Sesquiterpene lactone mix as a diagnostic tool for Asteraceae allergic contact dermatitis: chemical explanation for its poor performance and Sesquiterpene lactone mix II as a proposed improvement.

BACKGROUND: Two preparations are currently in use for the diagnosis of allergic contact dermatitis caused by Asteraceae: (i) Sesquiterpene lactone (SL) mix [three pure sesquiterpene lactones (STLs)], whose use has been questioned, owing to an insufficient rate of true-positive results; and (ii) Compositae mix, consisting of five Asteraceae extracts, which is problematic because of lack of standardization and questionable reproducibility. OBJECTIVES: To analyse the reasons for the narrow sensitivity of SL mix from a chemoinformatic point of view, and to propose a solution by rational selection of alternative constituents for a new SL mix II covering a broader cohort of allergic patients. MATERIALS/METHODS: Structural and biological information on allergenic STLs was retrieved from databases and the literature, and molecular modelling and chemoinformatic computations were performed. RESULTS: An explanation for the insufficient hit rate of SL mix is that the three constituents possess extremely similar molecular structures/properties and do not represent well the structural diversity of allergenic STLs. STLs that are known as constituents of Compositae mix plants show much a wider diversity, which explains the higher positive rate. CONCLUSIONS: On the basis of their positions in chemical property space, a new collection of STLs that more evenly cover the overall structural diversity spectrum is proposed. SL mix II is likely to detect a larger number of patients sensitized to Asteraceae.

Determination of formaldehyde in formaldehyde-releaser patch test preparations.

BACKGROUND: Positive patch test reactions to formaldehyde-releasers in patients co-reacting to formaldehyde are often ascribed to formaldehyde allergy. However, the formaldehyde content of patch test materials has not been investigated. OBJECTIVES: To demonstrate and quantify free formaldehyde in commercial patch test materials and in prepared aqueous solutions of formaldehyde releasers. MATERIALS: Free formaldehyde was measured by (13)C NMR Spectroscopy in (i) all formaldehyde-releasers in water available from Chemotechnique and Brial, (ii) 5 releasers in petrolatum, (iii) 12 prepared aqueous solutions of formaldehyde-releasers and (iv) water that had been in contact with petrolatum test samples. RESULTS: In none of the five petrolatum test substances was free formaldehyde found. In all nine commercial aqueous patch test substances and 9 of the 12 prepared solutions, free formaldehyde was demonstrated with concentrations ranging from 0.019% to 0.37% (detection limit 0.01%). Contact of the petrolatum test samples with water resulted in the release of formaldehyde. CONCLUSIONS: Most aqueous solutions of formaldehyde-releasers contain free formaldehyde. Petrolatum-based patch test materials with formaldehyde-releasers do not contain free formaldehyde, but probably start releasing it upon contact with water. Therefore, in future studies, determination of free and releasable formaldehyde may be preferable.

The impact of intraoperative neuromonitoring (IONM) on surgical strategy in bilateral thyroid diseases: is it worth the effort?

BACKGROUND: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve and the vagal nerve can detect nonfunctioning nerves (recurrent laryngeal nerve palsy, RLNP) that are visibly intact. The use of IONM is questionable, however, as we still lack evidence that it reduces the rate of postoperative nerve injuries. Since negative IONM results after thyroid dissection of the first side could change our surgical strategy and thus could prevent patients from bilateral RLNP, we questioned whether IONM results are reliable enough to base changes in surgical strategy and whether this has any effect on surgical outcome. METHODS: We retrospectively analyzed the data of 1333 consecutive patients with suggested benign bilateral thyroid disease who had been operated on under a defined protocol, including the use of a specific IONM technique (tube electrodes and stimulation of the vagal nerve and the inferior recurrent nerve before and after thyroid resection), between January 1, 2006 and December 31, 2008. RESULTS: In four patients the IONM system did not work, two nerves had not been found, and in eight patients the tube had to be readjusted. Of five permanent nerve injuries, four were visible during surgery and one was suspected. Sensitivity of IONM in detecting temporary nerve injuries of macroscopically normal-appearing nerves was 93%. Specificity was 75-83% at first side of dissection and 55-67% at the second side, with an overall specificity of 77%. In 11 of 13 patients (85%) with known nerve injury (preexisting or visible) and in 20 of 36 patients (56%) with negative IONM stimulation at the first side of dissection, the surgical strategy was changed (specific surgeon or restricted resection) with no postoperative bilateral RLNP. This was in contrast to 3 of 18 (17%) bilateral RLNP (p < 0.05), when surgeons were not aware of a preexisting or highly likely nerve injury at the first side of thyroid dissection. CONCLUSIONS: Failed IONM stimulation of the vagal or recurrent laryngeal nerve after resection of the first thyroid lobe is specific enough to reconsider the surgical strategy in patients with bilateral thyroid disease to surely prevent bilateral RLNP.

Quality assurance and standardisation of patch tests for contact allergens skin testing.

The misbranding of raw materials used in the manufacturing of patch tests and the counterfeiting of the final product of these test materials have gained increasing importance in the last decade with respect to the production process in the pharmaceutical industry. To guarantee the performance and safety of a semi-solid pharmaceutical testing form, it is important to make oneself acquainted with the different quality standards and official requirements demanded by the national and international regulations. Moreover it will be necessary to get an idea about the major factors which influence the quality of patch tests and therefore finally the quality of the medical allergic diagnosis.