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Biomedical subjects

H Gollnick

Publications and source records attributed to H Gollnick.

At least 127 records · Page 7Linked to original sources
PubMed1989

Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study.

The effects of azelaic acid (AZA) on the epidermis of 47 individuals (12 with normal skin, 15 with seborrheic skin and 20 suffering from acne) and on in vitro cultured keratinocytes are reported. Topical application of a 20% AZA cream significantly improved the lesions of acne patients, but failed to induce clinically detectable changes in normal or seborrheic epidermis. Complementary investigations clearly showed that AZA treatment failed to induce specific changes in sebum composition, excretion rate, or in the size of sebaceous glands, but modified epidermal keratinization. Keratohyalin granules and tonofilament bundles were reduced in size and number, mitochondria were swollen and the rough endoplasmic reticulum of malpighian keratinocytes enlarged. The infundibular epidermis of acne individuals showed marked reduction of the horny layer thickness, widening of the horny cell cytoplasm, transitional corneal cells, normalization of filaggrin distribution, and the comedo contained few bacteria and spores. In vitro, AZA exerted marked time- and dose-dependent antiproliferative cytostatic effects on cultured keratinocytes, with a 50% inhibitory dose of 20 mM, decreased some keratinocyte proteins (highly soluble fractions S2, keratohyalin macroaggregate R2, and non-cross-linked fibrous protein S4) and a 95 kD and a 35 kD protein of the cytosolic fraction. Mitochondria were frequently damaged and the rough endoplasmic reticulum enlarged. Our results indicate that AZA is an antikeratinizing agent, displaying antiproliferative cytostatic effects on keratinocytes and modulating the early and terminal phases of epidermal differentiation.

Acne Vulgaris↗
PubMed1989

[Low dosage retinol and L-cystine combination improve alopecia of the diffuse type following long-term oral administration].

In a pilot study (I) the efficacy of a new combination therapy for hair loss of the diffuse type was tested in 36 patients, followed by a double blind study with 47 patients. The daily dosage was 18,000 IE retinol, 70 mg L-cystine and 7000 mg gelatin. The clinical efficacy was evaluated by standard methods, such as the preparation of trichograms and measurement of the hair density before and after treatment. The pilot study demonstrated a significant improvement, with reduction of the telogen rate by 8.3%, an increase of the anagen rate by 11%, and an increase of the hair density by 6.9%. In the double blind study (II) the trichogram showed a significant decrease of the telogen rate by 13.5% compared with pathological baseline values. There was no change in the placebo group. The lowered anagen rate of 47.2% was improved by 8%, whereas the mean value in the placebo group decreased from 47.7% to 39.9%. In addition, the percentage of dysplastic anagen hairs improved by 7.4%, as against further impairment with an increase of 26% in the placebo group. During oral therapy no systemic side-effects were detected. We conclude that long-term oral therapy with high doses of L-cystine and gelatin in combination with vitamin A may have beneficial effects on diffuse hair loss.

Administration, Oral↗
PubMed1989

[Borrelia burgdorferi-induced pseudolymphoma with pathogen cultivation in an HIV-1 positive patient].

Cutaneous symptoms and skin diseases are common findings in almost all HIV-1-positive patients. In many cases the clinical presentation and course of the skin diseases are atypical, and occasionally the development of the appropriate circulating antibodies is lacking or impaired. In this report we present a patient seen in our multidisciplinary outpatient clinic for HIV patients. This patient had a Borrelia burgdorferi infection with an unusual course. The acute inflammatory phase of the arthropod reaction was maintained over a period of 9 months with development into pseudolymphoma showing unusual cytological characteristics. Immunohistological evaluation revealed an almost complete lack of T-helper and Langerhans cells, but an increased number of activated cytotoxic cells with class II antigen expression. A marked serological response was observed on IgG-ELISA and in the IgG-immunofluorescence test. Borrelia burgdorferi was cultured in vitro from a skin biopsy of the involved area. To our knowledge this is the first reported case of skin borreliosis in an HIV-1-positive patient.

Bacteriological Techniques↗
PubMed1988

Acitretin versus etretinate in psoriasis. Clinical and pharmacokinetic results of a German multicenter study.

