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Biomedical subjects

U F Haustein

Publications and source records attributed to U F Haustein.

At least 37 records · Page 2Linked to original sources

Management of endemic outbreaks of scabies with allethrin, permethrin, and ivermectin.

BACKGROUND: At three residences for the elderly, recurrent scabies infestations became out of control. Due to the failure of repeated, nonsynchronized therapeutic efforts with conventional external anti-scabies treatments, an eradication program had to be developed. We describe a protocol for the management of outbreaks of scabies. METHODS: According to the clinical examination and microscopically identified mites, all individuals of the population (IOP: patients, staff, and family members) were divided into two groups: (a) healthy and infested IOP; and (b) cases with crusted scabies. The first group was treated simultaneously once with external scabicides (allethrin or permethrin). All others were hospitalized and treated either with systemic ivermectin or with the latter in combination with permethrin. RESULTS: In 252 IOP living in three residences for the elderly, clinical signs of scabies were reported in 91.5%, 78.5%, and 15.4% of the patients (age 55-97 years; mean, 80.5 years), 54.1%, 32.9%, and 16.6% of staff members, and in 7%, 3%, and 0% of family members. The infested IOP showed crusted scabies (index cases) in 5.3%, 5.0%, and 1.7%, common scabies in 43.1%, 36.7%, and 7.1%, and postscabiotic dermatitis in 10.3%, 7.6%, and 3.5%. In 99.2% of the synchronously treated IOP in group (a) (n = 240), the conventional treatment with permethrin cream 5% or allethrin spray was effective. Group (b) (n=12) received ivermectin (12 mg) once (n=5) or twice (n= 7) after an interval of 8 days. One index case received permethrin three times. CONCLUSIONS: Outbreaks of scabies in populations of elderly people require special management for disease control. Synchronous treatment with external permethrin cream 5% or allethrin spray, including all IOP once, and close control offers a time-saving, cheap, and reliable method. Crusted scabies should be treated by oral administration of ivermectin once or twice after an interval of 8 days. Additional applications of permethrin and mechanical clearing of hyperkeratotic subungual areas shorten the course.

Aged↗

Differentiation of Candida strains by lectin-mediated agglutination kinetics.

The lectin-mediated agglutination kinetics of Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, Candida kefyr, and Candida parapsilosis strains isolated from immunocompromised patients was investigated. The rate of the lectin-induced cell agglutination depends on the physiological state of the yeast cell population. Therefore, the Candida strains have to be cultivated and investigated under identical conditions. Lentil lectin (prepared from Lens culinaris), castor lectin, and concanavalin A were used. Different yeast species showed different agglutination behaviour. Furthermore, the lectin-mediated rate of agglutination is a strain-specific property which makes it possible to distinguish between different yeast strains of the same species. It is concluded that the lectin-mediated agglutination kinetics allows reproducible differentiation of yeast strains of the same species.

Agglutination↗

Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatment.

OBJECTIVE: To evaluate the efficacy, safety and side-effects of methotrexate (MTX) in psoriasis. DESIGN: A 26-year retrospective study. SETTING: Department of Dermatology, Leipzig University, Leipzig, Germany. PATIENTS: One hundred and fifty-seven patients with extensive plaque psoriasis, erythrodermic, pustular and arthropathic forms, were treated with low-dose methotrexate (15-20 mg maximum weekly dosage [Weinstein schedule]), the majority for long-term periods. The mean cumulative dose was 3394 mg, the mean duration 237 weeks. RESULTS: The effect of MTX treatment was good in 76%, moderate in 18% and poor in 6% of subjects; 61% experienced side-effects, most frequently due to liver function abnormalities, bone marrow suppression, nausea, gastric complaints and hair loss. In 20% of cases the subjects were forced to discontinue therapy; 9% refused therapy due to physical and psychological discomfort, 2% wanted to become pregnant, 16% were lost to follow-up, 6% died from multimorbidity and old age. Three subjects (2%) developed cancer of the lung, breast or cervix uteri, possibly in relation to long-term MTX treatment. Altogether there were no deaths or life-threatening side-effects attributable to MTX treatment, and no cases of progressive liver cirrhosis apart from two extensive skin necroses due to overdosage (misunderstanding, suicidal attempt) that were treated successfully with citrovorum factor. CONCLUSION: Low-dose MTX (<15-20 mg/week) is an effective therapy for extensive and severe forms of psoriasis if patients are selected carefully and monitored regularly, particularly with respect to liver and bone marrow toxicity. This helps to reduce severe side-effects even during long-term treatment. Drug interactions must be avoided. MTX therapy according to the guidelines is relatively safe and still has a place in the systemic treatment of psoriasis with 40 years of experience and an acceptable safety record.

