Severe Cutaneous Adverse Reactions to Drugs in Latin America: The RACGRAD Study.

BACKGROUND AND OBJECTIVE: Severe cutaneous adverse reactions to drugs (SCARs) are associated with high morbidity and mortality and with sequelae. Objective: To characterize patients with SCARs in 8 health care institutions in Latin America. METHODS: We performed a cross-sectional, descriptive, multicenter study of patients diagnosed with SCARs in Latin America between January 2009 and December 2018. The analysis was carried out using a database in BD Clinic. RESULTS: We collected 70 patients, of whom 42 (60%) were women. Mean age was 38.7 years. Forty-two patients (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other reactions not classified as SCARs, and 1 (1.4%) overlapping SJS-TEN. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), ß-lactam antibiotics in 11 cases (15.7%), and non-ß-lactam antibiotics in 6 cases (8.6%). In all of the cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%), and 3 patients died (4.3%). Thirteen patients (18.6%) had sequelae. CONCLUSIONS: This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity, and anticonvulsants were the main triggers. Most of the patients received systemic corticosteroids. Complications were frequent, and 3 patients died.

First case of fatal equine meningoencephalitis caused by Halicephalobus gingivalis in Mexico.

Aberrant nematode larval migration in the CNS of horses is rare but frequently fatal; one of the main etiological agents involved in this illness is Halicephalobus gingivalis. This soil nematode has been associated with several fatal equine meningoencephalitis reports worldwide; however, it had never been diagnosed in horses of Mexico. A 10 year-old Andalusian horse presented dysphagia, fever, weakness, prostration and ataxia; the patient expired during the medical attention. Post mortem examination was performed and no gross alterations were found. Histopathology revealed meningoencephalitis, vasculitis and intralesional adult nematodes, larvae and eggs compatible with Halicephalobus spp. A polymerase chain reaction (PCR) for the nuclear large subunit ribosomal RNA gene (LSU rDNA) of nematodes was performed from formalin-fixed and paraffin wax-embedded sections of brain. Posterior nucleotide sequence analysis of the amplified fragment identified the agent as H. gingivalis. To our knowledge, this is the first confirmed report of Halicephalobiasis in Mexico.

Learnings from real-life experience of using omalizumab for chronic urticaria in Latin America.

BACKGROUND: Updated urticaria guidelines recommend that patients should be assessed for disease activity, severity, control, and quality of life at baseline and follow up. Regarding treatment, guidelines consider second generation antihistamines as the cornerstone in therapy for chronic urticaria (CU), while other drugs, such as omalizumab, are conceived as second-line alternatives. In regards to omalizumab, despite advances in the management of CU, there are still open questions about timing, dosing, and objective measures for clinical response. This study was designed to portray the use of patient-reported outcomes (PROs) in chronic urticaria management, as well as the effectiveness and treatment patterns of omalizumab in CU, as seen in a real-life setting in Latin America. METHODS: This is a retrospective observational study, involving 72 Latin American patients with chronic urticaria treated with omalizumab. Patient reported outcomes and treatment patterns, response, quality of life improvement and discontinuation were analyzed. RESULTS: From the 72 patients, 91.7% (n = 66) were assessed through PROs, where urticaria control test (UCT) was the most used (79.2%; n = 57). Overall, 80.0% (n = 44) responded to omalizumab at some point of the treatment. Omalizumab 300 mg was associated with earlier response compared to lower doses. Regardless of dosage, most patients assessed with CU-Q2oL improved quality of life (80.8%; n = 21). With respect to omalizumab discontinuation, 20.8% (n = 15) patients interrupted omalizumab before the 3rd month of treatment (p = .000). CONCLUSIONS: The present study highlights how the use of PROs and omalizumab in Latin America differ from guidelines' recommendations and clinical trials. Even though most patients were initiated under omalizumab 300 mg, most of them finished with lower doses. Regardless of dosage, most patients responded to omalizumab and improved quality of life at some point during treatment. However, such features were seen earlier with omalizumab 300 mg. Regarding treatment discontinuation, one-fifth of patients interrupted omalizumab before the third month.

