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Article ; Online: Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

Pennini, Silmara Navarro / de Oliveira Guerra, Jorge Augusto / Rebello, Paula Frassinetti Bessa / Abtibol-Bernardino, Marília Rosa / de Castro, Luigui Lima / da Silva Balieiro, Antonio Alcirley / de Oliveira Ferreira, Cynthia / Noronha, Ariani Batista / Dos Santos da Silva, Camila Gurgel / Leturiondo, André Luiz / Vital de Jesus, Denison / de Araújo Santos, Felipe Jules / Chrusciak-Talhari, Anette / Guerra, Maria Das Graças Vale Barbosa / Talhari, Sinésio

Tropical medicine & international health : TM & IH

2023 Volume 28, Issue 12, Page(s) 871–880

Abstract: Objective: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous ... ...

Abstract	Objective: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. Methods: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). Results: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. Conclusion: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.
MeSH term(s)	Humans ; Antiprotozoal Agents ; Leishmania guyanensis ; Leishmaniasis, Cutaneous/drug therapy ; Leishmaniasis, Cutaneous/pathology ; Pentamidine/therapeutic use ; Tamoxifen/therapeutic use
Chemical Substances	Antiprotozoal Agents ; Pentamidine (673LC5J4LQ) ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2023-11-08
Publishing country	England
Document type	Clinical Trial, Phase II ; Equivalence Trial ; Journal Article ; Randomized Controlled Trial
ZDB-ID	1314080-2
ISSN	1365-3156 ; 1360-2276
ISSN (online)	1365-3156
ISSN	1360-2276
DOI	10.1111/tmi.13943
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Article ; Online: Leishmaniasis and AIDS coinfection.

Hozannah, Adriana / Santos, Monica / Chrusciak-Talhari, Anette / Talhari, Carolina

Anais brasileiros de dermatologia

2014 Volume 88, Issue 6, Page(s) 992–993

Abstract: Cutaneous leishmaniasis and HIV coinfection has been reported in Brazil since the initial description of AIDS in the country. We report an HIV-positive patient under antiretroviral treatment who presented with cutaneous leishmaniasis which was ... ...

Abstract	Cutaneous leishmaniasis and HIV coinfection has been reported in Brazil since the initial description of AIDS in the country. We report an HIV-positive patient under antiretroviral treatment who presented with cutaneous leishmaniasis which was successfully treated with meglumine antimoniate.
MeSH term(s)	Acquired Immunodeficiency Syndrome/pathology ; Adult ; Coinfection/pathology ; Humans ; Leishmaniasis, Cutaneous/drug therapy ; Leishmaniasis, Cutaneous/pathology ; Male ; Treatment Outcome
Language	English
Publishing date	2014-01-29
Publishing country	Spain
Document type	Case Reports ; Journal Article
ZDB-ID	433655-0
ISSN	1806-4841 ; 0365-0596
ISSN (online)	1806-4841
ISSN	0365-0596
DOI	10.1590/abd1806-4841.20132191
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Article ; Online: A Single Haplotype of IFNG Correlating With Low Circulating Levels of Interferon-γ Is Associated With Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis.

da Silva, George A V / Mesquita, Tirza G / Souza, Victor C / Junior, José do Espírito Santo / Gomes de Souza, Mara Lúcia / Talhari, Anette Chrusciak / Talhari, Sinésio / Naveca, Felipe G / Ramasawmy, Rajendranath

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2019 Volume 71, Issue 2, Page(s) 274–281

Abstract: Background: Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop ... ...

Abstract	Background: Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop the disease. This suggest that host genetics may play a role in this response. We investigated whether single nucleotide polymorphisms (SNPs) in IFNG may be associated with elevated or decrease risk in the development of cutaneous leishmaniasis (CL). Methods: We assessed 9 SNP and cytosine-adenine (CA) repeats in IFNG by nucleotide sequencing in 647 patients with CL caused by Leishmania guyanensis and 629 controls. Circulating plasma IFN-γ levels were also assayed in 400 patients with CL and 400 controls. Results: The rs2069705TT genotype is associated with elevated risk of developing CL compared with the rs2069705CC genotype (OR, 1.7; 95% CI, 1.3-2.4; P = .0008). There is a 70% chance that this genotype raises the risk of developing CL. In a dominant model, carriers of the rs2069705T allele compared with the rs2069705CC genotype showed a 50% (range, 20-100%) increased risk of developing CL (OR, 1.5; 95% CI, 1.2-2.0; P = .0004). Haplotype analysis showed 1 haplotype (H1) associated with low levels of IFN-γ presented an increased risk of 60% of developing CL (OR, 1.6; 95% CI, 1.3-1.9; P = 5 × 10-5) compared with non-H1. Conclusions: IFNG variant rs2069705 seems to be a genetic modifier of clinical outcome of Leishmania infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL.
MeSH term(s)	Animals ; Haplotypes ; Humans ; Interferon-gamma/genetics ; Leishmania guyanensis/genetics ; Leishmaniasis, Cutaneous/genetics ; Mice ; Polymorphism, Single Nucleotide
Chemical Substances	IFNG protein, human ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2019-11-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciz810
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region.

