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Biomedical subjects

P Fritsch

Publications and source records attributed to P Fritsch.

At least 37 records · Page 2Linked to original sources
PubMed2003

In vivo measurement of Pu dissolution parameters of MOX aerosols and related uncertainties in the values of the dose per unit intake.

The aim of this study was to compare dissolution parameter values for Pu from industrial MOX with different Pu contents. For this purpose, preliminary results obtained after inhalation exposure of rats to MOX containing 2.5% Pu are reported and compared to those obtained previously with MOX containing 5% Pu. Dissolution parameter values appear to increase when the amount of Pu decreases. Rapid fractions, f(r), of 4 x 10(-3) (s.d. = 2 x 10(-3)) and 1 x 10(-3) (s.d. = 6 x 10(-4)) and slow dissolution rates, s(s) of 2 x 10(-4) d(-1) (standard deviation, sigma = 5 x 10(-5)) and 5 x 10(-5) d(-1) (sigma = 1 x 10(-5)) were derived for MOX containing 2.5 and 5% of Pu, respectively. Simulations were performed to assess uncertainties on dose due to experimental errors. The relative standard deviations of the dose per unit intake (DPUI) due to f(r) (4-8%), are far less than those due to s(s) (about 20%), which is the main parameter altering the dose. Although quite different dissolution parameter values were derived, similar DPUIs were obtained for MOX aerosols containing 2.5 and 5% Pu which appear close to that for default Type S values.

Absorption↗
PubMed2003

Uncertainties on the committed equivalent dose to the thyroid as a function of age for different iodine isotopes.

This study compares uncertainties of equivalent doses after internal contamination by 125I, 129I or 131I. Uncertainties were calculated using reported distributions of physiological parameters and Monte Carlo simulation. In adults, uncertainties increase from 131I to 125I and 129I with 1% of the population receiving 3.9, 4.0 and 7.2 times the median dose for the respective isotopes. In newborns, these values were 7.5, 12.3 and 19.0 for 131I, 125I and 129I respectively. The ratio of the beta dose delivered to the epithelium versus a homogeneous distributed dose was estimated for different iodine concentrations in colloid, epithelium and interstitium. In adults, for 131I, about 40% of the beta dose was delivered to the epithelial cells, whereas this fraction varied depending on the concentration for 125I and 129I, i.e. 20-30% at a relative epithelial concentration of 20% and 7-14% at a concentration of 3%. Small variations were observed depending on age.

Absorption↗
PubMed2003

Comparative decorporation efficacy of 3,4,3-LIHOPO, 4,4,4-LIHOPO and DTPA after contamination of rats with soluble forms of 238Pu and 233U.

The aim of this study was to compare the efficacies of DTPA, 3,4,3-LIHOPO and a newly synthesised molecule, 4,4,4-LIHOPO, in removing 233U and 238Pu after internal contamination by soluble forms of those nuclides. For this purpose, intravenous injections of DTPA (30 micromol kg(-1)) or 3,4,3-LIHOPO or 4,4,4-LIHOPO at dosages of 0.3 or 30 micromol kg(-1) were performed 1, 6 and 24 h after contamination of rats by intravenously injected 238Pu citrate and 1 h after intravenous injection of 233U nitrate. Actinide content in the main retention organs and cumulated excretion were measured 48 h after contamination. These experiments show similar decorporation efficacies of 4,4,4-LIHOPO and 3,4,3-LIHOPO for Pu, which are much higher than that of DTPA. At a dosage of 0.3 micromol kg(-1), the two LIHOPO analogues were as efficient as DTPA at a dosage of 30 micromol kg(-1). After U contamination, a 20% decorporation efficacy was obtained for either 3,4,3-LIHOPO or 4,4,4-LIHOPO at a dosage of 30 micromol kg(-1).

Animals↗
PubMed2003

RBDATA-EULEP: providing information to improve internal dosimetry.

