[Human intestinal spirochetosis]. / Die intestinale Spirochätose des Menschen.

Whenever biopsy material obtained from endoscopically normal colorectal mucosa reveals the blue haematoxyphilic line between the microvilli of the covering epithelium, the rare condition of intestinal spirochetosis is diagnosed. The classification of the bacteria detected with the aid of special stains (e.g. the Warthin Starry silver stain) and in the electron microscope, continues to be something of a problem. A further point of contention is the question whether this spirochetal infection is of pathological significance or not. A point mitigating against pathogenicity is the fact that no histological signs of an inflammatory reaction are to be seen. Also, the symptoms of patients with intestinal spirochetosis are such that they provide no basis for a pronouncement on whether the infection is of a pathological or a pathological nature. On the other hand, however, a number of studies do seem to indicate that the spirochetes might be the cause of such symptoms as diarrhoea, constipation and abdominal pain. A point that would appear to support this view is the fact that such symptoms may disappear after successful treatment with metronidazole. The histological diagnosis is easily established when, faced by an apparently normal histological appearance of the colorectal mucosa, the pathologist considers the possibility of spirochetosis, and undertakes a specific search for the blue haematoxyphilic line in the covering epithelium of the colorectal mucosa.

Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: a prospective controlled trial.

BACKGROUND: Both interferon alpha and extracorporeal photochemotherapy have been shown to be effective in primary cutaneous T-cell lymphomas (CTCLs). However, no prospective trial has been published on the combination of both treatments, although retrospective investigations suggested a better efficacy than for either interferon or extracorporeal photochemotherapy. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of combined interferon alfa-2a with extracorporeal photochemotherapy in a prospective controlled trial. METHODS: A prospective controlled study was performed. Fourteen patients (all male) aged 38 to 72 years with CTCL of the mycosis fungoides type, stage IIa/IIb, and a 72-year-old male patient with a Ki-1 lymphoma were treated twice a month for 6 months with extracorporeal photochemotherapy using oral 8-methoxypsoralen as photosensitizer in combination with interferon alfa-2a subcutaneously 3 times a week in the maximal tolerable dosage (ie, up to 18 x 10(6) U). The effects were investigated by a skin score, staging, histologic score (density of the T-cell infiltrate; from 0 = absent to 3 = heavy), immunohistology, and laboratory investigations including total peripheral T-cell count, CD4/CD8 ratio, and soluble interleukin 2 receptor (sIL-2R). RESULTS: After 6 months, best response was a complete response (CR) in 4 patients, a partial response (PR) in 3, and a stable disease (SD) in 7 of 14 patients (overall response rate [CR + PR] 50%). In responders the time to best response was 4.3 +/- 1.4 months. The skin score decreased from 22.5 +/- 8.1 to 15.1 +/- 11.0 (P <.001), the histologic score decreased from 2.57 +/- 0.51 to 1.21 +/- 0.80 (P <.001). In the lesional skin the percentage of CD4 cells decreased from 75% to 51% (P =.038) and Ki-67-positive cells decreased from 6.7% to 2.4% (P =.001). The total T-cell count/microL decreased from 1018.9 +/- 557.1 to 667.9 +/- 417.9 (P =.012), and the CD4/CD8 ratio also decreased from 1.88 +/- 0.92 to 1.51 +/- 0.67 (P =.038). The sIL-2R levels did not change significantly during the first 4 months of treatment. Among patients of stage IIa the response rate was 60% in contrast to only 25% of those in stage IIb. Side effects were seen temporarily, ranging from grade 0 to grade 3. There was no need for additional therapy, but interferon dose was decreased because of side effects. After 1 year of follow-up the total response rate was 46.2% (6 of 13 patients): 5 of 9 with stage IIa(55.6%) and 1 of 4 with stage IIb (25.0%). CONCLUSION: These results indicate that patients with CTCL stage IIa can achieve a total response rate of 56% with combined interferon alfa-2a and extracorporeal photochemotherapy. Responders seem to experience their best response within the first 6 months of treatment. The treatment is well tolerated and does not cause severe side effects.

[50 years Zwickau Dermatologic Clinic in the Heinrich-Braum Hospital]. / 50 Jahre Hautklinik im Heinrich-Braum-Krankenhaus Zwickau.