Gadelha, Ellen Priscilla Nunes / Ramasawmy, Rajendranath / da Costa Oliveira, Bruna / Morais Rocha, Nágila / de Oliveira Guerra, Jorge Augusto / Allan Villa Rouco da Silva, George / Gabrielle Ramos de Mesquita, Tirza / Chrusciak Talhari Cortez, Carolina / Chrusciak Talhari, Anette

PLoS neglected tropical diseases

2018 Volume 12, Issue 10, Page(s) e0006850

Abstract: Background: American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in ... ...

Abstract	Background: American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, pentamidine isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. Objectives: The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. Materials and methods: This study was conducted as a controlled, randomized, open-label clinical trial for a total number of 159 patients with CL. Individuals aged 16-64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. Results: From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p<0.0001) and two-dose groups (p = 0.03). No serious adverse events occurred. Conclusion: The present study shows that PI is a safe drug and its efficacy varied with the number of doses. The administration of PI in patients with ACL, predominantly caused by L. guyanensis, was mostly efficient in three or two doses of 7 mg/kg. Trial registration: ClinicalTrials.gov NCT02919605.
MeSH term(s)	Adolescent ; Adult ; Antiprotozoal Agents/administration & dosage ; Antiprotozoal Agents/adverse effects ; Brazil ; Dose-Response Relationship, Drug ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Drug-Related Side Effects and Adverse Reactions/pathology ; Female ; Humans ; Injections, Intramuscular ; Leishmaniasis, Cutaneous/drug therapy ; Male ; Middle Aged ; Pentamidine/administration & dosage ; Pentamidine/adverse effects ; Treatment Outcome ; Young Adult
Chemical Substances	Antiprotozoal Agents ; Pentamidine (673LC5J4LQ)
Language	English
Publishing date	2018-10-31
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0006850
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Article ; Online: Lobomycosis.

Talhari, Carolina / Rabelo, Renata / Nogueira, Lisiane / Santos, Mônica / Chrusciak-Talhari, Anette / Talhari, Sinésio

Anais brasileiros de dermatologia

2010 Volume 85, Issue 2, Page(s) 239–240

Abstract: A case of lobomycosis in a patient from the Brazilian Amazon region is presented. Lobomycosis is a subcutaneous mycosis caused by the yeast Lacazia loboi. It often affects adult males and has been reported in dolphins. Therapeutical options for localized ...

Abstract	A case of lobomycosis in a patient from the Brazilian Amazon region is presented. Lobomycosis is a subcutaneous mycosis caused by the yeast Lacazia loboi. It often affects adult males and has been reported in dolphins. Therapeutical options for localized lesions, such as the ones shown by the patient in this report, are eletrocoagulation, surgical exeresis, and cryotherapy. Disseminated lesions may be treated with Itraconazole or combination therapy with Clofazimine. There is still no curative therapy for disseminated lesions of lobomycosis.
MeSH term(s)	Ascomycota ; Brazil ; Dermatomycoses/pathology ; Humans ; Male
Language	English
Publishing date	2010-04-05
Publishing country	Spain
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	433655-0
ISSN	1806-4841 ; 0365-0596
ISSN (online)	1806-4841
ISSN	0365-0596
DOI	10.1590/s0365-05962010000200019
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Zs.A 359: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Efficacy and safety of a single dose pentamidine (7mg/kg) for patients with cutaneous leishmaniasis caused by L. guyanensis: a pilot study.

Gadelha, Ellen Priscilla Nunes / Talhari, Sinésio / Guerra, Jorge Augusto de Oliveira / Neves, Leandro Ourives / Talhari, Carolina / Gontijo, Bernardo / Silva Junior, Roberto Moreira da / Talhari, Anette Chrusciak

Anais brasileiros de dermatologia

2016 Volume 90, Issue 6, Page(s) 807–813

Abstract: Background: There have been few studies on pentamidine in the Americas; and there is no consensus regarding the dose that should be applied.: Objectives: To evaluate the use of pentamidine in a single dose to treat cutaneous leishmaniasis.: Methods! ...

