[Phthiriasis, the mysterious lousy disease of antiquity. Fact or fiction?]. / Phthiriasis, die geheimnisvolle Läusekrankheit der Antike. Fakt oder Fiktion?

The lousy disease (phthiriasis) and its potentially deadly consequences is well attested from antiquity until the 19th century. Intensely itching, vesicular or tumorous skin lesions defile the body and release swarms of insects spontaneously or after incision. Several well-known persons from antiquity and the early modern period are supposed to have died of the lousy disease. Both classicists and physicians have questioned the credibility of said accounts. By means of our interdisciplinary approach based on an analysis of different descriptions of the lousy disease from antiquity to the 19th century, this paper will present strong arguments for the existence of a potentially lethal form of phthiriasis. In contrast to its name, the lousy disease was most likely caused by a species of mites, similar to the one causing cystic subepidermal tumors in birds.

[Cutaneous melanoma - "black death" of modern times? Traces in contemporary literature]. / Melanom der Haut - der "Schwarze Tod" der Neuzeit? Spurensuche in der zeitgenössischen Literatur.

Cutaneous melanoma, sometimes labeled as "black skin cancer", is increasing in frequency and becoming a more common literary motive. In US literature, Sylvia Plath and Charles Bukowski depicted melanoma more than 50 years ago, later Stephen King and Thomas C. Boyle. In German literature, Charlotte Roche shortly mentioned this tumor. Jörg Pönnighaus, both poet and dermatologist, intensively deals in his poems with the effects melanoma has on patients and doctors alike. Melanoma definitely is not the "Black Death" of modern times. However, the perception of this tumor as extremely malignant and as life-threatening makes melanoma a metaphor of the deadly danger of cancer.

[Charles Bukowski's acne]. / Charles Bukowskis Akne.

In his autobiography, Charles Bukowski (1920-1994) describes his severe acne conglobata, his experience with therapy, family conflicts and emotional tension. Despite the stigmatization by his acne scars, Bukowski became a philobatic writer and a true chronist of the American way of life in the second half of the 20th century, writing in a coarse and obscene language.

["Wetlands". Charles Bukowski and Charlotte Roche on hemorrhoids]. / "Feuchtgebiete". Charles Bukowski und Charlotte Roche über Hämorrhoiden.

More than 40 years ago Charles Bukowski described his experiences with coloscopy and the ensuing surgery on his hemorrhoids, both performed by a doctor pictured as sadistic. Bukowski not only depicts these procedures but also characterizes his compassionate inpatients as well as the nursing staff. In her bestseller published in 2008 Charlotte Roche's protagonist Helen needs surgical inpatient treatment because of hemorrhoidal bleeding. Her stay in the hospital, prolonged by a postoperative self-inflicted bleeding, provides the basis not only for strategies to bring her divorced parents together but also for thoughts on genitalia, manifold sexual practices, as well as on rules of hygiene. From a psychodynamic viewpoint the protagonists in both stories suffer from a depressive basic conflict, compensated in Bukowski's work by a dependent, self-destructive, philobatic form of coping and in Roche's alter ego Helen by an impulsive, sexualized behaviour.

[The phenomen of sudden graying of the hair in the poem "Die Füsse im Feuer" by Conrad Ferdinand Meyer]. / Das Phänomen des plötzlichen Ergrauens in der Ballade "Die Füsse im Feuer" von Conrad Ferdinand Meyer.

In his poem "Die Füsse im Feuer" Conrad Ferdinand Meyer (1825-1898) describes in detail the phenomenon of sudden graying of the hair. The protagonist is a Huguenot nobleman who hosts the man who has tortured to death his wife some years ago without killing him despite ample opportunities. Sudden whitening of the hair has been used as literary stylistic means with the aim to demonstrate extreme psychological stress to the world, without confirmation of its occurrence in each case.

[Clinical dermatology at the Central Hospital Sankt-Jürgen-Strasse in Bremen.. A 110-year history]. / Zur Geschichte der klinischen Dermatologie am Zentralkrankenhaus Sankt-Jürgen-Strasse Bremen. Eine Rückschau auf 110 Jahre.

The history of clinical dermatology in Bremen began in 1891 with a dermatology unit founded in the main building of the then so-called "Big Hospital", nowadays Central Hospital Sankt-Juergen-Street. Friedrich B. Hahn became the first director and served in this position for more than four decades. In 1913, the dermatology wards moved to a new building, still home to the Dermatologic Clinic today. In 1933, the son of F.B. Hahn, Carl F. Hahn, became director until 1938, when the state officials named Konrad Burchardi as head of the department. Immediately after World War II, Friedrich Fölsch replaced K. Burchardi. He served as director until his retirement in 1964, when Joachim J. Herzberg became his successor until 1979. Wolfgang P. Herrmann then directed the clinic until 1994, when the author of this article was elected.

