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Notizen: Synopsis The murine local lymph node assay (LLNA) can be used to determine the relative skin sensitizing potency of chemicals via interpolation of the quantitative dose response data generated. Using this approach we have demonstrated previously that the vehicle matrix in which a chemical allergen is encountered on the skin can have a significant influence on sensitizing potency. Estimates of relative potency are calculated from LLNA dose responses as a function of the mathematically derived EC3 value, this being the concentration estimated to induce a stimulation index (SI) of 3. To investigate further the influence of application vehicle on sensitizing potency, the LLNA has been used to examine the activity of four recognized human contact allergens: isoeugenol and cinnamic aldehyde, two fragrance chemicals; 3-dimethylaminopropylamine (a sensitizing impurity of cocamidopropyl betaine, a surfactant used in shower gel) and dibromodicyanobutane (the sensitizing component of Euxyl K 400, a preservative used in cosmetics). The four chemicals were applied in each of seven different vehicles (acetone: olive oil [4 : 1]; dimethylsulphoxide; methylethylketone; dimethyl formamide; propylene glycol; and both 50 : 50 and 90 : 10 mixtures of ethanol and water). It was found that the vehicle in which a chemical is presented to the epidermis can have a marked effect on sensitizing activity. EC3 values ranged from 0.9 to 4.9% for isoeugenol, from 0.5 to 1.7% for cinnamic aldehyde, from 1.7 to 〉 10% for dimethylaminopropylamine and from 0.4 to 6.4% for dibromodicyanobutane. These data confirm that the vehicle in which a chemical is encountered on the skin has an important influence on the relative skin sensitizing potency of chemicals and may have a significant impact on the acquisition of allergic contact dermatitis. The data also demonstrate the utility of the LLNA as a method for the prediction of these effects and thus for the development of more accurate risk assessments. Résumé Le test local des ganglions lymphatiques murins (LLNA) peut être utilisé pour déterminer le potentiel relatif de sensibilisation de la peau de produits chimiques, par interpolation des données quantitatives de dose/réponse obtenues. En utilisant cette approche, nous avions démontré précédemment que la matrice vecteur par laquelle un allergène chimique est mis en contact avec la peau peut avoir une influence significative sur le potentiel de sensibilisation. Des estimations d’activité relative sont calculées à partir des doses/réponses de LLNA en fonction de la valeur EC3 dérivée mathématiquement, celle-ci étant la concentration estimée comme induisant un indice de stimulation (IS) de 3. Pour examiner plus avant l’influence du vecteur d’application sur l’activité de sensibilisation, on a utilisé le LLNA pour déterminer l’activité de quatre allergènes de contact humains reconnus: isoeugénol et aldéhyde cinnamique, deux substances chimiques de parfumerie; la 3-diméthylaminopropylamine (une impureté sensibilisante de la cocamidopropyl bétaïne, un tensioactif utilisé dans les gels douches) et le dibromodicyanobutane (le composant sensibilisant de Euxyl K 400, un conservateur utilisé dans les cosmétiques). Les quatre produits chimiques ont été appliqués dans chacun de sept vecteurs différents (acétone: huile d’olive [4: 1]; diméthylsulfoxyde; méthyléthylcétone; diméthylformamide; propy- lène glycol; et deux mélanges 50: 50 et 90: 10 d’éthanol et d’eau). On observe que le vecteur dans lequel le produit chimique est présentéà l’épiderme peut avoir un effet marqué sur l’activité sensibilisatrice. Les valeurs EC3 vont de 0,9 à 4,9 % pour l’isoeugénol, de 0,5 à 1,7 % pour l’aldéhyde cinnamique, de 1,7 à 〉 10 % pour la diméthylaminopropylamine et de 0,4 à 6,4 % pour le dibromodicyanobutane. Ces données confirment que le vecteur dans lequel un produit chimique est mis en contact avec la peau a une influence importante sur le potentiel relatif de sensibilisation de la peau des produits chimiques, et peut avoir un impact significatif sur l’apparition de dermatite allergique par contact. Les données démontrent aussi l’utilité du LLNA comme méthode de prévision de ces effets et donc pour le développement d’évaluations plus précises des risques.

Notizen: With the SUSS XRS 200 a synchrotron compatible stepper is available which combines high positional accuracy and high throughput using the scanning exposure method. With 1 s each for exposure, alignment, and stepping time, 20 6-in. wafers/h can be processed with the smallest stepfield size of 26×26 mm. The excellent linewidth control, irrespective of topography and surface characteristics, with a large gap and exposure dose window, show the capability of x-ray lithography to be used as the next generation production lithography method. The SUSS XRS-200 provides the user with a tool to take full advantage of this wide process latitude and make production of sub-half-micron features an economical operation.

Notizen: Normal values for serum cystine aminopeptidase (CAP) during pregnancy are established and compared with results from abnormal pregnancies. Steadily rising CAP values suggest adequate lacental function. A correlation exists between the final CAP value and birthweight in normal pregnancies. The implications of various trends in CAP results in abnormal pregnancies are considered.

