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Biomedical subjects

T Hunziker

Publications and source records attributed to T Hunziker.

At least 55 records · Page 3Linked to original sources

Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B.

We describe a 33-year old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell population in different tissues.

Adult↗

Successful treatment of chronic leg ulcers with epidermal equivalents generated from cultured autologous outer root sheath cells.

The outer root sheath cells of hair follicles can substitute for interfollicular epidermal keratinocytes, as during healing of skin wounds when these cells migrate onto the denuded area and contribute to epidermal regeneration. Using improved culture techniques, we generated epidermal equivalents from cultured outer root sheath cells of patients suffering from recalcitrant chronic leg ulcers, primarily of vascular origin. In such epidermal equivalents, tissue organization as well as immunolocalization of epidermal differentiation products (keratin 10, involucrin, filaggrin) and integrins were indistinguishable from normal epidermis. As determined by the number of bromodeoxyuridine-incorporating cells, the basal layer contained a large compartment of proliferative cells irrespective of donor age. FACS analysis of the outer root sheath cells, used to prepare the epidermal equivalents, disclosed a fraction of small cells with enhanced expression of beta1-integrin, a potential stem cell marker. in contrast to acute wounds, a major definitive take of grafted cultured autologous keratinocytes has not been convincingly demonstrated in chronic wounds. In a pilot study, grafting of epidermal equivalents generated in vitro from autologous outer root sheath cells on 11 ulcers in five patients resulted in a definitive take rate of about 80%, with subsequent complete healing within 2 to 3 wk of five out of seven ulcers grafted with densely arranged cultures. This improvement in the treatment of chronic leg ulcers with cultured autologous keratinocytes probably depends on the large compartment of proliferative cells as well as on a well-developed horny layer which prevents disintegration of the grafts. Practical advantages of the new technique are its noninvasiveness, the lack of need for surgical facilities or anesthesia, and a short immobilization period after grafting.

Aged↗

IL-1 beta protein in human skin lymph does not discriminate allergic from irritant contact dermatitis.

Recent data suggest a key rôle for IL-1 beta in the induction phase of allergic contact dermatitis. In the present study, the protein levels of IL-1 beta were measured in skin lymph derived from normal untreated skin as well as from irritant and allergic (induction and elicitation phase) contact dermatitis. IL-1 beta increased in the course of both types of contact dermatitis, displaying the highest levels in irritant CD. Using a reverse transcriptase-polymerase chain reaction, low signal strength of IL-1 beta mRNA was demonstrated in lymph cells derived from normal skin and allergic CD. In lymph cells collected 2 x daily during the induction phase of allergic contact dermatitis, no upregulation of the IL-1 beta mRNA signal was found. Isolated CD1a+ lymph cells derived from normal skin as well as from the induction and elicitation phase of allergic contact dermatitis did not express IL-1 beta mRNA. Our results demonstrate that in human skin lymph, the IL-1 beta profiles do not discriminate between irritant and allergic contact dermatitis and that besides resident epidermal and dermal cells, circulating lymph cells may also contribute to IL-1 beta protein production.

Adult↗

Combined surgical and X-ray treatment for angiosarcoma of the scalp: report of a case with a favourable outcome.

Classic angiosarcoma is an uncommon malignant neoplasm of vascular differentiation which is highly aggressive. The diagnosis is often delayed and, since the response to treatment mainly depends on the size of the tumour, the prognosis is usually poor. Here we report a 76-year-old man in whom an extensive angiosarcoma of the scalp was treated by excision followed by wide-field radiotherapy. More than 4 years later there are no signs of local recurrence or of metastasis.

Aged↗

Endogeneously regulated site-specific differentiation of human palmar skin keratinocytes in organotypic cocultures and in nude mouse transplants.

