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Biomedical subjects

P von den Driesch

Publications and source records attributed to P von den Driesch.

At least 19 recordsLinked to original sources

Multiple vascular abnormalities and a paradoxical combination of vitamin B12 deficiency and thrombocytosis in a case with POEMS syndrome.

POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with elevated vascular endothelial growth factor (VEGF), which clinically presents with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. We report a case of POEMS syndrome due to a gammopathy of undetermined significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF and in addition to glomeruloid angiomas two previously undescribed proliferative vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We assume that the high VEGF levels caused the vascular abnormalities observed in our patient.

Adult↗

Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM).

The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m(-2), days 1-3), carmustine (150 mg m(-2), day 1, cycles 1 and 3 only), dacarbacine (220 mg m(-2), days 1-3) and oral tamoxifen (20 mg m(-2), daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-alpha. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10 x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6) IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2), day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-alpha was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively.

Administration, Oral↗

Lymphoma molluscatum.

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Combined Modality Therapy↗

Dapsone and colchicine inhibit adhesion of neutrophilic granulocytes to epidermal sections.

A frozen section adhesion assay was used to study the influence of dapsone and colchicine on cell-cell adhesion between neutrophils and epidermal cells. Sections were prepared from small punch biopsies from healthy donors after preincubation with IFN-A. Freshly prepared neutrophils were activated with TNF-. or PAF after exposure to dapsone or colchicine, incubated on these sections, and the adhered cells were enumerated after washing. In the presence of dapsone (at concentrations of 0.1-80 Ig/ml) adherence of neutrophils could be blocked dose-dependently and 50% inhibition of adhesion was achieved at a concentration of 10 Ig/ml. Colchicine at concentrations of 10-200 ng/ml inhibited neutrophil binding with a clear correlation between inhibition and colchicine concentration. At a colchicine concentration of 110 ng/ml, 50% blocking was achieved. Since the function of CD11b/ paragraph signCD18 is necessary for neutrophil adhesion in this assay, we monitored CD11b expression on neutrophils after dapsone and colchicine exposure. CD11b expression on neutrophils was significantly reduced 5 h after incubation with dapsone at a concentration of 80 Ig/ paragraph signml, whereas no effects of colchicine on CD11b expression could be demonstrated. Our study showed that both drugs significantly inhibited adhesion between neutrophils and the epidermis.

Cell Adhesion↗

Is psoriasis a T-cell disease?

The etiology and pathogenesis of psoriasis--one of the most common chronic, inflammatory, hyperproliferative skin disorders of man--have long fascinated dermatologists, pathologists and biologists alike. Here, we have a model disease that offers to study neuroectodermal-mesenchymal interactions in the widest sense possible. Epithelial, endothelial, and hematopoietic cells as well as neurons projecting into the skin apparently all interact with each other to generate the characteristic psoriatic lesion. For decades, the ongoing controversy on the molecular nature, choreography and hierarchy of these complex interactions e.g. between epidermal keratinocytes, T cells, neurotrophils, endothelial cells and sensory nerves has served as a driving force propelling investigative dermatology to ever new horizons. This debate has not only been at the heart of our quest to develop more effective forms of therapy for this socially crippling disease, but it also has profoundly influenced how we view the skin as a whole: the numerous competing theories on the pathogenesis of psoriasis published so far also are reflections on the evolution of mainstream thought in skin biology over the last decades. These days, conventional wisdom infatuated with a T-cell-centered approach to inflammatory skin diseases-- portrays psoriasis as an autoimmune disease, where misguided T lymphocyte activities cause secondary epithelial abnormalities. And yet, as this CONTROVERSIES feature reminds us, some authoritative "pockets of academic resistance" are still quite alive, and interpret psoriasis e.g. as a genetically determined, abnormal epithelial response pattern to infectious and/or physicochemical skin insults. Weighing the corresponding lines of argumentation is not only an intriguing, clinically relevant intellectual exercise, but also serves as a wonderful instrument for questioning our own views of the skin universe and its patterns of deviation from a state of homeostasis.

