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Biomedical subjects

H Gollnick

Publications and source records attributed to H Gollnick.

At least 19 recordsLinked to original sources

Comparative activity of the topical quinolone OPC-7251 against bacteria associated with acne vulgaris.

The antibacterial activity of the topical quinolone OPC-7251 against bacteria commonly found in acne vulgaris was tested in vitro by an agar dilution method. The MIC50 was 0.25 mg/l for Propionibacterium acnes, 0.125 mg/l for Propionibacterium granulosum, 0.03 mg/l for Staphylococcus aureus and 0.06 mg/l for coagulase-negative staphylococci. Compared with seven other antibiotics tested (ciprofloxacin, penicillin, erythromycin, tetracycline, clindamycin, fusidic acid and gentamicin), OPC-7251 had potent activity against both propionibacteria and staphylococci and the lowest incidence of resistant strains.

Acne Vulgaris

Growth characteristics and differentiation of basal cell carcinoma in vitro--immunohistochemical, gel electrophoretic, and ultrastructural analysis.

Cell cultures were established from 48 solid basal cell carcinomas (BCC) and from the normal epidermis of the same patients. The growth characteristics and differentiation of BCC cells in vitro were compared with normal keratinocytes (nKC) by using immunohistochemistry, two-dimensional gel electrophoresis including immunoblots, transmission electron microscopy, and soft agar suspension culture. After isolation of the tumor tissue under a stereodissection microscope, explants were cultured on feeder layers of mitomycin-treated 3T3 cells. After 3-5 d, 73% of all explants of BCC could be successfully cultured showing spindle-shaped outgrowing cells. Compared to nKC, cultured BCC cells had a lower growth rate and showed a wider intercellular polymorphism regarding size and shape. Their labeling pattern with a wide panel of monoclonal antibodies showed significant differences from that of nKC. In particular, only weak reactions for various cytokeratins, filaggrin and vimentin depending on the BCC cell type (small, middle, large) were found. Two-dimensional gel electrophoresis revealed expression of keratins 5, 6, 14, 16, and 17 in BCC cells and of K 5, 6, 13, 14, 16, 17, and 19 in nKC. These findings were confirmed by immunoblot. On the ultrastructural level, only a few desmosomes and a lower degree of keratinization markers were detected in BCC cells; finally, when cultured in soft agar BCC cells formed colonies whereas nKC did not. Our findings indicate that cultured BCC cells may preserve in vitro some in vivo characteristics and maintain a growth and differentiation pattern that differs from cultured nKC. The culture model presented here provides further insights into the cytogenetic and histogenetic characteristics of BCC.

Aged

Elephantiasis nostras verrucosa: beneficial effect of oral etretinate therapy.

Elephantiasis nostras verrucosa is characterized by chronic secondary, non-filarial lymphoedema due to recurrent lymphangitis, dermal fibrosis, and epidermal changes consisting of hyperkeratotic, verrucous and papillomatous lesions. Histologically, there is pseudoepitheliomatous hyperplasia. Therapeutic efforts should aim to reduce lymph stasis, which will also lead to improvement of the cutaneous changes. In this study, rapid disappearance of the hyperkeratotic and verrucous lesions, remarkable flattening of the papillomatous nodules and improvement of lymphoedema occurred in three obese patients treated with etretinate in an initial dose of 0.6-0.75 mg/kg/day for 4-6 weeks. Monitoring of plasma concentrations of etretinate, acitretin and 13-cis-acitretin by HPLC revealed sufficient short-time absorption (4 h) and bioavailability of the drug (30 days; two out of three patients). Long-term maintenance therapy in one patient produced a remarkable improvement in the lymphoedema; another patient relapsed after discontinuation of the etretinate and responded again after this was reintroduced. In the third patient treatment was withdrawn because of an increase in triglycerides, but improvement persisted 6 months later. The clinical side-effects of oral retinoid therapy were moderate and well tolerated.

Administration, Oral

Nonsegmental vitiligo: decrease of the CD45RA+ T-cell subset and evidence for peripheral T-cell activation.

Peripheral T-lymphocytes from 16 randomly selected patients with nonsegmental vitiligo were labeled with monoclonal antibodies recognizing T-cell receptor (TCR) alpha/beta, TCR gamma/delta, CD3, CD4, CD8, CD45RA, CD45RO, CD11b, CD11c, CD16, CD56, CD25, CD54, and HLA-DR antigens. In comparison with matched controls, a significant decrease of the CD45RA+ subset (P less than 0.03) together with significant increase of the circulating HLA-DR+ cells (P less than 0.02) was found. No other alterations were detected. These findings may point to some autoimmune phenomena involved in the pathogenesis of the disease. The increased HLA-DR expression indicates the presence of activated peripheral T-cells. Thus, our data provide new and further evidence for T-cell dysregulation in nonsegmental vitiligo.