Quality of life and clinical characterization of patients with vernal keratoconjunctivitis in a pediatric population in Colombia.

Vernal keratoconjunctivitis is one of the most serious ocular allergies that have the potential to induce large ocular morbidity and significant visual changes affecting the quality of life of these individuals. METHODOLOGY: This study was conducted in two phases. The first phase consisted of the clinical characterization of 32 patients from the Clinical Allergology center of the I.P.S. Universitaria from July 2014 to February 2015. A retrospective analysis of medical records was performed. In the second phase, the evaluation of quality of life was conducted using the questionnaire KIDSCREEN 27, which was validated in our population and evaluated as recommended by the creators of this instrument. RESULTS: A total of 24 patients (75%) were men, mean age of 12.1 (SD 2.6) years. 100% of the patients had clinical evaluation and were monitored by Allergology and Ophthalmology, 12 patients (37.5%) were found in mild level, 5 patients (15.6%) were moderate and 14 patients (43.8%) were severe level. The most common symptoms were pruritus (75%), photophobia (50%), lacrimation (37.5%), and secretions (28.1%). 65.6% had a family history of atopy and 84.4% had an allergic comorbidity. Aeroallergen skin tests were found positive in 25 patients (78.1%). All patients had initiated ocular treatment by the time the survey of quality of life was conducted; but, they still had low quality of life scores in the 5 domains assessed. When the scores were evaluated by gender, the only statistically significant difference was found in the domain of family life and free time, which was lower for women. CONCLUSION: The vernal keratoconjunctivitis is a disease more prevalent in men. It apparently has an important atopic base in our environment, which due to its severe ocular involvement causes a marked decrease in the quality of life of the children who present it.

Genome-wide association analysis of body conformation traits in Mexican Holstein cattle using a mix of sampled and imputed SNP genotypes.

In arid and semi-arid zones, animal health and production are closely correlated with body conformation traits. These selected traits, in turn, allow livestock to adapt unfavorable soil and environmental conditions. The primary objective of this study was to perform a genome-wide association analysis for a set of sampled and imputed SNPs with 16 conformation traits in a population of Holstein cows from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was performed as a low-cost optimization strategy. Results show eight SNPs associated with two conformation traits. The Udder Depth trait resulted in seven associated SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield, Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body Depth trait resulted in one associated SNP from chromosome 2, although no QTL relation was found. The discovery of genes associated with conformation traits may be indicative of the adaptive selection pressures the Holstein breed has undergone in response to the extreme weather conditions found in the northwestern areas of Mexico. Results of this study indicate that traits such as stature and body depth may be used as indicators of cows' potential genetic merits for milk, fat, and protein production.

Composição centesimal e mineral de plantas medicinais comercializadas no mercado do Porto de Cuiabá, Mato Grosso, Brasil / Centesimal and mineral composition of medicinal plants commercialized in the Cuiabá Port Market, Mato Grosso, Brazil

