RESUMO
Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação , Feminino , Genética Populacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México , Taxa de MutaçãoRESUMO
We evaluated the in vitro antifungal activity of essential oils obtained from the aromatic plants Laurus nobilis, Thymus vulgaris, Mentha piperita, Cymbopogon citratus and Lippia junelliana against the following Candida species isolated from clinical samples: C. krusei (n = 10); C. albicans (n = 50); C. glabrata (n = 70) and C. parapsilosis (n = 80). The minimal inhibitory concentration (MIC) was determined according to EDef 7.3.1 document from EUCAST. Amphotericin B and fluconazole were the antifungal drugs used as inhibition control. The concentration ranges evaluated were 0.4-800 and 0.03-128 mg l-1 for essential oils and antifungal drugs, respectively. MIC50 and MIC90, mode and ranges were calculated. All the Candida spp. evaluated were susceptible to amphotericin B (MIC ≤ 1 mg l-1), while fluconazole was inactive for C. krusei (MIC ≥ 32 mg l-1) and intermediate for C. glabrata (MIC≤ 32 mg l-1). The essential oils showed antifungal activity on Candida spp. tested with MIC90 values ranging from 0.8 to 800 mg l-1. In general, the most active essential oils were L. nobilis and T. vulgaris (MIC90 0.8-0.16 mg l-1), and the least active was C. officinalis (MIC90 400-800 mg l-1). C. krusei was inhibited by 5/6 of the essential oils evaluated, and C. glabrata was the least susceptible one. This in vitro study confirms the antifungal activity of these six essential oils assayed which could be a potential source of new molecules useful to control fungal infections caused by some Candida species, including those resistant to antifungal drugs.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Óleos Voláteis/farmacologia , Candida/isolamento & purificação , Candidíase/microbiologia , Cymbopogon/química , Humanos , Laurus/química , Lippia/química , Mentha piperita/química , Testes de Sensibilidade Microbiana , Óleos Voláteis/isolamento & purificação , Thymus (Planta)/químicaRESUMO
Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 µg/ml for the CLSI method and 0.25 µg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 µg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 µg/ml. The tentative ECOFFinder ECV with SYO was 0.06 µg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 µg/ml (CLSI, EUCAST, Etest) or 0.06 µg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants.
Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Mutação/genética , Triazóis/farmacologia , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana , Voriconazol/farmacologiaRESUMO
Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 µg/ml for C. dubliniensis and 2, 8, 2, and 16 µg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.
Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Aspergillus/crescimento & desenvolvimento , Aspergillus/isolamento & purificação , Candida/crescimento & desenvolvimento , Candida/isolamento & purificação , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Europa (Continente) , América Latina , África do Sul , Estados UnidosRESUMO
Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.
Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Equinocandinas/farmacologia , Flucitosina/farmacologia , Lipopeptídeos/farmacologia , Naftalenos/farmacologia , Sporothrix/efeitos dos fármacos , Esporotricose/tratamento farmacológico , Triazóis/farmacologia , Caspofungina , Humanos , Testes de Sensibilidade Microbiana , Sporothrix/classificação , Sporothrix/isolamento & purificação , TerbinafinaRESUMO
The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi, 82 F. proliferatum, 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for amphotericin B, 4 µg/ml (F. verticillioides) and 8 µg/ml (F. oxysporum SC and F. solani SC); for posaconazole, 2 µg/ml (F. verticillioides), 8 µg/ml (F. oxysporum SC), and 32 µg/ml (F. solani SC); for voriconazole, 4 µg/ml (F. verticillioides), 16 µg/ml (F. oxysporum SC), and 32 µg/ml (F. solani SC); and for itraconazole, 32 µg/ml (F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.