Animals↗

Treatment of erythrodermic cutaneous T-cell lymphoma with intermittent chlorambucil and fluocortolone therapy.

BACKGROUND: Erythrodermic cutaneous T-cell lymphomas (CTCL) including Sézary syndrome have been successfully treated with daily administration of chlorambucil and prednisone (Winkelmann regimen). OBJECTIVES: Our purpose was to determine the efficacy and safety of a low-dose pulse chemotherapy with chlorambucil and fluocortolone in this stage of the disease. Fluocortolone has the same potency as prednisone but lacks a mineralocorticoid effect. PATIENTS/METHODS: Thirteen patients with erythrodermic CTCL (stages III-IVb) were treated with chlorambucil and fluocortolone therapy (chlorambucil 10-12 mg day-1 for 3 days and fluocortolone, first day 75 mg, second day 50 mg and third day 25 mg) as primary therapy in an uncontrolled pilot study. Treatment was started with pulses every 2 weeks; subsequently, the intervals were prolonged according to the clinical status. Clinical outcome, side-effects and long-term survival were assessed. RESULTS: Seven patients achieved a complete remission and six had a partial response (improved significantly). The mean duration of remissions was 16.5 (median 12) months. The mean number of cycles necessary during the first year was one cycle every 5 weeks. No treatment-related severe side-effects occurred. The long-term follow-up (mean 31.5, median 27 months) showed that six patients remained in complete remission and three showed a stable partial remission. Four patients died, two of them from their lymphoma. CONCLUSIONS: We conclude that pulse chemotherapy with chlorambucil and fluocortolone is effective and safe in the treatment of erythrodermic CTCL and should be considered as an alternative to the classical Winkelmann treatment scheme.

Aged↗

Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma.

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 10(6) and 12 x 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1-specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC "vaccines" can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL-tumor cell interaction in situ as well as escape by lack of tumor antigen expression.

Adult↗

Modulation of irritation-induced increase of E-selectin mRNA in vivo by topically applied corticosteroids.

There is a continuous need for methods to evaluate the biologic effects of topically applied drugs in the skin. Irritation of the epidermis with sodium dodecyl sulfate leads to an upregulation of E-selectin on endothelial cells and E-selectin mRNA can be detected in vivo within a short time. This study was aimed to investigate whether this biologic response can be used as a read-out for the anti-inflammatory effect of topically administered corticosteroids. We investigated skin of healthy volunteers treated according to the two following experimental protocols: (i) topical application of different corticosteroids (versus basic ointments as controls) for 12 h and irritation with sodium dodecyl sulfate 1% for 4 h; (ii) irritation with sodium dodecyl sulfate 1% for 12 h and application of the corticosteroids for 5 h. The biopsy specimens were subjected to RNA extraction and reverse transcription and competitive reverse transcriptase-polymerase chain reaction was performed using defined concentrations of a pre-constructed mimic DNA. As result, we found strong positive signals for wild-type E-selectin mRNA in all biopsies pretreated with basic ointments, whereas in biopsies from areas pretreated with corticosteroids the bands for wild-type E-selectin DNA could be detected at 10-1000 lower levels of mimic DNA concentrations. The reverse experiment, application of corticosteroids after the irritation, again yielded significantly reduced signals for E-selectin mRNA. In both experimental settings, the different strength of the topical corticosteroids used was reflected by significant differences in the amount of E-selectin mRNA found in the biopsies. This study demonstrates the pharmacologic effect of topical corticosteroids on the irritation-induced E-selectin mRNA expression on dermal endothelial cells in vivo using very small tissue samples and this approach may be of value for further pharmaceutical studies.

Administration, Topical↗

Idiopathic recurrent palmoplantar hidradenitis in children. Report of 22 cases.