RESUMO O presente trabalho teve como objetivo determinar a composição centesimal (cinzas, umidade, proteínas, lipídeos e carboidratos totais) e mineral (Na, K, Ca, Cu, Fe, Mg, Mn e Zn) das plantas medicinais Barbatimão (Stryphnodendron adstringens (Mart.) Coville), Carqueja (Baccharis trimera (Less) D.C.), Mangava-Brava (Lafoensia pacari A. St.-Hil.), e Quebra Pedra (Phyllanthus niruri L.) comercializadas no mercado do Porto de Cuiabá, MT. As amostras foram identificadas botanicamente por meio da exsicata feita no Instituto de Botânica da Universidade Federal de Mato Grosso, Campus Cuiabá. A composição centesimal foi determinada de acordo com as recomendações da Association of Official Analytical Chemists e a concentração dos minerais foi quantificada por Espectrometria de Absorção Atômica em Chama. Os resultados obtidos foram: umidade (7,72% a 12,10%); cinzas (1,64% a 8,44%); proteínas (2,36% a 9,35%); lipídeos (0,41% a 2,05%); carboidratos totais (72,09% a 82,37%) e, foram encontradas diferenças significativas entre as amostras (p < 0,05). As concentrações dos minerais nas amostras variaram de 0,01 a 21,57 mg/g nas plantas secas e 0,01 a 32,17 mg/200mL das infusões. Os resultados médios obtidos indicam que, exceto para o K, Ca e Mn todas as amostras não apresentaram diferenças significativas (p ≥ 0,05) nas concentrações de minerais. A capacidade de extração dos minerais da matéria seca para a infusão obedeceu à seguinte ordem: Na>K>Zn>Cu>Mg>Mn>Ca>Fe. Os valores obtidos em 200 mL das infusões quando comparados aos índices diários recomendados para minerais sugerem que os chás avaliados podem ser fonte de minerais, principalmente de K e Mn.

ABSTRACT The purpose of this study was to determine the proximal (ash, moisture, protein, lipids, and total carbohydrates) and mineral (Na, K, Ca, Cu, Fe, Mg, Mn, and Zn) composition of the medicinal plants barbatimão (Stryphnodendron adstringens (Mart.) Coville), carqueja (Baccharis trimera (Less) D.C.), mangava-brava (Lafoensia pacari A. St.-Hil.), pau-tenente (Quassia amara L.), and quebra pedra (Phyllanthus niruri L.), commercialized in the Cuiabá Port Market in Mato Grosso. The samples were botanically identified by the voucher specimen grown in the Botanical Institute of the Federal University of Mato Grosso, at the Cuiabá campus. Proximal composition was determined according to the recommendations of the Association of Official Analytical Chemists and the concentration of minerals was quantified by flame atomic absorption spectrometry. The results obtained were: moisture content (7.72% to 12.10%); ashes (1.64% to 8.44%); protein (2.36% to 9.35%); lipids (0.41% to 2.05%), and total carbohydrates (72.09% to 82.37%), and significant differences were found between the samples (p≥0.05). The mineral concentrations varied from 0.01 to 21.57 mg/g in the plants and 0.01 to 32.17 mg/200mL in the infusions. No significant differences (p≥0.05) were found between the samples for mineral composition, except for K, Ca, and Mg. The mineral extraction capacity of the dry matter for infusions was as follows: Na>K>Zn>Cu>Mg>Mn>Ca>Fe. The daily index values of the metal species quantified in 200 mL infusions suggest that teas can be a source of minerals, especially K and Mn.

Health-related quality of life in children and adults with respiratory allergy in Colombia: prospective study.

BACKGROUND: Allergic diseases are very common, with the estimated cumulative prevalence in Colombia for asthma and allergic rhinitis being 22.7% and 31.3% respectively, and with a clear upward trend. A major social as well as economic impact associated with allergic disease has been described. Because in Colombia there are no studies that assess the Health-Related Quality of Life (HRQOL) in allergic respiratory diseases, our aim is to describe the HRQOL in subjects with respiratory allergy and its association with clinical control variables. METHODS: A prospective descriptive study was conducted among 76 Colombian subjects with rhinitis and asthma/allergic rhinitis. In order to evaluate the HRQOL, the instruments Kidscreen-27 and SF-36 were applied. The scores obtained in the HRQOL fields were correlated with the following clinical variables: peak expiratory flow (PEF) and peak nasal inspiratory flow (PNIF). RESULTS: In children, the better HRQL domain is present in the school environment (55.9) and the worst in psychological well-being (39.9). For adults the worst HRQL was found in the emotional function domain (55.6) while the physical function (81.7) had the best. There were no statistical differences between groups of asthma/allergic rhinitis and allergic rhinitis. Subjects with allergic asthma showed a strong correlation between the mental health domain and PEF values (r=-0717, p=0.046). CONCLUSION: Mental health is more affected than physical health in Colombian subjects with respiratory allergy. There was a strong correlation between the mental health domain and the values of PEF in patients with asthma/allergic rhinitis.