Drug Administration Schedule↗

A ligand of human thy-1 is localized on polymorphonuclear leukocytes and monocytes and mediates the binding to activated thy-1-positive microvascular endothelial cells and fibroblasts.

Thy-1 is known to be expressed on fibroblasts, nerve cells, and blood stem cells. Previous studies have shown the induction of Thy-1 on phorbol ester stimulated human dermal microvascular endothelial cells in vitro. In situ Thy-1 expression was found on activated endothelium. In this study we were interested in the localization of a Thy-1 ligand and the characterization of the function of Thy-1 on human dermal microvascular endothelial cells and fibroblasts. Human Thy-1 purified from fibroblast extracts was labeled and used as a probe for the detection of a Thy-1 ligand. In cryostat sections of bullous pemphigoid skin a Thy-1 ligand was found on inflammatory cells, whereas the Thy-1 antigen was expressed on the endothelial cells and fibroblasts. By flow cytometry we could show the expression of a Thy-1 ligand on polymorphonuclear leukocytes and monocytes, whereas lymphocytes did not express this Thy-1 ligand. To study whether Thy-1 is involved in cell-cell adhesion we separated Thy-1-positive and Thy-1-negative cells by magnetic cell separation using the monoclonal antibody AS02. Cell adhesion assays and blocking experiments revealed a direct involvement of the Thy-1/Thy-1 ligand interaction in the binding of monocytes and polymorphonuclear leukocytes to Thy-1-positive activated endothelial cells and fibroblasts.

Adult↗

Histologic subtyping and malignancy assessment of cutaneous squamous cell carcinoma.

BACKGROUND: Squamous cell carcinomas (SCCs) of the skin have a wide range of histologic subtypes and there are indications of differences in prognosis. OBJECTIVE: The morphologic variety of SCCs with respect to its biological behavior and the further course of disease is analyzed, with emphasis on histopathologic criteria, briefly quoting the main clinical and pathogenetic aspects. METHODS: Referring to the international tumor classification of the World Health Organization, histologically different carcinoma variants are presented and discussed, based on a review of the literature regarding each subtype, and also including the desmoplastic SCC type. RESULTS: Histologically, common invasive SCCs are most frequently found, while metastases mainly occur in tumors of high thickness and poor differentiation. The immature spindle cell carcinoma type resembles sarcoma and may grow rapidly with an aggressive clinical course. Lymphoepithelioma-like carcinoma of the skin is extremely rare and its histogenesis remains to be elucidated. Thus far, one case with metastasis and lethal outcome has been reported. As details determining the progression ability have so far only been scanty and partially contradictory, more investigations are necessary, especially for acantholytic SCCs and invasive SCCs developing from Bowen's disease, whereas verrucous carcinomas can be categorized as low malignancy neoplasms. Desmoplastic SCCs, especially with large tumor thickness, should be separated from other SCC subtypes due to their high risk of local recurrence and metastatic spread. CONCLUSION: The future outcome of SCCs of the skin is significantly influenced by their histologic grade and tumor thickness. In addition, subtyping represents another valuable histopathologic tool for improving the assessment of malignancy.

Bowen's Disease↗

Penicillin G does not alter collagen type I metabolism of dermal fibroblasts in culture.