Palmar and plantar epidermis is characterized by specific features such as the development of a striking lucidum, a very thick stratum corneum, prominent rete ridges and the unique expression of keratin K9. Using organotypic cocultures of keratinocytes and fibroblasts, we investigated to which extent the specific phenotype of palmar keratinocytes is maintained in vitro and under systemic host influences after transplantation onto nude mice. In vitro, palmar keratinocytes developed a thick epithelium with a prominent, although parakeratotic stratum corneum showing no significant differences in proliferation and differentiation in coculture with either palmar or nonpalmoplantar fibroblasts. All differentiation markers including keratohyaline and membrane coating granules as well as keratin K9 were also found, but at reduced levels and with slightly altered localization. In transplants, substantial normalization towards the palmar phenotype occurred. In 3-week-old grafts, a homeostatic state was reached, as illustrated by a constant thickness of the stratum Malpighii, presence of keratin K10 throughout the entire suprabasal compartment, increased numbers of K9- and filaggrin-positive cells, and reduction of keratins K16 and K17. At the ultrastructural level, numerous membrane coating granules and an enlargement of keratohyaline granules were seen accordingly, and immunofluorescence showed intense continuous lining of the dermo-epidermal junction by laminin, type IV collagen and integrin alpha 6. The high percentage of bromodesoxyuridine-positive cells, mainly in the basal compartment, underlined the hyproproliferative state, comparable to palmoplantar epidermis. In conclusion, (i) palmar keratinocytes can preserve the potential to express their specific phenotype upon transfer to culture conditions, and (ii) this intrinsic property is not significantly modulated by the type of cocultured fibroblasts. This suggests that fibroblasts act primarily by sustaining keratinocyte proliferation which is permissive for the fully differentiated phenotype.

Adolescent↗

Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine.

To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed in vitro the drug-induced activation of CD4+ and CD8+ T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic individuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vivo on CD4+ and CD8+ T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivity syndrome with hepatitis. Our results show that, in vitro, drug-induced proliferation of PBMC from patients with allergy to sulfamethoxazole, phenytoin, or carbamazepine was specific and dose dependent. CD4+ as well as CD8+ T cells expressed elevated levels of CD25 and HLA-DR molecules after drug stimulation. Drug-activated lymphocytes secreted high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, IL-4, and TNF-alpha. An enhanced expansion of TCR V beta 17+ T cells 9 days after in vitro stimulation with sulfamethoxazole was observed in one patient with sulfamethoxazole allergy. The drug specificity of the in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4+ and CD8+ T cell clones. T cell analysis of patients with acute drug allergy to carbamazepine, phenytoin, allopurinol, or paracetamol confirms the in vitro data, because all patients had activated CD4+ or CD8+ T cells in the circulation. Our data clearly show the involvement of drug-specific T cells in drug allergies.

Anticonvulsants↗

Formation of a regular neo-epidermis by cultured human outer root sheath cells grafted on nude mice.

The outer root sheath of hair follicles mainly consists of basal-like keratinocytes which can substitute for interfollicular epidermal keratinocytes, as during healing of skin wounds when outer root sheath cells migrate onto the denuded area, thus contributing to epidermal regeneration. Human outer root sheath cells represent a repeatedly available source of keratinocytes which can be easily and extensively expanded in culture. Close comparison of organotypic cultures of either outer root sheath cells or epidermal keratinocytes grafted onto nude mice demonstrated that outer root sheath cells formed a stratified epithelium resembling normal epidermis that is virtually indistinguishable from that developed by epidermal keratinocytes. Typical epidermal differentiation markers, such as the suprabasal keratins 1 and 10, involucrin, filaggrin, the basement membrane components collagen type IV and laminin, and the integrin chains alpha 2, alpha 3, alpha 6, and beta 1, were readily expressed in a mostly regular localization. These data suggest that outer root sheath cells, bearing essential advantages as compared with interfollicular keratinocytes, are suitable for skin replacement.

Animals↗

[Lymphocyte stimulation test, a possible alternative for verifying chloroacetophenone sensitization].

We report on a case of pronounced sensitization to chloroacetophenone tear gas that developed after repeated occupational skin exposure in a 57-year-old police officer. Mainly in the presence of moisture and occlusion, cutaneous application of chloroacetophenone leads to severe irritant, and often also allergic, skin reactions. In patch testing the demonstration of allergic contact dermatitis in response to chloroacetophenone is hampered by the irritative potential of this substance even at low concentrations. This diagnostic bias can be overcome by the lymphocyte proliferation assay.

Dermatitis, Occupational↗

[Angiokeratoma corporis diffusum without associated metabolic disorder].

