Uso del dermatoscopio en la lectura de pruebas epicutáneas: ¿qué puede aportar? / Dermoscopy in Patch Testing: How Can It Help?

La lectura de los parches de pruebas epicutáneas no es sencilla, presenta una gran variabilidad inter- e intraobservador y requiere experiencia. En ocasiones es realmente difícil determinar si se trata de una reacción alérgica de intensidad leve o si estamos ante una reacción irritativa. Recientemente se han publicado algunos trabajos que han estudiado las características dermatoscópicas de las distintas reacciones que se producen tras realizar pruebas epicutáneas. La característica dermatoscópica más frecuentemente observada en los parches alérgicos es el eritema homogéneo, si bien vasos puntiformes, vesículas o costras y áreas amarillo-anaranjadas también parecen indicar una reacción alérgica, guardando cierta similitud con lo observado en patología inflamatoria como en el eccema. Por otro lado, en cuanto a las reacciones irritativas, el patrón más indicativo sería el «patrón del poro», acompañado de eritema perifolicular. Estos hallazgos dermatoscópicos pueden ser de utilidad al clínico en su toma de decisiones ante una reacción dudosa (AU)

Interpreting patch test reactions is not easy. It requires experience and is characterized by high intraobserver and interobserver variability. It can sometimes be truly difficult to discern between a weak allergic reaction and an irritant reaction. A number of recent studies have investigated the dermoscopic features of patch test reactions. Homogeneous erythema is the main feature observed in patients with a positive allergic reaction, although dotted vessels, vesicles, crusts and yellow-orange areas may also provide clues. These features are somewhat similar to those observed in inflammatory conditions, such as eczema. In patients with an irritant reaction, the most common dermoscopic findings are the pore reaction pattern and perifollicular erythema. Dermoscopy could be useful for establishing a diagnosis in the case of doubtful patch test reactions (AU)

[Translated article] Dermoscopy in Patch Testing: How Can It Help? / Uso del dermatoscopio en la lectura de pruebas epicutáneas: ¿qué puede aportar?

Interpreting patch test reactions is not easy. It requires experience and is characterized by high intraobserver and interobserver variability. It can sometimes be truly difficult to discern between a weak allergic reaction and an irritant reaction. A number of recent studies have investigated the dermoscopic features of patch test reactions. Homogeneous erythema is the main feature observed in patients with a positive allergic reaction, although dotted vessels, vesicles, crusts and yellow-orange areas may also provide clues. These features are somewhat similar to those observed in inflammatory conditions, such as eczema. In patients with an irritant reaction, the most common dermoscopic findings are the pore reaction pattern and perifollicular erythema. Dermoscopy could be useful for establishing a diagnosis in the case of doubtful patch test reactions (AU)

La lectura de los parches de pruebas epicutáneas no es sencilla, presenta una gran variabilidad inter- e intraobservador y requiere experiencia. En ocasiones es realmente difícil determinar si se trata de una reacción alérgica de intensidad leve o si estamos ante una reacción irritativa. Recientemente se han publicado algunos trabajos que han estudiado las características dermatoscópicas de las distintas reacciones que se producen tras realizar pruebas epicutáneas. La característica dermatoscópica más frecuentemente observada en los parches alérgicos es el eritema homogéneo, si bien vasos puntiformes, vesículas o costras y áreas amarillo-anaranjadas también parecen indicar una reacción alérgica, guardando cierta similitud con lo observado en patología inflamatoria como en el eccema. Por otro lado, en cuanto a las reacciones irritativas, el patrón más indicativo sería el «patrón del poro», acompañado de eritema perifolicular. Estos hallazgos dermatoscópicos pueden ser de utilidad al clínico en su toma de decisiones ante una reacción dudosa (AU)

Dermoscopy in Patch Testing: How Can It Help? / Uso del dermatoscopio en la lectura de pruebas epicutáneas: ¿qué puede aportar?

Interpreting patch test reactions is not easy. It requires experience and is characterized by high intraobserver and interobserver variability. It can sometimes be truly difficult to discern between a weak allergic reaction and an irritant reaction. A number of recent studies have investigated the dermoscopic features of patch test reactions. Homogeneous erythema is the main feature observed in patients with a positive allergic reaction, although dotted vessels, vesicles, crusts and yellow-orange areas may also provide clues. These features are somewhat similar to those observed in inflammatory conditions, such as eczema. In patients with an irritant reaction, the most common dermoscopic findings are the pore reaction pattern and perifollicular erythema. Dermoscopy could be useful for establishing a diagnosis in the case of doubtful patch test reactions.

Effectiveness of adalimumab for rheumatoid arthritis in patients with a history of TNF-antagonist therapy in clinical practice.

