PL004 Wound healing

PL004 Wound healing

Sl Plenary Lectures PLO01 Androgenic disorders T.J. McKenna. St. Vincent’s Hospital, Dublin 4, Ireland Androgen excess is characterized clinical...

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Plenary Lectures

PLO01 Androgenic disorders T.J. McKenna. St. Vincent’s

Hospital,

Dublin

4, Ireland

Androgen excess is characterized clinically by hirsutism, acne, alopecia, increasing muscle bulk, deepening of the voice and clitoromegaly. The causes of androgen excess include idiopathic hirsutism (IH)/polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), Cushing’s syndrome, androgensecreting tumours of the ovaries and the adrenal glands. Greater than 95% patients presenting with an androgenic disorder have mild excess associated with IIUPCOS. These usually can be recognised clinically by the occurrence of slowly progressive hirsutism presenting in the decade between 15 and 25 years of age with (PCOS) or without (IH) menstrual disorders and are never associated with virilisation. For the patient presenting with the typical features of IH/PCOS the diagnosis can be made clinically. If it is decided to screen for more sinister disorders measurement of the testosterone (T): sex hormone binding globulin (SHBG) ratio is the test of choice. When hirsutism presents with atypical features investigation is indicated. Investigations include the measurement of TSHBG, dehydroepiandrosterone sulphate, imaging of the adrenals and ovaries. In some ethnic groups it is advisable to measure an early morning 170H-progesterone level or the 170H-progeserene response to stimulation with ACTH to screen for CAH. Normal suppression of cortisol following administration of dexamethasone 1 mg at midnight excludes Cushing’s syndrome.

PLO02 Recent advances in psoriasis E. Christophers. Dept. of Dermatology,

University

of Kiel,

Germany

Psoriasis is a common skin disease of which possible pathogenetic mechanisms still are under discussion. Recently major insight into pathophysiology was provided by localization of susceptibility gene loci on several chromosomes in familial psoriasis. These findings support the multifactorial nature of psoriasis In addition, substantial evidence is provided by immunopathology studies showing that T-cell-autoimmunity plays 1 major role. Finally, therapeutical regimens such as cyclosporin A, FK 506, fumerates as well as bath PUVA and vitamin D derivatives have shown to possess a distinct mode of action. Taken to the other these findings have helped in the understanding of the pathophysiological complexity of psoriasis.

PLO03 Recent advances in the understanding of melanogenesis and melanin pigmentaty disorders J.-P. Ortonne. U385 INSERM, Dermatologie,

Hdpital

Faculte’de de 1‘Archet, Nice,

Mddecine, France

Service

de

The past decide has brouhgt a great deal of new knowledge regarding the biochemistry of melanins, the regulation of melanogenesis, and the biology of melanocytes. This progress is largely due to the ability to grow normal human melanocytes in culture. Mutations affecting mouse coat colour have been characterized in recent years. The wealth of genetic information arising from these studies has been an impetus for understanding the enzymology, cell biology, and developmental biology of melanocytes and melanin synthesis. Most of the data obtained in mouse melanocytes can be extrapoled to their human counterparts. They have led to the discovery of new growth factors of regulatory proteins influencing human skin colour and to a better knowledge of the pathophysiology of hereditary and acquired disorders characterized by disturbances of skin melanin pigmentation. The genes involved in several pigmentary genodermatoses, including piebaldism, Waardenburg’s syndromes, different forms of oculo-cutaneous albinism, Hermansky-Pudlak, etc have been identified as well as candidate genes for other unusual disorders such as Griscelli-Prunieras syndrome. The cloning of the agouti and MSH receptor genes will also be most informative, for the molecular characterization of human phototypes as suggested by recent investigations. Melanocytes have long been considered as highly specialized cells with the unique function of synthesizing melanins. Accumulating evidence suggest that melanocytes display a considerably wider range of secretory activities than those involved in melanin production. They are capable of producing a variety of biologically active compounds. Other findings suggest that melanocytes are active participants in the skin immune system. These observations throw new lights for our understanding of acquired melanin pigmentary disorders such as vitiligo, melasma, post-inflammatory dyspigmentation, pigmentary abnormalities of chronologically and photodamaged skin.

PLO04 Wound healing M.W.J. Ferguson. School Manchestel; Manchester

3.239 Stopford Ml3 9PT, UK

of Biological Building,

Sciences, University Onford Road,

of

Wound healing presents two major clinical problems: chronic wounds which fail to heal and scarring following acute or chronic wounds. This presentation will concentrate on novel

