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Biomedical subjects

T Luger

Publications and source records attributed to T Luger.

At least 19 recordsLinked to original sources
PubMed2001

[Imiquimod: a new treatment possibility in bowenoid papulosis?].

Bowenoid papulosis is a highly characteristic condition of the anogenital region which is histologically similar to bowenoid carcinoma in situ. Some evidence suggests a viral origin on the basis of infection with high-risk oncogenic genotypes of human papilloma viruses (HPV 16/18 and others) and an association with cervical carcinoma. Malignant transformation is rare in bowenoid papulosis. The condition usually shows a good response to immuno-modulatory treatment. In the following we present our first case of successful treatment with imiquimod, a topical immune response modifier which is successfully used in the USA for local treatment of condylomata acuminata. Imiquimod creme (Aldara) proved to be a safe, efficious and practical patient-applied therapeutic option for the treatment of bowenoid papulosis. In view of the oncogenic potential of high-risk HPV infections, irrespective of the treatment used, all patients with bowenoid papulosis and their sexual partners must be included in long-term follow-up and regularly examined for malignant transformation.

Adjuvants, Immunologic↗
PubMed2001

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. METHODS: This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

Adolescent↗
PubMed2001

Treatment of prurigo nodularis with topical capsaicin.

BACKGROUND: Prurigo nodularis is an eruption of lichenified or excoriated nodules caused by intractable pruritus that is difficult to treat. Therefore the antipruritic efficacy of capsaicin seemed to be of particular interest because this alkaloid, extractable from red pepper, interferes with the perception of pruritus and pain by depletion of neuropeptides in small sensory cutaneous nerves. OBJECTIVE: The aim of this concentration- and regimen-ranging study was to evaluate the efficacy, safety, and practicability of capsaicin in the topical treatment of prurigo nodularis in a large series of patients. METHODS: A total of 33 patients with prurigo nodularis of various origins were selected to receive capsaicin (0.025% to 0.3%) 4 to 6 times daily for 2 weeks up to 10 months. The consecutive follow-up period was up to 6 months. In 7 patients, skin biopsy specimens were taken before, during, and after therapy and investigated histologically, immunohistochemically, and ultrastructurally. RESULTS: All 33 patients could be evaluated for efficacy. After cessation of the symptoms of neurogenic inflammation, such as burning sensations or erythema, all of them experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to the gradual healing of the skin lesions. After discontinuation of the therapy, pruritus returned in 16 of 33 patients within 2 months. At the ultrastructural level, no degenerative changes of cutaneous nerves could be found during or after capsaicin therapy. Depletion of substance P was demonstrated by confocal laser scanning microscopy thus confirming the specific effect of capsaicin in vivo. CONCLUSION: Topical treatment of prurigo nodularis with capsaicin proved to be an effective and safe regimen resulting in clearing of the skin lesions.

Administration, Topical↗
PubMed2000

alpha-Melanocyte stimulating hormone acts as a selective inducer of secretory functions in human mast cells.

In the present study, we have investigated the pro-opiomelanocortin (POMC)-derived neuropeptide alpha-MSH for its ability to modulate activation of human mast cells. The in vitro ability of purified human skin mast cells to secrete various types of mast cell mediators was monitored in response to alpha-MSH at the mRNA and at the protein level. Picomolar concentrations of alpha-MSH induced a dose-dependent release of histamine from isolated human skin mast cells and from skin punch biopsies. However, no effect of alpha-MSH was seen regarding the expression of IL-1, IL-6, IL-8, TGF-beta, and TNF-alpha. Melanocortin receptor MC-1 was identified at the transcriptional level by RT-PCR analysis but not at the protein level, whereas, in leukemic human mast cells (HMC-1), the mRNAs and the proteins for the MC-1 and MC-5 receptor were identified. These results suggest that alpha-MSH may selectively induce acute inflammatory effects via secretion of histamine.

Biopsy↗
PubMed2000

[Hydroxyethyl starch accumulation in the skin with special reference to hydroxyethyl starch-associated pruritus].

