RESUMO
OBJECTIVES: Estimates of prehospital transport times are an important part of emergency care system research and planning; however, the accuracy of these estimates is unknown. The authors examined the accuracy of three estimation methods against observed transport times in a large cohort of prehospital patient transports. METHODS: This was a validation study using prehospital records in King County, Washington, and southwestern Pennsylvania from 2002 to 2006 and 2005 to 2011, respectively. Transport time estimates were generated using three methods: linear arc distance, Google Maps, and ArcGIS Network Analyst. Estimation error, defined as the absolute difference between observed and estimated transport time, was assessed, as well as the proportion of estimated times that were within specified error thresholds. Based on the primary results, a regression estimate was used that incorporated population density, time of day, and season to assess improved accuracy. Finally, hospital catchment areas were compared using each method with a fixed drive time. RESULTS: The authors analyzed 29,935 prehospital transports to 44 hospitals. The mean (± standard deviation [±SD]) absolute error was 4.8 (±7.3) minutes using linear arc, 3.5 (±5.4) minutes using Google Maps, and 4.4 (±5.7) minutes using ArcGIS. All pairwise comparisons were statistically significant (p < 0.01). Estimation accuracy was lower for each method among transports more than 20 minutes (mean [±SD] absolute error was 12.7 [±11.7] minutes for linear arc, 9.8 [±10.5] minutes for Google Maps, and 11.6 [±10.9] minutes for ArcGIS). Estimates were within 5 minutes of observed transport time for 79% of linear arc estimates, 86.6% of Google Maps estimates, and 81.3% of ArcGIS estimates. The regression-based approach did not substantially improve estimation. There were large differences in hospital catchment areas estimated by each method. CONCLUSIONS: Route-based transport time estimates demonstrate moderate accuracy. These methods can be valuable for informing a host of decisions related to the system organization and patient access to emergency medical care; however, they should be employed with sensitivity to their limitations.
Assuntos
Transporte de Pacientes/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania , Análise de Regressão , Fatores de Tempo , WashingtonRESUMO
Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.
Assuntos
Humanos , Análise por Conglomerados , Citocinas/genética , Citocinas/metabolismo , Contagem de Colônia Microbiana , Glicoproteínas de Membrana/imunologia , Hanseníase Tuberculoide/classificação , Hanseníase Tuberculoide/fisiopatologia , Hanseníase Tuberculoide/genética , Hanseníase Tuberculoide/imunologia , Hanseníase Virchowiana/classificação , Hanseníase Virchowiana/fisiopatologia , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/imunologia , Imunidade Celular , Imunidade Inata , Macrófagos Alveolares/microbiologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/imunologia , Perfilação da Expressão Gênica , Reação em Cadeia da Polimerase , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Receptores de Superfície Celular/imunologia , Regulação da Expressão Gênica , Algoritmos , Análise de Componente Principal , Análise de Sequência com Séries de Oligonucleotídeos , Genes de Imunoglobulinas , Regulação para CimaRESUMO
Nerve damage is a clinical hallmark of leprosy and a major source of patient morbidity. We investigated the possibility that human Schwann cells are susceptible to cell death through the activation of Toll-like receptor 2 (TLR2), a pattern recognition receptor of the innate immune system. TLR2 was detected on the surface of human Schwann cell line ST88-14 and on cultured primary human Schwann cells. Activation of the human Schwann cell line and primary human Schwann cell cultures with a TLR2 agonist, a synthetic lipopeptide comprising the N-terminal portion of the putative Mycobacterium leprae 19-kDa lipoprotein, triggered an increase in the number of apoptotic cells. The lipopeptide-induced apoptosis of Schwann cells could be blocked by an anti-TLR2 monoclonal antibody. Schwann cells in skin lesions from leprosy patients were found to express TLR2. It was possible to identify in the lesions Schwann cells that had undergone apoptosis in vivo. The ability of M. leprae ligands to induce the apoptosis of Schwann cells through TLR2 provides a mechanism by which activation of the innate immune response contributes to nerve injury in leprosy.
