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Biomedical subjects

P Fritsch

Publications and source records attributed to P Fritsch.

At least 73 records · Page 4Linked to original sources
PubMed1999

Chemical toxicity of some actinides and lanthanides towards alveolar macrophages: an in vitro study.

PURPOSE: To compare the toxicity of lanthanides (cerium, gadolinium) with actinides (thorium, neptunium, uranium) added in soluble form to rat alveolar macrophage cultures. MATERIALS AND METHODS: The metals were added 1 day after seeding alveolar macrophages extracted by pulmonary lavage, and the metal toxicity was scored 3 days later. Cell death was measured after vital staining to distinguish between apoptosis and necrosis; relative cell density was also quantified. The physico-chemical form of the metals in the culture medium was characterized using filtration and radioactive measurements. RESULTS: Except for thorium, induction of cell death was observed for all the elements studied and the death mechanism involved was apoptosis. Graduated toxicity was observed from uranium to neptunium, cerium and gadolinium, in the range of concentration from 10(-3)-10(-6) M. From pilot experiments, it was hypothesized that soluble compounds were mainly involved in lanthanide toxicity, whereas insoluble forms were mainly involved in actinide toxicity. CONCLUSION: This study demonstrates that the toxicity of neptunium and uranium was concomitant with the presence of insoluble forms in the culture medium. Further studies are needed to characterize the cell death mechanisms involved and the potential synergistic effects of chemical toxicity and irradiation.

Actinoid Series Elements↗
PubMed1999

Lung carcinogenesis in rats after inhalation exposure to (237)NpO2.

The results of several studies of experimental carcinogenesis suggest that, after inhalation of alpha-particle emitters, lung tumor incidence varies depending on the exposure rate and dose distribution in the tissue. In the case of transuranics, the main influencing factor would be the specific alpha-particle activity of the inhaled actinide. To confirm these results, long-term studies were performed using male Sprague-Dawley rats exposed to (237)NpO(2) by inhalation. The initial lung burdens of the animals ranged from 0. 1 to about 7 kBq. The rats were followed during their life span and weighed regularly, and their lung burdens were determined in vivo and at death to estimate the lung dose. At death, the incidence of lung tumors and their malignancy and histological types were analyzed. The analysis revealed a typically linear-quadratic dose response for incidence of malignant lung neoplasm and a differential dose response for various types of tumors. Although these results confirm the influence of the activity of the inhaled actinide oxide, further experiments are needed to be able to compare a more homogeneous population of animals.

Administration, Inhalation↗
PubMed1998

Expression of maturation-/migration-related molecules on human dendritic cells from blood and skin.

Progress in dendritic cell research has been overwhelming in the past few years. This was made possible by the recent development of simple methods to generate large numbers of dendritic cells. These methods use as starting populations for culture either CD34+ progenitor cells from cord blood or bone marrow, or monocytes from peripheral blood. The latter approach is critically dependent on the combination of GM-CSF and interleukin 4. Such "priming cultures" yield populations of immature dendritic cells (CD83-/CD86 +/- /CD115+/antigen uptake high/antigen processing high/T cell sensitization low). In order to generate mature dendritic cells a subsequent "differentiation culture" has to be added whereby monocyte-conditioned medium appears to be the optimal stimulus for maturation. This results in terminally mature dendritic cells (CD83+/CD86++/CD115-/antigen uptake low/antigen processing low/T cell sensitization high). We investigated the expression of some molecules involved in maturation and migration on human monocyte-derived dendritic cells from blood in comparison with dermal dendritic cells and epidermal Langerhans cells. We present a method to highly enrich epidermal Langerhans cells. Survival of purified Langerhans cells in culture is dependent on the presence of GM-CSF and TNF-alpha. During maturation a substantial part of the Langerhans cells loses expression of the cutaneous lymphocyte antigen (CLA); mature dendritic cells from the dermis are completely devoid of CLA. Similarly, CLA as well as CD15s (Sialyl Lewis x) and CD31 (PECAM-1) that can be readily detected on immature monocyte-derived dendritic cells are down-regulated upon maturation. CD68 expression is very low in cutaneous dendritic cells; in monocyte-derived dendritic cells this molecule is abundantly present. Subsets of monocyte-derived dendritic cells express E-cadherin; CD87 (urokinase plasminogen activator receptor) is weakly expressed on both immature and mature monocyte-derived dendritic cells. Taken together, these data suggest that the phenotype of monocyte-derived dendritic cells (E-cadherin low to negative, CD68++) is not indicative for a cutaneous destiny. Furthermore, the downregulation upon maturation of molecules involved in migration through vessel walls (CD31, CLA, CD15s) indicates that the entry of mature dendritic cells into lymphatic vessels may not be as rigidly regulated by adhesion molecules as the process of extravasation from blood vessels.