The overall aim of the concerted action RBDATA-EULEP is to provide information to improve the assessments of intakes of radionuclides and of the resulting doses. This involves a review of the behaviour of radionuclides following intake, and the transfer of expertise on methodology by organising small training workshops. The main activity is the development of an electronic database, effectively an annotated bibliography, but the electronic format used facilitates extension, updating and information retrieval. It consists of linked tables of references and experiments, with details and comments on the materials, procedures and results. By June 2002 it contained information on 524 inhalation, 282 ingestion and 164 injection experiments from 391 references. It will be extended, and Internet access provided. Prospective users include groups developing standards for internal dosimetry, scientists conducting research on radionuclide biokinetics and health physicists assessing the consequences of accidental intakes.

Body Burden↗
PubMed2002

Expression of the C-C chemokine MIP-3 alpha/CCL20 in human epidermis with impaired permeability barrier function.

External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP-3 alpha (CCL20, LARC, Exodus-1, Scya20) is a recently described C-C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP-3 alpha in human skin using semi-quantitative polymerase chain reaction. In vivo, MIP-3 alpha mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeability barrier MIP-3 alpha mRNA was upregulated in the epidermal fraction, whereas dermal MIP-3 alpha mRNA levels remained unchanged. In vitro, MIP-3 alpha was increased in cultured keratinocytes treated with IL-1 alpha and TNF-alpha and was present in immature and mature dendritic cells, THP-1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP-3 alpha mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased immunosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.

Cells, Cultured↗
PubMed2002

Outcome of a latex avoidance program in a high-risk population for latex allergy - a five-year follow-up study.

BACKGROUND: Children with a shunted hydrocephalus are at highest risk for developing an immediate type allergy to latex. Limited data are available for preventive or therapeutical approaches. OBJECTIVE: To evaluate the effectiveness of latex avoidance, with special regard to status of sensitization and compliance. METHODS: In 1995, 131 children with a shunted hydrocephalus were screened for sensitization to latex by skin prick test and determination of specific IgE. Patients and parents were instructed on latex-avoiding strategies. Hospital physicians, family doctors and dentists were advised to perform further surgical and other medical interventions under latex-free conditions. In 2000, 100 of these 131 patients were re-evaluated according to the same testing procedures. Special attention was directed at the extent prophylaxis had been performed. RESULTS: In 1995, 30/100 patients re-evaluable in 2000 proved sensitized to latex, 70 had negative testing results. In 2000, 64/70 patients were still negative, six had meanwhile developed latex-specific IgE. Seven out of thirty subjects with former positive testing had changes within the same RAST-class, 20 showed a decline of at least one RAST-class, whereas in three cases an increase of latex-specific IgE was found. However, only 34 patients, mainly those being already sensitized, had thoroughly followed both medical and private prophylaxis. Within this group, 16 subjects (47.1%) had improved and another nine (26.5%) were still negative. Only three (8.8%) already previously sensitized patients presented with a further increase of latex-specific IgE. Medical prevention contributed more to the outcome than home prevention. No statistically significant correlation with latex-avoidance was observed, however, in previously unsensitized subjects. Underlying disease, atopy, number of operations, and age did not prove as significant variables. CONCLUSION: Secondary prevention results in a decrease of specific IgE in latex-sensitized patients with hydrocephalus. This is due to medical more than home prophylaxis. Sensitization obviously occurs mainly in early childhood, thus primary prevention remains to be the main target.

Adolescent↗
PubMed2002

[Specific parameters for the calculation of dose after aerosol inhalation of transuranium elements].