BACKGROUND AND OBJECTIVE: Hydroxyethyl starch (HES) is a colloidal infusion fluid that has for a long time been used in emergency situations and to improve impaired blood perfusion. In the last few years there have been numerous reports about treatment resistant pruritus, often persisting for months, after HES infusion. We investigated the intracellular uptake of HES in the skin, special attention being focused on associated pruritus. PATIENTS AND METHODS: Skin biopsies were obtained from 120 patients (120 men, 35 women) and examined immunohistochemically and for their ultrastructure. Three patients had received various HES preparations, while 22 had been given dextran. Five patients who had received no infusions served as controls. RESULTS: All patients given HES had lysosomal deposits in the histiocytes, some of them also in cutaneous epithelium and endothelium. The extent of lysosomal storage correlated with the amount of infused HES and the interval between biopsy and last HES infusion. Consecutive biopsies in some cases demonstrated a definite decrease over the years of HES deposits in the vacuoles. This suggests that HES is regularly metabolized in the skin. Pruritus after high cumulative doses of HES was closely correlated with HES deposition in cutaneous nerves. CONCLUSIONS: These results emphasize the need for starch derivatives that can be better metabolized and for better adapted infusion schedules to reduce the high incidence of pruritus.

Adolescent↗
PubMed2000

[Hyperkeratosis lenticularis perstans (Flegel's disease) - a complex disorder of epidermal differentiation with good response to a synthetic vitamin D3 derivate].

Hyperkeratosis lenticularis perstans (Flegel's disease) is a rare but clinically and histologically highly characteristic genodermatosis. We report on new immunohistochemical and ultrastructural findings suggesting a complex disorder of epidermal differentiation. In this context, a good response to calcipotriol, a synthetic vitamin D3 derivative is of particular interest.

Aged↗
PubMed2000

[Topical administration of capsaicin in dermatology for treatment of itching and pain].

BACKGROUND AND OBJECTIVES: Treatment of pruritus as observed in many dermatological and internal diseases may be very often disappointing. There are many reports describing the topical use of capsaicin, the pungent agent in red pepper. Long term administration of capsaicin depletes neuropeptides in unmyelinated, polymodal C-type and small myelinated A delta-type cutaneous nerves that conduct pruritus and pain. PATIENTS/METHODS: The aim of this study was to evaluate the efficacy, safety and practicability of capsaicin in the treatment of pruritus and pain of different origin in a total of 40 patients. RESULTS: Capsaicin suppressed completely itch in all patients. CONCLUSIONS: In addition to its excellent antipruritic and analgetic effect, capsaicin significantly contributed to healing of some dermatoses, such as prurigo nodularis and psoriasis.

Administration, Topical↗
PubMed2000

[Control of section margins without any gaps in paraffin sections of melanoma of the face].

BACKGROUND AND OBJECTIVE: Malignant melanomas on sun-exposed skin are often poorly circumscribed and thus recur frequently. The aim of our clinical trial was to compare conventional to a modified micrographic surgery of primary melanoma. PATIENTS/METHODS: 28 patients with in-situ (n = 7) and invasive (n = 21) melanoma were treated with conventional surgical excision with wide margins; eight of these patients developed a local recurrence. In comparison, 20 patients with primary in-situ (n = 7) and invasive (n = 13) melanoma as well as four patients with recurrence after conventional surgery underwent modified micrographic surgery with delayed closure of the wound. RESULTS: Paraffin specimens of the margins revealed in half of the patients remnants of melanoma although excision was extended to non-lesional skin. Within a mean follow-up period of 21.3 months, none of our patients treated by modified surgery developed a recurrence. CONCLUSIONS: Local recurrencies of melanoma on sun exposed skin may be avoided by means of a modified micrographic surgery using permanent histologic sections.

Adult↗
PubMed2000

Safety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections.

BACKGROUND: Insect venom immunotherapy (VIT) is initiated by a dose increase protocol administered usually over 7 to 9 days. Shorter protocols have the advantage of reducing the patient's stay in the hospital. Very few data are currently available on the safety of shorter VIT dose increase protocols. OBJECTIVE: The aim of this study was to investigate whether a reduction in the duration of the VIT dose increase protocol from 7 to 9 days to 2 days causes an increase in the incidence and severity of adverse reactions. METHODS: Between 1992 and 1997 we administered VIT to 1055 patients allergic to bee or wasp venom. We shortened the 7- to 9-day rush protocol stepwise to 2 days by reducing the number of injections and increasing the initial dose and compared the incidence and severity of adverse reactions. The patients were retrospectively divided into 3 cohorts: 20 injections over 7 to 9 days (cohort 1, 317 patients), 10 to 14 injections over 3 to 6 days (cohort 2, 335 patients), and 9 injections over 2 days (cohort 3, 403 patients). RESULTS: We observed no severe adverse reactions in any of the cohorts during VIT. Adverse reactions were treated in 7.1% of the patients by oral and in 2.9% by intravenous antihistamines and in 0.8% by systemic corticosteroids. The incidence of adverse reactions declined significantly from 22.4% in cohort 1 to 13.7% in cohort 2 and 10.7% in cohort 3 with reduced number of injections (P <.001). CONCLUSION: The incidence and severity of adverse reactions decline if the VIT dose increase protocol is shortened to 2 days.