In a 22-year-old woman with mental impairment and some signs of dysmorphism, numerous angiokeratomas developed, starting when she was 3 years old and resulting in the clinical picture of angiokeratoma corporis diffusum. Extensive laboratory analyses did not disclose any associated metabolic disorder,and electron microscopy failed to demonstrate lysosomal inclusions. Therefore, this patient can be classified as one of the rare cases of angiokeratoma corporis diffusum without associated metabolic disease (idiopathic angiokeratoma corporis diffusum).

Adult↗

[Angioma serpiginosum, a skin change along Blaschko lines?].

We present a 34-year-old woman with angioma serpiginosum on the medial aspect of the left thigh, extending to the groin and the lower abdomen, and on the volar aspect of the left forearm. In addition to the late onset, the distribution along the lines of Blaschko was a remarkable feature of this case. We therefore reexamined our recent cases of angioma serpiginosum. In 6 of 7 cases, the distribution indeed corresponded to the lines of Blaschko. Thus, we suggest adding angioma serpiginosum to the list of skin lesions that may follow the lines of Blaschko.

Adolescent↗

Activated immunocompetent cells in human skin lymph derived from irritant contact dermatitis: an immunomorphological study.

By means of microsurgical lymph cannulation, skin lymph was sampled in the course of a sodium lauryl sulphate (SLS)-induced irritant contact dermatitis in human volunteers. The lymph cells were isolated by centrifugation, and then characterized immunocytochemically using different monoclonal antibodies, and in the late phase of the skin reaction also by electron microscopy. Analyses of lymph cells before the induction of the contact dermatitis revealed median values of about 60% T cells (CD4/CD8 ratio about 2:1), 4% Langerhans cells (LCs), and 1% B cells. The remainder were varying proportions of erythrocytes and uncharacterized cells. During the skin reaction, and even after resolution of the clinical signs of dermatitis, a relative and absolute increase of T and B cells, as well as of HLA-DR positive cells, paralleled the previously reported increased of LCs; a high percentage of the T cells were CD4 and CD8 negative. In addition, surface markers such as CD11a, CD25, CD54 and CD58 were detected on lymph cells sampled during the irritant skin reaction. Cell rosettes observed in the lymph throughout the experiment were analysed in the late phase of the skin reaction, and showed a central LC with three to five peripheral, in part activated, T cells, ultrastructurally revealing gap junction-like structures between the two cell types. These data indicate that immunocompetent cells in the skin are activated by a variety of non-immunological stimuli such as operative trauma and irritant contact dermatitis.

Adult↗

Contact hypersensitivity to corticosteroids in routine patch test patients. A multi-centre study of the Swiss Contact Dermatitis Research Group.

BACKGROUND: Contact hypersensitivity to corticosteroids is increasingly reported and has been identified as a problem of considerable clinical relevance. The prevalence of positive patch tests to corticosteroids ranges from 0.2 up to 5%. OBJECTIVE: The prevalence of positive patch tests to corticosteroids in Switzerland was determined in a multi-centre study of patients undergoing routine patch tests. METHODS: As representatives of corticosteroid groups, the following substances were used for screening: tixocortol pivalate and hydrocortisone for group A (hydrocortisone type), hydrocortisone butyrate for group D (hydrocortisone butyrate type) and budesonide for both groups B (triamcinolone type) and D. Patients positive for at least one corticosteroid were retested with the screening series and 12 corticosteroids commonly used in Switzerland. RESULTS: Among 3,016 consecutive patients, 65 individuals (2.2%) with a total of 106 positive reactions were found. Retesting showed a concordance of 70-98%, depending on the corticosteroid and the score of the positive reaction. In the subsequently tested corticosteroid series including 12 substances, 19 out of 56 screening-positive patients had a positive result to one or several corticosteroids. There were only few evident cross-reactive patterns in between the corticosteroids tested. CONCLUSIONS: Corticosteroids should be included in routine patch testing, because contact sensitization to a corticosteroid is of considerable practical importance. We confirm that as markers of corticosteroid sensitization tixocortol pivalate, budesonide and hydrocortisone butyrate may be suited, because there is no single corticosteroid which is a marker for all four corticosteroid groups. Patch test reactions of 2+ or higher have a better reproducibility than 1+ reactions.

Administration, Topical↗