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Biomedical subjects

M Streit

Publications and source records attributed to M Streit.

At least 19 recordsLinked to original sources

[Clinical classification of chronic pruritus. Interdisciplinary consensus proposal for a diagnostic algorithm].

Chronic pruritus is a frequent symptom in dermatology caused by a variety of dermatologic, neurologic and other systemic diseases. For adequate, economically-appropriate medical care of patients with chronic pruritus, a clinical classification of pruritus which also serves as a diagnostic algorithm is necessary. Currently suggested classifications are etiologic and not helpful in daily clinical routine. The proposed clinical classification is oriented at the clinical appearance of the patients and differentiates between disorders with or without primary or secondary skin lesions.

Algorithms↗

[Pruritus with systemic diseases].

Chronic itch is a frequent symptom not only associated with skin diseases. In a number of internal, neurological and psychiatric illnesses pruritus can be a prominent and distressing symptom. Diagnosis is frequently very cumbersome because pruritus in these diseases often does not cause any specific skin lesions. This report focuses on the most important internal disease entities causing pruritus and highlights the most successful diagnostic and therapeutic approaches.

Diagnosis, Differential↗

Stewart-Treves syndrome: MR imaging of a postmastectomy upper-limb chronic lymphedema with angiosarcoma.

The rare occurrence of angiosarcoma in postmastectomy upper-limb lymphedema with magnetic resonance (MR) imaging is discussed. Unfamiliarity with this aggressive vascular tumor and its harmless appearance often leads to delayed diagnosis. Angiosarcoma complicating chronic lymphedema may be low in signal intensity on T2-weighting and short tau inversion recovery (STIR) imaging reflecting the densely cellular, fibrous stroma, and sparsely vascularized tumor histology. Additional administration of intravenous contrast medium revealed significant enhancement of the tumorous lesions. Awareness of angiosarcoma and its MR imaging appearance in patients with chronic lymphedema may be a key to early diagnosis or allow at least inclusion in the differential diagnosis.

Aged, 80 and over↗

Successful treatment of chemotherapy-refractory Sézary syndrome with alemtuzumab (Campath-1H).

INTRODUCTION: Sézary syndrome (SS) is a cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical T cells. Median survival after diagnosis is 10 yr, with chemotherapy resistance being a major problem in advanced disease. Alemtuzumab (Campath-1H) is a monoclonal antibody directed against the lymphocytic antigen CD52, expressed on B- and T-cells. Alemtuzumab is approved for relapsing chronic B-cell leukemia and seems to be active also in T-cell lymphomas such as T-cell prolymphocytic lymphoma, SS and mycosis fungiodes. CASE HISTORY: A 32-yr-old male patient presented with advanced stage, extensively pretreated SS with heavily itching erythroderma, peripheral lymphadenopathy, circulating Sézary cells and bone marrow infiltration. The disease had not responded to PUVA/interferon-alpha and progressed on chemotherapy with CHOP, 2-CDA, vinorelbine, etoposide and liposomal doxorubicin. Following treatment with alemtuzumab (30 mg i.v. three times per week for 10 wk), itching resolved rapidly and an almost complete remission was achieved within 3 months after starting this treatment. At 12-month follow up, no disease progression was present. CONCLUSION: In accordance with previous data, this single case underlines the potent activity of alemtuzumab in advanced, chemotherapy-refractory SS.

Adult↗

Progressive respiratory failure in paraneoplastic pemphigus associated with chronic lymphocytic leukemia.

A 70-year-old Caucasian man with chronic lymphocytic leukemia suffered from widespread, histologically proven cutaneous lichen planus responding to topical corticosteroids. 2 years later, he presented with painful erosive stomatitis and increasing dyspnea. Histology, direct and indirect immunofluorescence were diagnostic for paraneoplastic pemphigus. A full diagnostic workup could not disclose the cause of the progressive respiratory insufficiency. Despite aggressive treatment of the lymphocytic leukemia and the paraneoplastic pemphigus, the patient died 3 months after diagnosis. Paraneoplastic pemphigus may lead to pulmonary failure which is refractory to treatment and has a fatal outcome.

Aged↗

Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism.