Antigens, CD↗
PubMed1998

Leg ulcers associated with long-term hydroxyurea therapy.

Hydroxyurea is commonly used in the treatment of various hematologic disorders, e.g., chronic myelogenous leukemia (CML), polycythemia vera, and occasionally, at lower doses, for severe psoriasis vulgaris. Cutaneous side effects such as alopecia, diffuse hyperpigmentation, poikiloderma, atrophy of the skin, or nail changes occur, especially with long-term treatment. Painful leg ulcers in association with hydroxyurea have only rarely been reported. We describe 2 patients who developed spontaneous painful leg ulcers during long-term hydroxyurea therapy for a myeloproliferative disorder; these ulcers healed only after hydroxyurea was withdrawn.

Aged↗
PubMed1998

Vulval and vaginal adenosis.

Vaginal adenosis is defined by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, thought to be derived from persistent Müllerian (synonymous with paramesonephric) epithelium islets in postembryonic life. Spontaneous vaginal adenosis appears to be a fairly common (present in about 10% of adult women) but mostly insignificant coincidental finding. In women prenatally exposed to diethylstilboestrol (DES), vaginal adenosis may arise in up to 90% and is associated with a high risk of vaginal carcinoma. Since the withdrawal of DES from the market, vaginal adenosis has virtually disappeared from the medical literature. A case of vaginal adenosis is presented in a middle-aged woman who had not been prenatally exposed to DES. The lesions differed from the spontaneous type by their sudden appearance, their extent and their pronounced subjective symptoms. It is speculated that protracted oral contraceptive intake may have played a causative role.

Adult↗
PubMed1998

The distribution of plutonium between the mineral and organic components of rat bone: a biochemical study after in vivo and in vitro contamination.

PURPOSE: To measure the distribution of plutonium between the mineral and organic components of rat bone after chemical extraction of powdered bones, 48 h after contamination of rats with 238Pu-citrate. MATERIALS AND METHODS: Chemical extractions were performed by EDTA treatment or by formic acid followed by guanidine treatments. The extracts were analysed for proteins and Pu content after chromatography experiments. Complementary experiments have been performed, mainly the addition of citrate and/or Pu to the formic acid medium during the extraction of contaminated or uncontaminated bones. RESULTS: EDTA extracted most of the Pu in an ultrafilterable form. By contrast, formic acid extracted only about 20% of Pu, whereas the remaining Pu was solubilized by guanidine. Gel permeation chromatography showed that it was mostly associated with 20-40 kD macromolecules. The high affinity of these macromolecules for Pu was confirmed after in vitro contamination of dialysed EDTA extracts. The complementary experiments suggested that deposition of the solubilized Pu on the residue during the formic acid treatment might occur, and showed that the amount of extracted Pu increased by adding citrate. CONCLUSION: The results show that the initially observed distribution of Pu in mineral (20%) and organic (80%) bone matrix may be in error due to Pu deposition on the organic residue during the extraction procedure.

Animals↗
PubMed1998

Urticaria pigmentosa: a clinical, hematopathologic, and serologic study of 30 adults.

Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of the bone marrow (nodular type, 10 patients; diffuse interstitial type, 8 patients). Bone marrow involvement was not correlated with massive cutaneous mast cell infiltration, clinically or histologically, or with the incidence of clinical symptoms and associated hematologic disorders. None of the patients had experienced progression of clinical symptoms, skin or organ involvement, or development of hematologic malignant neoplasms since UP was first diagnosed (10 years on average). Urticaria pigmentosa was found associated with mast cell infiltration of the bone marrow in 18 patients (60%). However, bone marrow involvement does not seem to predict adverse clinical course.

Adult↗
PubMed1998

Need for supportive counselling--the professionals' versus the patients' perspective. A survey in a representative sample of 236 melanoma patients.

BACKGROUND: The aim of the study was to identify melanoma patients who suffered significant distress and were judged to be in need of supportive counselling, on the one hand, and, on the other, to investigate patient interest in such support. METHODS: Out of 236 melanoma patients, who constitute a representative sample of melanoma patients in Western Austria, 215 patients participated in the study and were assessed with regard to psychosocial distress, coping strategies, social networks and interest in receiving psychosocial support. Multiple logistic regression analyses were performed with regard to patient interest in receiving psychosocial support either from the attending oncologist or from a mental health professional. RESULTS: 65 patients (30.2%) experienced moderate and 30 patients (14.0%) severe distress, which was predominantly caused by tumour-related fears, tension and disturbance of emotional well-being. 83% of the severely distressed patients wanted psychosocial support from their oncologists, whereas only half of them were interested in additional support from a psychotherapist. In particular, patients who showed fear of tumour progression and felt that they were insufficiently informed about their disease preferred to consult their dermatologist for psychosocial support. On the other hand, patients with poor prognosis, receiving only low levels of support from their social network, and exhibiting a depressive coping style, showed interest in getting supplementary support from a psychotherapist. CONCLUSIONS: These findings underline the importance of educating oncologists with a view both to improve their communication skills and to help them identify patients making poor adjustment to illness in order to offer them appropriate emotional support.

Adaptation, Psychological↗
PubMed1998

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.

PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.

Adjuvants, Immunologic↗
PubMed1998

Induction of apoptosis in human dermal microvascular endothelial cells and infantile hemangiomas by interferon-alpha.

BACKGROUND: Hemangioma of infancy is an angiomatous disorder characterized by the proliferation of capillary endothelium. It has been shown that interferon-alpha (IFN-alpha) may induce involution of proliferating, life-threatening hemangiomas in children. This IFN-alpha-induced regression of hemangiomas is not accompanied by any T cell response nor by the occurrence of necrosis. METHODS: To determine whether IFN-alpha may induce apoptosis, we cultured human dermal microvascular endothelial cells (HDMEC) with IFN-alpha at concentrations of 100, 500, 1,000 and 2,000 U/ml for 24-72 h and detected apoptosis by terminal deoxynucleotidyl transferase mediated FITC-dUTP nick end labeling (TUNEL). Quantitative analysis was performed using the FACScan and morphological alterations were studied by confocal laser scanning microscopy. In addition to the in vitro study we also analyzed frozen skin sections from proliferating, spontaneously regressing, and IFN-alpha-treated hemangiomas by simultaneous determination of endothelial cells and apoptotic nuclei using an indirect immunofluorescence test in combination with TUNEL. RESULTS: Apoptosis was detected in up to 20% of the IFN-alpha-treated endothelial cells compared to the untreated controls. A maximum of apoptosis was observed after 48 h of stimulation with IFN-alpha in a dose-dependent manner. The analysis of hemangioma biopsies revealed apoptotic endothelial cells in IFN-alpha-treated as well as in spontaneously regressing hemangiomas, but not in proliferating ones. CONCLUSION: These data indicate that the therapeutic effect of IFN-alpha on hemangiomas is based on apoptosis induction of endothelial cells, which might also explain the clinically and histologically observed involution without any sign of inflammation or necrosis.