Assuntos
Antifúngicos/farmacologia , Fusarium/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , América , Farmacorresistência Fúngica Múltipla , Europa (Continente) , Fusarium/genética , Fusarium/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase/métodosRESUMO
Properdin (P) stabilizes the alternative pathway (AP) convertases, being the only known positive regulator of the complement system. In addition, P is a pattern recognition molecule able to initiate directly the AP on non-self surfaces. Although P deficiencies have long been known to be associated with Neisseria infections and P is often found deposited at sites of AP activation and tissue injury, the potential role of P in the pathogenesis of complement dysregulation-associated disorders has not been studied extensively. Serum P levels were measured in 49 patients with histological and clinical evidence of C3 glomerulopathy (C3G). Patients were divided into two groups according to the presence or absence of C3 nephritic factor (C3NeF), an autoantibody that stabilizes the AP C3 convertase. The presence of this autoantibody results in a significant reduction in circulating C3 (P < 0·001) and C5 levels (P < 0·05), but does not alter factor B, P and sC5b-9 levels. Interestingly, in our cohort, serum P levels were low in 17 of the 32 C3NeF-negative patients. This group exhibited significant reduction of C3 (P < 0·001) and C5 (P < 0·001) and increase of sC5b-9 (P < 0·001) plasma levels compared to the control group. Also, P consumption was correlated significantly with C3 (r = 0·798, P = 0·0001), C5 (r = 0·806, P < 0·0001), sC5b-9 (r = -0·683, P = 0·043) and a higher degree of proteinuria (r = -0·862, P = 0·013). These results illustrate further the heterogeneity among C3G patients and suggest that P serum levels could be a reliable clinical biomarker to identify patients with underlying surface AP C5 convertase dysregulation.
Assuntos
Convertases de Complemento C3-C5/imunologia , Via Alternativa do Complemento , Glomerulonefrite/imunologia , Properdina/imunologia , Proteinúria/imunologia , Adolescente , Adulto , Biomarcadores/sangue , Criança , Complemento C3/genética , Complemento C3/imunologia , Fator Nefrítico do Complemento 3/genética , Fator Nefrítico do Complemento 3/imunologia , Convertases de Complemento C3-C5/genética , Complemento C5/genética , Complemento C5/imunologia , Fator B do Complemento/genética , Fator B do Complemento/imunologia , Inativadores do Complemento/sangue , Complexo de Ataque à Membrana do Sistema Complemento/genética , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Feminino , Regulação da Expressão Gênica , Glomerulonefrite/sangue , Glomerulonefrite/genética , Glomerulonefrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Properdina/genética , Proteinúria/sangue , Proteinúria/genética , Proteinúria/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Transdução de SinaisRESUMO
Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 µg/ml, those for M. circinelloides were 1 and 2 µg/ml, those for R. arrhizus were 2 and 4 µg/ml, and those for R. microsporus were 2 and 2 µg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 µg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica Múltipla/efeitos dos fármacos , Itraconazol/uso terapêutico , Mucorales/efeitos dos fármacos , Mucormicose/tratamento farmacológico , Triazóis/uso terapêutico , Humanos , Testes de Sensibilidade MicrobianaAssuntos
Edema/parasitologia , Leishmaniose Mucocutânea/diagnóstico , Doenças Labiais/parasitologia , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Doença Crônica , Edema/patologia , Humanos , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Mucocutânea/patologia , Doenças Labiais/tratamento farmacológico , Doenças Labiais/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Alkaptonuria (AKU) occupies a unique place in the history of human genetics because it was the first disease to be interpreted as a mendelian recessive trait by Garrod in 1902. Alkaptonuria is a rare metabolic disorder resulting from loss of homogentisate 1,2 dioxygenase (HGO) activity. Affected individuals accumulate large quantities of homogentisic acid, an intermediary product of the catabolism of tyrosine and phenylalanine, which darkens the urine and deposits in connective tissues causing a debilitating arthritis. Here we report the cloning of the human HGO gene and establish that it is the AKU gene. We show that HGO maps to the same location described for AKU, illustrate that HGO harbours missense mutations that cosegregate with the disease, and provide biochemical evidence that at least one of these missense mutations is a loss-of-function mutation.