Assuntos
Humanos , Apoptose , Células Cultivadas , Células de Schwann/patologia , Dano ao DNA , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/fisiologia , Hanseníase/imunologia , Hanseníase/patologia , Imunidade Inata , Lipoproteínas/fisiologia , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/fisiologiaRESUMO
The expression and activation of Toll-like receptors (TLRs) was investigated in leprosy, a spectral disease in which clinical manifestations correlate with the type of immune response mounted toward Mycobacterium leprae. TLR2-TLR1 heterodimers mediated cell activation by killed M. leprae, indicating the presence of triacylated lipoproteins. A genome-wide scan of M. leprae detected 31 putative lipoproteins. Synthetic lipopeptides representing the 19-kD and 33-kD lipoproteins activated both monocytes and dendritic cells. Activation was enhanced by type-1 cytokines and inhibited by type-2 cytokines. In addition, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced TLR1 expression in monocytes and dendritic cells, respectively, whereas IL-4 downregulated TLR2 expression. TLR2 and TLR1 were more strongly expressed in lesions from the localized tuberculoid form (T-lep) as compared with the disseminated lepromatous form (L-lep) of the disease. These data provide evidence that regulated expression and activation of TLRs at the site of disease contribute to the host defense against microbial pathogens.
Assuntos
Humanos , Animais , Camundongos , Citocinas/fisiologia , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/fisiologia , Hanseníase/imunologia , Imunidade Inata , Lipoproteínas/análise , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/fisiologiaRESUMO
Changes in peripheral blood platelet counts associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing, in each patient, the value obtained on the day thalidomide therapy commenced with the average of the three preceding values. In the 11 patients studied, the mean platelet count rose from 235 to 322 x 10(3)/mm3, p < 0.001. In 3, the platelet count was above the normal limit, qualifying as thrombocytosis, in 7 the rise was appreciable, and in 2 it was negligible. In the 3 patients studied 1-2 weeks after beginning thalidomide, the mean count was 414 x 10(3)/mm3. Counts obtained after 3 or more weeks of thalidomide therapy were within normal limits. This study provided no direct evidence as to the mechanism responsible for the elevated platelet count, but mediation by interleukin-6 (IL-6) was concluded to be an attractive hypothesis, consistent with prior studies of IL-6 in reactive thrombocytosis and of IL-6 in ENL.
Assuntos
Eritema Nodoso/sangue , Hanseníase Virchowiana/sangue , Trombocitose/sangue , Adulto , Eritema Nodoso/induzido quimicamente , Feminino , Humanos , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Masculino , México/etnologia , Pessoa de Meia-Idade , Filipinas/etnologia , Contagem de Plaquetas , Estudos Retrospectivos , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Trombocitose/induzido quimicamente , Estados UnidosRESUMO
Changes in peripheral blood platelet counts associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing, in each patient, the value obtained on the day thalidomide therapy commenced with the average of the three preceding values. In the 11 patients studied, the mean platelet count rose from 235 to 322 x 10(3)/mm3, p < 0.001. In 3, the platelet count was above the normal limit, qualifying as thrombocytosis, in 7 the rise was appreciable, and in 2 it was negligible. In the 3 patients studied 1-2 weeks after beginning thalidomide, the mean count was 414 x 10(3)/mm3. Counts obtained after 3 or more weeks of thalidomide therapy were within normal limits. This study provided no direct evidence as to the mechanism responsible for the elevated platelet count, but mediation by interleukin-6 (IL-6) was concluded to be an attractive hypothesis, consistent with prior studies of IL-6 in reactive thrombocytosis and of IL-6 in ENL.