BACKGROUND: Penicillin G (PenG) has successfully been used for therapy of dermal fibrosis in patients suffering from systemic sclerosis (SSc). However, there is little knowledge on the mechanism of the antifibrotic action of PenG. OBJECTIVE: We studied the effects of PenG on dermal fibroblasts by analysing the influence of various amounts of PenG on the proliferation, synthesis and degradation of collagen by human dermal fibroblasts from healthy donors and 1 SSc patient (collagen high producer). METHODS: Collagen metabolism of cultured dermal fibroblasts was studied by Northern hybridisation for mRNA of collagen I, proline-4-hydroxylase, lysyl hydroxylase, matrix metalloproteinase I and determination of collagen content in culture supernatants. RESULTS: PenG did not alter the expression of the investigated mRNA, independently of the dosage and the incubation times used. The amount of collagen I protein was not influenced. CONCLUSION: There is no evidence of a direct antifibrotic effect of PenG on dermal fibroblasts; therefore, other mechanisms might be responsible for its effect in the treatment of SSc patients.

Cell Division↗

Pemphigus vulgaris in association with silicosis.

We report on a sixty-seven year old miner with pemphigus vulgaris characterised clinically by a three month history of relapsing oral lesions and blisters/erosions on the trunk, axillae and extremities, histologically by suprabasal cleavage due to acantholysis, immunologically by the epidermal intercellular net-like pattern due to deposits of IgG- and IgM-antibodies and complement C3 in the direct immunofluorescence as well as by serum antibodies to desmoglein 3 (130 KD) and plakoglobin (85 KD) by immunoblotting analysis. Silicosis has already been known for 6 years. In addition, antinuclear antibodies, anti-ssDNA-antibodies and anti-topoisomerase antibodies were found. Clinical improvement and clearing of skin symptoms could be achieved by systemic steroids in combination with cyclophosphamide. However, the patient died of sepsis deriving from recalcitrant pneumonia. Although the association of silicosis with various autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and dermatomyositis has been reported many times, our patient is, to the best of our knowledge, the second case with features of the two diseases: pemphigus vulgaris and silicosis.

Aged↗

The small proteoglycan fibromodulin is expressed in mitotic, but not in postmitotic fibroblasts.

The small proteoglycan fibromodulin is involved in a variety of adhesion processes of connective tissue, binds to collagen and seems to influence fibrillogenesis by regulating collagen fibril spacing and thickness. Using subtractive hybridisation and Northern blotting, we found expression of the fibromodulin gene only in mitotic but not in mitomycinC-induced postmitotic fibroblasts. Furthermore, we could show that in skin only fibroblasts but not endothelial cells and keratinocytes express fibromodulin. With age the thickness of collagen fibrils increases as well as the occurrence of postmitotic fibroblasts. We could show with different chemotaxis and similar collagen gel contraction experiments further physiological differences between mitotic and postmitotic fibroblasts. This is the first report showing the switch of mitotic to postmitotic fibroblasts at the molecular level. Therefore, fibromodulin provides a specific marker for mitotic versus postmitotic fibroblasts and could indicate cell ageing. Mitomycin C is therapeutically used in bladder carcinoma and could thus induce premature ageing of fibroblasts.

Base Sequence↗

[Histological and clinical prognostic factors in squamous cell carcinoma of the skin. A contribution to the multicenter carcinoma study of the association of surgical and oncological dermatology].

The guidelines of the International Union against Cancer are generally used to assess malignancy of squamous cell carcinoma of the skin. Beside TNM-staging, histological grading is performed. This system has been extended by a selection of histological parameters which were studied with respect to prognosis, based on a review of 184 patients with squamous cell carcinoma. An increased malignancy was found in carcinomas with the following features: clinical diameter greater than 2 cm, low degree of keratinization, high degree of cellular polymorphism, high mitotic index and high tumor thickness index (metastases only from tumor thickness 2.4 mm and subcutaneous infiltration), desmoplasia and ulceration. Consideration of histological tumor parameters improved prognosis assessment. Multivariate analyses with large case series are necessary to determine ranks of the prognostic factors. Therefore, the data analysis of all centers that contribute to the carcinoma registry will make a precise definition of high- and low-risk carcinomas possible and can thus influence therapy and follow-up procedures.