s2

Plenary

research to reduce/eliminate scarring following wound healing. Wounds created on early gestation, embryonic mammals, heal with a reduced inflammatory response, altered cytokine profile and absence of scarring. Manipulation of the cytokine profile of healing adult dermal rat wounds can prevent scarring. Thus neutralisation of transforming growth factor beta 1 and beta 2 (TGFBl and 2) or addition of TGFB3 results in healing with restitution of the normal dermal histological architecture and the absence of scarring. Exogenous addition of interleukin-10, interleukin-4 or neutralisation of interleukin-1 or interleukin-6 or PDGF, also improve scarring. Interestingly, most cytokines are released as inactive precursors and activation is a key regulatory step. In the case of the TGF#l family, the latency associated peptide binds via its carbohydrate chains to the mannose-6-phosphate receptor, where a protease such as plasmin cleaves the active TGF/I from the inactive precursor. Competition for the mannose-6-phosphate binding sites by exogenous mannose-6-phosphate results in a reduction of TGF#l activation and marked improvement of scarring in rodent and porcine models. Formulations of mannose-6-phosphate are entering clinical trial as potential anti-scarring therapies. Normal acute wound healing is optimised for speed of closure under dirty conditions and the overdrive inflammatory response and resulting cytokine profile mask the innate regenerative response of the dermis. Manipulation of this cytokine profile early in the wound healing cascade can result in wounds which heal with the absence of scarring and no adverse sequelae. These findings have important new therapeutic implications.

PLO05 Advances in the immunobiology

of the skin

Stephen I. Katz. National Musculoskeletal USA

Institute of Arthritis & & Skin Disease, Bethesda, MD 20892-2350,

During the past ten years there has been an explosion of knowledge relating to the skin immune system. This knowledge has had an enormous impact on our understanding of the mechanisms involved in disease pathogenesis. Using allergic contact dermatitis as the paradigm, I will describe the various constituents of the skin immune system and their products and discuss their relevance in inflammatory skin diseases.

PLO06 HIV in the year 2000 Christine Katlama. AIDS of Infectious

Diseases,

Clinical Research Unit, Department H6pital Pitie’ Salp&%ri&e, Paris, France

In the last recent years there have been major changes in therapeutic management of HIV infection. Introduction of both combination therapies and protease inhibitors (PI) have induced marked changes of HIV clinical spectrum with 2 major optimal consequences: a delayed occurrence by 40-50% of AIDS cases; a decreasing death rate; a reduction in incidence of opportunistic infections; in a prospective cohort of 300 patients in our unit, with less than 100 CD4/mm3 (Prevoco), the CMV disease incidence has decreased from 14.6/100 patients-years (py) before PI to 6.3/100 py after P I; similarly incidence of MAC infection has been reduced from 7.8 to 1.2/100 p-y and

Lectures

cryptosporidiosis from 5.5 to 1.2/100 py; death rate dropped from 21.7/100 py to 9.6/100 py. This is accompanied by a restoration in immune functions with an increase in both number and functionality of lymphocytes CD4. Whether this immune restoration will be maintained and strong enough to prevent occurrence or relapses of opportunistic infections remains to be investigated. An effective control of viral replication is the major step of controlling HIV disease. Optimal therapeutic strategies with an optimal compliance and tolerance to treatments represent major issues in long-term chronic therapies.

PLO07 Urticaria and autoimmunity M.W. Greaves, R. Sabroe. St John’s St Thomas’ UK

Hospital

Lambeth

Palace

Institute Road,

of Dermatology, London SE1 7EH,

The cause of chronic urticaria in the great majority of cases is unknown. We have identified a subgroup (representing 2533% of the total) in whom functional anti FCsRIa autoantibodies with disease specificity can be demonstrated. A small minority also have IgG anti-IgE autoantibodies of uncertain significance. Studies of HLA haplotypes and of thyroid autoimmunity in this subgroup of chronic u&aria are in keeping with its autoimmune status. The anti FCERI autoantibodies which have been shown to be of the IgGr, IgGs isotypes cross link the basophil or mast cell high affinity IgE receptor and evoke histamine release and consequent whealing. Autoimmune disease generated by anti-receptor antibodies is well recognised but in most cases (e.g. myasthenia gravis) the antibodies inhibit receptor function. In the case of chronic u&aria these autoantibodies cross link receptors to evoke the “normal” function of the mast cell or basophil (histamine release), thereby causing symptoms.

PLO08 Genital ulcer disease 1997 T. Rosen. Baylor

College

of Medicine,

Houston,

Texas,

USA

Although the incidence of non-herpetic genital ulcer diseases (GUD) has been decreasing in the USA, this remains a major health hazard throughout the world. Travel for business, recreation and education places individuals at risk. Morphology alone is inaccurate for diagnosis of genital ulcers. Despite the use of standard diagnostic tests, studies from many different countries demonstrate about 20% of genital ulcers do not have a firm diagnosis. Immunodiagnostic tests (fluorescent antibody, immunoperoxidase) and increasing availability of DNA probes may allow better classification of genital ulcers in the near future. Recent work suggests that the transmission of several GUD depends largely upon those with subclinical, asymptomatic or unrecognized infection. This is particularly true of HSV, but may be true for other disorders. HIV coinfection may confound clinical and serologic diagnosis and may reduce the efficacy of standard therapy for virtually all GUD. Conversely, GUD (especially HSV) may accelerate HIV progression. Rapid treatment of GUD may be associated with reduced risk of subsequent HIV seroconversion. GUD knows no racial, age or economic boundaries; STD’s must be included in the dif-