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In an effort to develop a quantitative ligand-binding model for 5-HT 1A receptors, a pharmacophore mapping procedure, DIStance COmparison (DISCO) was used to identify structural features that are common in a novel set of pyridazinothiazepines and pyridazinooxazepines with moderate-to-high affinity to 5-HT 1A -receptors. The pharmacophore thus obtained provided a good starting point for a Comparative Molecular Field Analysis (CoMFA) study. The CoMFA gave acceptable statistical measure ( R CV 2 =0.52 by using six latent variables, whereas it afforded a noncross-validated R 2 value of 1.00). Predictability of our model was tested by a separated prediction set of four compounds, for them the relative deviations between calculated and measured biological activity values did not exceed 10%.

As it is not clear whether mutations in hemochromatosis gene (HFE) and hepatitis C virus (HCV) act independently in the pathogenesis of porphyria cutanea tarda (PCT), and prevalence of both risk factors reveals a great variety in different parts of the world, PCT patients from our Central East European country were investigated for this aspect. The occurrence of the C282Y and H63D mutations in HFE gene were determined in 19 PCT patients and compared with the reported control frequencies. Furthermore, the presence of HCV infection was determined and related to the patients' HFE status. The C282Y mutation was found in 3/19 cases (one patient was homozygous and two heterozygous), with an 10.5% allele frequency (vs. 3.8% control) (p0.05). Five patients were heterozygous for the H63D mutation, allele frequency 13.1%, which did not differ from the reported control prevalence of 12.3%. Six patients (31.7%) were HCV-RNA positive, out of the six one was heterozygous for H63D mutation and one was compound heterozygous. HCV infection and HFE C282Y mutations may probably be independent predisposing factors for development of PCT in Hungarian patients.

Pachyonychia congenita (PC) is a group of inherited ectodermal dysplasias, the characteristic phenotype being hypertrophic nail dystrophy. Two main clinical subtypes, PC-1 and PC-2, are inherited as autosomal dominant disorders, but other less well characterized clinical forms also exist. The PC-1 phenotype may be distinguished by the absence of the epidermal cysts found in PC-2, and it has been shown to be caused by mutations in either keratin K16 or its expression partner, the K6a isoform of K6. Mutations in K16 have also been shown to cause a milder related phenotype, focal non-epidermolytic palmoplantar keratoderma. Recently, we have developed a long-range polymerase chain reaction (PCR) strategy which allows specific amplification of the entire functional K16 gene (KRT16A), without amplification of the two K16 pseudogenes (psiKRT16B and psiKRT16C), enabling mutation analysis based on genomic DNA. Here, using this methodology, we describe novel mutations R127P and Q122P in the helix 1A domain of K16 in two families presenting with PC-1. Both mutations were excluded from 50 normal unrelated individuals by restriction enzyme analysis of K16 PCR fragments. In one family, ultrastructural analysis was performed, revealing distinctive tonofilament abnormalities. Specifically, keratin filament bundles were greatly condensed, but did not form the dense amorphous aggregates seen in a number of other keratin disorders. In the second kindred, autosomal dominant cataract was present in some but not all members affected by PC. As the cataract phenotype did not fully cosegregate with the K16 mutation, and given that K16 is not expressed in the lens, these two phenotypes may be coincidental.

A 7-year-old girl with generalized erythematous, scaling plaques and vesiculobullous lesions on the extremities was diagnosed as having pemphigus foliaceus. Lesional direct immunofluorescence revealed intercellular IgG, IgA and C3 deposition. The patient's serum gave positive reactions against one epitope of desmoglein 3 and the epitope of desmoglein 1 in enzyme-linked immunosorbent assays, but the blood sample for indirect immunofluorescence did not display any circulating antibodies. The patient was successfully treated systemically with prednisolone and dapsone. Currently, she is taking dapsone, 12.5 mg daily. She has been free of lesions for the last 3 years.

Developments in the fields of laser technology and application have significantly broadened its clinical use over the past two decades. As lasers became more smaller, more reliable and less expensive, dermatology will benefit new laser-based therapeutic and diagnostic methods. Relevant laser systems and their clinical applications are presented, as are investigational laser systems, which may be of importance for the future in dermatology. We review advances in the use of pulsed lasers for treating vascular and non-vascular, pigmented epidermal and dermal lesions, for precise cutting of tissue, for photodynamic therapy and the future role of diode lasers in dermatological laser surgery is also discussed.