Assuntos
Eritema Nodoso/diagnóstico , Eritema Nodoso/fisiopatologia , Hanseníase/fisiopatologia , Trombocitose/diagnóstico , Trombocitose/fisiopatologiaRESUMO
Changes in hemoglobin (HGB) and serum albumin (SA) concentration associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing the values obtained on the day thalidomide or prednisone therapy commenced, with each patients' preceding values. In three groups of ENL patients mean HGB values fell with statistical significance: 1) in 38 patients who had been begun on thalidomide in the decade of the 1990s and who had been receiving dapsone for a minimum of 6 months, mean HGB values fell from 13.19 gm/dl to 12.27 gm/dl, or 7.0%, p = 6.0 x 10(-6); 2) in 8 patients who were in the active patient file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean HGB values feel from 13.40 gm/dl to 11.96 gm/dl, or 10.7%, p = 0.0015; and 3) in 8 patients not overlapping with the preceding groups, who were treated with rifampin and minocylcine or clarithromycin mean HGB values fell from 13.25 gm/dl to 12.48 gm/dl, or 5.8%, p = 0.0035. In two groups of ENL patients SA values also fell with statistical significance: 1) in 34 patients who were begun on thalidomide in the decade of the 1990s and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.14 gm/dl to 3.77 gm/dl, or 8.9%, p = 1.2 x 10(-5); and 2) in 10 patients from the active file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.45 gm/dl to 4.06 gm/dl, or 8.8%, p = 0.039. A brisk fall in HGB values was often accompanied by a fall in SA concentration, and vice versa. Recovery from extreme falls in HGB and SA values was complete in 13 weeks. Recovery occurred in the presence of continued dapsone treatment. The falls could be rapid, occurring too soon to be the result of decreased erythropoiesis or hepatic SA synthesis. This study provides no direct evidence as to the mechanism responsible for the fall in these two parameters, but an interleukin-6 mediated hemodilution is an attractive hypothesis. The ENL-associated fall in HGB values was distinct from dapsone-induced hemolysis and the anemia of chronic disease. The ENL-associated anemia is not a good reason to discontinue dapsone therapy.
Assuntos
Humanos , Albuminas/imunologia , Eritema Nodoso/imunologia , Hanseníase/imunologia , Hemoglobinas/imunologiaAssuntos
Anti-Infecciosos/imunologia , Antígenos de Diferenciação de Linfócitos T/biossíntese , Antígenos de Diferenciação de Linfócitos T/imunologia , Hanseníase Tuberculoide/imunologia , Hanseníase Tuberculoide/patologia , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/patologia , /imunologiaAssuntos
Antígenos de Bactérias/imunologia , Ativação Linfocitária/imunologia , Células Cultivadas , Fosforilação , Hanseníase Tuberculoide/imunologia , Hanseníase Virchowiana/imunologia , Imunidade Celular , Interferon gama/biossíntese , /fisiologia , /metabolismo , Linfócitos T/imunologia , Mycobacterium leprae/imunologia , Proteínas de Ligação a DNA/metabolismo , Receptores de Interleucina/biossíntese , Receptores de Interleucina/fisiologia , Tolerância Imunológica , Transativadores/metabolismo , Transdução de Sinais/imunologiaRESUMO
Using 28 specimens of clinically normal skin from lepromatous leprosy subjects as a standard for comparison, the mean thickness of the nucleated epidermis was found to be significantly increased in untreated lesions from 16 borderline tuberculoid, 21 erythema nodosum leprosum (ENL), and 14 reversal reaction patients, but was unchanged in borderline lepromatous and lepromatous patients. Using specimens from 36 untreated lepromatous and borderline lepromatous lesions as the standard for comparison with the lesions of reversal reactions or ENL which these patients eventually developed, there was a significant thickening of the nucleated epidermis in both reactional states. In both comparison groups, there was a greater mean increase and a larger frequency of thickening in the ENL lesions than in those with reversal reactions. In the borderline tuberculoid and reversal reaction lesions the increase can be understood as secondary to the presence of gamma interferon or interleukin-2. The increase in thickness in the ENL lesions is more difficult to explain, but it is not inconsistent with a role for these same two cytokines.