Study of sunless tanning formulas using molted snake skin as an alternative membrane model.

Sunless tanning formulas have become increasingly popular in recent years for their ability to give people convincing tans without the dangers of skin cancer. Most sunless tanners currently on the market contain dihydroxyacetone (DHA), a keto sugar with three carbons. The temporary pigment provided by these formulas is designed to resemble a UV-induced tan. This study evaluated the effectiveness of carbomer gels and cold process self emulsifying bases on skin pigmentation, using different concentrations of a chemical system composed of DHA and N-acetyl tyrosine, which are found in moulted snake skins and their effectiveness was tested by Mexameter(®) MX 18. Eight different sunless tanning formulas were developed, four of which were gels and four of which were emulsions (base, base plus 4.0%, 5.0% and 6.0% (w/w) of a system of DHA and N-acetyl tyrosine). Tests to determine the extent of artificial tanning were done by applying 30 mg cm(-2) of each formula onto standard sizes of moulted snake skin (2.0 cm × 3.0 cm). A Mexameter(®) MX 18 was used to evaluate the extent of coloration in the moulted snake skin at T(0) (before the application) and after 24, 48, 72, 168, 192 and 216 h. The moulted snake skins can be used as an alternative membrane model for in vitro sunless tanning efficacy tests due to their similarity to the human stratum corneum. The DHA concentration was found to influence the initiation of the pigmentation in both sunless tanning systems (emulsion and gel) as well as the time required to increases by a given amount on the tanning index. In the emulsion system, the DHA concentration also influenced the final value on the tanning index. The type of system (emulsion or gel) has no influence on the final value in the tanning index after 216 h for samples with the same DHA concentration.

Early and late complications among 15 victims exposed to indoor fire and smoke inhalation.

AIM: To evaluate early and late complications among victims exposed to indoor fire and smoke inhalation. METHOD: An observational, descriptive and prospective longitudinal study of 15 victims of smoke inhalation admitted to the intensive care unit. RESULTS: Although without significant burns, 13 of the victims were unconscious, with airway injury, abnormal temperature and hypokalaemia, and underwent mechanical ventilation. Initial carbon monoxide concentration averaged 20.4+/-8.3%, dropping to 3.9+/-3.3% 4h later. On the 1st day, two victims recovered and were transferred, and another two died. Creatine kinase levels (2594+/-2455 U/l) correlated with duration of intensive care. Of the remaining 11 patients, 10 had early pneumonia. Steroid treatment was initiated for four patients receiving prolonged mechanical ventilation, because of persistent fever and dry cough without evidence of infection. CONCLUSIONS: Mortality and systemic involvement were related to burn of the upper airway and contact with combustion products. Initial creatine kinase levels emerged as a prognostic marker of injury severity. Bronchoscopy was useful in grading airway injury and obtaining bronchoalveolar culture. Corticosteroids were effective, after the acute phase, in treating non-infectious pulmonary complications.

Amnioinfusión transabdominal profiláctica anteparto en pacientes con oligoamnios severo previo a la inducción de parto / Prophylactic transabdominal amnioinfusion in patients with severe oligoamnios before labor induction

Se presentan los resultados obtenidos en relación a la realización de amnioinfusión transabdominal en pacientes con oligoamnios severo previo a la inducción del parto. El principal objetivo fue establecer si este procedimiento contribuye a disminuir la morbimortalidad perinatal y la frecuencia de parto operatorio por sufrimiento fetal (cesárea), en aquellas pacientes con oligoamnios severo con indicación de interrupción de la gestación. Dentro de la metodología de trabajo, se incluyeron en forma prospectiva y randomizada aquellas pacientes que no tenían contraindicación de parto vaginal y que cumplían además con los criterios de inclusión. Se obtuvo un total de 24 pacientes, realizándose amnioinfusión en 12 de ellas. La frecuencia de desaceleraciones durante la inducción y trabajo de parto, el estado ácido base fetal al nacer, así como la frecuencia de parto operatorio por sufrimiento fetal, no fue estadísticamente significativo en ambos grupos de pacientes. En base a los datos obtenidos, se concluye que la amnioinfusión anteparto no disminuye la morbimortalidad materna ni perinatal, así como tampoco contribuye a reducir la frecuencia de parto operatorio por sufrimiento fetal en pacientes con oligoamnios severo