175 patients with severe psoriasis of different types were treated with 10, 25, or 50 mg acitretin and compared with patients receiving 50 mg etretinate over a period of 8 weeks in a randomized, double-blind multicenter study in the Federal Republic of Germany. Plasma concentrations of etretinate and its metabolite acitretin were measured during therapy and also 3 weeks after cessation of treatment. After 4 weeks of treatment, a trend toward clinical improvement was shown in all groups with increasing dosage. Those groups receiving the lower acitretin doses (i.e., 10 and 25 mg/day) had more dropouts than the groups taking 50 mg acitretin or 50 mg etretinate. Complete remissions before the end of therapy occurred only among those receiving higher doses. Enlargement of psoriatic lesions, however, could be observed during treatment with both retinoids, despite improvement of other parameters, as measured by psoriasis area and severity index (PASI) and psoriasis severity index (PSI). After 8 weeks, a significant improvement was calculated by the PASI score and by a newly defined, corrected PASI score for all four dose regimens compared with baseline levels. A greater than 50% PSI score improvement was seen in 50% of patients treated with 10 mg acitretin, 40.5% with 25 mg acitretin, 53.8% with 50 mg acitretin, and 61.1% with 50 mg etretinate. No statistical differences were found among these groups at any time during the 8-week period. No new or unexpected side effects occurred during acitretin treatment. Moreover, cholesterol levels did not significantly change. Three weeks after cessation of drug administration, the plasma concentrations of acitretin were below the sensitivity level of the assay, whereas etretinate was still quantifiable. It is interesting that acitretin plasma concentrations during therapy with 50 mg acitretin were markedly lower (means = 18 ng/ml) than were acitretin levels during treatment with 50 mg etretinate (means = 36 ng/ml).

Acitretin↗
PubMed1988

Monoclonal antibody labeling for cytokeratins and filaggrin in the human pilosebaceous unit of normal, seborrhoeic and acne skin.

The distribution of cytokeratins and filaggrin in human pilosebaceous unit was investigated in specimens obtained from normal (n = 15), seborrhoeic (n = 6), and acne skin (n = 6), using the monoclonal antibodies CK8.12, CK8.13, CK4.62, CK8.60, KL1, PKK2, RPN 1160, and an antibody for filaggrin. The type and amount of cytokeratin content was correlated with the stage of cell differentiation in these three skin types. In all specimens studied the sebocytes. The sebaceous duct cells, and the infundibular cells contained cytokeratins, no clear differences were found between normal, seborrhoeic, and acne skin. During sebocytic maturation the amount and type of cytokeratin content changed gradually and the labeling pattern was partly different compared to the interfollicular epidermal pattern. In the sebaceous duct and the infundibulum, the labeling pattern using KL1, CK8.12, and CK8.13 was similar to that seen in interfollicular epidermis, whereas labeling with CK8.60 and PKK2 was different. These findings indicate that sebaceous duct and infundibular cells express transitional patterns of differentiation between epidermal keratinocytes and sebocytes. Filaggrin was expressed only in some sebaceous duct cells and in infundibular cells. In seborrhoeic and in acne skin, however, the reactivity of antibody to filaggrin was more intense and was already observed in the lower parts of the sebaceous duct and the infundibulum. Although no filaggrin was found in the intermediate cells of the sebaceous duct and the infundibulum in normal skin, these cell types clearly contained filaggrin in seborrhoeic and acne skin.

Acne Vulgaris↗
PubMed1988

[Presence and distribution of cytokeratins and filaggrin in human anagen follicles].

The presence and distribution of several types of cytokeratins and of filaggrin in human anagen hair follicles were investigated using the following monoclonal antibodies (McAB): KL 1, CK 8.60, CK 8.12, PKK-2, CK 18, CK 19 and anti-filaggrin McAb. Constant and characteristic patterns of McAb labelling were obtained in distinct compartments of the hair follicle, except for CK 18, which failed to label any of the follicular cells. Anti-filaggrin McAb was regularly bound to the Henle's layer of the internal root sheath, showing for the first time the presence of "filament aggregating protein" in the human hair follicle.

Antibodies, Monoclonal↗
PubMed1988

[Cutaneous B cell lymphoma in chronic Borrelia burgdorferi infection. Report of 2 cases and a review of the literature].