Assuntos
Alcaptonúria/genética , Dioxigenases , Oxigenases/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 3 , Clonagem Molecular , DNA Complementar , Feminino , Homogentisato 1,2-Dioxigenase , Humanos , Masculino , Dados de Sequência Molecular , Oxigenases/metabolismo , Mutação Puntual , Prolina/genética , Serina/genética , Distribuição TecidualRESUMO
BACKGROUND: Leishmaniasis, an endemic infection in Spain, is caused by protozoan parasites of the Leishmania genus. Between 2010 and 2012, there was an outbreak of cutaneous and visceral leishmaniasis in Fuenlabrada, Madrid. OBJECTIVES: To describe the cases of cutaneous leishmaniasis diagnosed over a 17-month period at the dermatology department of Hospital de Fuenlabrada. MATERIAL AND METHODS: We analyzed the epidemiological, clinical, histological, and microbiological features of each case and also evaluated the treatments administered and outcomes. RESULTS: We studied 149 cases. The incidence of cutaneous leishmaniasis showed a peak in the age range between 46 and 60 years and was similar in men and women. At the time of consultation, the lesions had been present for between 2 and 6 months in the majority of patients. The most common clinical presentation was with erythematous plaques and papules without crusts (52% of cases). Lesions were most often located in sun-exposed areas and were multiple in 57% of patients. In 67% of cases, the histological study showed non-necrotizing granulomatous dermatitis with no evidence of parasites using conventional staining methods. Diagnosis was confirmed by polymerase chain reaction (PCR) in 98% of patients. In the remaining cases, the histological study revealed Leishman-Donovan bodies in the skin. Intralesional pentavalent antimonials were the most commonly used drugs (76% of cases) and produced satisfactory results. CONCLUSIONS: We have presented a large series of cases of cutaneous leishmaniasis diagnosed in the context of an outbreak. Multiple papules were the most common clinical presentation, with histology that showed non-necrotizing granulomatous dermatitis with no evidence of parasites. PCR of skin samples was the test that most frequently provided the diagnosis.
Assuntos
Surtos de Doenças , Leishmaniose Cutânea/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Saúde da População Urbana , Adulto JovemRESUMO
OBJECTIVE: To analyze data corresponding to patients who underwent dermatological surgery in an operating room. MATERIAL AND METHODS: This was a descriptive, retrospective study of operating room activities in the dermatology department of Hospital Universitario de Fuenlabrada in Madrid between January 2005 and December 2010. We analyzed the relative frequency of a range of patient and procedure-related variables, as well as substitution and cancellation rates, the proportional risk of complications, and operating room efficiency. RESULTS: In the period analyzed, 11,516 patients underwent surgery: 9351 required minor surgery, 1998 major ambulatory surgery, and 167 surgery requiring hospitalization. Simple excision was the most common procedure (64.7%), and in the majority of cases (85%), the condition was benign. The mean number of patients treated per day was 9.7, and mean operating room efficiency was 71.9%. CONCLUSIONS: Accurate record-keeping is essential for analyzing operating room activities and comparing results with those from other centers. The analysis of patterns over time shows the effect of changes made on different indicators. In our case, a decrease in operating room efficiency was seen with an increase in the number of patients per day undergoing surgery.
Assuntos
Procedimentos Cirúrgicos Dermatológicos/estatística & dados numéricos , Hospitais Universitários , Salas Cirúrgicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Adulto JovemRESUMO
OBJECTIVES: To analyze the characteristics of the dermatologic surgery lists and to compare different indicators of surgical productivity. MATERIALS AND METHODS: This was a retrospective, descriptive study of the routine surgical activity undertaken in the Dermatology Department of Fuenlabrada University Hospital, Madrid, Spain, between January 2005 and December 2010. Data about the procedures performed and about the surgical lists were analyzed and an analysis was made of operating room occupancy. Surgical productivity was analyzed using standard operating times (SOTs) and surgical scheduling adequacy values (SA1 and SA2). Variables were recorded as relative frequencies. Covariance and the Pearson linear correlation index were used for comparisons. RESULTS: The study period included a total of 11,481 surgical sessions, of which 71% were minor surgery and the remainder were major outpatient surgery. A mean of 9.7 operations were performed in each session and the overall operating room occupancy was 71.9%. Four SOT descriptors (minor surgery, multiple minor skin lesions, nail surgery, and malignant tumors with primary closure) were sufficient to classify 86.7% of the operations performed. The operating room down-time was 0.15 SOT (9minutes) in 91.3% of operations. The mean SA1 index was 1.20. Overall surgical productivity measured using the SA2 index was 96.46%. The Pearson correlation showed a statistically significant relationship between the increase in the number of patients per surgical session, the reduction in operating room occupancy, and the increase in SA2 operating room productivity. CONCLUSIONS: The application of SOT descriptors enables us to quantify the complexity of the operations included in the surgical waiting list and to obtain indicators for the evaluation of surgical activity, improving efficiency in surgical time management.
