Peri-urban visceral leishmaniasis (VL) caused by Leishmania chagasi is emerging in a new epidemiologic pattern in Brazilian cities. We studied peri-urban VL in endemic neighborhoods surrounding Natal, Brazil, identified through hospitalized individuals with VL. Clinical and environmental information obtained for 1106 members of 216 families living in endemic neighborhoods enabled us to identify 4 groups: VL: individuals with current or prior symptomatic visceral leishmaniasis (n = 135); DTH+: individuals with positive delayed-type hypersensitivity response with no history of VL (n = 390); Ab +: individuals with negative DTH response and seropositive (n = 21); DTH -: individuals with negative DTH and seronegative (n = 560). The mean +/-SD age of VL was 9.3+/-12.3 y. The gender distribution was nearly equal below age 5, but skewed toward males at higher ages. Acutely infected VL subjects had significantly lower hematocrits, neutrophils, and eosinophils than other categories. AB+ subjects also had lower eosinophil counts than others, a possible immune marker of early infection. VL was not associated with ownership of dogs or other animals, raising the question whether the reservoir differs in peri-urban settings. This new pattern of L. chagasi infection enables us to identify epidemiological and host factors underlying this emerging infectious disease.

We have isolated 64 different missense mutations at 36 out of 53 residue positions in the Arc repressor of bacteriophage P22. Many of the mutant proteins with substitutions in the C-terminal 40 residues of Arc have reduced intracellular levels and probably have altered structures or stabilities. Mutations in the N-terminal ten residues of Arc cause large decreases in operator DNA binding affinity without affecting the ability of Arc to fold into a stable three-dimensional structure. We argue that these N-terminal residues are important for operator recognition but that they are not part of a conventional helix-turn-helix DNA binding structure. These results suggest that Arc may use a new mechanism for sequence specific DNA binding.

A periurban outbreak of visceral leishmaniasis (VL) caused by the protozoan Leishmania chagasi is ongoing outside Natal, northeast Brazil. Manifestations range from asymptomatic infection to disseminated visceral disease. Literature reports suggest that both genetic and environmental factors influence the outcome of infection. Due to the association of the tumor necrosis factor (TNF) locus with other infectious diseases, we examined whether polymorphic alleles at this locus are associated with the outcome of L. chagasi infection. Neighborhoods with ongoing transmission were identified through patients admitted to local hospitals. Altogether, 1,024 individuals from 183 families were classified with the following disease phenotypes: (i) symptomatic VL, (ii) asymptomatic infection (positive delayed-type hypersensitivity [DTH؉]), or (iii) no evidence of infection (DTH؊). Genotypes were determined at a microsatellite marker (MSM) upstream of the TNFB gene encoding TNF-␤ and at a restriction fragment length polymorphism (RFLP) at position ؊307 in the promoter of the TNFA gene encoding TNF-␣. Analyses showed that the distribution of TNFA RFLP alleles (TNF1 and TNF2) and the TNF MSM alleles (TNFa1 to TNFa15) differed between individuals with VL and those with DTH؉ phenotypes. TNF1 was transmitted more frequently than expected from heterozygous parents to DTH؉ offspring (P ‫؍‬ 0.0006), and haplotypes containing TNF2 were associated with symptomatic VL (P ‫؍‬ 0.0265, transmission disequilibrium test). Resting serum TNF-␣ levels were higher in TNF1/2 heterozygotes than in TNF1/1 homozygotes (P < 0.05). These data led us to hypothesize that an individual's genotype at the TNF locus may be associated with whether he or she develops asymptomatic or symptomatic disease after L. chagasi infection. The results preliminarily suggest that this may be the case, and follow-up with larger populations is needed for verification.The Leishmania spp. are obligate intracellular protozoa that cause a spectrum of diseases, including cutaneous, mucocutaneous, and visceral leishmaniasis (VL), in tropical or subtropical countries. In Latin America, the form of leishmaniasis leading to most fatalities, VL, is caused by Leishmania chagasi (44). The outcome of L. chagasi infection ranges in severity from asymptomatic infection to a severe progressive wasting disease called VL, which has 10% mortality even with medical treatment (5,33,34,44). The factors that determine whether an individual will develop asymptomatic or symptomatic disease after L. chagasi infection are not defined.Malnutrition, young age, and gender in those over age 10 predispose individuals to develop VL (21, 31). In addition, studies of inbred mice have led investigators to hypothesize that genetic factors may also contribute to the outcome of human disease (10,12). Supporting this hypothesis, several groups of researchers have independently documented familial aggregation of either symptomatic VL or positive delayed-type hypersensitivity (DTH) to leishmania antigen, a measure ...

