom use by adolescents.

The use of condoms as part of the prevention of unintended pregnancies and sexually transmitted diseases (STDs) in adolescents is evaluated in this policy statement. Sexual activity and pregnancies decreased slightly among adolescents in the 1990s, reversing trends that were present in the 1970s and 1980s, while condom use among adolescents increased significantly. These trends likely reflect initial success of primary and secondary prevention messages aimed at adolescents. Rates of acquisition of STDs and human immunodeficiency virus (HIV) among adolescents remain unacceptably high, highlighting the need for continued prevention efforts and reflecting the fact that improved condom use can decrease, but never eliminate, the risk of acquisition of STDs and HIV as well as unintended pregnancies. While many condom education and availability programs have been shown to have modest effects on condom use, there is no evidence that these programs contribute to increased sexual activity among adolescents. These trends highlight the progress that has been made and the large amount that still needs to be accomplished.

Adolescent↗
PubMed2001

Care of the adolescent sexual assault victim.

Sexual assault is a broad-based term that encompasses a wide range of sexual victimizations, including rape. Since the American Academy of Pediatrics published its last policy statement on this topic in 1994, additional information and data have emerged about sexual assault and rape in adolescents, the adolescent's perception of sexual assault, and the treatment and management of the adolescent who has been a victim of sexual assault. This new information mandates an updated knowledge base for pediatricians who care for adolescent patients. This statement provides that update, focusing on sexual assault and rape in the adolescent population.

Adolescent↗
PubMed2000

Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies.

Despite the fact that Leishmania are transmitted exclusively by sand flies, none of the experimental models of leishmaniasis have established infection via sand fly bites. Here we describe a reproducible murine model of Leishmania major infection transmitted by Phlebotomus papatasi. Prior exposure of mice to bites of uninfected sand flies conferred powerful protection against Leishmania major that was associated with a strong delayed-type hypersensitivity response and with interferon-gamma production at the site of parasite delivery. These results have important implications for the epidemiology of cutaneous leishmaniasis and suggest a vaccination strategy against this and possibly other vector-borne diseases.

Animals↗
PubMed2000

A natural model of Leishmania major infection reveals a prolonged "silent" phase of parasite amplification in the skin before the onset of lesion formation and immunity.

A model of Leishmania major infection in C57BL/6 mice has been established that combines two main features of natural transmission: low dose (100 metacyclic promastigotes) and inoculation into a dermal site (the ear dermis). The evolution of the dermal lesion could be dissociated into two distinct phases. The initial "silent" phase, lasting 4-5 wk, favored establishment of the peak load of parasites in the dermis in the absence of lesion formation or any overt histopathologic changes in the site. The second phase corresponds to the development of a lesion associated with an acute infiltration of neutrophils, macrophages, and eosinophils into the dermis and was coincident with the killing of parasites in the site. The onset of immunity/pathology was correlated with the appearance of cells staining for IL-12p40 and IFN-gamma in the epidermal compartment, and an expansion of T cells capable of producing IFN-gamma in the draining lymph node. Parasite growth was not enhanced over the first 4.5 wk in anti-CD4-treated mice, SCID mice, or C57BL/6 mice deficient in IL-12p40, IFN-gamma, CD40 ligand, or inducible NO synthase. These mice all failed to ultimately control infection in the site, but in some cases (anti-CD4 treated, IL-12p40-/-, CD40 ligand-/-, and SCID) high dermal parasite loads were associated with little or no pathology. These results extend to a natural infection model a role for Th1 cells in both acquired resistance and lesion formation, and document the remarkable avoidance of this response during a prolonged phase of parasite amplification in the skin.

Animals↗
PubMed2000

Evolution of lesion formation, parasitic load, immune response, and reservoir potential in C57BL/6 mice following high- and low-dose challenge with Leishmania major.

A model of cutaneous leishmaniasis using 10(2) Leishmania major metacyclic promastigotes inoculated into the footpads of genetically resistant C57BL/6 mice was studied in order to more accurately reproduce the evolution of lesion formation and the kinetics of parasite growth and immune response as they might occur in naturally exposed reservoirs and in human hosts. In contrast to the more conventional experimental model employing 10(6) metacyclic promastigotes, in which the rapid development of footpad lesions was associated with an increasing number of amastigotes in the site, the low-dose model revealed a remarkably "silent" phase of parasite growth, lasting approximately 6 weeks, during which peak parasitic loads were established in the absence of any overt pathology. Footpad swelling was observed after 6 weeks, coincident with the onset of parasite clearance and with production of high levels of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in draining lymph nodes. Low-dose challenge of IL-12- and IFN-gamma-depleted or -deficient mice provided strong evidence that the induction or expression of cellular immunity is essentially absent during the first 6 to 8 weeks of intracellular growth, since the concentration of amastigotes in the site was not enhanced compared to that for wild-type animals during this time. By monitoring the ability of infected mice to transmit parasites to vector sand flies, it was observed that following low-dose challenge, footpads without apparent lesions provided an efficient source of parasites for exposed flies and that the low-dose challenge actually extended the duration of parasite transmissibility during the course of infection.

Animals↗