Abstract	Background: There have been few studies on pentamidine in the Americas; and there is no consensus regarding the dose that should be applied. Objectives: To evaluate the use of pentamidine in a single dose to treat cutaneous leishmaniasis. Methods: Clinical trial of phase II pilot study with 20 patients. Pentamidine was used at a dose of 7 mg/kg, in a single dose. Safety and adverse effects were also assessed. Patients were reviewed one, two, and six months after the end of treatments. Results: there was no difference between the treatment groups in relation to gender, age, number or location of the lesions. Pentamidine, applied in a single dose, obtained an effectiveness of 55%. Mild adverse events were reported by 17 (85%) patients, mainly transient pain at the site of applications (85%), while nausea (5%), malaise (5%) and dizziness (5%) were reported in one patient. No patient had sterile abscess after taking medication at a single dose of 7mg/kg. Conclusions: Clinical studies with larger samples of patients would enable a better clinical response of pent amidine at a single dose of 7mg, allowing the application of more powerful statistical tests, thus providing more evidences of the decrease in the effectiveness of that medication. Hence, it is important to have larger studies with new diagrams and/or new medications.
MeSH term(s)	Adolescent ; Adult ; Antiprotozoal Agents/administration & dosage ; Antiprotozoal Agents/adverse effects ; Benzamidines/administration & dosage ; Benzamidines/adverse effects ; Blood Glucose/analysis ; Dose-Response Relationship, Drug ; Female ; Humans ; Leishmania guyanensis ; Leishmaniasis, Cutaneous/drug therapy ; Male ; Middle Aged ; Phenyl Ethers/administration & dosage ; Phenyl Ethers/adverse effects ; Pilot Projects ; Reproducibility of Results ; Time Factors ; Treatment Outcome ; Young Adult
Chemical Substances	Antiprotozoal Agents ; Benzamidines ; Blood Glucose ; Phenyl Ethers ; phenamidine isethionate (4X07Z2Z1W5)
Language	English
Publishing date	2016-01-06
Publishing country	Spain
Document type	Clinical Trial, Phase II ; Journal Article
ZDB-ID	433655-0
ISSN	1806-4841 ; 0365-0596
ISSN (online)	1806-4841
ISSN	0365-0596
DOI	10.1590/abd1806-4841.20153956
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Zs.A 359: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Exfoliative cytology as a rapid diagnostic tool for lobomycosis.

Talhari, Carolina / Chrusciak-Talhari, Anette / de Souza, João Vicente Braga / Araújo, José Ribamar / Talhari, Sinésio

Mycoses

2009 Volume 52, Issue 2, Page(s) 187–189

Abstract: Lobomycosis is a common subcutaneous mycosis in South America. It is caused by Lacazia loboi. We report two cases of lobomycosis which were diagnosed by exfoliative cytology without any special staining. We highlight this diagnostic tool as a simple, low- ...

Abstract	Lobomycosis is a common subcutaneous mycosis in South America. It is caused by Lacazia loboi. We report two cases of lobomycosis which were diagnosed by exfoliative cytology without any special staining. We highlight this diagnostic tool as a simple, low-cost, painless, non-invasive and fast method for the diagnosis of lobomycosis.
MeSH term(s)	Adult ; Brazil ; Cytodiagnosis ; Dermatomycoses/diagnosis ; Dermatomycoses/microbiology ; Dermatomycoses/pathology ; Humans ; Leg Dermatoses/diagnosis ; Leg Dermatoses/microbiology ; Leg Dermatoses/pathology ; Male ; Middle Aged ; Onygenales/classification ; Onygenales/isolation & purification ; Skin/microbiology ; Time Factors
Language	English
Publishing date	2009-03
Publishing country	Germany
Document type	Case Reports ; Letter
ZDB-ID	392487-7
ISSN	1439-0507 ; 0933-7407
ISSN (online)	1439-0507
ISSN	0933-7407
DOI	10.1111/j.1439-0507.2008.01551.x
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Article: Exfoliative cytology as a rapid diagnostic tool for lobomycosis

Talhari, Carolina / Chrusciak-Talhari, Anette / de Souza, João Vicente Braga / Araújo, José Ribamar / Talhari, Sinésio