Assuntos
Dermatologia , Departamentos Hospitalares/estatística & dados numéricos , Salas Cirúrgicas/estatística & dados numéricos , Duração da Cirurgia , Procedimentos Cirúrgicos Operatórios/normas , Hospitais Universitários , Humanos , Salas Cirúrgicas/organização & administração , Estudos Retrospectivos , Espanha , Fatores de TempoRESUMO
Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 µg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 µg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 µg/ml (VGII); itraconazole, 0.25 µg/ml (VNI), 0.5 µg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 µg/ml (VGIV); posaconazole, 0.25 µg/ml (C. neoformans nontyped and VNI) and 0.5 µg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 µg/ml (VNIV), 0.25 µg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 µg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.
Assuntos
Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/epidemiologia , Cryptococcus gattii/efeitos dos fármacos , Fluconazol/uso terapêutico , Itraconazol/uso terapêutico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Antifúngicos/farmacologia , Austrália/epidemiologia , Criptococose/microbiologia , Cryptococcus gattii/crescimento & desenvolvimento , Cryptococcus gattii/isolamento & purificação , Farmacorresistência Fúngica/efeitos dos fármacos , Europa (Continente)/epidemiologia , Fluconazol/farmacologia , Humanos , Índia/epidemiologia , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , América do Norte/epidemiologia , Pirimidinas/farmacologia , África do Sul/epidemiologia , América do Sul/epidemiologia , Triazóis/farmacologia , VoriconazolRESUMO
BACKGROUND: The pentavalent antimonials are considered the first-choice drugs for treatment of leishmaniasis. Intralesional therapy is used to minimize the systemic effects of the drug. METHODS: Seventy patients were treated with weekly intralesional infiltrations of Glucantime(®) (meglumine antimoniate) for cutaneous leishmaniasis. Nine of them had infiltrated itchy erythematous and vesiculous plaques at the injection sites. Cutaneous tests were undertaken in eight patients. RESULTS: Prick tests were negative and seven of the eight patients showed positive intradermal tests with Glucantime(®) dilutions reading at D2 and D4. Only one patient had positive patch test to Glucantime a.i. Local reactions at the site of injection have been briefly mentioned in some reported series of leishmaniasis treated with intralesional or intramuscular meglumine antimoniate but the mechanism has never been explained before. CONCLUSIONS: We report the first series of patients with local reactions at the injection sites of meglumine antimoniate in whom type IV hypersensitivity could be involved.
Assuntos
Hipersensibilidade a Drogas/etiologia , Hipersensibilidade Tardia/induzido quimicamente , Meglumina/efeitos adversos , Compostos Organometálicos/efeitos adversos , Adulto , Idoso , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Hipersensibilidade Tardia/diagnóstico , Injeções Intralesionais , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Meglumina/administração & dosagem , Meglumina/uso terapêutico , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/uso terapêutico , Testes CutâneosAssuntos
Dermatite/etiologia , Edema/etiologia , Eritema/etiologia , Ceratose/etiologia , Mesoterapia/efeitos adversos , Abdome , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Benzimidazóis/uso terapêutico , Carnitina/administração & dosagem , Carnitina/efeitos adversos , Clobetasol/uso terapêutico , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Lipólise , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/efeitos adversos , Piperidinas/uso terapêutico , Prednisona/uso terapêutico , Gordura Subcutânea/patologia , Coxa da PernaAssuntos
Vesícula/induzido quimicamente , Dermatoses da Mão/induzido quimicamente , Medicina Tradicional/efeitos adversos , Transtornos de Fotossensibilidade/induzido quimicamente , Fitoterapia/efeitos adversos , Extratos Vegetais/efeitos adversos , Ruta/efeitos adversos , Adulto , Feminino , Humanos , Transtornos Mentais/complicaçõesAssuntos
Síndrome de Hipersensibilidade a Medicamentos/etiologia , Testes do Emplastro/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Ciclosporina/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Humanos , Masculino , Prednisona/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto JovemRESUMO
The genetic relationships of quantitative and structural variations of the C3b/C4b receptor (CR1) in human erythrocytes have been analyzed in informative families. Our results demonstrate the existence of multiple discrete quantitative variations of CR1 controlled by a locus, C3bRQ, closely linked to the CR1 structural locus, C3bR. Since the amounts of CR1 produced by each C3bR allele are shown to be independently regulated, we propose that a cis-acting genetic mechanism controls the level of expression of the C3bR alleles, and that this quantitative control plays a major, if not the sole, role in determining the total amounts of CR1 on normal human erythrocytes.