Antibodies↗
PubMed1997

Attitude toward alternative therapy, compliance with standard treatment, and need for emotional support in patients with melanoma.

OBJECTIVE: To examine the attitude of patients with melanoma toward alternative therapies, their compliance with standard treatment, social support received by them, and their ways of coping with illness. DESIGN: Survey in a representative sample. SETTING: University hospital; central melanoma clinic serving Tyrol region in Austria. PATIENTS: Two hundred thirty-six consecutive patients with melanoma were approached in a 3-month-period, and 215 of them participated in the study. OUTCOME MEASURES: Results of a self-developed questionnaire to record patients' interest in alternative therapies, the Hornheide Questionnaire to assess patients' distress and social support, and the Freiburg Questionnaire of Coping With Illness. RESULTS: One hundred seventeen patients (54.4%) reported interest in nonconventional therapy. Thirty (14%) patients admitted actual use of such methods. The latter group more often suffered from advanced cancer (P < .001). Compared with uninterested patients, subjects interested in alternative therapy were younger (95% confidence intervals [CI] = 41.3-46.5 vs 48.7-56.7; P < .001), showed a more active coping style (95% CIs = 3.45-3.75 vs 2.91-3.50; P = .001) and a tendency toward religiousness and search for personal meaning in the disease (95% CIs = 2.56-2.85 vs 2.17-2.64; P < or = .08). Their faith in conventional medicine and ready compliance with physicians' suggestions were not less than those of uninterested patients (95% CIs = 4.26-4.46 vs 4.35- 4.64; P = .25). However, they believed that they were receiving less emotional support from their physicians (95% CIs = 0.95-1.74 vs 0.21-0.93; P = .04) and expressed interest in getting more such support (P = .04). CONCLUSIONS: Patients with melanoma consider non-conventional therapies as supplementary to standard medical methods and as a way of avoiding passivity and coping with feelings of hopelessness. This does not lessen the need to educate patients about the lack of efficacy of unorthodox methods but stresses the importance of offering them adequate emotional support.

Adolescent↗
PubMed1997

Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita is an uncommon autoimmune bullous disease of the skin and mucous membranes. It is chronic, disabling, and difficult to treat. We describe a case of severe epidermolysis bullosa acquisita of 7 years' duration that had been treated with azathioprine, corticosteroids, chlorambucil, plasma exchanges, cyclophosphamide, cyclosporine, and colchicine without any lasting effect. Seven cycles of treatment were administered with immunoglobulin given intravenously at a low dose, 40 mg/kg body weight daily for 5 days. The patient was free of disease for 10 months after the initiation of therapy. We suggest that low-dose regimens of immunoglobulins may be as effective in this disease as the high-dose regimens suggested in the literature, and at much lower cost.

Adult↗
PubMed1997

Human papillomavirus DNA in non-melanoma skin cancers of a renal transplant recipient: detection of a new sequence related to epidermodysplasia verruciformis associated types.

The detection of human papillomavirus (HPV) types originally isolated from patients with epidermodysplasia verruciformis (EV) in skin tumors of transplant recipients may point to a role of this HPV subgroup in non-melanoma skin cancer in immunosuppressed people. We analyzed 17 formalin-fixed, paraffin-embedded biopsies of benign or malignant skin tumors of a renal transplant patient with unusually widespread cutaneous carcinomas. Using a nested polymerase chain reaction (PCR), HPV-specific DNA was demonstrated in 11 specimens (65%). Analysis of nine PCR amplification products revealed four different sequences related to EV-associated HPVs. Three sequences occurred only in one lesion. In six samples identical sequences were found that differed from all HPV sequences published to date and may therefore represent a novel EV-HPV type, preliminarily labeled RTRX7. RTRX7 was found in benign, premalignant, and malignant skin lesions. Alignments identified HPV12 as the closest relative of RTRX7, both in the DNA (81% homology) and in the amino acid sequence (84% homology).

Adult↗