Adolescent

[Linear hyperpigmentation caused by bleomycin].

We report on an uncommon but characteristic cutaneous side-effect of bleomycin. A 52-year-old woman being treated for carcinoma of the cervix developed linear hyperpigmentation in wheals in the lumbosacral region, the lateral thorax and above the elbow. The skin lesions appeared during the fourth cycle of chemotherapy with bleomycin. Histologically, incontinence of melanin, focal parakeratosis and a lymphocytic infiltrate with epidermotropism were prominent. By electron microscopic examination metabolically highly active melanocytes were found, with increased number of melanosomes at all stages of maturation and deposits of extracellular melanin in the underlying dermis. The epidermal keratinocytes were unchanged.

Antineoplastic Agents

Intravascular coagulation necrosis of the skin associated with cryofibrinogenemia, diabetes mellitus, and cardiolipin autoantibodies.

Intravascular coagulation necrosis of the skin is rare and appears as hemorrhagic infiltrates that may develop ulcerating necrosis, mainly on the acral areas. The face, arms, and legs were severely involved in our patient. In this patient intravascular coagulation necrosis was associated with cryofibrinogenemia, diabetes mellitus, and IgM cardiolipin autoantibodies. In addition, rheumatoid factor, elevated polyclonal IgA, and haptoglobin were present as risk factors for the vasculopathy. Skin biopsy specimens showed plugging of dermal venules by thrombi formed of fibrin and erythrocytes. Immunohistologic staining revealed a strong positive reaction for fibrinogen, with some positivity for C3, C4, IgG, IgA, and IgM. Erythrocyte extravasation occurred in late lesions without being accompanied by perivascular leukocytic infiltrates. Detailed clinical examination failed to identify an underlying malignancy. Treatment with heparin and prednisolone produced only a brief remission. However, the combination of chlorambucil (7 mg/day orally) with low-dose oral prednisolone (10 mg/day) for several weeks controlled the disease and greatly reduced the cryofibrinogen. No relapse occurred after discontinuation of treatment.

Aged

Effects of 13-cis-retinoic acid, all-trans-retinoic acid, and acitretin on the proliferation, lipid synthesis and keratin expression of cultured human sebocytes in vitro.

The aim of this study was to determine the effects of 13-cis-RA, all-trans-RA, and acitretin on the proliferation, lipid synthesis, and keratin expression of human sebocytes in vitro and to elucidate possible mechanisms of retinoid action on sebaceous glands at the cellular level. It was found that 13-cis-RA and all-trans-RA decreased sebocyte proliferation in a dose- and time-dependent manner, with a 13-cis-RA-IC50 of 10(-5) M (after 7 d) and 10(-6) M (after 14 d) and an all-trans-RA-IC50 of 10(-7) M (after 14 d; no IC50 after 7 d). Acitretin inhibited sebocyte proliferation only at 10(-5) M. Furthermore, 13-cis-RA was the most potent inhibitor of acetate incorporation into lipids, which indicated lipid synthesis (48.2% reduction), followed by all-trans-RA (-38.6%), and by acitretin (-27.5%). All retinoids tested markedly decreased the synthesis of triglycerides, wax/stearyl esters, and free fatty acids in cultured sebocytes, whereas squalene synthesis remained uninfluenced and cholesterol synthesis slightly increased. On the other hand, keratin 5 was down-regulated, keratin 17 was up-regulated, and the expression of keratin 13 was virtually unaffected by all retinoids tested. Keratins 6 and 16 were down-regulated by 13-cis-RA and by all-trans-RA, keratin 14 was down-regulated by 13-cis-RA only, and keratin 19 was up-regulated by all-trans-RA. These investigations indicate that 13-cis-RA and, to a lesser extent, all-trans-RA are potent inhibitors of both cell proliferation and lipid synthesis in human sebocytes in vitro, whereas acitretin only decreases lipogenesis in this model. In addition, retinoids may modify the differentiation of sebocytes in vitro by modulating keratin expression. Models of cultured human sebocytes are useful tools for further investigations on the sebaceous gland and its activity at the cellular level.

Acitretin

Culture of human sebocytes and markers of sebocytic differentiation in vitro.