The dermatological clinic in Zwickau celebrated 50 years of existence in 1996. We review the clinics history, starting with its founding in 1946 because of the upsurge in venerological diseases during the post-world war II years. The most important clinic directory and their scientific activities are described.

Vasoactive-intestinal-Peptide (vip) modulates early events of migration in human keratinocytes.

Vasoactive intestinal peptide (VIP) has been shown to affect the proliferative activity of human keratinocytes in vitro. In our present study, we investigated whether VIP affects early events of keratinocyte migration, i.e. the formation of pseudopodia-like protrusions and the zeta-potential which was assessed by the electrophoretic mobility (EM). Under optimal culture conditions (10% fetal calf serum supplement; FCS) VIP changed the total percentage of migrating HaCaT cells by increasing the Ki67-negative portion. Migration was maximally stimulated in the range of 10(-9) M VIP (+121.1%) and 10(-7) M VIP (+78.9%). Under suboptimal conditions (i.e. 2% FCS or serum free medium) low concentrations of VIP (10(-7) M to 10(-13) M VIP) decreased spontaneous migration up to 70%. The EM of pooled normal keratinocytes (0.59 +/- 0.018 mu/s/V/cm) was slightly increased by Phe6-Leu17-VIP and more markedly by VIP in a dose-dependent manner. Our observations suggest a modulatory effect of VIP on early events of human keratinocyte migration in vitro. These findings might be of importance for spontaneous migration within the epidermal compartment both under physiological conditions and in wound healing.

[Monosymptomatic Melkersson-Rosenthal syndrome with subsequent vulvitis and perivulvitis granulomatosa]. / Monosymptomatisches Melkersson-Rosenthal-Syndrom mit nachfolgender Vulvitis und Perivulvitis granulomatosa.

We report on an 40-year-old woman with granulomatous facial swelling followed by vulvitis and perivulvitis granulomatosa. The characteristic histopathology with epitheloid cell granulomas was seen in samples from both the face and the vulva. By immunohistochemistry the lesions were characterized as consisting mainly of histiocytic and CD-30-positive T cells. The possible aetiology is discussed briefly.

The initial steps of tumor progression in melanocytic lineage: a histochemical approach.

Antigen expression was studied by immunohistochemistry in 133 human melanocytic skin lesions to gain insight into the initial steps of tumor development, i.e. in particular the change from melanocytes to benign nevi. We refer to the proposed progression model of Clark and co-workers. The following types of antigens were investigated: (i) intermediate filament antigens (vimentin), (ii) melanoma-associated antigens (HMB-45, NKI/C3, MA-930, LS59), (iii) proliferation-associated antigens (S-100, Ki67, Ro/SSA, calmodulin), (iv) progression-associated antigens (HLA-DR, ICAM-1), and (v) basal membrane antigens (bullous pemphigoid antigen, laminin, fibronectin, collagen type IV). The intensity of expression and the topography of immunoreactive pigment cells were compared with the stage of tumor progression. Special attention was paid to the early steps of this process, i.e. the disturbance of the epidermal melanin unit and the development of melanocytic ("nevocellular")nevi. A dramatic shift of antigen expression (antigen types [i] to [v]) was noted in benign nevi compared with melanocytes. Nevi with cellular atypia disclosed a tendency towards an increased percentage of tumor cells reactive for melanoma- and progression-related antigens (types [ii] and [iv]). However, there was no clear cut level of distinction of antigen expression (types [i] to [v]) between benign and primary malignant melanocytic tumors. So-called dysplastic nevi resembled benign tumors or melanocytes rather than malignant melanoma. Metastatic melanoma of skin showed a relatively high number of Ki67-positive, cycling melanoma cells. The results have a bearing on the concepts of melanocytic nevus ontogenesis and "maturation". It appears that melanocytes lose maturity on their way down to the dermis in contrast to traditional concepts (Abtropfung); this might be of importance for our understanding of melanoma development in association with melanocytic nevi. Our findings are discussed with regard to Clark's model of tumor progression.

Pachyonychia congenita. Immunohistologic findings.

