Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report [Dapson-induzierte agranulozytose. Die rolle fremdstoffmetabolisierender enzyme am beispiel einer kasuistik]

A 34-year-old female patient with a three year history of generalized granuloma annulare was treated systemically with dapsone (DADPS). Six weeks after the onset of treatment, the patient developed an extensive tonsillitis of the base of the tongue with fever and malaise. Routine laboratory work showed a leukocytopenia with agranulocytosis. Further investigation revealed a marked decrease of the enzyme activity of N-acetyltransferase 2, which plays an important role in dapsone metabolism. Treatment included the cessation of dapsone, antibiotic coverage, and G-CSF leading to the rapid improvement of symptoms and normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a rare event and is interpreted as an idiosyncratic reaction. Depending on genetic polymorphisms of various enzymes, dapsone can be metabolized to immunologically or toxicologically relevant intermediates. Because of the risk of severe hematologic reactions, dapsone should only be employed for solid indications and with appropriate monitoring.

Genomics and virulence factors of Fusobacterium necrophorum

Fusobacterium necrophorum, a Gram negative, anaerobic bacterium, is a common cause of acute pharyngitis and tonsillitis and a rare cause of more severe infections of the head and neck. At the beginning of the project, there was no available genome sequence for F. necrophorum. The aim of this project was to sequence the F. necrophorum genome and identify and study its putative virulence factors contained using in silico and in vitro analysis. Type strains JCM 3718 and JCM 3724,F. necrophorum subspecies necrophorum (Fnn) and funduliforme (Fnf), respectively, and strain ARU 01 (Fnf), isolated from a patient with LS, were commercially sequenced by Roche 454 GS-FLX+ next generation sequencing and assembled into contigs using Roche GS Assembler. Sequence data was annotated semi-automatically, using the xBASE pipeline, BLASTp and Pfam. The F. necrophorum genome was determined to be approximately 2.1 – 2.3 Mb in size, with an estimated 1,950 ORFs and includes genes for a leukotoxin, ecotin, haemolysin, haemagglutinin, haemin receptor, adhesin and type Vb and Vc secretion systems. The prevalence of the leukotoxin gene was investigated in strains JCM 3718, JCM 3724 and ARU 01, as well as a clinical collection of 25 Fnf strains, identified using biochemical and molecular tests. The leukotoxin operon was found to be universal within the strain collection by PCR. HL-60 cells subjected to aliquots of concentrated high molecular weight culture supernatant, predicted to contain the secreted leukotoxins of strains JCM 3718, JCM 3724 and ARU 01, were killed in a dose-dependent manner. The cytotoxic effect of the leukotoxin against human donor white blood cells was also tested to validate the HL-60 assay. The differences in the results between the two assays were not statistically significant. Ecotin, a serine protease inhibitor, was found to be present in 100 % of the strain collection and had a highly conserved sequence with primary and secondary binding sites exposed on opposing sides of the protein. During enzyme inhibition studies, a purified recombinant F. necrophorum ecotin protein inhibited human neutrophil elastase, a protease that degrades bacteria at inflammation sites, and human plasma kallikrein, a component of the host clotting cascade. The recombinant ecotin also prolonged human plasma clotting times by up to 7-fold for the extrinsic pathway, and up to 40-fold for the intrinsic pathway. The genome sequence data provides important information about F. necrophorum type strains and enables comparative study between strains and subspecies. Results from the leukotoxin and ecotin assays can be used to build up an understanding of how the organism behaves during infection.

Iscensättanden av halsfluss : relationella göranden av en sjukdom i medicinska praktiker

Enacting tonsillitis: Relational performances in medical practices In this paper the diagnostic process of bacterial tonsillitis at two Swedish health centres is described and analysed as to how this disease comes into being, or how it is enacted. The concept of enactment implies that disease is constituted in, and through, relational practises involving human and non-human elements. The study is based on interviews with nurses and doctors as well as field observations from the health centres. In the analysis it becomes apparent that different – and sometimes conflicting – enactments of tonsillitis appear in medical practices, depending on the organization of relations between different elements. It is concluded that diagnostic agency is created in relations between both humans and non-humans, and who and what is given diagnostic agency is changeable depending on the relations at hand. The diagnostic process of tonsillitis shows how the most mundane medical diagnoses involves a number of complex relations, that stretches beyond categories such as social and medical.