Low-grade malignant B-cell lymphomas of the skin can be distinguished from lymphadenosis benigna cutis (Bäfverstedt) by immunohistological methods developed in the last few years. Its coexistence with Borrelia burgdorferi infection can be shown by clinical and serological findings. In the chronic stage of this infection, lymphocytic cell infiltrations consistent with histological and immunohistological findings of malignant B-cell lymphoma can be found. Predominantly at the extremities, multiple plaque-shaped or nodular lesions are seen, showing a follicular pattern in their periphery. The tumors do not respond to antibiotic therapy. They regress totally after X-ray treatment, but local recurrences are rather common. They show a long persistent course with only slow progression and seem to be of low-grade malignancy independent from the cytological findings. In most cases the tumors remain limited to the skin and to one anatomical site; nevertheless, the development of systemic involvement has been reported. We present two cases of malignant B-cell lymphoma of the skin in patients with chronic B. burgdorferi infection. Both cases showed the typical clinical and histological features of this entity. Similar reports from the literature indicate close relationships with the chronic stage of Borrelia infection, with the simultaneous presence of acrodermatitis chronica atrophicans as an indicator. We conclude that an elevated titer indicating Borrelia infection is an important finding for the diagnosis and prognosis of this particular type of cutaneous B-cell lymphoma.

Aged↗
PubMed1987

New indications and new retinoids.

In addition to well-accepted indications, etretinate has a beneficial effect in a variety of other dermatoses such as the hyperkeratotic eczema of the palms and soles, prurigo nodularis, and other nonpsoriatic, sterile, pustular eruptions. Due to its influence on dermal inflammatory processes and immunomodulation of the tissue response, etretinate is effective in cutaneous lupus erythematosus, certain bullous disorders like pemphigus herpetiformis, the persistent variant of Grover's disease, dermatitis herpetiformis, and bullous pemphigoid. Isotretinoin is reported to be effective in cutaneous sarcoidosis, disseminated granuloma annulare, systemic sclerosis and tumors of the cutaneous appendages. New synthetic retinoids have been developed. Etretin, the main metabolite of etretinate, was shown to be effective and to have a short elimination half-life of approximately equal to 50 h. Arotinoid ethyl ester and arotinoid-free carboxylic acid are effective in minimal doses 500-fold lower than etretinate. Arotinoid ethyl ester was shown not to increase serum lipids. Arotinoid ethyl sulfone is the first retinoid without bone toxicity in animal experiments. Motretinide is the ethylamide of tretinoin and is reported to be effective in the local treatment of acne. Some of the new polyaromatic retinoids appear to have sebosuppressive, antikeratinizing and/or anti--inflammatory effects via topical application.

Administration, Cutaneous↗
PubMed1987

The retinoids. A review of their clinical pharmacology and therapeutic use.

With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids, arotinoid ethylester (Ro 13-6298) has revealed the best anti-psoriatic and anti-inflammatory effects at extremely low dose levels. Furthermore, no significant elevations of serum lipids have been observed. Taking its prolonged elimination half-life and its efficacy/side effect ratio into account, the drug is comparable to etretinate. The free arotinoid carboxylic acid (Ro 13-7410) is currently undergoing clinical investigation. Another arotinoid, the parent compound Ro 15-0778, has not demonstrated any convincing clinical efficacy in acne or psoriasis, but topical anti-inflammatory effects were evident in some models.(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Interactions↗
PubMed1987

Azelaic acid vs. placebo: effects on normal human keratinocytes and melanocytes. Electron microscopic evaluation after long-term application in vivo.

The effects of topically applied 20% azelaic acid (AA) on normal human epidermis were investigated vs. placebo in a double blind study by electron microscopy in 15 volunteers. After 3 months of local application twice daily, the pattern of epidermal keratinization was found altered in skin treated with AA. In particular, the number and thickness of tonofilament bundles and the number of keratohyaline granules seemed decreased; the remaining granules were smaller, occasionally showing irregular electron densities. The perinuclear endoplasmic reticulum and the cytoplasmic cisternae were enlarged and swollen mitochondria were regularly observed in most malpighian keratinocytes. Thorough quantitative evaluation of the number and distribution of melanocytes by a MOP-videoplan computer system showed no differences between verum and placebo sites, although, the mean number of melanocytes had increased in both, as compared to the untreated controls taken before onset of therapy. No significant qualitative changes of the normal melanocytes were found. These findings indicate that azelaic acid may influence the differentiation of normal human keratinocytes by reducing the synthesis of keratin precursors and may, therefore, act as a mild antikeratinizing agent, whereas, the pigmentary system in normal human epidermis does not show any specific change after 3 months of treatment with AA.

