Observations on the Antipruritic Effect of Guanethidine in Atopic Dermatitis

Guanethidine, 0.75 to 1.25 mg. per kg. per day, was found to alleviate the pruritus of acute atopic dermatitis in 19 out of 20 patients. It was not effective in patients with other dermatoses. An apparent partial tolerance to this treatment developed in six out of 10 patients re-treated. It had little or no therapeutic effect in 10 patients with a variety of other pruritic dermatoses, suggesting that this drug has a specific antipruritic action in patients with atopic dermatitis. In a double-blind study, 11 of 12 patients with atopic dermatitis treated with guanethidine experienced relief of pruritus. Four out of 12 patients using a placebo had complete or partial relief. Guanethidine, 1% to 10%, used topically was therapeutically no more effective than placebo. In view of the reported side effects and the anesthetic hazard encountered with guanethidine, further long-term studies are indicated before this drug is adopted for clinical use in the treatment of atopic dermatitis. The findings support the hypothesis that atopic dermatitis may be a manifestation of a hereditary defect in cutaneous noradrenaline binding.     

Skin disease in a geriatric patients group in outpatient dermatologic clinic Karlovac, Croatia

To determine the characteristic pattern and frequency of dermatoses in dermatologic patients over 65 years we used electronic data base of General hospital Karlovac and conducted a retrospective cross sectional study evaluating age, sex and proportion of dermatoses. Total number of patients was 3200. There were 822 (25.69%) patients older than 65 years, and 2378 (74.31%) patients aged from 18-64 years. Ratio male/female in population over 65 years in our study was 0.76:1. Males had higher frequncy of verrucae vulgares 26 (7.3%) and dermatitis nummularis 47 (13.2%) then female and that difference was statistically significant. Female had higher frequency of keratosis acitinca 124 (26.61%) and fibroma 23 (4.94%), and that difference was statistically significant. The ten most common diagnosis in population over 65 years old were: keratosis actinica in 184 patients (22.38%) verrucae seborrhoicae in 156 (18.98%), dermatitits nummularis in 77 patients (9.37%), dermatitis allergica e contactu in 60 (7.30%) patients, mycosis in 56 (6.81%) patients, psoriasis in 51 (6.20%), verrucae vulgares in 39 (4.74%), fibromas in 27 (3.28%), naevi in 9 (1.09%) and acne in 1 (0.12%) patient. The number of patients with diagnosis of keratosis actinica, verrucae seborrhoicae and mycoses in population over 65 years old are greater then in younger subpopulation and that difference was statistically significant. There are specific pattern of frequency of dermatoses in elderly. Verrucae seborrhoica, keratosis actinica and mycoses are more common then in general population. In elderly risk for development of skin cancer is increased. Early detection of skin cancers and treatment of precanceroses is of utmost interest of health providers.     

Rhabdomyolysis and acute myoglobinuric renal failure following heroin use.

Four life-threatening dermatoses—Stevens-Johnson syndrome, toxic epidermal necrolysis, Kaposi''s varicelliform eruption and purpura fulminans—are unique in their abrupt onset and rapid progress to death, but prompt diagnosis and proper therapy can often cure the condition or prevent undesirable sequelae. Since two of the four conditions can follow the use of a variety of drugs and all may be secondary to an infectious agent, any physician may encounter them in practice and should be aware of their seriousness.     

circRNA: Regulatory factors and potential therapeutic targets in inflammatory dermatoses

The skin is the largest organ of the human body and acts as the first line of defence against injury and infection. Skin diseases are among the most common health problems and are associated with a considerable burden that encompasses financial, physical and mental consequences for patients. Exploring the pathogenesis of skin diseases can provide insights into new treatment strategies. Inflammatory dermatoses account for a large proportion of dermatoses and have a great impact on the patients'' body and quality of life. Therefore, it is important to study their pathogenesis and explore effective treatment. Circular RNAs (circRNAs) are a special type of RNA molecules that play important regulatory roles in several diseases and are involved in skin pathophysiological processes. This review summarizes the biogenesis, properties and functions of circRNAs as well as their roles in the pathogenesis of inflammatory dermatoses, including psoriasis, lupus erythematosus, atopic dermatitis, lichen planus and severe acne and their potential as therapeutic targets.     