Assuntos
Humanos , Epiderme/anormalidades , Epiderme/lesões , Hanseníase/cirurgia , Hanseníase/fisiopatologiaRESUMO
Daily, long-term treatment with minocycline 100 mg and rifampin 600 mg was initiated in 24 previously untreated borderline lepromatous (BL) and lepromatous (LL) patients for a total of 646 patient-months, averaging 26.9 months per patient. The same regimen was started in 12 BL and LL patients having a bacteriologic relapse for a total of 379 patient-months, averaging 32.5 months per patient, and in 12 patients judged to be at high risk for relapse for a total of 354 patient-months, averaging 29.5 months per patient. Daily, long-term treatment with clarithromycin 500 mg and rifampin 600 mg was initiated in 8 previously untreated BL and LL patients for a total of 174 patient-months, averaging 21.8 months per patient. The results in these 56 patients were compared to those obtained in 34 previously untreated BL and LL patients who were treated concurrently receiving daily, long-term dapsone 100 mg and rifampin 600 mg. No evidence of dangerous drug reactions or bone marrow, kidney or liver toxicity was seen in any of these five patient groups. Drug intolerance in 10 of the 90 patients studied necessitated discontinuing the chosen regimen, 4 from rifampin, 3 from dapsone, 2 from minocycline and 1 of undetermined attribution. The use of either minocycline or clarithromycin in conjunction with rifampin appears to pose no great risk when used long term.
Assuntos
Claritromicina/uso terapêutico , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/tratamento farmacológico , Minociclina/uso terapêutico , Rifampina/uso terapêuticoAssuntos
/biossíntese , /fisiologia , /genética , /metabolismo , Citocinas/biossíntese , Células Th1/imunologia , Células Th1/metabolismo , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/fisiologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Hanseníase Tuberculoide/imunologia , Hanseníase Tuberculoide/metabolismo , Hanseníase Tuberculoide/patologia , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/metabolismo , Hanseníase Virchowiana/patologia , Imunidade Celular , /biossíntese , Ligantes , Monócitos/imunologia , Monócitos/metabolismo , Mycobacterium leprae/imunologiaAssuntos
Antígenos CD1/imunologia , Antígenos CD1/metabolismo , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Antígenos/biossíntese , Glicolipídeos/imunologia , Glicolipídeos/metabolismo , Hanseníase/imunologia , Hanseníase/patologia , Mycobacterium leprae/imunologia , Proteínas/biossíntese , Receptores Imunológicos/biossíntese , Ácidos Micólicos/imunologia , Ácidos Micólicos/metabolismoRESUMO
Reported herein are 13 borderline lepromatous (BL) or subpolar lepromatous (LLs) patients who presented with or developed delayed-type hypersensitivity (DTH) reactions after initiation of antibacterial therapy, but who subsequently developed erythema nodosum leprosum (ENL), the DTH to ENL group. During the same time, three LLs patients had ENL followed by relapse-associated DTH, a significant (p < 0.05) difference in sequence of the two conditions. The DTH to ENL group had statistically significant higher biopsy indexes at the time of diagnosis of the DTH reaction compared with two DTH control groups, 7 multibacillary patients presenting with DTH reactions and 15 BL or LLs who developed DTH reactions after starting treatment but had no ENL. DTH-associated histologic changes were less well developed in the DTH to ENL group than in either of the two control groups. In the DTH to ENL group, 77% required prednisone in addition to thalidomide to achieve a complete remission in contrast to only 10% of 21 ENL clinical controls. In the DTH to ENL group, the classical histologic ENL pattern was present in only 31% of these patients, in contrast to 88% of 33 ENL histologic controls. In 9 of 9 of the DTH to ENL patients studied, after the ENL remitted, Mycobacterium leprae-sonicate-stimulated lymphocyte transformation tests gave stimulation indexes within the range of our tuberculoid (TT) and borderline tuberculoid (BT) patients, in contrast to absent responses in 6 ordinary, longterm-treated patients who had had ENL.