OBJECTIVE:We developed an instructional program to teach aspiration and injection techniques of the knee and shoulder to medical students and residents. METHODS:Residents and fourth-year medical students participating in a rheumatology elective were assigned by deterministic allocation into 3 groups: the Traditional group received no specific instruction in arthrocentesis but simply rotated through rheumatology, learning injection techniques only if they saw patients who required them; the Lecture-only group received only the didactic lecture and did not have the opportunity to practice on the models; the Program group participated in the newly developed program of instruction that combined a didactic lecture and a hands-on workshop using the anatomic models to practice arthrocentesis techniques. RESULTS:The scores on the written examination for those in the Program group (mean score 37.46 out of 40 possible) and the Lecture-only group (mean 37.75) were significantly higher than those of the Traditional group (mean 33.15) (P < .05). The scores on the practical examination for those in the Program group (mean score 24.08 out of 26 possible) were significantly higher than those of the Lecture-only (mean 20.50) and Traditional (mean 17.33) (P < .05) CONCLUSION:The addition of this type of instruction to supplement a traditional internal medicine rotation can enhance a learner's ability to perform joint/soft-tissue injection and aspiration. J oint/soft-tissue injection and aspiration (JSIA) are procedures frequently performed by both specialists and primary care providers. Seventy-two percent of general internists and 87% of family physicians use these procedures in their practice. 1,2 Instruction in injection techniques should be a part of residency training. When queried however, only 36% of internal medicine residency program directors reported that all of their residents master JSIA compared to 87% for blood gas analysis and 83% for ECG interpretation. 3 Traditionally, JSIA is taught without the benefit of an organized approach. Experience in JSIA depends on whether a patient is seen who requires JSIA, and whether the staff physician feels comfortable supervising a learner. It is possible under such a system for a learner to complete his/her training without adequate instruction or experience in JSIA. Elnicki et al. have noted that, unfortunately, only a minority of office-level procedures are taught by faculty in medical training settings. 4 How then should teaching JSIA be approached? Instruction in core procedural skills is an essential component of almost all residencies. Since the didactic lecture format is not well suited for the acquisition of complex manual operations, these skills have been primarily taught through demonstration, followed by supervised performance on patients. However, concerns regarding the safety of patients and the lack of readily available faculty and patient populations limit the utility of such an approach. For this reason, there is a need for an instructional alternative that all...

Studies suggest that high dose NSAID use may be associated with a reversible impairment of cognition in the elderly. Prolonged NSAID use, on the other hand, may prevent the decline in cognition associated with aging. However, it has yet to be to be definitively determined whether this protection arises from an anti-inflammatory effect that modifies pathways involved in Alzheimer's dementia, or is mediated by a platelet effect that decreases the risk of cerebrovascular disease. Further large-scale, randomised, controlled trials using NSAIDs are needed before patients can be advised that the known risks of NSAIDs are outweighed by their potential long term benefits on cognition. While clinicians await the results of such studies, they should continue to be alert to the possibility of acute CNS adverse effects in their elderly patients who are receiving NSAIDs and to prescribe the minimum dose that is necessary to control pain and inflammation.