Estudio comparativo para el tratamiento de la amigdalitis recidivante, entre el uso de penicilinas y amigdalectomizados, en el H.V.C.M. Cuenca Enero-Junio, 1994

La amigdalitis es una de las infecciones más comunes generalmente acusada por el estreptococo bata hemofílico del grupo A y con menor frecuencia debido a infecciones víricas. La amigdalitis recidivante es desde hace muchos años, la indicación más frecuente para practicar amigdalotomía aunque esta intervención tiene escasa complicaciones, su utilidad en la prevención de las recidivas no ha sido demostrada prospectivamente hasta estudios actuales en el que se compara la eficacia del tratamiento quirúrgico con una pauta antibiótica clásica la penicilina. Varios son los estudios en cuales se ha puesto en evidencia la incapacidad de la penicilina para acabar con el estado de portador del estreptococo beta hemolítico del grupo A. Entre las posibles explicaciones de esta aparente pérdida de eficacia de la penicilina, la más aceptada supone que la administración repetida del antibiótico selecciona flora productora de beta lactamasa. Los objetivos del tratamiento de la amigdalitis recidivante incluyen tanto la resolución de los signos clínicos y los síntomas de infección y la erradicación del agente causal de la cavidad oro faríngeo, por otro lado será importante evitar las complicaciones supurativas y no suporativas. La penicilina G es el agente antimicrobiano más efectivo para el tratamiento de la amigdalitis y debe emplearse almenos que el paciente sea alérgico lo que evita en lo posterior complicaciones

Diez primeras causas de morbilidad en emergencia del Hospital Homero Castanier Crespo en el periodo de octubre a diciembre del 2014. Azogues-Ecuador

Antecedentes: Es preciso mencionar que en México en el 2005 estadísticas muestran que las principales causas de morbilidad en su servicio de emergencias las constituyen: Infecciones respiratorias agudas (19,4%), los traumatismos y envenenamientos (18,8%) y las enfermedades diarreicas (8%). (14). En Perú la principal causa de morbilidad se debió a traumatismos (12% del total), seguido en segundo lugar de asma (10%) y en tercer lugar por anormalidades y complicaciones del embarazo, parto o puerperio (8% del total). (5) Objetivo: Determinar las 10 primeras causas de morbilidad en emergencia del Hospital Homero Castanier Crespo en el período de octubre a diciembre 2014. Materiales y métodos: Se realizó un estudio observacional indirecto, mediante el registro de emergencia del total de pacientes que han acudido a emergencia en el Hospital Homero Castanier Crespo en período comprendido entre octubre – noviembre del 2014. El instrumento utilizado fue el formulario de recolección de datos (ver anexo 2). Resultados: la principal causa de morbilidad en la emergencia del Hospital Homero Castenier Crespo constituyen las enfermedades infecciosas: Enfermedades infecciosas intestinales, Amigdalitis aguda con un 10.86%. Gran parte de las morbilidades atendidas en la emergencia 20.85%, no son emergencias reales. En grupos edad pediátrica y adultos mayores, la principal causa fueron las Enfermedades infecciosas intestinales 14.52%, 6.96% respectivamente, que en este grupo si constituyen un verdadera emergencia. En ginecobstetricia: Falso trabajo de parto a las 37 y más semanas completas de gestación Conclusión: el estudio muestra las principales causas de morbilidad en el Hospital Homero Cartanier Crespo, revela una saturación del sistema por la cantidad de no emergencias que se atienden. Probablemente por la falta de un triage adecuado