A strikingly constant ratio exists between Langerhans cells and other epidermal cells in human skin. A stereologic study using the optical disector method and the confocal laser scanning microscope.

Langerhans cells play an important part in the immune surveillance of the human epidermis. Therefore, a certain distribution and numerical relationship to other epidermal cells can be expected. To quantify epidermal Langerhans cells population extensive studies have been performed using two-dimensional quantification methods on vertical sections or epidermal sheet preparations. Whereas methods using vertical sections were complicated considerably by the sampling procedure, the dendritic shape, and the suprabasal, nonrandom distribution of Langerhans cells, epidermal sheet preparations have their limitations regarding the numerical relationship of Langerhans cells to total epidermal cells and the epidermal morphology as such. In order to improve the validity of data the three-dimensional dissector method combined with confocal laser scanning microscopy has been applied to quantify the number of Langerhans cells and other epidermal cell nuclei per volume unit in cryosections of 24 punch biopsies of normal breast skin of eight women. Furthermore, the ratio of Langerhans cells to other epidermal cells, their number per biopsy, and per skin surface area were calculated. To minimize the bias by shrinkage the reference volume was estimated using Cavalieri's principle. A constant ratio of one Langerhans cells to 53 other epidermal cells was identified in breast skin (interindividual correlation coefficient: 0.952, p < 0.0001). Thus, Langerhans cells represent 1.86% of all epidermal cells; however, a wide interindividual range was found for the number of Langerhans cells per mm2 (912-1806; mean +/- SD 1394 +/- 321) and other epidermal cells per mm2 (47,315-104,588; mean +/- SD 73,952 +/- 19,426). This explains the conflicting results achieved by conventional morphometric assessments relating cell numbers to skin surface area, ignoring the varying thickness of the epidermis. The surprisingly constant relationship of Langerhans cells to other epidermal cells stresses the hypothesis of an epidermal Langerhans cells unit where one Langerhans cells seems to be responsible for the immune surveillance of 53 epidermal cells.

Evaluation of the growth dynamics of Trichophyton rubrum cultures by morphometry and non-linear curve fitting analysis.

To determine the size of dermatophyte thalli, a point-counting procedure with a square lattice grid is proposed instead of using the one-dimensional diameter as the size parameter. For an analysis of the growth dynamics of such colonies, the area values might be subjected to a non-linear curve-fitting procedure. To demonstrate the method, samples of 15 Trichophyton rubrum strains, isolated from human skin and cultured concomitantly on Sabouraud and Selective agar during a period of 8 weeks, were used. The morphometric assessment of the area of the thalli, subjected to non-linear curve fitting, disclosed only a slight difference in the growth dynamics.

Oral lesions and symptoms related to metals used in dental restorations: a clinical, allergological, and histologic study.

BACKGROUND: Allergy to mercury as a cause of oral lichenoid lesions (OLL) remains controversial. Some authors reported high frequency of sensitization to mercury and beneficial effect from removal of amalgam fillings in such patients, whereas others state that this procedure affects favorably all OLL, whether patients are sensitized to inorganic mercury or not. OBJECTIVE: Our purpose was to determine the frequency of sensitization to metal salts in 194 patients (patients with OLL partly adjacent to amalgam fillings: 19, oral lichen planus (OLP) without close contact to amalgam: 42, other oral diseases: 28, oral complaints: 46, control group: 59). We further studied the histologic changes of biopsy specimens from positive patch tests to metal salts, and investigated the effect of removal of amalgam in OLL, to clarify whether it is possible to identify patients who will benefit from this procedure. METHODS: Patch testing was performed with the German standard series, a dental prosthesis series, and a metal salt series including gold, mercury, and palladium salts as well as other salts of metals used in dental restorations. Late readings (10 and 17 days after application of the patch tests) were performed in all patients. RESULTS: Of 19 patients with OLL adjacent to amalgam fillings, 15 (78.9%) were sensitized to inorganic mercury (INM), significantly more than those with OLL not adjacent to amalgam, other oral diseases or complaints, and the control group. In 5 of 15 (33.3%) of the patients with OLL, a positive patch test to INM was observed only at D10 or D17. Amalgam was removed in 18 patients with OLL (sensitization to INM: 15), and in 11 patients with OLP (sensitization to INM: 2). After removal, the lesions of 13 of 15 of the INM-sensitized patients with OLL (86. 7%) and 2 with OLP healed or improved significantly, but this was not observed with the INM negative patients. Frequency of sensitization to gold sodium thiosulfate (GST) and palladium chloride 1% pet (PDC) was high in all groups. This was partly because readings were performed late. Lesions of 2 patients with allergic contact stomatitis caused by gold and 1 caused by palladium healed completely after removal of these restorations. Histologically, lichenoid changes were observed in 14 of 36 biopsy specimens of positive patch tests from INM (9/21), GST (2/10), and PDC (3/5) in all patient groups, mainly in persistent patch tests at D10 or D17. This was not observed in 12 biopsy specimens taken from persistent patch tests from other substances, including nickel sulfate. CONCLUSION: Our results suggest that sensitization to mercury is an important cause of OLL, whether all lesions or only a part of them are adjacent to amalgam fillings. Sensitization to GST may reflect true gold allergy and should be considered as a cause of oral diseases in some patients. Sensitization to PDC is frequent but has yet only little clinical relevance. Patch tests may be positive only at D10 or D17. This suggests the importance of additional readings of GST, PDC, and mercury salts at this time.

