The induction of epidermal ornithine decarboxylase following tape stripping is inhibited by a topical vitamin D3 analogue (MC903)

The efficacy of MC903, a vitamin D3 analogue, in reducing hyperproliferation as determined by levels of ornithine decarboxylase (ODC) was investigated in a double-blind study of 15 patients with chronic plaque psoriasis. The lesions of psoriasis were treated for 8 weeks with MC903 in one of two different cream bases or with a placebo cream. Biopsies were taken before and after treatment. In addition an uninvolved area of skin was treated during the last 3 weeks and this as well as control areas were then sellotape stripped and biopsied after 8 h. Clinical improvement was seen in eight out of 11 patients treated with MC903 but there was no reduction in the level of ODC in psoriatic lesions after 8 weeks of treatment. The levels of ODC in the tape-stripped uninvolved skin after 3 weeks of treatment with MC903 averaged 22.5 +/- 4.2 pmol/min/mg protein as compared to 58.6 +/- 12.6 pmol/min/mg protein (P = 0.004). The trauma-induced induction of ODC activity was markedly inhibited by the application of MC903.     

LIVER BIOPSY VERSUS ULTRASOUND IN METHOTREXATE-TREATED PSORIASIS: A DECISION ANALYSIS

Before starting methotrexate therapy for cases of recalcitrant psoriasis, a liver biopsy has been usual in order to exclude cirrhosis and moderate or severe fibrosis, which are contraindications for methotrexate treatment. As mortality and morbidity of liver biopsy are not negligible, and as this invasive procedure is unpleasant for the patient and urges clinical admission, we evaluated the possibility of ruling out severe liver pathology by means of ultrasonography, which we compared to liver biopsy. We made this comparison by means of a decision tree. The advantages of this analysis are the clear definition of the decision problem and its alternatives, and the possibility of calculating the risk of each alternative, thus being able to choose the best diagnostic method. In this study, the results of various research groups are discussed, in which liver biopsy and liver ultrasound were compared. In our decision tree we used some of these results and other assumptions, based on comparable studies. We varied the biopsy mortality and the sensitivity of ultrasound to show the change in the risk of each alternative. Our analysis shows that the differences of expected values between the liver biopsy branch and the ultrasonography branch are relatively small. Therefore, we advise each center, which has at its disposal a specialist in liver ultrasonography, to re-evaluate its guidelines with regard to the detection of severe liver pathology before starting methotrexate for the treatment of psoriasis.     

The decay of house dust mite allergens, Der p I and Der p II, under natural conditions

Background: Fluctuations in the level of mite allergens in domestic house dust are the result of changes in the balance between synthesis, removal and decay. Purely physical forces as well as enzymatic degradation, mediated by house dust inhabiting microbes, may contribute to the decay of allergens in domestic dust. Knowledge about the speed of decay is essential for an understanding of the dynamics of allergen levels. Objective: The present study is a quantitative assessment of the speed of decay at nine combinations of temperature (15°C, 20°C and 25°C) and relative humidity (33%, 55% and 75%). Methods: Samples of mite infested material of an old rug were stored at these temperature/relative humidity-combinations for 6, 12 or 18 months, after the mites were killed by cither a freezing treatment or an acaricide (lindane). The microbes living in the rug presumably survive these treatments. Concentrations of Der p I and Der p II + Der f II. in extracts of the rug material, were measured by a radio immunoassay. Results: No significant changes in the levels of Der p I and Der p II +Der f II, could be detected even after 1¹/₂ year at a high temperature and humidity. Conclusion: These findings incidate that mite allergens can be extremely stable under normal domestic circumstances.     

Recognition of Rat Dendritic Cells by a Monoclonal Antibody

A mouse monoclonal IgM antibody reactive with dendritic cells (DC) from the Brown Norway (BN) rat was prepared. This antibody (1F119) binds to a membrane-bound antigen present on DC from thoracic duct lymph, spleen, thymus, and lymph node. The antigen is present only in low density on 5% of splenic macrophages (M phi) and absent from peritoneal M luminal diameter. In situ, the antibody exhibits a strong reactivity towards DC in the thymic medulla, whereas no reaction is observed with cortical cells. Furthermore, cells positive for 1F119 can be identified in T-cell areas of spleen, lymph node, and Peyers' patches. 1F119 was genetically restricted in that a strong reactivity was found with DC from rats of the RT1n and RT1u haplotypes, an intermediate reactivity with the RT1c haplotype, only a weak reactivity with the RT1l and RT1b haplotypes, and no reactivity with the RT1a and RT1k haplotypes. The relatively weak reactivity of 1F119 with respect to the RT1l haplotype also appeared from a weak binding of 1F119 to DC from Lewis rats, as was assessed by FACS analysis. This result was comparable to the binding of OX3 (RT1.Bl and RT1.Bu) to DC from BN rats. Studies performed on thymus sections of recombinant rat strains indicate that 1F119, despite its apparent specificity for DC, reacts with a polymorphic RT1.B product.     

Flow cytometric quantification of T6-positive cells in psoriatic epidermis after PUVA and methotrexate therapy

We describe a flow cytometric technique for measuring the percentage of T6-positive cells in suspensions prepared by trypsinization of human epidermis. The value obtained for healthy controls (1.55 ± 0.52%) corresponds to about 600 T6-positive cells per mm2 of skin surface, a figure in line with histological estimates. No significant change was found in the percentage of T6-positive cells in either the uninvolved or lesionat epidermis of untreated psoriatic patients. PUVA treatment resulted in a significant reduction in T6-positive cells. A cyclic fluctuation in the numbers of T6-positive cells was shown to accompany methotrexate administration on a weekly divided dose schedule.     

PHARMACOKINETICS OF ALFENTANIL DURING AND AFTER A FIXED RATE INFUSION

Twenty-nine patients (age range 14–81 yr) undergoing orthopaedicsurgery received alfentanil 100 µg kg^–1 given astwo i.v. boluses followed by a fixed rate infusion of 1 µgkg^–1 min^–1 for 44–445 min. Additional 1-mgbolus doses of alfentanil were administered as required. Plasmasamples were assayed for alfentanil using radio-immunoassay.Pharmacokinetic parameters were estimated by a model-independentapproach and by curve-fitting. Regression analysis showed nostatistical relationship between T, CI or Vd and the durationof the infusion, total dose or body weight. We found no significantcorrelation between age and T of alfentanil for patients youngerthan 40 yr. For patients older than 40 yr, T increased linearlywith age. There was no significant decrease in Cl with age,although the lower values for CI (100–200 ml min^–1)were generally found in subjects older than 60 yr. The presentstudy demonstrated that a 100-µg kg^–1 loading doseand a 1-µg kg^–1 min^–1 infusion may be appropriatefor analgesia in general surgical procedures.