代谢组学及其应用

对代谢组学的概念、特性、发展历史做了简要介绍,综述了当前代谢组学研究中的数据采集、数据分析中采用的技术,及代谢组学在疾病诊断、药物毒性研究、植物和微生物等邻域的应用,并对代谢组学的发展作了展望。     

Uncommon cases of pityriasis versicolor

Malassezia may play a role in several dermatoses. It is responsible for foliculitis and mainly for pityriasis versicolor. Pityriasis versicolor is the most known dermatitis because of its clinical aspects and frequently for its poor response to the therapy, mainly in chronic forms. The clinical aspects of uncommon and rare forms of pityriasis versicolor have been reported. The data related to the patients observed in the last thirty years in Siena are reported. In addition, a study was carried out in Pisa by Professor F. Mancianti to identify species of Malassezia isolated in 37 patients.     

Identifying and understanding drug allergies

Drug hypersensitivity reactions frequently occur in hospitalized and out-patients. Clinical presentations are numerous and heterogeneous, from a mild urticaria to a dramatic anaphylactic shock and an extensive bullous skin disease. Allergic reactions are unpredictable reactions, related to immunologic mechanisms. Some reactions mimic allergic reactions but no drug specific antibody or T cell proliferation can be demonstrated. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on the available epidemiological data concerning these reactions, including data on incidence and mortality and on the most recent advances in the pathophysiology and allergy diagnosis of drug hypersensitivity reactions.     

Affections dermatologiques de la muqueuse genitale masculine et de la verge

A wide variety of infectious, inflammatory or dysplasic disorders may affect both male genital skin and mucous membranes. We review here the clinical patterns or the most common disorders. The diagnosis is based upon the existence of erythematous balanitis, erosions or ulcerations. Among infections, candidiosis, genital herpes, HPV papillomas are the most common. Most of inflammatory skin disorders may affect the male organ, especially psoriasis, lichen planus or erosive lichen planus, allergic dermatitis, auto-immune bullous dermatoses, drug-reactions. Chronic balanitis, or recurrent inflammatory balanitis, lichen sclerosus may lead to the emergence of intraepithelial neoplasias (PIN) or invasive carcinomas. The management of genital lesions needs in fact: the observation or oral mucous membrances and of the skin it-self with a special attention to very peculiar body sites for the presence of typical skin disease lesions; a surgical biopsy for microscopic observation; in some cases immunopathology with direct and indirect immunofluorescence for the diagnosis of auto-immune disorders.     

Effect of Genetic Background on the Ratios between Different Types of Dermatoglyphic Patterns: Recessive Genodermatoses

The ratios between dermatoglyphic patterns of different types were studied in males and females with and without hereditary diseases of the skin. It was found that ridge patterns of fingers are determined by special polygenes. Patients with monogenic dermatoses (X-linked ichthyosis and autosomal recessive ichthyosiform erythroderma) exhibited a suppressed formation of the loop pattern compared to control subjects.     

Effect of genetic background on the ratios between different types of dermatoglyphic patterns: recessive genodermatoses

The ratios between dermatoglyphic patterns of different types were studied in males and females with and without hereditary diseases of the skin. It was found that ridge patterns of fingers are determined by special polygenes. Patients with monogenic dermatoses (X-linked ichthyosis and autosomal recessive ichthyosiform erythroderma) exhibited a suppressed formation of the loop pattern compared to control subjects.     