[Metabolic changes in arachidonic acid during aspirin desensitization]. / Cambios metabólicos del ácido araquidónico en la desensibilización a la aspirina.

Aspirin sensitivity occurs in 10% of all asthmatics patients. In this subset of asthmatics, nasal congestion and bronchospasm occurs between 30-180 minutes after ingestion of aspirin. Following a respiratory reaction to aspirin, all patients can be desensitized to aspirin by repetitively introducing small and then larger doses of aspirin until the asthmatic subject can ingest 650 mg of aspirin without adverse effect. The mechanism of aspirin sensitivity are incompletely understood. And the reasons why ASA desensitization occurs universally are unknown. In this study, known ASA sensitive and control insensitive asthmatics were challenged with ASA. Urine was collected before, during induced bronchospasm, and after ingestion of 650 mg of ASA when the adverse effect (ie., acute desensitization) had subsided. Excretion levels of cyclo-oxygenase and lipoxygenase products in the urine were determined.

Ecografía muscular: bases para su interpretación / Muscular ultrasound study: basis for interpretation

En los últimos años, ha sido ampliamente difundida la utilización de los ultrasonidos, para el diagnóstico de las lesiones del sistema muscular y tendinoso. Creemos que la utilidad mayor de la ecografía muscular, radica en el diagnóstico de pequeñas lesiones, en donde la clínica no es tan precisa. Siendo un método operador dependiente, se torna imprescindible reconocer la importancia de la disposición de los elementos ecorrefringentes, base fundamental del estudio, para descartar áreas hipoecogénicas, que son interpretadas erróneamente como lesiones. En base a nuestra propia experiencia, damos algunas pautas para considerar estos factores de error

Ecografía muscular: bases para su interpretación / Muscular ultrasound study: basis for interpretation

En los últimos años, ha sido ampliamente difundida la utilización de los ultrasonidos, para el diagnóstico de las lesiones del sistema muscular y tendinoso. Creemos que la utilidad mayor de la ecografía muscular, radica en el diagnóstico de pequeñas lesiones, en donde la clínica no es tan precisa. Siendo un método operador dependiente, se torna imprescindible reconocer la importancia de la disposición de los elementos ecorrefringentes, base fundamental del estudio, para descartar áreas hipoecogénicas, que son interpretadas erróneamente como lesiones. En base a nuestra propia experiencia, damos algunas pautas para considerar estos factores de error (AU)

[Asthma induced by aspirin and arachidonic acid metabolites. II. The role of leukotrienes (part four)]. / Asma inducida por aspirina y metabolitos del ácido araquidónico. II. La participación de los leucotrienos (cuarta parte).

Although the mechanism of aspirin-induced asthma is unknown, it has be suggested that adverse nasal and bronchial reactions are caused by an increased production of lipoxygenase products. We have measured the release of urinary LTE4, TXB2 and 11-dehydro-TXB2 of aspirin induced asthmatics and controls by radioimmunoassay and HPLC methods during aspirin challenge and after desensitization. The overproduction demonstration of urinary LTE4 during aspirin challenge and the decrease after desensitization in inversal direct proportion manner with TXB2 suggest a "shunting" of the arachidonic acid metabolites of the target cells. Whichever theory is to be pursued further, it must also accommodate the clinical effect of aspirin densitization.