Pachyonychia congenita (PC) is a very rare hereditary disorder of keratinization. Immunohistological findings has so far been lacking. Reported in this paper is a case of Jadassohn-Lewandowsky type PC in a woman aged 18 years on which immunohistological investigations could be performed. Several monoclonal antibodies to filaggrin and keratin were used to stain tissue sections of lesional plantar skin, with a view to studying impairment of epidermal differentiation. While staining patterns comparable to those of normal skin were exhibited by anti-filaggrin and some antikeratins (RPN 1161, A51-B/H4), substantially altered immunostaining was recordable from other anti-keratins. Only superficial vital keratinocytes were stained by RKSE 60 against keratin 10 and K 8.12 against keratins 13 and 16. The authors, in other words, obtained information on expression of keratin 10, normally occurring in all suprabasal keratinocytes, as well as of the basal proliferation keratin 16 in the uppermost vital cell positions of PC lesion. The above results are likely to suggest impairment of keratin expression in cases of PC.

Human eccrine sweat glands--a histochemical approach.

Histogenesis of eccrine sweat glands is incompletely understood. Histochemistry of the human eccrine sweat gland of adult skin by the use of lectins as well as antibodies to neuroglandular antigen (NGA) and urokinase was in favour of a relative independent differentiation from interfollicular epidermis. Expression of NGA by sweat glands is a feature unique among skin appendages. The possible impact of our findings for sweat gland histogenesis is briefly discussed.

[Pachyonychia congenita. Presentation of a case and histological-histochemical findings]. / Pachyonychia congenita. Falldarstellung und histologisch-histochemische Befunde.

We report on two cases of pachyonychia congenita, Jadassohn-Lewandowsky type, in a father and daughter. Histopathological examination revealed thickened, aggregated bundles of tonofilaments and an increased number of atypical keratohyalin granula, which is suggestive of an altered keratinization. Immunohistological staining with antibodies to cytokeratins (A45-B/B3, A51-B/H4, A53-B/A2, RPN 1161) was unchanged. Filaggrin could not be detected. Basal cells immunoreactive for calmodulin were markedly reduced or even absent in the rete ridges. Staining with a monoclonal antibody against Ki67 made epidermal cell hyperproliferation seem unlikely. The epidermal lectin binding was normal. C3 was detectable in vessel walls mainly of the stratum reticulare. The findings are discussed with reference to pachyonychia pathogenesis.

[Psoriatic osteopathy--results of histomorphometric studies]. / Die psoriatische Osteopathie--Ergebnisse histomorphometrischer Untersuchungen.

In 23 patients with psoriatic arthritis and 9 patients with psoriasis without joint involvement, we took bone biopsies from the iliac crest. Histomorphometrical investigations showed that the volume density of the bone was not decreased in either group of patients, but we found a high rate of turnover remodelling. An elevated rate of bone turnover is regarded as the characteristic principle of "psoriatic osteopathy", which--more exactly--should be called "latent osteopathy". Deficiency of vitamin D is discussed as a possible etiological factor.

[Hydroxyproline excretion in psoriasis and psoriatic arthritis]. / Hydroxyprolinausscheidung bei Psoriasis (Ps) und Arthritis psoriatica (Ap).

In the morning urine of 24 patients with psoriasis and that of 24 patients with psoriatic arthritis, we determined the excretion of hydroxyproline (mg HP/mumol crea), after preceding diet low in collagen. Surprisingly, psoriatic patients without articular involvement showed a significantly higher excretion of HP than those with psoriatic arthritis. Further differentiation revealed that there were no clear-cut correlations between the amount of HP excretion and the activity of the articular process; we proved, however, that the amount of HP excretion was definitely related to the activity of the skin eruptions in both groups of patients. We discuss whether an osteopathy pathogenetically associated with the skin disease (irrespective of synovitis in psoriatic arthritis) may possibly be responsible for these results.

[Occlusive therapy of psoriasis--comparison of clinical effectiveness of short-term and prolonged use]. / Okklusivtherapie der Psoriasis--Vergleich der klinischen Wirksamkeit von kurzzeitiger und prolongierter Anwendung.