The angiogenic switch during tumorigenesis is thought to be induced by a change in the balance of pro- angiogenic and anti-angiogenic factors. To elucidate the biological role of the endogenous angiogenesis inhibitor thrombospondin-2 (TSP-2) during multistep carcinogenesis, we subjected TSP-2-deficient and wild-type mice to a chemical skin carcinogenesis regimen. Surprisingly, TSP-2 expression was strongly upregulated in the mesenchymal stroma of wild-type mice throughout the consecutive stages of tumorigenesis whereas the angiogenesis factor, vascular endothelial growth factor, was induced predominantly in tumor cells. TSP-2 deficiency dramatically enhanced susceptibility to skin carcinogenesis and resulted in accelerated and increased tumor formation. The angiogenic switch occurred in early stages of pre-malignant tumor formation, and tumor angiogenesis was significantly enhanced in TSP-2-deficient mice. While TSP-2 deficiency did not affect tumor differentiation or proliferation, tumor cell apoptosis was significantly reduced. These results reveal upregulation of an endogenous angiogenesis inhibitor during multi step tumorigenesis and identify enhanced stromal TSP-2 expression as a novel host anti-tumor defense mechanism.

9,10-Dimethyl-1,2-benzanthracene↗

EEG-correlates of facial affect recognition and categorisation of blurred faces in schizophrenic patients and healthy volunteers.

The ability to recognise emotional expressions of faces and the ability to categorise blurred and non-blurred faces and complex objects was tested in 16 schizophrenic in-patients and 16 healthy volunteers. EEGs were recorded during performance of the tasks and event-related potentials were compared between groups. Patients performed worse than healthy volunteers in recognition of facial affect but not in categorisation of blurred faces. Furthermore, within a 180-250ms latency range patients showed reduced amplitudes during affect recognition compared with controls but not during categorisation of blurred faces. Amplitudes recorded at frontal electrode sites were associated with performance in facial affect recognition. These results provide a first clue to the neurophysiological basis of the widely reported facial affect recognition deficit in schizophrenic patients.

Adult↗

Successful induction of immune responses against mutant ras in melanoma patients using intradermal injection of peptides and GM-CSF as adjuvant.

The rapidly increasing incidence and mortality rate of malignant melanoma, together with the lack of efficient treatment of the late stages, makes it a serious threat to public health. Innovative new treatments are needed. The proteins of the ras-family of proto-oncogenes, functioning as relay switches for signalling pathways between cell surface and nucleus, are involved in cell proliferation, differentiation, apoptosis and transformation. If over-expressed or mutated they can induce and/or maintain a transformed state of a cell. Codon 61 mutations of N-ras seem to be involved in melanoma development on sun exposed sites. In order to induce an immune response towards mutated N-ras proteins we performed a phase 1 feasibility study. Ten melanoma patients were immunized intradermally 6 times with N-ras peptides (residue 49-73) with 4 codon 61 mutations using GM-CSF as adjuvant. HLA typing was not used as an inclusion criterion. Eight patients responded with strong delayed type hypersensitivity reactions. In 2 of the patients an in vitro response to the vaccine could also be detected. The specificity of the reaction could be confirmed by cloning of peptide-specific CD4 positive T cells from peripheral blood of the patients. Intradermal injection of ras peptides using GM-CSF as adjuvant is simple to perform and seems to be efficient in inducing cellular immune responses. Since a majority of the patients showed positive skin reactions and 2 of the patients analysed showed a T-helper response to this melanoma specific antigen, these promiscuous HLA class II binding mutant ras peptides may be candidates for inclusion into vaccine cocktails containing various established CTL epitopes.

Adjuvants, Immunologic↗

The angiogenesis inhibitor vasostatin does not impair wound healing at tumor-inhibiting doses.