A review on specific parameter measurements to calculate doses per unit of incorporation according to recommendations of the International Commission of Radiological Protection has been performed for inhaled actinide oxides. Alpha activity distribution of the particles can be obtained by autoradiography analysis using aerosol sampling filters at the work places. This allows us to characterize granulometric parameters of "pure" actinide oxides, but complementary analysis by scanning electron microscopy is needed for complex aerosols. Dissolution parameters with their standard deviation are obtained after rat inhalation exposure, taking into account both mechanical lung clearance and actinide transfer to the blood estimated from bone retention. In vitro experiments suggest that the slow dissolution rate might decrease as a function of time following exposure. Dose calculation software packages have been developed to take into account granulometry and dissolution parameters as well as specific physiological parameters of exposed individuals. In the case of poorly soluble actinide oxides, granulometry and physiology appear as the main parameters controlling dose value, whereas dissolution only alters dose distribution. Validation of these software packages are in progress.

Actinoid Series Elements↗
PubMed2002

[Methods to measure the cutaneous transfer of radionuclides across the intact or lesioned epidermis, application to radiotoxicology].

Although skin contamination by radionuclides is the most common cause of nuclear workers accidents, few studies dealing with the penetration of radioactive contamination through the skin are available. This work is a review of experimental methods that allow to assess transfer of radionuclides through the skin in occupational conditions, with or without skin trauma. The first section describes the different methods applied for skin transfer assessment of chemicals used in pharmacology. Major radionuclide contamination accidents can be associated with skin traumas. Thus, the second section describes the adaptation of these methods to radiotoxicology. Finally, the third section is an in vivo investigation of cobalt transfer (57CoCl2) through undamaged and damaged skin which simulates different industrial accident conditions (excoriation, acid or alcalin burn, scalding, branding).

Accidents, Occupational↗
PubMed2002

[The effect of dose distribution on risk of lung cancer after inhalation of actinide oxides].

The aim of this work was to estimate risk of lung tumour occurrence after inhalation of actinide oxides from published studies and rat studies in progress. For the same delivered dose, the risk increases when homogeneity of irradiation increases, i.e., the number of particles deposited after inhalation increases (small particles and (or) low specific alpha activity). The dose-effect relationships reported appear linear up to a few gray, depending on the aerosol considered, and then the slope decreases. This slope, which corresponds with the risk, can vary over one order of magnitude depending on the aerosol used. An effective threshold at about 1 Gy was not observed for the most homogeneous dose distributions. A dosimetric and biological approach is proposed to provide a more realistic risk estimate.

Actinoid Series Elements↗
PubMed2001

Production of IL-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by IL-4.

Dendritic cells produce IL-12 both in response to microbial stimuli and to T cells, and can thus skew T cell reactivity toward a Th1 pattern. We investigated the capacity of dendritic cells to elaborate IL-12 with special regard to their state of maturation, different maturation stimuli, and its regulation by Th1/Th2-influencing cytokines. Monocyte-derived dendritic cells were generated with GM-CSF and IL-4 for 7 days, followed by another 3 days +/- monocyte-conditioned media, yielding mature (CD83(+)/dendritic cell-lysosome-associated membrane glycoprotein(+)) and immature (CD83(-)/dendritic cell-lysosome-associated membrane glycoprotein(-)) dendritic cells. These dendritic cells were stimulated for another 48 h, and IL-12 p70 was measured by ELISA. We found the following: 1) Immature dendritic cells stimulated with CD154/CD40 ligand or bacteria (both of which concurrently also induced maturation) secreted always more IL-12 than already mature dendritic cells. Mature CD154-stimulated dendritic cells still made significant levels (up to 4 ng/ml). 2) Terminally mature skin-derived dendritic cells did not make any IL-12 in response to these stimuli. 3) Appropriate maturation stimuli are required for IL-12 production: CD40 ligation and bacteria are sufficient; monocyte-conditioned media are not. 4) Unexpectedly, IL-4 markedly increased the amount of IL-12 produced by both immature and mature dendritic cells, when present during stimulation. 5) IL-10 inhibited the production of IL-12. Our results, employing a cell culture system that is now being widely used in immunotherapy, extend prior data that IL-12 is produced most abundantly by dendritic cells that are beginning to respond to maturation stimuli. Surprisingly, IL-12 is only elicited by select maturation stimuli, but can be markedly enhanced by the addition of the Th2 cytokine, IL-4.