Clinical Trials as Topic↗
PubMed1986

[Acne conglobata: personality and psychological sequelae in 13-cis-retinoic acid therapy. Initial results].

16 patients suffering from acne conglobata were prospectively examined by means of analytical interviews and 5 psychometric procedures before and 6 months after oral treatment with 13-cis retinoic acid (isotretinoin). In comparison with a control group of psychosomatic patients, acne conglobata patients are more frequently affected by childhood influences leading to a neurotic personality structure already before the outbreak of acne; the patients more often complain of disturbed social contact, depressive moods, or general disorders. After successful treatment with isotretinoin, we observed augmented self-confidence and positive aggressiveness, on one hand, and increase of anxiety depressive moods, and general complaints, on the other. These effects are not drug related in a pharmacological way. These observations suggest the influence of psychic factors in the pathogenesis of acne conglobata. Regarding the medical management of these patients, it should be considered that psychic and psychosomatic disorders might be intensified after successful drug therapy.

Acne Vulgaris↗
PubMed1986

[Subpopulations of peripheral T lymphocytes (Th/Ts) in atopic dermatitis and in psoriasis].

In 32 patients with widespread psoriasis (PS) and 23 patients with atopic dermatitis (AD) the numbers of peripheral blood pan-T-lymphocytes and their subsets, T-helper (Th) and T-suppressor (Ts) lymphocytes were estimated, using monoclonal antibodies, and compared with the corresponding values in 34 healthy controls. In PS patients, there was a trend towards lowered values (Th/Ts ratio: 1.0-2.6; median value: 1.6), but no other significant changes were seen. In patients with AD, however, the number of circulating pan-T-lymphocytes was increased, with significantly increased Th values and significantly lowered values for Ts lymphocytes (P less than 0.01). The calculated Th/Ts ratio, therefore, was significantly elevated in patients with AD (1.9-4.2; median value 2.8), compared to normal controls (1.4-2.0; median value 1.7). No significant correlation could be detected between Th/Ts ratio and IgE levels in 16 patients with severe AD (r = 0.451). We conclude that quantitative changes in circulating T-cell subsets may represent a characteristic feature of atopic dermatitis.

Adolescent↗
PubMed1985

[Etretinate: pro and con. Risk-benefit analysis of systemic retinoid therapy in psoriasis and recent developments: free aromatic acid, arotinoids].

Synthetic retinoids were first evaluated 15 years ago for systemic treatment of psoriasis in the Federal Republic of Germany. Etretinate was introduced 2 years ago into the market for systemic treatment of all severe types of the disease. Today etretinate is administered as monotherapy and/or combined with other modalities (anthralin, tar, topical corticosteroids, selective UV therapy, RePUVA), which leads to successful clearing in most cases. Nevertheless, thorough consideration of the risk-benefit ratio is required in each individual patient. The advantages and disadvantages are presented that should be taken into consideration. As a rule, severe cases of psoriasis are admitted to the hospital; initial treatment is given and then continued on an outpatient basis. In some patients, particularly those with pustular eruptions and/or erythroderma, low-dosage oral etretinate may be continued for prophylactic reasons over several months or years. Since the amount of hospitalization is reduced, the overall treatment costs are reduced in spite of the high cost of the drug. The main disadvantage of oral retinoids is their teratogenicity, although no severe cases of retinoid toxicity have been reported in the last 2 years in the Federal Republic of Germany since their introduction. As a successor drug to etretinate, its free aromatic acid, Ro 10-1670 is now under clinical investigation. It seems to be clinically effective, is rapidly eliminated, and requires only 4 weeks contraception after discontinuation of oral administration. Arotinoids then follow.

Abnormalities, Drug-Induced↗
PubMed1983

[Oral treatment of acne conglobata using 13-cis-retinoic acid. Results of the German multicentric study following 24 weeks of treatment].