In an open clinical trial on stationary psoriatic plaques, we compared the effects of shortime occlusive (SO) dressing (24h) and prolonged occlusion (PO: 5-28 days). IN SO, Weinstein's index decreased from 7.3 +/- 1.7 to 3.3 +/- 1.8 (n = 21), in PO from 6.5 +/- 1.1 to 3.7 +/- 1.7 (n = 15). The results were even better in cases with optimal PO dressing (decrease from 6.8 +/- 1.4 to 2.5 +/- 0.9). The most important side effects were itching and exsudation with ensuing smell. In only one of the cases did the side effects cause a drop-out after 5 days. Regarding stationary psoriatic plaques on the extensor sides of the lower legs and forearms. We recommend continuous occlusive dressing for 8-10 days--either as an alternative mode of therapy, or as an intermediate regimen.

[Seborrheic keratoses. Intact epidermal differentiation despite disordered morphogenesis]. / Seborrhoische Keratosen (SK). Intakte epidermale Differenzierung trotz Morphogenesestörung.

Seborrheic keratoses were investigated by means of histo- and biochemical techniques in order to define the epidermal differentiation and proliferation of this most common epithelial tumor in adults. The following markers have been used in our study: cytokeratins, epidermal proteins binding zinc, insulin receptors, tissue plasminogen activator (tPA), as well as calmodulin (immunohistochemical and quantitative evaluation). Immunohistochemical investigation of seborrheic keratoses revealed a decreased tPA expression; their epidermal concentration of calmodulin was doubled. The differentiation markers failed to show any significant deviation from normal skin. Thus, seborrheic keratoses are associated with normal epidermal differentiation in spite of morphogenic alterations. Pathogenetically, we have to consider epidermaldermal interactions.

[Immunohistologic studies of the distribution of proliferative compartments in the appendages of adult human skin]. / Immunhistologische Untersuchungen zur Verteilung proliferativer Kompartimente in den Anhangsgebilden humaner adulter Haut.

Both, calmodulin (CaM) as well as the antigen Ki67 show a close relationship to cell proliferation. By means of specific antibodies against them, it has become possible to study the spatial distribution of proliferative compartments in tissues. We performed an indirect immunofluorescence study on unfixed frozen sections of human adult skin to gain more informations about the spatial distribution of immunoreactive CaM and Ki67 in skin appendages, i.e. anagen hair follicle, sebaceous and eccrine sweat gland. Two major patterns of immunoreactivity were seen: Type (1) or epidermis-like, which was present in the interfollicular epidermis and the pilosebaceous unit. Type (2) or sweat gland type, which was seen in eccrine sweat glands. Both types disclosed significant differences in the relative number of proliferative cells in S-phase, which might be a consequence of a quiet different tissue architecture. Furthermore, myoepithelial cells of secretory coils were likely to represent mainly SQ-cells. Their immunoreactivity in human skin was quiet different from other parts of eccrine sweat glands suggesting another ontogenetic pathway.

[Hyde's nodular prurigo--preference for creases of the skin]. / Prurigo nodularis Hyde--Bevorzugung der Hautspaltlinien.

The arrangement of papules in prurigo nodularis Hyde along the cleavage lines of the skin, but not Blaschko's lines, supports the classification of prurigo nodularis Hyde as a traumatic chronic papulosis with cutaneous neural hyperplasia of xerodermal skin.

[The effect of monochromatic and polychromatic UV irradiation and of 8-MOP on phagocytosis of neutrophilic granulocytes]. / Zum Einfluss von monochromatischer und polychromatischer UV-Bestrahlung sowie von 8-MOP auf die Phagozytose neutrophiler Granulozyten.

We investigated the inhibition of granulocyte phagocytosis by 8-MOP and monochromatic or polychromatic UV light. After application of 8-MOP and UV there was an additional inactivation compared with UV alone, as expected from studies on other cell species. This additional inhibition of phagocytosis was found to be increasing with 8-MOP level. The action spectra of granulocyte inactivation by 8-MOP and UV involves the investigated UVB range (until 300 nm). A marked inactivation of granulocytes was seen after erythemogenic fluences only. Therefore we assume that inactivation of granulocytes by direct UV action does not play an essential role in UV therapy in vivo.