Topical calcitriol (1,25-dihydroxyvitamin D3) treatment of psoriasis: an immunohistological evaluation.

The potent calciotropic hormone calcitriol (1,25-dihydroxyvitamin D3, 1,25(OH)2D3) has been shown to be very effective and safe in the topical treatment of psoriasis. In vitro, 1,25(OH)2D3 inhibits proliferation and stimulates differentiation of human keratinocytes. Increasing evidence suggests an immunoregulatory function of this potent steroid hormone. To further characterize the biological effects of topical calcitriol treatment in psoriasis, we have analyzed immunohistochemically the expression of markers for epidermal proliferation (proliferating cell nuclear antigen=PCNA) and differentiation (transglutaminase K, involucrin, cytokeratin 16), as well as inflammation (CD1a, 55 kDa TNF-receptor, NAP-1/IL-8) in calcitriol-treated psoriatic skin in situ. Our findings strongly support the hypothesis that calcitriol modulates keratinocyte proliferation/differentiation as well as inflammation in human skin in vivo. The immunoreactivity of markers for epidermal proliferation and differentiation, as well as of CD1a and NAP-1/IL-8, changed after 8 weeks of calcitriol treatment almost completely to the pattern characteristic for non-lesional psoriatic skin, while a large number of 55 kDa TNF-receptor positive cells could be found in the dermal compartment.

Expression of NM23 protein in acquired melanocytic nevi, malignant melanoma and metastases of malignant melanoma: an immunohistological assessment in human skin.

BACKGROUND: It has been suggested that nm23 may exert metastasis suppressor function in human tumors. OBJECTIVE: We have analyzed expression of nm23 polypeptide in acquired melanocytic nevi (n = 19), dysplastic nevi (n = 19), malignant melanomas (n = 22) and metastases of malignant melanomas (n = 47) in situ. METHODS: Nm23 protein was detected immunohistochemically on paraffin sections using the highly sensitive labeled avidin-biotin technique. RESULTS: We found that (1) nm23 polypeptide is predominantly expressed in the cytoplasmic but also in nuclear and membrane compartments of melanocytic human cells, (2) expression of nm23 protein does not correlate with benign or malignant phenotype in melanocytic tumors of human skin. CONCLUSION: Our study challenges the hypothesis that nm23 may function in malignant melanomas as a tumor suppressor gene.

Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin.

BACKGROUND: The biologically active vitamin D analog calcipotriol is effective and safe in the topical treatment of psoriasis, but its exact mechanism of action is unknown. OBJECTIVE: We investigated expression of 1,25-dihydroxyvitamin D3 receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP-1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67), and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic skin during topical calcipotriol treatment. METHODS: For immunohistochemical staining we used the labeled avidin-biotin technique on cryostat-cut sections. RESULTS: We found a significant increase of 1,25-dihydroxyvitamin D3 receptor expression in epidermal basal keratinocytes of lesional psoriatic skin during calcipotriol treatment. In all patients analyzed, effects on proliferation and differentiation of epidermal keratinocytes were stronger than effects on dermal inflammation. Effects on inflammation were more pronounced in the epidermal than in the dermal compartment. CONCLUSION: Our findings indicate that analogs of 1,25-dihydroxyvitamin D3 upregulate their corresponding receptor in human keratinocytes in vivo. This mechanism may be important in the therapeutic efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects in the epidermal and dermal skin compartments may be due to a reduced bioavailability of calcipotriol in the dermal compartment.