Aged↗

[Stevens-Johnson syndrome with transition to toxic epidermal necrolysis after carbamazepine administration, heroin and alcohol abuse].

A 28 year old patient developed a severe bullous exanthem and enanthem combined with hepatitis, fever and blood count abnormalities after taking carbamazepine and consumption of heroin and alcohol. After discontinuing carbamazepine, prednisolone was given over a five day period accompanied by intravenous fluid and electrolyte substitution and local therapy which lead to improvement. Severe bullous skin reactions nowadays are classified into erythema exsudativum multiforme majus (EEMM), Stevens-Johnson syndrome (SJS), overlap Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS/TEN), TEN with maculae and TEN on large erythema, and they are most often caused by antibiotics and anticonvulsant drugs. Heroin and alcohol abuse alters host immunity which subsequently may increase susceptibility to allergic reactions. There is a high (40%) mortality rate for TEN, and patients with organ involvement are at increased risk.

Adult↗

Detection of human soluble Thy-1 in serum by ELISA. Fibroblasts and activated endothelial cells are a possible source of soluble Thy-1 in serum.

The functions of Thy-1, a 35-kDa cell-surface glycoprotein, and its natural ligand are still unknown. Anchoring to the membrane via linkage to phosphatidyl-inositol (PI) raises the possibility of cleavage off the membrane by PI-specific phospholipases. Soluble Thy-1 (sThy-1) could interfere with the binding of the unknown natural ligand followed by regulation of different cell functions. In this study we established an enzyme-linked immunosorbent assay (ELISA) to measure and quantify sThy-1 in serum and wound fluid. Recombinant human Thy-1 (rhThy-1) was expressed in Drosophila S2 cells, purified from culture supernatant and used as standard for quantitation of sThy- by the ELISA technique. There were no differences in sThy-1 levels in serum of healthy donors and patients with systemic sclerosis, leg ulcers, or rheumatoid arthritis, respectively, detected by ELISA. In contrast, at the local site of inflammation, in wound fluid of venous leg ulcers and in synovial fluid from joint puncture, we found strongly elevated levels of sThy-1 compared with sThy-1 in the serum of the same patient. Thy-1 is expressed in humans on brain cells, fibroblasts, a subpopulation of CD34+ blood stem cells, and possibly activated human dermal microvascular endothelial cells. In this study, we never found Thy-1 mRNA or protein expression in resting endothelial cells as shown by reverse transcriptase polymerase chain reaction (RT-PCR) and flow-cytometry. Thy- expression could be induced on endothelial cells by phorbol myristate acetate and to a lesser extent by tumor necrosis factor-alpha (TNF-alpha). In situ, monoclonal antibodies to Thy-1 did not stain endothelial cells in normal skin, whereas endothelial cells in the synovial membrane of rheumatoid arthritis patients and endothelial cells surrounding melanoma express Thy-1. In summary, our data indicate that Thy-1 is present in soluble form in serum. Furthermore, Thy-1 seems to be a marker for endothelial cell activation. Therefore, activated endothelial cells as well as fibroblasts might be a possible source of sThy-1.

Arthritis, Rheumatoid↗

In vitro activity of rilopirox against fluconazole-susceptible and fluconazole-resistant Candida isolates from patients with HIV infection.