Mycoses diagnosis, therapy and prophylaxis of fungal diseases. 2009 Mar., v. 52, no. 2

2009

Abstract	Lobomycosis is a common subcutaneous mycosis in South America. It is caused by Lacazia loboi. We report two cases of lobomycosis which were diagnosed by exfoliative cytology without any special staining. We highlight this diagnostic tool as a simple, low-cost, painless, non-invasive and fast method for the diagnosis of lobomycosis.
Language	English
Dates of publication	2009-03
Size	p. 187-189.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	392487-7
ISSN	1439-0507 ; 0933-7407
ISSN (online)	1439-0507
ISSN	0933-7407
DOI	10.1111/j.1439-0507.2008.01551.x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil.

de Araujo, Felipe Jules / da Silva, Luan Diego Oliveira / Mesquita, Tirza Gabrielle / Pinheiro, Suzana Kanawati / Vital, Wonei de Seixas / Chrusciak-Talhari, Anette / Guerra, Jorge Augusto de Oliveira / Talhari, Sinésio / Ramasawmy, Rajendranath

PLoS neglected tropical diseases

2015 Volume 9, Issue 6, Page(s) e0003875

Abstract: Introduction: The clinical outcome to Leishmania-infection is determined by the individual adaptive immune T helper cell responses and their interactions with parasitized host cells. An early development of a proinflammatory immune response (Th1 ... ...

Abstract	Introduction: The clinical outcome to Leishmania-infection is determined by the individual adaptive immune T helper cell responses and their interactions with parasitized host cells. An early development of a proinflammatory immune response (Th1 response) is necessary for Leishmania-infection resolution. The Toll-interacting protein (TOLLIP) regulates human Toll-like receptors signaling pathways by down regulating the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inducing the ant-inflammatory cytokine interleukin-10 (IL-10). Polymorphisms in the TOLLIP gene are associated with infectious diseases. Material and methods: The polymorphisms rs5743899 and rs3750920 in the TOLLIP gene were genotyped by polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis in 631 patients with cutaneous leishmaniasis (CL) caused by L. guyanensis and 530 individuals with no history of leishmaniasis. Results: The G and T alleles of the rs5743899 and rs3750920 were more common in patients with CL than in healthy individuals (P = 2.6 x10(-8) odds ratio [OR], 1.7 [ 95% confidence interval (CI) 1.4-2.0] and P = 1.9 x10(-8) OR, 1.6 [95% CI 1.4-1.9] respectively). The r2 and D' linkage disequilibrium between the two polymorphisms are 0.05 and 0.473 with a confidence bounds of 0.37 to 0.57 respectively. Conclusion: The two polymorphisms are independently associated with an increased risk of developing CL.
MeSH term(s)	Adolescent ; Adult ; Brazil/epidemiology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Leishmania guyanensis/drug effects ; Leishmania guyanensis/genetics ; Leishmania guyanensis/isolation & purification ; Leishmaniasis, Cutaneous/epidemiology ; Leishmaniasis, Cutaneous/parasitology ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Signal Transduction ; Young Adult
Chemical Substances	Intracellular Signaling Peptides and Proteins ; TOLLIP protein, human
Language	English
Publishing date	2015-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0003875
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Article: Immune reconstitution inflammatory syndrome or upgrading type 1 reaction? Report of two AIDS patients presenting a shifting from borderline lepromatous leprosy to borderline tuberculoid leprosy.

Talhari, Carolina / Ferreira, Luiz Carlos de Lima / Araújo, José Ribamar / Talhari, Anette Chrusciak / Talhari, Sinésio

Leprosy review

2008 Volume 79, Issue 4, Page(s) 429–435

MeSH term(s)	AIDS-Related Opportunistic Infections/chemically induced ; Adult ; Antiretroviral Therapy, Highly Active/adverse effects ; Diagnosis, Differential ; HIV-1 ; Humans ; Immune Reconstitution Inflammatory Syndrome/diagnosis ; Leprostatic Agents/therapeutic use ; Leprosy, Borderline/chemically induced ; Leprosy, Borderline/diagnosis ; Leprosy, Tuberculoid/chemically induced ; Leprosy, Tuberculoid/diagnosis ; Male
Chemical Substances	Leprostatic Agents
Language	English
Publishing date	2008-12
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	415137-9
ISSN	0305-7518 ; 0024-1032
ISSN	0305-7518 ; 0024-1032
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