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Biomedical subjects

T Hunziker

Publications and source records attributed to T Hunziker.

At least 37 records · Page 2Linked to original sources
PubMed1998

Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.

Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.

Adolescent↗
PubMed1998

Circadian elevation of IL-6 levels in Muckle-Wells syndrome: a disorder of the neuro-immune axis?

Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary disorder characterized by chronic recurrent urticaria, arthralgia, sensorineural deafness, and in some cases nephropathy due to amyloidosis (AA type). We report a 21-year-old woman and her father, both suffering from this syndrome, in whom elevated serum levels of IL-6 could be documented during the flares of urticaria, and discuss the relevance of this finding for MWS.

Acute Disease↗
PubMed1997

[Atopic dermatitis].

Atopic dermatitis is a type of eczema determined by polygenic inheritance which is often associated with further phenotypes of the atopic syndrome such as extrinsic asthma and allergic rhinoconjunctivitis. Discussion of pathogenesis includes complex immunological and biochemical disorders as well as various triggering environmental factors. Characteristic patterns of distribution and morphology of the lesions vary with the patient's age. In addition, there is a broad spectrum of clinical variants. Diagnosis is based on stage-dependent eczematous morphology, if necessary validated by histology, family and personal history and clinical features of atopy, as well as on the results of allergologic assessment primarily comprising intra- and epicutaneous testing. Topical corticosteroids still are the main therapeutic approach.

Administration, Topical↗
PubMed1997

Signal generation in a non-EU country.

One of the most important objects of post-marketing surveillance is the early detection of serious, unknown and unexpected adverse events. As spontaneous reported adverse events vary considerably in their signal-generating value the Swiss Drug Monitoring Center SANZ implemented an early signal detection system in 1991. With a set of screening criteria the individual case reports are automatically checked by the system and read into a signal file. Subsequently these potential signals are processed to quantify the signal generating value of the particular case. According to the screening criteria 2072 (53%) of the reported cases were considered as potential signals. After validating and quantifying their signal value 27% (565) were drug-related and unlabelled, 8% (173) were also rated as serious. On the basis of these cases 114 labelling changes were made. Some of the most interesting cases are discussed. This computer-assisted early signal generation model in a small country with 7 million inhabitants has a high detectability of new, rare, serious and quality of life affecting adverse drug reactions (ADRs). These newly detected ADRs must be interpreted in cognizance of the limitations and restrictions of spontaneous reporting and do not allow pharmacoepidemiologic conclusions.

Journal Article↗
PubMed1997

[Erythema elevatum diutinum. A rare dermatosis with a broad spectrum of associated illnesses].

Erythema elevatum diutinum (EED) is a rare disease presenting with persistent red to yellow-brown papules or plaques which are mainly localized symmetrically on the extensor aspects of the hands and fingers, the elbows and the knees. The histology shows a leucocytoclastic vasculitis in early lesions and fibrosis of the dermis later on. Dapsone is the treatment of choice. Today, EED is usually assigned to the neutrophilic dermatoses in which an association with hematological disturbances is well documented. We report on a patient with EED and glioma WHO grade IV, a coincidence unreported hitherto. Additionally, we review the literature on diseases associated with EED.

Adult↗
PubMed1997

Autologous versus allogeneic T cell-stimulated IL-6 production by dermal fibroblasts.

T cells adhere to human dermal fibroblasts (HDF). This cellular interaction leads to a pronounced secretion of the proinflammatory cytokines IL-6 and IL-8 via a juxtacrine stimulation induced by HDF-associated IL-1. Upon stimulation, fibroblasts express various surface proteins such as MCH-I molecules, which may interact with corresponding receptors on T cells. The present study was conducted to further investigate the mechanism of this complex interaction with regard to the secretion of IL-6 in cocultures of T cells and HDF. IL-6 was time- and dose-dependently upregulated in such cocultures. Spatial separation of the cells by microporous membranes resulted in a 90% reduction of IL-6 secretion, but when cells had limited cell contact IL-6 secretion was increased again. Allogeneic cocultures of T cells and HDF showed increased capacity of IL-6 stimulation as compared to autologous cultures. Our results suggest that MHC-I/T cell receptor interaction modulates IL-6 secretion in allogeneic and autologous cocultures.

Cell Communication↗
PubMed1997

Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey.