In a considerable proportion of the patients with chronic renal failure, skin changes resembling porphyria cutanea tarda (PCT) develop some months to years after the onset of maintenance hemodialysis. This can be either real PCT, or secondary PCT, or PCT-like bullous dermatosis. In a minor proportion, real PCT can be diagnosed. In such cases, elevated total porphyrin levels with a predominance of uro- (IIII) and heptacarboxyl porphyrins (IIII) can be measured in the plasma (also in the urine, if not anuric), and fecal (perhaps urinary as well) isocoproporphyrin can be detected. The activity of the hepatic uroporphyrinogen decarboxylase (UD) is decreased in every type of PCT; in PCT-II, also that of the erythrocyte UD. In a higher proportion, secondary PCT (pseudo-PCT) develops. In this group, porphyrins are accumulated in the plasma due to the unsatisfactory renal function. Uro and hepta are the dominant fractions here as well, but alteration in the ratio of the uro isomers or the presence of isocoproporphyrin can not be expected. The UD activity is probably normal in every tissue. In 1% to 18% of the cases, PCT-like bullous dermatoses develop, but porphyrins are at normal levels in all compartments. The phototoxic agent here is other than porphyrin (e.g. nalidixic acid, furosemide, tetracycline, etc., or unknown). The authors review the knowledge on chronic hemodialysis-related PCT or the PCT-like bullous dermatoses: development of the above-mentioned conditions, clinical and morphological and biochemical features, difficulties in diagnosis, or the possibilities in therapy.

Ninety two patients suffering from porphyria cutanea tarda were examined ophthalmologically in a paired case-control study. The incidence of pinguecula and that of pterygium were 8 times and 2 times higher, respectively, in PCT patients that in the control group. The photodamage of the conjunctiva is presumed to be a result of the photoactivity of uroporphyrin in the tissues.

Summary To estimate the prevalence of the subgroups of porphyria cutanea tarda (PCT), erythrocyte uroporphyrinogen decarboxylase (UD) activity was measured in 80 unrelated patients with PCT, and in 45 of their relatives by using pentacarboxyl-porphyrinogen III as substrate. The subgroups were differentiated by analysis of the urinary porphyrins of the patients and 119 of their relatives. Of the patients, 77·5% were found to be suffering from the sporadic form of PCT (type I PCT), and 22·5% from the familial form (type II PCT), Every patient with PCT had previously been affected by alcohol, oestrogen or some other liver-damaging factor. The relative frequency of familial PCT was higher in females (nine of 15) than in males (nine of 65), which suggests that inheritance of the gene for type II PCT may predispose to oestrogen-precipitated PCT. The onset of type II PCT occurred at a lower age than that of type I (42·6 vs. 47·0 years). The findings suggest an increased risk of precipitating factors in carriers of an inherited UD deficiency.

Repigmentation has been observed under the influence of topically administered Efudix cream in 3 patients with vitiligo of symmetrical acral type. No response has been received in 2 patients with segmental vitiligo treated in the same way. Recurrence of vitiligo was seen in 1 patient. Histologic and electron microscopic characterization of recolonized melanocytes is described. The significance of topical 5-fluorouracil treatment in vitiligo is discussed.

We report on the appearance of porphyria cutanea tarda in a patient with systemic LE and in two patients with discoid LE. A review is given on the corresponding literature. It is suggested that both lupus erythematosus and porphyria cutanea tarda have multifactorial inheritance. The cause of coexistence can be common genes responsible for the genetic determination which also predispose to the occurrence of both diseases. The question of etiology still remains obscure. This coexistence raises, however, a more practical question as regards the therapeutic modalities for the two diseases.

We give a retrospective survey on the clinical, histological, biochemical, and pathogenetical aspects of sclerodermiform changes rarely accompanying porphyria cutanea tarda (PCT). Sclerodermiform changes were seen in 12 patients (2% of all our PCT cases). In these patients, no correlation was found between the severity of the dermatological signs and symptoms and the degree of disturbance in the porphyrin metabolism. Biochemical remission was not accompanied by improvement of the sclerodermiform changes. The proportion of porphyrins with 4 or 5 COOH-groups was higher than that of PCT patients without sclerosis. The findings are consistent with the view that the development of sclerodermiform changes cannot be merely explained by phototoxic reactions, but the "dark-effect" of the porphyrins may also play an important role in the pathogenesis.