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Biomedical subjects

P Fritsch

Publications and source records attributed to P Fritsch.

At least 91 records · Page 5Linked to original sources

[Radiotoxicology].

Radiotoxicology is a science aiming firstly to estimate the biological effects induced by radiation in workers and general population after internal contamination of radionuclides, secondly evaluate the risk on health. After internal contamination, the analysis of biokinetics of radioactive compounds allow to understand their behaviour in the body. Those complex processes describe routes of radionuclide intake, direct blood uptake or transfer of soluble form to blood from deposit area, urine and fecal excretions, distribution and retention of radionuclides in different target organs. These processes are modelled to establish mathematical calculations. Data obtained are important to the interpretation of bioassay measurement for initial activity deposit expressed in becquerel (Bq: transformation.s-1) and committed effective dose calculation, expressed in sievert (Sv). This committed effective dose corresponds to the absorbed dose expressed in gray (Gy), weighted by a radiation weighting factor related to the quality of radiation and a tissue weighting factor which represents the contribution of the target organ to the total detriment due to effects induced by uniform irradiation of the whole body. This committed effective dose is a specific parameter for risk assessment which characterizes the radiotoxicology as a special part of toxicology.

Humans↗

Werner syndrome: studies in an affected family reveal a cellular phenotype of unaffected siblings.

Werner syndrome is an inherited disease with symptoms of presenescence. The primary defect site either on the protein or at the DNA level is not known, nor is it possible to identify a heterozygous phenotype. On the basis of cellular peculiarities expressed in the homozygotes-lifespan reduction of cells in culture, length of population doubling time and chromosomal instability-we searched for a 'Werner-like' phenotype in otherwise phenotypically unaffected siblings. We established primary fibroblasts from eight members of a Tyrolean family, two of whom had been diagnosed as typical Werner syndrome, as well as from unrelated healthy young and old volunteers. Determination of the lifespan of each strain and studies on population doubling time and chromosomal instability revealed similar cellular characteristics in all family members, albeit to a lesser extent with the siblings than with the homozygotes when compared to age-matched controls. These features, also apparent in cultivated fibroblasts from old but healthy controls, appear to be indicative of Werner syndrome when expressed in young or middle aged persons. The possible identification of otherwise clinically healthy gene carriers of Werner syndrome is of utmost importance for genetic counselling and medical surveillance for this disorder.

Adolescent↗

[Cancer prognosis, psychosocial stress and attitude of melanoma patients to supportive psychotherapy].

A total of 205 patients suffering from stage I and stage II melanoma were investigated with reference to psychological stress, social support and attitude to offers of psychotherapeutic support. Additional counselling by their dermatologist was considered helpful by 59% of the patients, and interviews with a psychotherapist, by 20%. Patients who where more anxious about a progression of the cancer and thought they had not been given sufficient information about their illness preferred to seek help from the dermatologist. Patients who appreciated additional counselling by a psychotherapist were usually those with a poorer prognosis for their melanoma and those on whom psychosocial distress weighed especially heavily and who had less social support.

Adaptation, Psychological↗

Differentiation of primary and secondary cutaneous B-cell lymphoma by Southern blot analysis.

Malignant B-cell lymphomas represent a heterogenous group of lymphoreticular disorders that involve the skin in about 20% of reported cases. Skin involvement may be primary or secondary (ie, the result of hematogenous spread). Primary cutaneous B-cell lymphomas (PCBCLs) are thought to take a comparatively favorable course, respond readily to nonaggressive treatment, and lack evidence of extracutaneous spread. Nine primary B-cell lymphomas (7 centrocytic or centroblastic follicular, 1 immunoblastic, 1 centroblastic), three secondary (follicular) cutaneous B-cell lymphomas (SCBCLs) and two pseudolymphomas were studied. Staging revealed that bone marrow was involved only in SCBCLs. Centrocytes were detected in blood smear preparations of all SCBCLs. All lymphomas were treated with local irradiation. Patients with primary centroblastic and immunoblastic cutaneous lymphomas and those with secondary lymphomas received additional chemotherapy. Pseudolymphomas were treated by simple excision. Patients were monitored on average for 55 months. During this period, no patients with PCBCLs exhibited cutaneous relapses or hematogenous spread. In contrast, all patients with SCBCLs experienced cutaneous relapses. Peripheral blood, bone marrow, and skin samples from all patients were subjected to Southern blot analysis using a JH probe. Clonal rearrangement was found in all skin samples investigated except specimens from pseudolymphomas. Peripheral blood and bone marrow samples were positive in SCBCLs (the rearrangement pattern was different from that of the skin samples for two of the three patients), whereas it was negative in all PCBCLs and pseudolymphomas. In conclusion, Southern blot analysis of peripheral blood may be useful in differential diagnosis of PCBCLs and SCBCLs and a prognostic marker. Furthermore, these data confirm the comparatively favorable clinical course of PCBCLs and suggest that in these cases, local irradiation can be considered adequate treatment, whereas SCBCLs require additional systemic therapy.