Studies on the epidemiology of common adverse cutaneous drug reactions have rarely been reported, since they can only be successfully conducted in clinics of internal medicine employing consultant dermatologists and having a comprehensive or intensive system of monitoring. Between 1974 and 1993, the adverse skin reactions occurring in divisions of general internal medicine of three different hospitals were monitored by a computerized comprehensive system. The "drug-monitoring patient" was defined as the recipient of at least one drug during hospitalization. The relationship of the skin reactions to drug causality in these patients had to be either definite (proven by re-exposure) or probable (drug relation greater than that of nondrug causality). The skin reactions were classified into four diagnostic groups. Maculopapular exanthema, urticaria, and vasculitis were the three main groups. The fourth group comprised cases of nonhomogeneous but clinically well-defined special exanthema. For selected drugs and years of observation, special emphasis was placed on the study of time patterns (reaction time, exposure time). A total of 1317 definite or probable drug-induced skin reactions occurred during the hospitalization of 48,005 consecutively admitted "drug-monitoring patients": 1201 cases of maculopapular exanthema, 78 cases of urticaria, 18 cases of cutaneous vasculitis, and 20 cases of special exanthema (five of erythema multiforme minor, six of fixed eruption, one of photosensitivity reaction, and eight of acneiform eruption). The main drugs involved did not differ for the three main types of skin reactions, penicillins ranking in the first place, followed by sulfonamides--most often combined with trimethoprim--and in the third place nonsteroidal anti-inflammatory drugs. The reaction time (time from last drug exposure to first skin manifestation) for urticaria showed a relevant proportion of the acute type (within 1 h) and most of the subacute type (1-24 h). For maculopapular exanthema, the subacute or, rarely, the latent type (1-8 days, exceptionally more than 8 days) predominated. For aminopenicillins, the rate of occurrence of skin reactions increased with increasing exposure time up to 12 days, and then markedly diminished. Possibly due to the tendency to withdraw suspected drugs even in the case of minor (e.g., maculopapular) skin reactions, no severe events such as erythema multiforme major/Stevens-Johnson syndrome or toxic epidermal necrolysis occurred.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Malignant atrophic papulosis.

We describe a 34-year-old woman presenting with a 1-year history of asymptomatic, atrophic papules disseminated mainly on the trunk. The clinical features were characteristic of malignant atrophic papulosis, and the histopathologic features were confirmatory. The etiology of this rare condition, described for the first time in 1941, remains unknown. Also the pathogenesis is still controversial. A vascular disorder has been postulated by most authors, primary inflammatory or thrombotic vascular changes as well as primary endothelial proliferation being often mentioned in the literature. In the present case, the biopsy specimen of a recent efflorescence showed these three alterations all together, making it impossible to identify conclusively the primary event. Thrombosis, being already noticed in such early lesions, is likely to be of pathogenic importance. Rheological therapy as described in the literature may therefore be the most appropriate. In the present case, the lesions came spontaneously to a standstill without drug therapy.

Adult↗
PubMed1997

Toxocariasis and Wells' syndrome: a causal relationship?

BACKGROUND: The etiology of Wells' syndrome or eosinophilic cellulitis is unknown. Various triggering factors, such as myeloproliferative disorders, lymphoma, infections/infestations, insect bites and drugs have been reported. In 1979, Wells was the first who pointed out some common features of eosinophilic cellulitis and skin lesions in toxocariasis. OBJECTIVE: We report 2 patients who exhibited the characteristic clinical and histological features of Wells's syndrome together with elevated antibody titers to the excretory-secretory antigen of Toxocara canis. RESULTS: In both patients, the skin lesions disappeared after oral albendazole treatment and no recurrences were observed. The clinical response was followed by a normalization of the Toxocara antibody titer. In contrast, a patient with eczematoid skin lesions, eosinophilia and an elevated Toxocara antibody titer did not benefit from albendazole treatment despite serological normalization. CONCLUSION: Taken together, these cases lend support to a causal relationship of Toxocara in selected patients with Wells' syndrome.

Administration, Oral↗
PubMed1997

Human skin lymph derived from irritant and allergic contact dermatitis: interleukin 10 is increased selectively in elicitation reactions.