Surface and volume density of CD1a+ Langerhans cells in the human oral mucosa: a stereological study using vertical sections.

Quantification of the surface and volume density of CD1a+ Langerhans cells in the human oral mucosa was carried out using a recently described technique of intercept counting on vertical sections, and the point counting method, respectively. The surface density of LC, i.e. surface area of LC per unit epithelial volume, was estimated between 310.8 mm-1 621.0 mm-1 (mean 420.3 mm-1), and estimated coefficients of error (estCE) were between 2.92% and 22.15%. Estimates of the volume density of LC, i.e. fraction of epithelial volume occupied by LC, yielded values from 1.56% to 13.15% (mean 5.96%) with estimated CE's of 5.69% to 25.94%. The investigation demonstrates the value of newer and older stereological tools to quantify complex cells such as LC on ordinary vertical sections without expensive equipment.

Rapid and unbiased estimation of the volume of cutaneous malignant melanoma using Cavalieri's principle.

The Cavalieri volume estimator has been employed to determine the macroscopic tumor volume of 34 cutaneous malignant melanomas. With this rapid and unbiased method using histological specimens from slabs of known thickness, tumor volumes between 3.9 mm3 and 841.5 mm3 were found. The coefficient of error (CE) for tumor volumes ranged between 0.028 and 0.141, with a combined group CE of 0.043. There was a remarkably good correlation between tumor volume and maximal vertical tumor thickness estimated according to Breslow, with a correlation coefficient of r = 0.86 for all tumors, and of r = 0.82, if the one extremely big tumor is omitted. Both inter- and intraobserver variability was very low, with only approximately 1-2% difference. Thus, the method described allows for the reproducible, rapid, and unbiased estimation of tumor volume independent of the shape of the tumor.

Immunohistochemical detection of 1,25-dihydroxyvitamin D3 receptors (VDR) in human skin. A comparison of five antibodies.

Increasing evidence suggests an important regulatory function for 1 alpha,25-dihydroxyvitamin D3 in the growth control of epidermal cells and in skin immunology. Using immunohistochemical techniques we investigated the in situ expression of 1,25-dihydroxyvitamin D3 receptors (VDR) in normal human skin with one monoclonal rat antibody and four monospecific polyclonal rat antibodies to the VDR. Polyclonal rabbit antibodies have been raised against synthetic peptides corresponding to different amino acid residues of the human VDR, including regions close to the DNA binding domain and the hormone-binding domain. All antibodies revealed positive immunoreactivity in normal human skin. The antibodies showed differences in subcellular immunoreactivity and staining-intensity. Differences in subcellular distribution of VDR immunoreactivity are caused by the different epitopes recognized by the antibodies and not by the affinity of the antibodies for VDR. It seems that the antibodies may recognize different functional modifications of the receptor molecule (i.e.: hormone bound vs. hormone free; DNA bound vs. non-DNA bound; VDR vs. VDR/retinoid-X receptor [RXR] heterodimers). Using these newly raised antibodies future studies will be carried out to analyse subcellular distribution of VDR immunoreactivity in skin pathology.

Volume estimation of multicellular colon carcinoma spheroids using Cavalieri's principle.

Multicellular tumour-spheroids are regarded as suitable models for cancer research, similar to avascular tumour parts. As a size parameter of the spheroids, usually their maximum diameter is used, estimated on a section presumed to be equatorial or near equatorial. Estimation of the volume of spheroids is of interest for the detection of subtle changes in different kinds of investigations. Since spheroids are often not truly spherical, and because model-based methods for volume determination may be biased, Cavalieri's principle, rediscovered recently for stereology, was used to determine the volume of the spheroids. Here we report the results of the volume estimation of colon carcinoma spheroids, together with an outline of the basic stereological principle and formulas used. The spheroids investigated had a volume between 1.4 and 92.3 mm3 (mean 33.9). The volume fraction of necrotic to viable tissue cells was between 0.6:1 and 2.2:1. The coefficient of error (CE) was remarkably low with 3.7% for the volumes. Both inter- and intraobserver-variability were extremely low with correlation coefficients (r2) of 99%. Thus, the high precision of the stereological method, combined with a low workload, make it ideally suitable for routine volume estimation.