T. van Joost

USE OF CYCLOSPORIN IN PSORIASIS

In the treatment of severe psoriasis, cyclosporin may achieve improvement or remission at low doses, but relapse usually occurs on withdrawal of treatment. An initial dose of 3 mg/kg per day is recommended. Complete remission should not be the objective, and the role of long-term maintenance cyclosporin therapy is uncertain because of potential side-effects--especially nephrotoxicity, hypertension, and a predisposition to malignancy. Guidelines are proposed for the assessment of such treatment.

Prevalence of antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in infertile women.

A total of 57 infertile women, who had been referred for in vitro fertilisation or for diagnostic laparoscopy, were tested for the presence of antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis. Four were excluded from the study. Of the remaining 53, 33 had laparoscopically obvious tubal disorders, such as adhesions, distal occlusions and strictures, and 20 did not. Antibodies to C trachomatis were found in 7/33 (21.2%) v 0/20, antibodies to N gonorrhoeae in 20/38 (60.6%) v 5/20 (25%), and antibodies to M hominis in 18/24 (75%) women with tubal disorders v 13/19 (68.4%) of those with no disorder. Antibodies to C trachomatis and N gonorrhoeae were significantly (p less than 0.05) more common in women with tubal disorders. The high prevalence of antibodies to N gonorrhoeae in infertile women without tubal disorders suggests that ciliated tubal epithelium is damaged after inflammation without this being laparoscopically visible. Our results confirm the important role of N gonorrhoeae and C trachomatis in the aetiology of infertility after tubal inflammation.

Sexually communicable micro-organisms in human semen samples to be used for artificial insemination by donor.

Two hundred and thirty seven semen samples from 10 institutes for artificial insemination by donor (AID) in Belgium and the Netherlands were tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, herpes simplex virus, and cytomegalovirus. The incidence of these micro-organisms in the semen samples was 0%, 6.3%, 4.6%, 35.9%, 0%, and 0.4% respectively, and 47% of all samples were infected with one or more of the micro-organisms. As the ejaculates from which the samples had been taken had already been, or would be, used for AID, the exclusion of microbiological contamination with sexually communicable micro-organisms before insemination is indicated.

Comparison of oral treatment of uncomplicated urogenital and rectal gonorrhoea with cefuroxime axetil ester or clavulanic acid potentiated amoxycillin (Augmentin)

In a randomised study of two drugs for the oral treatment of uncomplicated urogenital and rectal gonorrhoea the therapeutic effect of cefuroxime axetil ester (CAE) and amoxycillin plus clavulanic acid (A + C) was compared. Cefuroxime axetil ester 1.5 g was given to 129 men and 118 women. Amoxycillin 3.0 g and clavulanic acid 0.25 g was given to 131 men and 122 women. Both treatments were combined with probenecid 1.0 g and administered in a single oral dose. Of the 500 patients thus treated, 376 were assessable. In the group taking CAE, failure rates were 0.9% for the men and 0% for the women; and the overall failure rate was 0.5%. In the group taking A + C the equivalent failure rates were 4.6%, 1.2%, and 3.1%. The differences were not significant. Penicillinase producing Neisseria gonorrhoeae (PPNG) was isolated from 5.6% of the assessable patients. All 10 PPNG infections in the group taking CAE and four of 11 PPNG infections in the group taking A + C were cured. These numbers were too small to draw a definite conclusion about the efficacy of both drugs in this type of infection. Postgonococcal urethritis was observed in 35% of the men in the group taking CAE and in 32% of those in the group taking A + C. Side effects were noted in 38% of the group taking CAE and 28% of the group taking A + C. Nausea and vomiting were more commonly observed in the group taking CAE; and diarrhoea was more commonly observed in the group taking A + C.

Mucopolysaccharides in suspensions of Treponema pallidum extracted from infected rabbit testes.

The amount and nature of mucopolysaccharides present in extraction fluids routinely obtained in the isolation procedure of Treponema pallidum from infected rabbit testes was investigated. The mean quantity of mucopolysaccharides extracted from both testes of groups of 10 rabbits was 3.09 mg after infection for seven days and 26.88 mg after infection for 12 days, while from the testes of uninfected rabbits a mean of 0.42 mg was obtained. On electrophoresis the isolated mucopolysaccharides showed only one single band with the migration characteristics of hyaluronic acid. This band disappeared completely after pretreatment with hyaluronidase from bovine testes, which showed that during infection with T pallidum increasing amounts of hyaluronic acid accumulate. They can, at least in part, be extracted by a gentle extraction procedure, suggesting that this material binds loosely. The amount of hyaluronic acid isolated 12 days after infection showed positive correlations with the wet weight of testes as well as the number of treponemes isolated; seven days after infection such correlations were not present.