Selective inhibition of human neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine by sulfones

The therapeutic efficacy of the sulfones, dapsone, and sulfoxone in neutrophilic dermatoses may be related to the effects of these drugs on neutrophil function. Therefore we determined whether neutrophil chemotactic migration to various chemoattractants could be inhibited by sulfones in vitro. The chemotactic responses of human neutrophils from healthy donors were tested by using N-formyl-methionyl-leucyl-phenylalanine (F-met-leu-phe), purified human C5a, and leukocyte-derived chemotactic factor (LDCF). Therapeutic concentrations of sulfones selectively inhibited neutrophil chemotaxis to F-met-leu-phe, but did not affect neutrophil chemotaxis to LDCF or C5a. Inhibition of neutrophil chemotaxis to F-met-leu-phe was induced by both dapsone and sulfoxone at a concentration of 10 micrograms/ml without affecting random migration, and the inhibition was reversed by washing the neutrophils. When dapsone- and sulfoxone-treated neutrophils (100 micrograms/ml) were stimulated with F-met-leu-phe, neutrophil superoxide generation was not inhibited. Sulfapyridine (10 micrograms/ml) also selectively inhibited neutrophil chemotaxis to F-met-leu-phe; however, sulfamethoxazole and sulfisoxazole did not affect chemotaxis. The inhibitory effects of dapsone, sulfoxone, and sulfapyridine could not be demonstrated with granulocytes from rabbits or guinea pigs nor with human monocytes. Experiments with radiolabeled dapsone showed rapid, nonspecific, and reversible binding of dapsone to human neutrophils. These data suggest that a mechanism of action of sulfones in neutrophilic dermatoses may be a selective inhibition of neutrophil migration to as yet undefined chemoattractants in the skin.     

Skin microbiocenosis in patient with chronic dermatoses

The skin microflora of patients with chronic dermatoses (atopic dermatitis and psoriasis) have been studied by the original "Bactotests" method. The data thus obtained indicate that the clinical picture of the disease is related to the severity of skin dysbacteriosis. The electron-microscopic study of 2 staphylococcal strains isolated from patients has revealed the presence of the immunoglobulin cover (capsule-like outer sheath consisting of immunoglobulins and other humoral protective factors) on the cell wall of these bacteria.     

Lymphocytes with antigen receptors in drug allergy

The data on the possibility of using the rosette-formation tests for the diagnosis of drug allergy are presented. Tests based on changes in the levels of activated T- and B-lymphocytes after their incubation with allergenic drugs have proved to be low informative. The test found to be highly informative is the antigen-specific rosette-formation test based on the detection of lymphocytes, capable of binding allogeneic erythrocytes loaded with antibiotics causing allergy in patients, in the peripheral blood. This test may be of importance not only in diagnosis, but also for prognosis, as it permits the detection of sensitization to a drug before the clinical manifestations of allergy.     

Non-dermatophyte Dermatoses Mimicking Dermatophytoses in Animals

Dermatophytoses in animals are fungal diseases of the skin caused by dermatophyte fungi of the genus Microsporum or Trichophyton. Because the infection is generally follicular, the most common clinical sign is one or many circular areas of alopecia with variable erythema, scaling and crusting, and the primary differential diagnoses are follicular infections, such as bacterial folliculitis and demodicosis. Although dermatophyte folliculitis or ringworm is the most commonly observed lesion of dermatophytoses in animals, other presentations may be observed according to the host species and the dermatophyte involved: dermatophyte folliculitis or ringworm, scaling and crusting in dermatophytosis due to Microsporum persicolor, nodule in case of kerion or mycetoma, matted hairs, seborrheic dermatosis or miliary dermatitis in cats, generalized exfoliative dermatoses in dogs, cats and horses, superficial non-follicular pustules, papules and macules in the Devon Rex cat, pruritic dermatophytoses in dogs, cats and horses, and onychomycosis in dogs, cats and horses. Since manifestations of dermatophytosis are highly variable, particularly in the cat, dermatophytosis should be considered in case of any annular, papular, nodular or pustular dermatoses, alopecic or not, sometimes pruritic, and nodular dermatoses as well.     

Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.     