Human sebocytes obtained as explants after in vitro culture of isolated sebaceous glands were recently shown to maintain in part a sebocytic differentiation. The aim of this study was to further identify markers of sebocytic differentiation in vitro. Therefore, the morphology of cultured human sebocytes, and their differentiation with lipid storing and expression of cellular proteins were investigated by microscopy, electron microscopy, study of cell kinetics, cytochemistry and immunocytochemistry, and were compared to cultured human keratinocytes obtained from the same skin specimens. At first, sebocytes in all stages of sebocytic differentiation were detected in vitro. Abundant cytoplasmic lipids and the absence of desmosomes were identified as their ultrastructural characteristics. Secondly, an increasing number of sebocytes storing lipids was detected during cell proliferation. Sebocytes contained up to 4 times more lipids than keratinocytes in vitro. Squalene and increased quantities of wax/sterol esters could be extracted from secondary sebocyte cultures. Thirdly, the monoclonal antibodies 6B10 (keratin 4), RPN1162 (keratin 7), and OM-1 labeled only sebocytes in vitro. Furthermore, sebocytes presented a marked expression of keratin 19 in comparison to keratinocytes, as detected with CK 4.62, and a lack of RPN1161 (keratins 1 and 2) expression, which was typically found to be expressed in cultured keratinocytes. The culture of human sebocytes possessing several characteristics of sebocytic differentiation in vivo offers unique possibilities in investigating direct effects on sebaceous cell growth, differentiation and their regulation.

Antibodies, Monoclonal

[Adverse drug reactions on hair].

Adverse drug reactions on the hair are common side effects. The spectrum of loss of hair reaches from diffuse telogen effluvium up to circumscribed or diffuse alopecia on the scalp, sometimes also including other body areas. Other side effects observed are the stimulation of hair growth with hypertrichosis and induction or worsening of hirsutism, as well as changes of the structure or color of the hair. In most cases--other than those treated with cytostatics, androgens, or hormonal contraceptives with some androgenic effect--it is rather difficult to determine the time of onset and primary cause, since the diffuse types often start subclinically, and other factors may play an additional part. As a rule, adverse drug reactions are reversible provided the causative drug is avoided.

Alopecia

[Pharmacokinetics of etretinate, acitretin and 13-cis-acitretin: new results and advantages of blood level oriented clinical use].

Plasma concentrations of etretinate (E), acitretin (A) and 13-cis-acitretin (13-cis A) were measured using a reverse phase HPLC assay in patients with psoriasis during 24h after the first dose (0.8 mg/kg) and after 3 weeks (group A), and in a second group with various skin diseases (B) under long-term treatment after 3 months. Group A (n = 8) showed median peak plasma concentration levels (Cmax) 578 ng/ml for E. and 161 ng/ml for A 4h after dosing (tmax). The plasma concentration profile of 13-cis A. was plateau-like with Cmax-levels of 138 ng/ml after 4 to 10 hours. In group B treated with 0.3 to 0.4 mg/kg etretinate a trend to increased Cmax-values with 123 ng/ml for E., 44 ng/ml for A. and, more pronounced, 210 ng/ml for 13-cis A. occurred (steady state). In a third group C (n = 17) it was found that after an eight month treatment free period measurements of the 13-cis A. plasma concentration are more sensitive than that of E. or A. Comparing the pharmacokinetics in two patients with the same clinical conditions under E. and A., resp., two fold higher Cmax-values of A. after A. were found than for A. after E. However, 13-cis A. values were higher after E. than after A. Our observations have shown that the metabolisation of A. to 13-cis A. may be disturbed and the clinical efficacy may appear only after dramatic increase of the oral doses. Routine monitoring of plasma concentration profiles of oral retinoids and their metabolites under short or long-term treatment enable us to early identify and understand better the so-called "non-responders", either due to a disturbed metabolism of retinoids or to non-compliance. Furthermore, monitoring of 13-cis A in plasma after cessation of treatment with E. or A. in women in childbearing age seems to be more sensitive than measurement of plasma levels of E. or A. These measurements are helpful for defining the strategy of oral retinoid therapy and for reliable information of females who wish to become pregnant after interrupting the drug.

Acitretin

[Pustular arthro-osteitis. Pustulosis palmaris et plantaris with arthritis of the sternoclavicular joint].

A 26-year-old female patient presented with pustulosis palmaris et plantaris simultaneously with arthritis of the sternoclavicular joint. This association is described as an entity and is called pustulotic arthroosteitis in the Japanese literature, as well as in publications from Scandinavia. To our knowledge, this is the first observation in the Federal Republic of Germany.

Adult

[Calcinosis cutis: cutaneous manifestations of generalized calcinosis in renal hyperparathyroidism].

In 2 female patients suffering from chronic renal insufficiency and secondary hyperparathyroidism total parathyroidectomy with autotransplantation was performed, but shortly afterwards tertiary hyperparathyroidism developed. Together with numerous generalized metastatic foci of severe smooth tissue calcification, extensive calcification of the skin occurred. Some of the hard painful areas with papules, nodules and large plaques of calcium deposits were inflamed and ulcerated, and the histological picture was that of severe disseminated calcification of the middle and deep reticular dermis, spreading over into the subcutaneous adipose tissue. Conventional X-ray examinations and computer tomography revealed large asymmetrical areas of bone-dense calcification of the soft tissue. After total excision of the autografts the severe calcifications of the skin diminished or disappeared completely.

Calcinosis