Results of the isotretinoin (13-cis-retinoic acid, Ro 4-3780) German Cooperative Study Group, with 198 acne conglobata patients being treated in 19 departments are reported. For the first 12 weeks (phase I) there was an open assignment to 0.2, 0.5 or 1.0 mg/kilogram bodyweight (kg bw). This was followed by further 12 weeks (phase II). If there was at least a two-third improvement of lesions, the 0.2 mg/kg bw was continued, and the 0.5 mg/kg bw dose lowered to 0.2 mg/kg bw. If there was no such improvement, the dose was elevated to 0.5 and 1.0 mg/kg bw respectively. The initial high dose group of 1.0 mg/kg bw was divided after twelve weeks into 0.2 mg/kg bw maintenance therapy, or no therapy at all. Non-inflammatory and inflammatory acne lesions from the entire body were counted. Seborrhea was graded on a four scale (0 to 3+). Subjective side effects were registered. Laboratory data included hematological profile with differential counts, creatinin, SGOT, SGPT, alkaline phosphatase, total bilirubin, serum cholesterol and serum triglycerides, and urine analysis. For statistical analysis 171 patients were available, 27 dropped out of the study, mostly for reasons unrelated to the drug. At least 75 per cent improvement was seen, in the 0.2 mg/kg bw group in 73.7 and 59.5 per cent respectively; in the 0.5 mg/kg bw group in 72.5 and 61.2 per cent respectively; and in the 1.0 mg/kg bw group in 85.4 and 92 per cent respectively (phase I t12 and phase II t24 values, respectively). Sebum suppression was dose-related. Subjective side effects were fairly well dose-related, particularly those of skin and mucous membranes. Myalgia was rare. There was a dose-related elevation of triglycerides and cholesterol, but not significant for the means of each group. Single patients did show significant elevation of blood lipids. All other laboratory parameters did not change significantly. Isotretinoin is presently the most effective drug to control severe forms of acne, leading to long lasting remissions.

Acne Vulgaris↗
PubMed1983

[Clinico-therapeutic index and dosimetry of oral treatment with aromatic retinoid. A comparison of different dosages].

Computer evaluation of 70 patients with skin diseases treated with different dose schedules of oral aromatic retinoid over 3 months revealed that high initial dosage decreasing to maintenance levels, as previously recommended (75 mg leads to 50 leads to 35 mg; approximately 1 mg/kg/d leads to approximately 0.5 mg/kg/d), leads to earlier clinical response but has no further advantages compared to a low initial dose schedule (35 mg leads to 50 mg/d leads to 75 mg/d; approximately 0.5 mg/kg/d leads to approximately 1.0 mg/kg/d). After 3 months treatment, the therapeutic index was nearly the same in both groups. In the group with high initial dosage, however, the side effects also appeared earlier, were more numerous and some of them more intense. A slightly better clinical-therapeutic index was found in the group of patients treated with moderate doses varying between 35-60 mg/d (approximately 0.4-0.8 mg/kg/d). According to these results, high initial dosage of retinoid seems only recommended if a rapid clinical response is required, p.e. in severe pustular psoriasis. If long-term treatment is achievable and in patients with poor compliance, low initial dosage seems preferable. For most other cases we recommend moderate constant doses (0.5-0.85 mg/kg/d), increasing or decreasing the dose according to the clinical response and the individual needs of each patient. Computer analysis showed in addition, that classical side effects such as cheilitis, desquamation and hair loss were significantly dependent among other things on the total given dose; whereas, elevations of serum triglycerides were not clearly dose-dependent, appearing more frequently in males. In females, hair loss was significantly more frequent.

Administration, Oral↗
PubMed1982

[Changes in serum lipid fractions as a side effect of oral retinoids].

Alterations in lipid metabolism have been reported under treatment of various skin disorders with oral retinoids. In 36 patients, mostly psoriatics, under administration of aromatic retinoid (Ro 10-9359) in various dosages serum triglycerides and cholesterol were estimated; in 25 out of 36 patients lipid analysis of the lipoproteins and apoproteins A (HDL) and B (LDL) has been performed. To reveal possible similarities of lipid changes under the two main retinoids we determined the same parameter in 10 patients with conglobate acne treated orally with 13-cis-retinoic acid (isotretinoin/Ro 4-3780 1mg/kg b.w.). Under both drugs serum triglyceride and cholesterol levels were significantly increased. In contrast to the results under the aromatic derivate the HDL- and LDL-cholesterol fractions were changed under isotretinoin. The apoprotein A (HDL) was found significantly increased under aromatic retinoid. Elevated serum lipids mostly occurred in patients having risk factors such as preexisting lipid abnormalities, obesity, diabetes mellitus, heavy smoking, alcohol abuse and hyperlipemia-inducing drugs. Patients to be treated with these drugs should be carefully followed up in order to minimize the risk for atheromatosis.

Acne Vulgaris↗