Inhibition of tumor angiogenesis represents a promising new approach for the treatment of human cancers. It has remained unclear, however, whether inhibition of tumor angiogenesis may also result in impaired wound healing, a process thought to be angiogenesis dependent. To determine the effects of the angiogenesis inhibitor vasostatin, a 180 amino acid calreticulin fragment, on wound healing at tumor inhibiting doses, full-thickness wounds were generated on the back of nude mice that were also injected intradermally with CA46 Burkitt lymphoma cells. Mice were treated with daily injections of vasostatin or vehicle control at a site between the wounds and the transplanted tumor cells over 14 d. Vasostatin potently inhibited tumor growth and significantly reduced tumor angiogenesis, as measured by computer-assisted image analysis of CD31-stained tumor sections. Moreover, vasostatin treatment resulted in an increased fraction of mature tumor-associated blood vessels. In contrast, no impairment of wound healing was observed in vasostatin-treated mice, despite a significantly reduced vascularity of the wound granulation tissue. Our results reveal a different sensitivity of malignant tumor growth and physiologic wound healing to inhibition of angiogenesis, and they suggest that therapeutic inhibition of tumor angiogenesis may be achieved without impairment of tissue repair.

Angiogenesis Inhibitors↗

Contact dermatitis: clinics and pathology.

Contact dermatitis or eczema is a polymorphic inflammation of the skin. It occurs at the site of contact with irritating or antigenic substances. In the acute phase there is occurrence of itching erythema, papules, and vesicles, whereas in the chronic phase there is dryness, hyperkeratosis, and sometimes fissures. Contact dermatitis can be divided into irritant and allergic types. Allergic contact dermatitis is a type-IV T-cell-mediated reaction occurring in a sensitized individual after contact with the antigen/allergen. Such antigens are usually low molecular weight substances (MW approximately 500), called haptens; 3000 contact allergens are known. The diagnosis of contact allergy is made on the basis of the history, clinical findings, and a positive epicutancous test result. Allergic, but not irritative, contact dermatitis can spread beyond the area of contact to other body parts. Eczematous lesions are characterized by a mononuclear infiltrate consisting mainly of T cells in the dermis and epidermis, together with an intercellular epidermal edema that is. spongiosis. In allergic contact dermatitis, skin-applied antigen is taken up by epidermal Langerhans cells and transported with the afferent lymph to the regional lymph nodes. Here, naive T lymphocytes are sensitized to become antigen-specific effector T cells, which then leave the lymph node, enter the circulation, and are recruited to the skin by means of specific cell surface molecules, to form the infiltrates. Cytokines released by infiltrating T cells eventually cause keratinocyte apoptosis.

Allergens↗

Ulcerative sarcoidosis successfully treated with apligraf.

The case of a 73-year-old female patient is reported with a 25-year-long history of widespread cutaneous sarcoidosis without any known extracutaneous manifestations. The skin manifestations started with erythematous and plaque-like lesions that had ulcerated on the legs for the last half-year. A relevant venous insufficiency or other etiology of the ulcers could not be found. Histology from lesions of the trunk and from the surroundings of the ulcers revealed the typical noncaseating granulomas. A systemic involvement could not be observed; leukopenia and a slightly elevated angiotensin-converting enzyme level in the serum were found. Topical steroids did not prove successful on the ulcers. Apligraf, a bilayered skin equivalent, was transplanted twice on the ulcers leading to complete closure within 3 months. A therapy with systemic steroids could thus be avoided.

Aged↗

Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4.

The syndecans make up a family of transmembrane heparan sulfate proteoglycans that act as coreceptors with integrins and growth factor tyrosine kinase receptors. Syndecan-4 is upregulated in skin dermis after wounding, and, in cultured fibroblasts adherent to the ECM protein fibronectin, this proteoglycan signals cooperatively with beta1 integrins. In this study, we generated mice in which the syndecan-4 gene was disrupted by homologous recombination in embryonic stem cells to test the hypothesis that syndecan-4 contributes to wound repair. Mice heterozygous or homozygous for the disrupted syndecan-4 gene are viable, fertile, and macroscopically indistinguishable from wild-type littermates. Compared with wild-type littermates, mice heterozygous or homozygous for the disrupted gene have statistically significant delayed healing of skin wounds and impaired angiogenesis in the granulation tissue. These results indicate that syndecan-4 is an important cell-surface receptor in wound healing and angiogenesis and that syndecan-4 is haplo-insufficient in these processes.

Animals↗

Disturbed facial affect recognition in patients with schizophrenia associated with hypoactivity in distributed brain regions: a magnetoencephalographic study.