BACKGROUND: Idiopathic recurrent palmoplantar hidradenitis (IRPH) is characterized by tender erythematous plaques and nodules on the soles and, less often, the palms of young patients. To date, 10 cases of IRPH have been documented in the literature. OBSERVATIONS: We describe 22 pediatric patients with characteristic cutaneous and histologic findings of IRPH. Their mean age was 6 years (age range, 1.5-15 years). The onset of the disease clustered in 2 peaks, in autumn and spring. All patients had complete resolution of their lesions within 3 weeks, in 16 cases without any treatment. Ten of the 22 patients experienced more than 1 episode of IRPH. CONCLUSIONS: Our study represents the largest number of cases of IRPH collected to date. Based on our data, the clinical picture is so characteristic that a histopathologic examination may not be necessary in every case. We suggest that there is a seasonality in the occurrence of this always benign and limited disease.

Administration, Cutaneous↗

[Recurrent angioedema with gastroenteritis in blood and tissue eosinophilia].

A 23-year-old patient suffered from episodic angioedema of the face and neck, accompanied by diarrhea and abdominal pain. Additionally, the patient had bronchial asthma, recurrent nasal polyps and allergic rhinoconjunctivitis. Blood examination revealed leucocytosis with eosinophilia. Histological studies showed eosinophilic infiltrates in the skin and the gastrointestinal mucosa. Allergic food reactions and parasites were ruled out. With systemic corticosteroid treatment, the clinical symptoms and the eosinophilia disappeared. This case shows some parallels to previously described syndromes (eosinophilic gastroenteritis, Samter's syndrome, episodic angioedema with eosinophilia), but to the best of our knowledge this combination of symptoms has not yet been reported.

Adult↗

[Inspiration-triggered vasoconstrictive episodes in healthy subjects, in patients with diabetes mellitus and in patients with clinically manifest polyneuropathy of variable origin. A simple Doppler ultrasound test to assess the autonomic vascular functional unit of the upper extremity].

BACKGROUND: A cost- and time efficient ultrasound-Doppler-test is introduced to evaluate the function of autonomic innervation of the upper limb. A voluntary inspiratory vasoconstrictor episode (VICE) after a provoked deep inspiration, transmitted via sympathetic nervous system, can be demonstrated at the radial artery using basic Doppler equipment. PATIENTS AND METHOD: VICEs were investigated in 30 healthy subjects (group A), in 20 patients with diabetes mellitus without clinical signs of polyneuropathy (group B) and in 20 patients with clinically manifest polyneuropathy (group C). RESULTS: In all healthy subjects a two minutes arterial occlusion led to a decrease of resistance index (RI) lower than 0.9 indicating sufficient hyperemia. RI during VICE increased to 1.0 in all healthy subjects. In 50% of the patients of group B as well as in 50% of the patients of group C the test revealed abnormal findings suggesting a disorder of the functional peripheral neurovascular unity.

Adult↗

Adhesion of neutrophils to epidermal cells: prerequisites for and blocking by anti-CD11b antibodies.

Immigration of neutrophils into the epidermis is a hallmark of several so-called neutrophilic dermatoses. In this study we used a frozen section adhesion assay to study the impact of different activation procedures as well as of CD11 integrins on cell-cell adhesion between neutrophils and epidermal cells. Serial sections from punch biopsies of healthy donors were incubated with freshly prepared neutrophils for 40 min and adherent cells were counted after washing. We found that preactivation of the biopsies with interferon-gamma in vitro is a prerequisite for neutrophil binding. Activation of neutrophils with N-formyl-methionyl-leucyl-phenylalanine (fMLP), tumor necrosis factor-alpha (TNF-alpha) or platelet activating factor (PAF) then leads to a three- to sixfold increase in neutrophil adhesion. This enhanced binding could be blocked by anti-CD11b monoclonal antibodies, whereas anti-CD11a and anti-CD11c antibodies exerted no significant effect. At a temperature of 6 degrees C, 50% inhibition of neutrophil binding was observed. Complement factor C3 and fibrinogen, known ligands for CD11b/CD18, could not be detected on epidermal cells by immunohistochemistry. In summary, our study showed that enhanced binding of neutrophils to epidermal sections can be achieved by prestimulation of both the keratinocytes with interferon-gamma and the neutrophils with fMLP, TNF-alpha and PAF. This adhesion was furthermore revealed to be dependent on the function of the leucocyte integrin CD11b/CD18.

Antigen-Antibody Reactions↗