Up-to-date approaches to clinical estimate of phenotype of multiple drug resistance associated with function of ABC-transporters in human solid tumors]

The data on the discovery, specific features and evolution of the aftereffects of functioning in the cells of the ABC-transporters Pgp, MRP and BCRP, the markers of multiple drug resistance (MDRABC), are discussed. The results of the estimate of the MDRABC phenotype of human solid tumors were critically analyzed using different methodic approaches. It was shown that the frequency of the MDRABC phenotype detection by expression of the genes, encoding the ABC-transporter synthesis, was higher than that in detection of transport proteins in the cell. It was concluded that the only adequate clinical method for diagnosis of the MDRABC phenotype could be differential estimate of the functional activity of the ABC-transporters controlling not only the drug release to the cell, but also the drug intracellular compartmentization or division between the cytoplasm and nucleus.     

Hepatitis non-A,non-B.

Evidence for the existence of hepatitis non-A, non-B includes epidemiologic data and results of transmission studies indicating the presence of hepatitis that could not be explained by known causative agents. The diagnosis is suggested in patients who have multiple episodes of acute hepatitis or who contract hepatitis after transfusion, hemodialysis or drug abuse. Sporadic cases are common. Three such cases are described to illustrate that the disease is clinically indistinguishable from hepatitis A or B. The diagnosis is based on the absence of serologic markers of hepatitis A and B and of infection by Epstein-Barr virus and cytomegalovirus, or on serologic evidence of previous infection with hepatitis A and B.     

Efficient and cost-effective experimental determination of kinetic constants and data: the success of a Bayesian systematic approach to drug transport, receptor binding, continuous culture and cell transport kinetics

Details about the parameters of kinetic systems are crucial for progress in both medical and industrial research, including drug development, clinical diagnosis and biotechnology applications. Such details must be collected by a series of kinetic experiments and investigations. The correct design of the experiment is essential to collecting data suitable for analysis, modelling and deriving the correct information. We have developed a systematic and iterative Bayesian method and sets of rules for the design of enzyme kinetic experiments. Our method selects the optimum design to collect data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. The rules select features of the design such as the substrate range and the number of measurements. We show here that this method can be directly applied to the study of other important kinetic systems, including drug transport, receptor binding, microbial culture and cell transport kinetics. It is possible to reduce the errors in the estimated parameters and, most importantly, increase the efficiency and cost-effectiveness by reducing the necessary amount of experiments and data points measured.     

Description and mission evaluation of the Hungarian case-control surveillance of congenital abnormalities, 1980-1996

BACKGROUND: The Hungarian Case-Control Surveillance of Congenital Abnormalities was established in 1980. This article describes how the Hungarian Case-Control Surveillance of Congenital Abnormalities was first organized and is currently maintained. The baseline statistics are provided and potential venues of postmarketing surveillance of drug teratogenicity and other public health tasks and research are proposed. METHODS: Cases with congenital abnormalities and patient controls with Down syndrome were selected from the Hungarian Congenital Abnormality Registry. Population controls without congenital abnormalities were selected from the National Birth Registry on the basis of three matching criteria: sex, week of birth, and district of parent's residence. Three sources of information concerning drug exposures, maternal disorders, and pregnancy complications, among others, were used: (1) prospective and medically recorded data from antenatal care logbooks and discharge summaries; (2) retrospective maternal self-reported data obtained with a structured questionnaire in all the three study groups; and (3) data collected by regional nurse in house visits to nonrespondent cases and patient controls. Twenty-five congenital abnormality groups were evaluated. During the 17-year period of data collection, 22,843 cases, 38,151 population controls, and 834 patient controls were incorporated into the data set, constituting the largest population-based case-control data set of congenital abnormalities to date. RESULTS: Demographic features of pregnant women and informative offspring are presented along with the distribution of 25 main groups of congenital abnormalities. CONCLUSIONS: This system is appropriate for postmarketing the surveillance of drug teratogenicity, for the improvement of congenital abnormality diagnosis, to get informed consent, to have a communication with parents and to provide material for research.