Adjuvants, Immunologic↗
PubMed2001

The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.).

Medical remedies of plant origin have gained increasing popularity in recent years. Both anaphylactic and eczematous allergic reactions are on the rise, accordingly. Arnica and marigold, both of the Compositae family, are in widespread use, but only limited data are available on their allergenic potential. We tested 443 consecutive patients, in addition to the European standard and other series, with Compositae mix, sesquiterpene lactone mix, arnica, marigold, and propolis. 5 subjects ( approximately 1.13%) reacted to arnica, 9 ( approximately 2.03%) to marigold. The Compositae mix was positive in 18 cases ( approximately 4.06%). Among them were 3 out of 5 individuals with a sensitization to arnica, and 4 out of 9 who reacted to marigold. Sensitization to arnica and marigold was often accompanied by reactions to nickel, Myroxylon Pereirae resin, fragrance mix, propolis, and colophonium. We conclude that Compositae allergy contributes significantly to the epidemiology of contact dermatitis and that sensitization to arnica and marigold cannot be assessed by testing with the Compositae or sesquiterpene mix alone. As extracts of these plants are frequently used in occupational and cosmetic products, patch testing with additional plant extracts or adjustment of the commercial Compositae mix to regional conditions is recommended.

Adult↗
PubMed2001

Lymphocytic infiltration of the skin is a photosensitive variant of lupus erythematosus: evidence by phototesting.

BACKGROUND: Lymphocytic infiltration of the skin (LIS) is a disorder in which photosensitivity has been suspected but never proven. OBJECTIVES: To carry out a systematic photobiological investigation in patients with LIS and to compare the photobiological features of LIS with those of other photosensitive disorders. METHODS: We performed provocative phototesting with ultraviolet (UV) A and UVB in 10 patients with active LIS. RESULTS: In all patients, UVA and/or UVB elicited abnormal papular phototest reactions resembling lesions of LIS both clinically and histologically. Lesions typically developed 3--6 days (mean +/- SD 100.8 +/- 20.9 h) after the first UV exposure. CONCLUSIONS: This characteristic latency interval together with certain clinical features, i.e. onset in summer, predilection for the face and persistence of the lesions, indicate that LIS is a photosensitive disorder distinct from polymorphic light eruption but indistinct from lupus erythematosus (LE). Both our photobiological findings and the effective treatment with hydroxychloroquine in half of our patients strengthen the proposal that the two entities LIS and LE tumidus are identical. As diagnosis cannot be made by histological, immunofluorescence or laboratory criteria, provocative phototesting may be a diagnostic aid in this disorder.

Adult↗
PubMed2001

Human papillomavirus infection in Netherton's syndrome.

BACKGROUND: Netherton's syndrome (NS) is a hereditary disorder with dermatological signs (e.g. ichthyosis) and a complex immunological dysfunction. In immunodeficient individuals human papillomavirus (HPV) types are associated with carcinomas on non-mucosal sites. OBJECTIVES: To study the presence of HPV infection in different skin lesions of three male NS patients and to investigate a possible association between HPV and malignancies in NS. METHODS: Patient 1 had extraordinary widespread multiple skin carcinomas on sunlight-exposed areas, as well as common viral warts. Patient 2 showed disseminated viral plane warts that resolved spontaneously, and patient 3 was free of skin lesions suspicious for HPV infection; only pseudoepitheliomatous wart-like lesions as a symptom of ichthyosis were apparent. We performed nested polymerase chain reaction analysis of DNA from benign and malignant skin lesions and HPV-8 serology in these three patients. RESULTS: Antibodies to HPV-8 were not detectable in our patients; however, seven of 22 (31%) biopsies of the three NS patients were positive for HPV DNA. Epidermodysplasia verruciformis (EV) -associated HPV types and normal cutaneous types (HPV-2, HPV-28) were detected. Interestingly, only the patient with cutaneous carcinomas harboured, preferentially in malignant lesions, EV-HPV types (HPV-19, 23, 38 and HPV-RTRX9, closely related to EV-HPVs), whereas plane warts of patient 2 were positive for HPV-28. The pseudoepitheliomatous skin lesions were HPV-DNA negative in all investigated probes. CONCLUSIONS: These data in NS patients further confirm an association of EV-HPVs with non-melanoma skin cancer (NMSC) and suggest a possible carcinogenic role similar to that assumed for NMSC in transplant recipients. A complex immunological disorder facilitating EV-HPV infection, negative HPV serology and photochemotherapy may all have contributed to the unusual occurrence of multiple cancers in one of our NS patients.