Adolescent↗
PubMed2000

Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress.

The skin is a known target organ for the proopiomelanocortin (POMC)-derived neuropeptides alpha-melanocyte stimulating hormone (alpha-MSH), beta-endorphin, and ACTH and also a source of these peptides. Skin expression levels of the POMC gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but are determined by such factors as the physiological changes associated with hair cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune cytokine release, or the presence of cutaneous pathology. Among the cytokines, the proinflammatory interleukin-1 produces important upregulation of cutaneous levels of POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates expression of all the components of the CRH/POMC system including expression of the corresponding receptors. Molecular characterization of the cutaneous POMC gene shows mRNA forms similar to those found in the pituitary, which are expressed together with shorter variants. The receptors for POMC peptides expressed in the skin are functional and include MC1, MC5 and mu-opiate, although most predominant are those of the MC1 class recognizing MSH and ACTH. Receptors for CRH are also present in the skin. Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses. The powerful effects of POMC peptides and probably CRH on the skin pigmentary, immune, and adnexal systems are consistent with stress-neutralizing activity addressed at maintaining skin integrity to restrict disruptions of internal homeostasis. Hence, cutaneous expression of the CRH/POMC system is highly organized, encoding mediators and receptors similar to the hypothalamic-pituitary-adrenal (HPA) axis. This CRH/POMC skin system appears to generate a function analogous to the HPA axis, that in the skin is expressed as a highly localized response which neutralizes noxious stimuli and attendant immune reactions.

Animals↗
PubMed1999

The skin POMC system (SPS). Leads and lessons from the hair follicle.

Human and murine skin are prominent extrapituitary sources and targets for POMC products. The expression of, for example, ACTH, alpha-MSH, beta-endorphin, and MC-1-receptors fluctuates during synchronized hair follicle cycling in C57BL/6 mice. Since hair growth can be induced by ACTH injections in mice and mink, and since high doses of MSH peptides modulate epidermal and/or follicle keratinocyte proliferation in murine skin organ culture, some POMC products may operate as locally generated growth modulators, in addition to their roles in cutaneous pigment and immunobiology. Intrafollicularly generated ACTH and alpha-MSH as well as their cognate receptors may assist in the maintenance of the peculiar immune privilege of the anagen hair bulb. Possibly, they are also involved in the development of the follicle pigmentary unit, with whose generation their expression coincides. Given that murine skin also expresses (in a hair-cycle-dependent way) CRH and CRH-R, which control pituitary POMC expression and in view of the fact that CRH arrests follicles in telogen, this suggests the existence of a local skin POMC system (SPS). This may be an integral component of cutaneous stress response-systems, and may most instructively be studied using the murine hair cycle as a model.

Adrenocorticotropic Hormone↗
PubMed1999

[Localized reticulate hyperpigmentation].

34 year-old pregnant woman presented with reticulate pigmentation of the flexures, the dorsum of the hands and the genitoperianal region. She was in good health and her family history was unremarkable. Histologic examination of the hyperpigmented patches revealed pigmented filiform downgrowths of the interfollicular epidermis and follicular infundibula, as well as small epithelial cysts. Upon immunohistochemical and ultrastructural studies, the number of melanocytes appeared normal. The elongated dendritic processes of the melanocytes contained many mature melanosomes. In the adjacent keratinocytes large melanosomes did not aggregate into complexes. The diagnosis of localized reticulate pigmentary disorder was established. The knowledge of the broad clinical spectrum of localized reticulate hyperpigmentations with its favorable prognosis is of practical importance. Genital or flexural pigmented lesions have to be differentiated from melanosis of the vulva or acanthosis nigricans. The presented case gives further evidence that many of the proposed entities characterized clinically by reticulate pigmented macules and hyperkeratotic follicular lesions are different phenotypic expressions of the same autosomal dominant genodermatosis.

Adult↗