The in vitro antifungal activity of the new hydroxypyridone antimycotic rilopirox has been evaluated against 38 fluconazole-susceptible and -resistant clinical isolates of Candida albicans together with other Candida species isolated from patients with human immunodeficiency virus (HIV) infection and oropharyngeal candidosis. Minimum inhibitory concentrations (MICs) of both rilopirox and fluconazole were measured by a microdilution method using high-resolution medium supplemented with asparagine and glucose at pH 7.0. In comparison, an agar dilution technique was carried out for susceptibility testing of the antifungal agents. Rilopirox was found to be able to inhibit growth of all clinical yeast isolates. The rilopirox MICs at which 50% and 90% of strains were inhibited (MIC50 and MIC90 respectively), as determined by the microdilution method, were 4 and 8 micrograms ml-1 respectively. The highest MIC values for rilopirox using microdilution and the agar dilution method were 32 or 25 micrograms ml-1 respectively. On the other hand, for fluconazole, the MIC50 and MIC90 achieved were 0.5 and 128 micrograms ml-1, respectively, which means that the MIC90 value of fluconazole was 16-fold higher than that of rilopirox. Using the agar dilution technique, the MIC values of rilopirox were in the range 0.006-25 micrograms ml-1 with a median of 3.12 micrograms ml-1. For fluconazole, the MIC90 value was four-fold higher than that for rilopirox, indicating a considerable proportion of yeast strains with high MICs of 100 micrograms ml-1, suggesting in vitro resistance to this azole antifungal. All strains with diminished fluconazole susceptibility were susceptible to rilopirox. Even Candida krusei and Candida glabrata exhibited good in vitro susceptibility to rilopirox. Therefore, this new antifungal agent may be used as an alternative not only in the treatment of vaginal candidosis, but also in oropharyngeal Candida infections, e.g. in AIDS patients.

AIDS-Related Opportunistic Infections↗

In vitro susceptibility of yeasts for fluconazole and itraconazole. Evaluation of a microdilution test.

In vitro susceptibilities were determined for a total of 159 clinical isolates and 12 reference strains of yeasts belonging to different Candida species including 94 Candida albicans strains, and further genera such as Cryptococcus, Trichosporon, Geotrichum and Saccharomyces. Minimum inhibitory concentration (MIC) values for fluconazole and itraconazole were assessed using a microdilution technique with the semisynthetic high resolution (HR) medium supplemented with glucose and asparagine but without sodium hydrogen carbonate (pH 7.0), according to a proposal of the working group 'Clinical Mycology' of the German Speaking Mycological Society. Fluconazole MIC values for C. albicans were between 0.125 and > or = 128 micrograms ml-1. Thus, the median of 1 microgram ml-1 showed that the overall fluconazole susceptibility was good. As expected, Candida krusei (seven strains) exhibited diminished in vitro susceptibility with MIC values for fluconazole of 8 to 128 micrograms ml-1 with a median of 64 micrograms ml-1. Some Candida kefyr strains seemed to be less susceptible against fluconazole which was indicated by a MIC90 of 64 micrograms ml-1. Surprisingly, no Candida glabrata isolate exhibited a MIC value greater than 16 micrograms ml-1. Other Candida species, Trichosporon cutaneum, Geotrichum candidum and Saccharomyces cerevisiae showed low MICs to fluconazole. In vitro susceptibility testing of itraconazole revealed that all Candida species except C. albicans, but also Trichosporon cutaneum, Geotrichum candidum, and Saccharomyces cerevisiae exhibited acceptable low MIC values against itraconazole (0.03-2 micrograms ml-1). Their MIC90 values for itraconazole were in the close range between 0.125 and 2 micrograms ml-1. MIC values between 0.125 and 2 micrograms ml-1 were obtained, even for C. krusei strains. On the other hand, the range of C. albicans MICs was between 0.0125 and > or = 16 micrograms ml-1 with MIC50 and MIC90 values of 0.125 and > or = 16 micrograms ml-1, respectively, indicating that a considerable number of yeast strains have high MICs. The comparative evaluation of different experimental conditions revealed that there exists a marked influence both of inoculum size and incubation time on the results of susceptibility testing. Therefore, for routine usage 10(2) CFU ml-1 and 18-24 h incubation time for this microdilution method with HR medium are recommended.

Antifungal Agents↗