Adult↗
PubMed2001

Interaction of HSV-1 infected peripheral blood mononuclear cells with cultured dermal microvascular endothelial cells: a potential model for the pathogenesis of HSV-1 induced erythema multiforme.

The effect of herpes virus infection on human dermal microvascular endothelial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of herpes-associated erythema multiforme. After infection of human dermal microvascular endothelial cells with native herpes virus and overnight culture, 60%--90% of human dermal microvascular endothelial cells showed cytopathic effects. HLA class I molecules and CD31 (PECAM-1) surface expression in herpes-virus-infected endothelial cells were substantially downregulated, whereas CD54 (ICAM-1) remained unchanged. Cocultivation with herpes-virus-1-infected peripheral blood mononuclear cells left characteristic plaques on the human dermal microvascular endothelial cell monolayer; however, very few human dermal microvascular endothelial cells (1%--3%) were infected. Adhesion molecule expression of human dermal microvascular endothelial cells cocultivated with herpes-virus-infected peripheral blood mononuclear cells demonstrated a 5-fold increase in CD54 expression, a 2-fold increase in HLA class I expression, but no change of CD31 by fluorescence-activated cell sorter analysis. Incubation of human dermal microvascular endothelial cells with ultraviolet-C irradiated herpes-virus-infected peripheral blood mononuclear cells had no effect on morphology or adhesion molecule expression levels. Changes of adhesion molecule expression by direct infection or cocultivation with peripheral blood mononuclear cells (with native and ultraviolet-C inactivated herpes virus infection) were also documented at the mRNA level. Adhesion assays demonstrated an increased binding of herpes-virus-infected peripheral blood mononuclear cells versus noninfected peripheral blood mononuclear cells to noninfected human dermal microvascular endothelial cells. Our results suggest that incubation of herpes-virus-infected peripheral blood mononuclear cells with human dermal microvascular endothelial cells induces significant upregulation of CD54 and major histocompatibility complex class I molecules in the surrounding noninfected human dermal microvascular endothelial cells, which is associated with an increased binding of peripheral blood mononuclear cells. Our in vitro findings may serve as a model for herpes-associated erythema multiforme possibly explaining the dermal inflammatory reaction seen in that condition.

Antigens, Surface↗
PubMed2001

Interleukin-16 supports the migration of Langerhans cells, partly in a CD4-independent way.