Detection of basal-cell determinant(s) in human psoriatic skin: a monoclonal antibody study.

Psoriasis is a disease characterized by abnormal epidermal keratinocyte proliferation and differentiation [1], clinically manifested by the excessive production of scales [8]. The increased proliferation of the epidermal cells is not restricted to the psoriatic lesions, but has also been observed in clinically unaffected skin [4]. In normal epidermis, keratinocytes undergo an orderly maturation as they migrate from the basal layer to the cornified layers via the spinous and granular layers. This migration is accompanied by sequential changes in the synthesis of water-insoluble protein subunits of tonofilaments the keratins [2]. Detailed analysis of keratins using monoclonal antibodies (MoAbs) has provided useful information concerning their tissue distribution and their expression during keratinocyte differentiation in normal epidermis and in epidermal diseases, including psoriasis and epithelial skin tumors [7, 9, 10]. In this communication, we report on three different MoAbs, 12G7, 253B7, and 244C6, which showed different reaction patterns with normal and psoriatic epidermis. Alll three MoAbs were produced, as described, at the Department of Cell biology and Genetics. MoAb 12G7 was generated after intraperitoneal immunization of BALB/C mice with cultured human mesothelioma cells. MoAbs 253B7 and 244C6 were obtained after intraperitoneal immunization of BALB/C mice with human skin squamous-cell carcinoma. Spleen cells from immunized mice were hybridized with P3 myeloma cells using somatic hybridization techniques [5]. In the case of MoAb 12G7, the hybridoma supernatants were prescreened using

Treatment regimens in severe psoriasis vulgaris with cyclosporin

In recent years, much attention has been focused on cyclosporin as a new alternative drug for the treatment of recalcitrant disabling psoriasis vulgaris. This drug has the important advantage of being non-myelotoxic as compared to other immunosuppressants. In conjunction with the earlier reported data concerning the clinical use of cyclosporin to treat severe psoriasis, three treatment schedules are outlined: short-term, intermittent and long-term. Uncontrolled treatment of psoriasis with cyclosporin could increase the risk of irreversible renal damage. The use of cyclosporin, therefore, requires a multidisciplinary ap proach in which regular consultations and monitoring by a dermatologist and, if warranted, by a nephrologist are imperative.

In Vitro Nickel-Specific T-Lymphocyte Proliferation: Methodological Aspects

The conditions necessary for optimal and reproducible test results in the nickel specific in vitro T-lymphocyte proliferation assay (NiPA) were studied. For this purpose peripheral blood mononuclear cells (PBMCs) of nickel-allergic subjects were isolated by density-gradient centrifugation and, when necessary, further separated into T cells and non-T cells. The influence of basic variables such as the number of cells per well, culture medium, serum-type and the type of culture dishes (round- or flat-bottomed) on the result of this assay, were investigated in parallel experiments. Furthermore, in this study enhancement of Ni-specific T-lymphocyte proliferation was attempted by the addition of epidermal cells from normal or patch-tested skin areas, recombinant IL-2 after antigen priming or pre-treatment of the cells with neuraminidase. Optimal and reproducible proliferation was obtained in cultures set up with 2 × 105 PBMCs or with purified T cells in the presence of 4–8 × 104 epidermal cells from patch-tested skin, using RPMI 1640 with HEPES and 15% pooled human AB serum in round-bottomed wells. Under the established optimal conditions the NiPA showed a 100% sensitivity and a specificity of 93%. Pre-treatment of PBMCs with neuraminidase and the addition of epidermal cells or rIL-2 after nickel priming enhanced the proliferative response in low-grade sensitized individuals.

Evaluation of an enzyme immunoassay for detection of herpes simplex viras antigen in genital lesions

To evaluate a non-marketed research prototype of a solid-phase enzyme immunoassay for detection of herpes simplex virus in genital lesions, 154 clinical specimens were collected from 127 men and 27 women with symptoms suggestive of herpes simplex virus infection (erythema, vesicles, ulcers and crustae). The samples were tested using the assay and cultures on four monolayers of human embryonic lung fibroblasts and Vero cells. When the culture was used as reference method, sensitivity was 76.9% and specificity 100% (prevalence 42.4%). Comparison of results by patient group showed that sensitivity was highest in material from patients with vesicles and ulcers. The highest sensitivity was obtained in specimens which developed a cytopathological effect within 48 h and in specimens with three or four positive cell cultures. These findings suggest that the assay is more successful in specimens with high virus titres. The enzyme immunoassay was found to be a rapid, moderately sensitive, highly specific test for detection of herpes simplex virus from genital lesions, but the usefulness of the assay is limited and culture methods should be preferred.