Notizen: Objective To assess the relative efficacy of three disposable plastic instruments in the retrieval of ‘missing’ IUCD threads.Design A prospective randomised comparative single centre study.Setting Family Planning Clinic in London, UK.Subjects 217 of 350 IUCD users referred to the research team with ‘missing’ IUCD threads entered the study.Intervention All women initially underwent exploration of the endocervical canal with Spencer Wells forceps. When this procedure did not retrieve the threads, the patients were entered into the study. A maximum of two randomly chosen plastic IUCD thread retrievers were then used in any one patient to explore the uterine cavity and capture the ‘missing’ threads. The order in which the two retrievers were employed was also determined at random. Four separate entries into the uterine cavity were permitted with each instrument, the endocervical canal being explored with Spencer Wells forceps after each retraction of the instrument to identify the possible descent of the threads.Main outcome measures Threads brought down beyond the external cervical os, or threads brought to within the endocervical canal and then grasped by Spencer Wells forceps.Results In approximately 40% of all patients, the threads were retrieved with Spencer Wells forceps alone and a further 40% with the disposable plastic retrievers. About 5% had no retrievable threads, and only 2.5% of the referred patients required general anaesthesia for removal of their IUCD. The analysis of the comparative trial was confined to the 197 patients with retrievable threads which could not be brought below the external os with Spencer Wells forceps. The first plastic retriever used was successful in 50% of patients. The Retrievette (59%) and the Emmett (53%) performed better than the Mi-Mark Helix (37%) in this study. The difference was statistically significant (P=0.03) and the 95% confidence interval for the difference of the Mi-Mark Helix from the other two retrievers was 4% to 33%. This retrieval rate for the Mi-Mark Helix was much worse than in previously reported studies, though one doctor did have a better success rate with this retriever. The success rates, using a second plastic retriever randomly chosen from the two not used in the first attempt, were almost identical to those observed with the first retrievers: 63%, 56% and 36%. The success rate did not appear to be influenced by the length of thread, day of cycle, device type or parity. The success of the second retriever tried did not seem to be influenced by the retriever that had failed previously.Conclusions Based on our experience, the initial exploration of the endocervical canal with Spencer Wells forceps is invaluable. If this simple manoeuvre fails to retrieve the ‘missing’ threads, either the Retrievette or the Emmett thread retrievers are useful tools in general practice or in the family planning clinic setting.

Notizen: There exists within the population subsets of individuals who display heightened skin reactivity to materials the majority find tolerable. In a series of investigations, we have examined interrelationships between many of the endpoints associated with the term ‘sensitive skin’. In the most recent work, 58 volunteers were treated with 10% lactic acid, 50% ethanol, 0.5% menthol and 0.1% capsaicin on the nasolabial fold, unoccluded, for 8 minutes. Sensory reactions were recorded at 2.5, 5 and 8 minutes. Urticant susceptibility was evaluated with 1 M benzoic acid and 125 mM trans-cinnamic acid applied to the volar forearm for 20 minutes. Visual assessments were taken at intervals for up to 4 hours after treatment. A 2 × 23 hour patch test was also conducted using 0.1% and 0.3% sodium dodecyl sulphate, 0.3% and 0.6% Tegobetain F50 and 0.1% and 0.2% benzalkonium chloride to determine irritant susceptibility. As found in previous studies, increased susceptibility to one endpoint was not predictive of sensitivity to another. In our hands, nasolabial stinging is a poor predictor of sensory as well general skin sensitivity. However, it may be possible to identify in the normal population individuals who are more generally sensitive to a range of non-immunologic adverse skin reactions. Whether such individuals are those who experience problems with skin care products is open to question.

Notizen: We have previously reported that, with suitable training and experience, skin irritation reactions can be graded visually with a high degree of sensitivity and precision. The objective of the work presented is to demonstrate the possibilities and limitations of the grading of skin irritation reactions by subjective visual assessment. In the present work, we have recorded a wide range of relatively minor skin irritation reactions using a high quality digital camera. The skin reactions recorded have then been graded by independent observers according to their appearance on a computer monitor. The results show that very subtle degrees of both erythema and skin dryness can be accurately described by trained skin graders in a reliable and reproducible manner. Examples of the grading scales and sensitivity of scoring will be shown. We conclude that visual scoring, when conducted well, represents a rapid and accurate method for the assessment of minor degrees of skin irritation. The present evidence, taken in combination with previously presented information on bioengineering techniques, leads us to the conclusion that visual assessment is both an adequate and a robust technique, delivering information of the quality necessary for safety assessment of consumer products.

Notizen: This study investigated the phenotype and function of different antigen-presenting cells (APC) present within the epidermis of patients with cutaneous T-cell lymphoma (CTCL). Involved epidermis of CTCL compared with uninvolved was found to contain increased numbers of CDI + DR+ APC. This population was heterogeneous and comprised both leucocytes of a novel CD1+DR+CD36 (OK.M5)+ phenotype and CD1+DR+CD36− indeterminate/Langerhans cells. The CD1+DR+CD36+ leucocytes did not express TcR-1, CD5, CD 15. or CD22, and only a minor population expressed CD11, demonslrating that they were neither T nor B cells, and did not belong lo the major CD11+ (OKM1+) blood monocyte population. Electron microscopy of purified CD36+ lesional epidermal cells (EC) demonstrated that they lacked Birbeck granules found on CD1+-selected Langerhans cells, and most cells exhibited features of indeterminate cells or macrophages.The capacity of EC from involved epidermis to present alloanttgens was found to be increased relative to uninvolved epidermis in all patients tested, and this capacity was critically dependent upon the presence of CD45+ DR+ bone marrow-derived cells but not on the presence of CD45+ DR+ keratinocytes. Positive selection using MoAb against CDI and CD36 demonstrated that both cell populations exhibited the capacity to stimulate T cells. The results indicate that a novel antigen-presenting cell population with a unique phenotype is present within involved skin of patients with mycosis fungoides. These cells express CD36 in addition to CD1 and have an ultrastructural appearance consistent with a dendritic antigen-presenting cell derivation.