BACKGROUND: Recent reports suggested an immunomodulatory role for interleukin 10 (IL-10) in contact hypersensitivity. OBJECTIVE: To investigate if IL-10 is important in the regulation of irritant and allergic contact dermatitis (CD), IL-10 and interferon gamma (IFN-gamma) protein levels were measured in normal skin lymph, in lymph derived from irritant and allergic (primary sensitization and elicitation) CD and in skin blister fluid from an elicitation reaction. METHODS: A superficial lymph vessel was cannulated microsurgically on the lower leg of 18 healthy volunteers. Lymph was collected twice daily. Protein levels of IL-10 and IFN-gamma were determined using commercially available ELISA kits and messenger RNA was estimated by a reverse-transcriptase polymerase chain reaction (PCR) method. RESULTS: Whereas the IL-10 levels in lymph derived from irritant CD and primary sensitization of allergic CD, similarly to those obtained from normal untreated skin, remained below 4.4 pg/ml, the IL-10 levels increased manifold both in the primary allergic reaction (928.5 pg/ml) and the elicitation of allergic CD (124 pg/ml). The levels of IFN-gamma also increased in all volunteers exhibiting an eczematous skin reaction and showed a tendency to be inversely correlated with IL-10. Using a reverse-transcriptase PCR, the expression of IL-10 and IFN-gamma in cells from lymph and from blister fluid was examined. While signals for IFN-gamma were not found, specific transcripts for IL-10 were detected in all samples examined, indicating that cells circulating in the lymph may also contribute to the IL-10 production measured. The IL-10 mRNA signal, however, was markedly stronger in lymph and epidermal blister cells from the elicitation reactions as compared to the signal in lymph cells derived from normal skin and from the primary sensitization of allergic CD. CONCLUSION: IL-10 may limit and down-regulate elicitation reactions by inhibiting cytokine and antigen-presenting cell functions in the skin and in the skin-associated lymphoid tissue.

Adjuvants, Immunologic↗
PubMed1996

Juxtacrine stimulation of cytokine production in cocultures of human dermal fibroblasts and T cells.

Adhesion of T cells to fibroblasts activates cells to produce cytokines, either by direct cell contact and/or soluble factors. A cell-associated form of IL-1 beta on fibroblasts might act through a cell contact mediated fashion. To test this hypothesis we analysed the activation of T cells and human dermal fibroblasts (HDF) in coculture experiments. Elevated levels of IL-1 beta, secreted by T cells as well as IL-6 and IL-8, mainly produced by HDF, were found in supernatant fluids of cocultured cells. IL-1 beta mRNA expression was induced in T cells as well as in HDF. While in HDF IL-1 beta remained cell-associated, T cells were activated to produce and secrete soluble IL-1 beta and IL-6. IL-1 beta and possibly other soluble factors increased IL-6 production by fibroblasts. These effects could be mainly attributed to CD8+ T cells. Our results suggest, that IL-1 beta, produced as a cell-associated cytokine by human dermal fibroblasts, acts as a juxtacrine molecule to stimulate T cells. Such a cellular cooperation, could be a powerful mediator in inflammatory response and possibly in wound healing.

Coculture Techniques↗
PubMed1996

Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin.

In humans and in animals, biotin deficiency causes pathological changes in the skin and its appendages. High doses of biotin may also have beneficial effects on skin, hair and fingernails in humans and animals with normal biotin status. Therefore, we investigated the effects of low and high concentrations of biotin on proliferation and differentiation of cultured outer root sheath cells from human hair follicles as an in vitro model for skin. The activities of biotin-dependent carboxylases were measured to evaluate the biotin status of the cells. In monolayer cultures of outer root sheath cells, proliferation and expression of the differentiation-specific keratins K1 and K10 were not influenced by extremely low concentrations of biotin (<2 x 10(-10) mol/l) or by pharmacological doses of biotin (10(-5) mol/l). Biotin deficiency of the cells was confirmed under the former condition by demonstrating decreased activities of the mitochondrial carboxylases. In organotypic cocultures of outer root sheath cells and dermal fibroblasts, in which stratified epithelia resembling epidermis were developed, the biotin concentration had no effect on the expression of all tested epidermal differentiation markers, including the suprabasal keratins K1 and K10, the hyperproliferation-associated keratin K16, involucrin and filaggrin.

Adult↗