Abuso de cocaína no parenteral en pacientes infectados con el virus de la inmunodeficiencia humana / Non parental cocaine abuse in HIV-1 infected patients

El uso de la cocaína en el Perú ha atravesado por tres etapas. En la época prehispánica mediante la masticación de la hoja y la absorción del alcaloide a través de las mucosas orales. En el comienzo de este siglo por la inhalación intranasal del clorhidrato de cocaína. En los años setenta fumando la pasta de cocaína. Las tres formas de consumo se mantienen hasta hoy, predominando la última entre los sectores populares. La infección por el virus de la inmunodeficiencia humana (VIH-1) hizo su aparición en el Perú hace diez años extendiéndose rápidamente a todas las capas sociales del país, especialmente entre las más pobres. En 163 países infectados con el VIH-1 en el Hospital Dos de Mayo, estudiados mediante un protocolo especial, se ha comprobado que treinta y cuatro (20.8 por ciento) abusaban de la cocaína en forma no parental. Todos los enfermos comenzaron a usar el alcaloide antes de contraer la infección por el VIH-1. Se analiza las caraterísticas demográficas, clínicas y epidemiológicas de estos sujetos. Asimismo, se describe otros factores de riesgo para la diseminación de la infección en este grupo. En conclusión, tanto el abuso de la cocaína como la contaminación con el VIH-1, son hoy graves problemas de salud pública. Se requiere tomar urgentes medidas preventivas y terapéuticas para evitar la extensión de ambas epidemias en nuestro país. Estas acciones correctivas sólo tendrán éxito si se adoptan tanto por las agencias gubernamentales como por los grupos vecinales, particulares y familiares.

[Asthma induced by aspirin and arachidonic acid metabolites. Role of leukotrienes (third part)]. / Asma inducida por aspirina y metabolitos del ácido araquidónico. La participación de los leucotrienos (tercera parte).

Although the mechanism of aspirin-induced asthma is unknown, it has been suggested that adverse nasal and bronchial reactions are caused by an increased production of lipoxigenase products. In examining the hypothesis of inhibition on cycloxigenase, we support evidence in favor of this theory. We have measure the release of urinary LTE4, TXB2 and 11-dehydro-TXB2 of aspirin-induced asthmatics and controls by radioimmunoassay and HPLC methods during aspirin challenge and after desensitization. The over production demonstration of urinary LTE4 during aspirin challenge and the decrease after desensitization in inversal direct proportion manner with TXB2 suggest a "shunting" of the arachidonic acid metabolites of the target cells. Whichever theory is to be pursed further, it must also accommodate the clinical effect of aspirin desensitization.

[Aspirin-induced asthma and arachidonic acid metabolites. In search of answers to an enigma. Part 2]. / Asma inducida por aspirina y metabolitos del ácido araquidónico. En búsqueda de respuestas a un enigma (segunda parte).

Acetylsalicylic acid is one of the most commonly used drugs and high on the list of causes of drug reactions. Since early publication on 1902 by Hirschberg, a great deal of information has emerged on aspirin sensitivity, including data on epidemiology, further characterization of the two major subtypes of sensitivity (bronchospastic and urticarial types), hereditary aspects, cross-reactions to other nonsteroidal antiinflammatory drugs, and methods of desensitization. Although the pathogenesis of aspirin-sensitive asthma remains unknown, several theories has been proposed to explain the disease enigma.

[Asthma induced by aspirin and arachidonic acid metabolites. I. In search of answers to an enigma (first part)]. / Asma inducida por aspirina y metabolitos del ácido araquidónico. I. En busca de respuestas a un enigma (primera parte).

Acetylsalicylic acid, one of the most commonly used drugs and high on the list of causes of drug reactions. Since early publication on 1902 by Hirschberg, a great deal of information has emerged on aspirin sensitivity, including data on epidemiology, further characterization of the two major subtypes of sensitivity (bronchospastic and urticarial types), hereditary aspects, cross-reactions to other nonsteroidal antiinflammatory drugs, and methods of desensitization. Although the pathogenesis of aspirin-sensitive asthma remains unknown, several theories has been proposed to explain the disease enigma.