OBJECTIVE: The authors sought to identify brain mechanisms underlying the well-documented facial affect recognition deficit in patients with schizophrenia. Since this deficit is stable over the course of the illness and relatively specific for schizophrenic disorders, it was expected that knowledge about the related brain mechanisms would provide substantial information about the pathophysiology of the illness. METHOD: Fifteen partly remitted schizophrenic inpatients and 12 healthy volunteers categorized facial expressions of emotion and performed two control tasks while magnetoencephalographic recordings were done by means of a 148-channel whole head system, which revealed foci of high cerebral activity and their evolution in time. Anatomical sites were defined through coregistrated magnetic resonance images. RESULTS: The magnetoencephalography data recorded in response to facial expressions of emotion revealed that patients generated weaker activations (primary current density) in inferior prefrontal, temporal, occipital, and inferior parietal areas at circumscribed latencies. Group differences did not occur in basic visual areas during a first sensory-related activation between 60 and 120 msec. Behavioral performance was associated with strength of activation in inferior prefrontal areas, the right posterior fusiform gyrus region, right anterior temporal cortex, and the right inferior parietal cortex. CONCLUSIONS: Disturbed facial affect recognition in schizophrenic patients might be a result of hypoactivity in distributed brain regions, some of them previously related to the pathophysiology of schizophrenic disorders. These regions are probably working within a spatially and temporally defined circuitry.

Adult↗

Thrombospondin-1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice.

The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in tissue repair has remained controversial. We established transgenic mice with targeted overexpression of TSP-1 in the skin, using a keratin 14 expression cassette. TSP-1 transgenic mice were healthy and fertile, and did not show any major abnormalities of normal skin vascularity, cutaneous vascular architecture, or microvascular permeability. However, healing of full-thickness skin wounds was greatly delayed in TSP-1 transgenic mice and was associated with reduced granulation tissue formation and highly diminished wound angiogenesis. Moreover, TSP-1 potently inhibited fibroblast migration in vivo and in vitro. These findings demonstrate that TSP-1 preferentially interfered with wound healing-associated angiogenesis, rather than with the angiogenesis associated with normal development and skin homeostasis, and suggest that therapeutic application of angiogenesis inhibitors might potentially be associated with impaired wound vascularization and tissue repair.

Animals↗

Electrophysiological correlates of emotional and structural face processing in humans.

In order to study brain potentials related to decoding of facial expressions of emotions and those, related to basic perception of faces 16 right-handed subjects performed tasks on facial emotion recognition and perception of blurred faces and objects. Electroencephalograph (EEG) recordings during performance of the tasks revealed similar event-related potentials during the presentation of faces at 120 and 170 ms after stimulus onset in both of the tasks but significant differences in amplitudes between 180 and 300 ms. Whereas faces in the emotion recognition task produced high amplitudes in that latency range, potentials in response to faces in the blurred object condition were virtually absent. These data point to the assumption that decoding of facial expressions starts early in the brain and might be processed separately from basic stages of face perception.

Adult↗

[Transitory acantholytic dermatosis (Grover disease). An analysis of the clinical spectrum based on 21 histologically assessed cases].

BACKGROUND AND OBJECTIVE: In 1970 Ralph W. Grover described a clinicopathologic entity characterized by pruritic keratotic papules and papulovesicles predominantly on the trunk, disappearing spontaneously after a few weeks or months and demonstrating the histological features of epidermal acantholysis. The etiology remains unknown; sweating, heat and sunlight are suspected trigger factors. In our survey the clinical spectrum of the disease will be examined. PATIENTS AND METHODS: We have analyzed 21 cases of Grover's disease histologically diagnosed in Berne in 1997 and 1998. RESULTS: In most cases we observed isolated papules disseminated on the trunk. The predominant histological type was the Darier-type; presumably there is no correlation between histological type and clinical features. At the time of diagnosis the skin disorder had been present on average for 83 months. There was a strong association with sweating and heat. Topical steroids were successful in 50% of patients. CONCLUSIONS: Our 21 cases reflect in general the literature. Nevertheless, the long persistence of the skin lesions was striking perhaps making the term transient somewhat inaccurate.

Acantholysis↗