OBJECTIVE: To evaluate the effectiveness and safety of adalimumab in patients with rheumatoid arthritis (RA) who previously discontinued tumour necrosis factor (TNF) antagonists for any reason in clinical practice. METHODS: ReAct (Research in Active Rheumatoid Arthritis) was a large, open-label trial that enrolled adults with active RA who had previously been treated with traditional disease-modifying anti-rheumatic drugs or biological response modifiers. Patients self-administered adalimumab 40 mg subcutaneously every other week for 12 weeks and were allowed to enter an optional long-term extension phase. Measures of adalimumab effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, Disease Activity Score 28 (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ DI). RESULTS: Of 6610 patients, 899 had a history of etanercept and/or infliximab therapy; these patients experienced substantial clinical benefit from adalimumab treatment. At week 12, 60% of patients had an ACR20 and 33% had an ACR50 response; 76% had a moderate and 23% had a good EULAR response. In addition, 12% achieved a DAS28 < 2.6, indicating clinical remission, and 13% achieved a HAQ DI score <0.5. The allergic adverse event rate, regardless of relationship to adalimumab, was 6.5/100-patient-years (PYs) in previously TNF-antagonist-exposed patients and 4.3/100-PYs in TNF-antagonist-naive patients. A multiple regression analysis indicated no statistically significantly increased risk of serious infections in patients who received prior TNF antagonists compared with TNF-antagonist-naive patients. CONCLUSION: In typical clinical practice, adalimumab was effective and well-tolerated in patients with RA previously treated with etanercept and/or infliximab.

A progesterone receptor affinity chromatography reagent: 17 alpha-hexynyl nortestosterone sepharose.

Several affinity chromatography reagents have been proposed for purification of progesterone receptor (PgR), and significant results have been achieved with some of these. None, however, have approached the results achieved in affinity chromatography of estrogen receptor. We have therefore synthesized a number of new 19-nortestosterone derivatives capable of chemically stable linkage with Sepharose beads, and have identified one with very high PgR affinity for further study. We first synthesized the epoxides of 17 alpha-allyl nortestosterone, by analogy with the estradiol derivatization of Greene and Jensen. The relative affinity of these epoxides for PgR from T47D human breast cancer cells, however, was only around 5% that of R5020, and affinity beads prepared from them bound very little PgR. We then reacted appropriately protected 17 alpha-ethynyl-nortestosterone with a series of diiodo alkanes, and found that 17 alpha-(6'-iodohex-1'-ynyl)nortestosterone had an affinity of 22% relative to R5020, equal to the affinity of progesterone itself. Reaction with Thiopropyl-Sepharose 6B yielded hexynyl-nortestosterone-Sepharose beads with a ligand density of about 7 micromoles/ml beads. One-hundred microliter of these beads adsorbed 71% of the PgR present in 1 ml of cytosol from T47D cells. This adsorption was inhibited by 10 microM progesterone but not cortisol, indicating the specificity of the binding. Comparisons with NADAC and Sterogel, other affinity beads used for PgR purification, show that the former takes up much less receptor, while the latter takes up and releases similar amounts of receptor but more extraneous protein, and is less stable. We therefore believe that hexynyl-nortestosterone-Sepharose, having a high density of a high affinity ligand, and having chemically and biochemically stable covalent bonds, should be a good reagent for affinity purification of PgR.

Androgen receptor affinity chromatography: synthesis and properties of 17 alpha-epoxypropyl-dihydrotestosterone Sepharose.

We have prepared a new affinity chromatography reagent, 17 alpha-epoxypropyl-dihydrotestosterone linked to Thiopropyl-Sepharose, with potential for use in purification of androgen receptor and other specific androgen binding proteins. The linkage is stable, and the ligand has reasonably high affinity for the receptor. Starting with 5 alpha-androstane-3 beta-ol-17-one, we synthesized in two steps 17 alpha-allyl-dihydrotestosterone, which was then oxidized to 17 alpha-epoxypropyl-DHT yielding 2 diastereomers in about a 4:1 ratio. The 17 alpha-allyl-DHT had about 50% of DHT's affinity for rat uterine androgen receptor, while the affinity of the major epoxide isomer was 9% and that of the minor isomer was 4%. Reaction of the epoxides with Thiopropyl-Sepharose-6B gave about 7 mumol of covalently bound DHT per ml of beads. These beads took up 83% of the androgen receptor from a rat uterine cytosol in a preliminary study, which more than equalled the performance of identically prepared estradiol beads successfully used for estrogen receptor purification. The use of the new DHT beads in purifications of the androgen receptor and other binding proteins is now being explored by other laboratories.

Promotion, termination, and anti-termination in the rpsU-dnaG-rpoD macromolecular synthesis operon of E. coli K-12.

The regulatory regions for the rpsU-dnaG-rpoD macromolecular synthesis operon have been fused to a structural gene whose product is readily assayed (the Cmr structural gene coding for chloramphenicol acetyl transferase, CAT). The promoters (P1, P2, P3, Pa, Pb, Phs) for the macromolecular synthesis operon have different strengths as shown by their relative abilities to drive expression of the CAT gene. Promoter occlusion by P1 can be demonstrated within this operon. Regions 5kb upstream have a profound effect on operon gene expression. There is a thermoinducible promoter located within the dnaG structural gene. One of the macromolecular synthesis operon promoters is under lexA control. Although the operon structure allows coordinate expression of rpsU, dnaG and rpoD these additional features suggest that expression of individual genes can be independently regulated in response to altered growth conditions.