Migration of cutaneous dendritic cells is essential for the induction of primary immune responses. Chemotaxis plays an important part in guiding migrating cells through the skin. Therefore, we investigated the influence of interleukin-16, a potent chemoattractant, on the migratory properties of cutaneous dendritic cells. Interleukin-16 added to murine and human skin explant cultures, enhanced emigration of Langerhans cells as well as dermal dendritic cells out of the skin. In contrast to tumor necrosis factor-alpha, intradermally injected interleukin-16 did not reduce the density of Langerhans cells suggesting a chemotactic rather than a mechanistic migration-inducing effect of interleukin-16. In support of these findings, the known migration-promoting effect of tumor necrosis factor-alpha in skin explant cultures could be neutralized by anti-interleukin-16 antibody and vice versa, indicating different but cooperative ways of action for both cytokines. In whole skin explant cultures blocking of the interleukin-16 effect was also achieved with a monoclonal antibody against CD4, the receptor for interleukin-16. In contrast, in cultures of murine epidermis alone no blocking by anti-CD4 became obvious and in CD4-deficient mice Langerhans cell migration in response to interleukin-16 was maintained. This suggests that another receptor for interleukin-16 might be operative for Langerhans cells in the mouse epidermis. Finally, we detected interleukin-16-positive cells in the dermis of skin explants, tumor necrosis factor-alpha-treated and contact allergen-treated skin. Taken together, it seems likely that locally secreted interleukin-16 might serve to enhance the migration of cutaneous dendritic cells and optimize the response to foreign antigen encountering the skin.

Animals↗
PubMed2001

Survival, lung clearance, dosimetry and gross pathology of rats exposed to either NpO2 or PuO2 aerosols.

PURPOSE: To compare survival, lung dosimetry and gross pathology after inhalation exposure of rats to either NpO2 or industrial PuO2 aerosols with similar granulometric parameters. Because the specific alpha activity ratio Pu/Np is about 600, a much more homogeneous lung irradiation was expected for NpO2. MATERIALS AND METHODS: Male Sprague Dawley rats were exposed once and their lung burdens were measured by X-ray spectrometry at different times post-exposure up to death. The time-course of doses delivered to the lungs were estimated, taking into account individual lung clearance parameters and body and lung weights. Gross lung pathologies were scored at autopsy. RESULTS: In the range of initial lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced lifespan were only observed after exposure to NpO2. For similar ILD or doses, the highest incidences of lung lesions assumed to be tumours were observed for NpO2 with a saturation of lung tumour induction for doses larger than 8 Gy (ILD: 1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO2. CONCLUSIONS: NpO2 appears much more toxic than PuO2. Before saturation, lung tumour incidence increased nearly linearly with dose, the slope of the curve for NpO2 being about twice as steep as that for PuO2.

Aerosols↗
PubMed2001

Delayed-type hypersensitivity and cross-reactivity to heparins and danaparoid: a prospective study.

BACKGROUND: Delayed-type hypersensitivity (DTH) reactions in patients receiving heparin may occur with both unfractionated (UFHs) and low molecular weight heparins (LMWHs). Skin testing is a clue to detect tolerated heparin or heparinoid preparations for further treatment. OBJECTIVE: To study in vivo cross-reactivity between LMWHs, UFHs, and danaparoid by skin testing in patients with suspected DTH to heparin. METHODS: Patients who fulfilled the criteria for the diagnosis of suspected heparin allergy were involved in a prospective study after informed consent. Patients presented with or had a history of typical erythematous plaques at the heparin injection sites. Skin testing was performed by subcutaneous injections of heparin (300-500 IU anti-Xa activity) and danaparoid (375 IU, eight patients). Desirudin (27,000 IU) was tested in three patients. We read skin reactions after 24, 48, and 96 hours and after 7 days. RESULTS: Fourteen female and 4 male patients were included in our series. Erythematous plaques had been reported or developed after 14-35 days in patients during first-time heparin treatment and after 2-10 days in reexposed patients. Positive skin test results were seen in 15 of 18 (83.3%) patients. Of these, 11 (73.3%) showed cross-reactivity between heparins and/or danaparoid. Six patients reacted to LMWHs only, nine patients to both LMWHs and UFHs. Danaparoid was tolerated in six of eight patients; desirudin was tolerated in all three patients tested. CONCLUSIONS: DTH to heparins is characterized by considerable cross-reactivity between LMWHs, UFHs, and danaparoid. UFHs may be tolerated even if LMWHs are not. Subcutaneous testing of a panel of heparins, danaparoid, and desirudin (hirudin) is recommended to determine acceptable treatment options for patients allergic to specific heparins.

Adult↗