Adult↗

Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a skin organ culture model.

The capacity to migrate from peripheral tissues, where antigen is encountered, to lymphoid organs, where the primary immune response is initiated, is crucial to the immunogenic function of dendritic cells (DC). The skin is a suitable tissue to study migration. DC were observed to gather in distinct nonrandom arrays ("cords") in the dermis upon culture of murine whole skin explants. It is assumed that cords represent lymphatic vessels. Using a similar organ culture model with human split-thickness skin explants, we investigated migration pathways in human skin. We made the following observations. 1) Spontaneous emigration of Langerhans cells took place in skin cultured for 1-3 d. Nonrandom distribution patterns of strongly major histocompatibility complex class II-expressing DC (cords) occurred in cultured dermis. A variable, yet high (>50%) percentage of these DC coexpressed the Birbeck granule-associated antigen "Lag." Ultrastructurally, the cells corresponded to mature DC. 2) Electron microscopy proved that the dermal structures harboring the accumulations of DC (i.e., cords) were typical lymph vessels. Moreover, markers for blood endothelia (monoclonal antibody PAL-E, Factor VIII-related antigen) and markers for cords (strong major histocompatibility complex class II expression on nonrandomly arranged, hairy-appearing cells) were expressed in a mutually exclusive pattern. 3) On epidermal sheets we failed to detect gross changes in the levels of expression of adhesion molecules (CD44, CD54/ ICAM-1, E-cadherin) on keratinocytes in the course of the culture period. The reactivity of a part of the DC in the dermal cords with Birbeck granule-specific monoclonal antibody "Lag" suggests that the migratory population is composed of both epidermal Langerhans cells and dermal DC. We conclude that this organ culture model may prove helpful in resolving pathways and mechanisms of DC migration.

Cell Movement↗

Immunoglobulin A (IgA) deposits in lesional skin of a patient with blepharochalasis.

We describe a 21-year-old male patient with blepharochalasis, a form of localized acquired cutis laxa. He had a 13-year history of recurrent swelling attacks of the eyelids of unknown origin leading to periocular localized cutis laxa. Histology of lesional skin confirmed almost complete loss of elastic fibres in the reticular and papillary dermis. Immunofluorescence and immunoelectron microscopy studies showed abundant immunoglobulin A (IgA) deposits around the remaining elastic fibres. Control skin of the forearm was negative. These findings support the hypothesis that immunopathogenetic mechanisms may contribute to the elastolytic process of blepharochalasis.

Adult↗

Efficacy of 3,4,3-LIHOPO for enhancing the excretion of plutonium from rat after simulated wound contamination as a tributyl-n-phosphate complex.

The siderophone analogue 3,4,3-LIHOPO, referred to hereafter as LIHOPO, has been examined for its ability to remove 238Pu in a tributyl-n-phosphate (TBP) complex from rat after intramuscular (i.m.) or subcutaneous (s.c.) contamination. The chelating agent was administered at a dosage of 30 mumol.kg-1, 30 min after the contamination, either by intravenous (i.v.) or local injection. By day 7 after exposure, local (i.m.) administration of LIHOPO reduced the amounts of i.m.-injected 238Pu in the would site, skeleton and liver to 75, 20 and 25% respectively of those in untreated animals. At the i.m. Pu would site, local treatment was superior to i.v. treatment; both ligands were equally effective. At the s.c. Pu would site, local and systemic treatments were equally effective and LIHOPO was superior to DTPA. After translocation, LIHOPO was the most effective treatment for enhancing Pu excretion, whatever the route of contamination and treatment: the administration of LIHOPO and DTPA reduced whole-body Pu retention by a factor of 1.8 and 1.4 respectively. All these results are encouraging for the use of LIHOPO in the future but more studies are needed, concerning both the toxicity of the compound and its use in man.

Animals↗

Sneddon's syndrome--an inflammatory disorder of small arteries followed by smooth muscle proliferation. Immunohistochemical and ultrastructural evidence.

Sneddon's syndrome is a rare, but potentially severe, arterioocclusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown cause. We have recently shown that, in skin, small to medium-sized arteries of the dermis-subcutis boundary are affected in a stage-specific sequence. An initial phase (stage I), characterized by the attachment of lymphohistiocytic cells and detachment of endothelial cells (endothelitis), is followed by an early phase (stage II), which displays partial or complete occlusion of the lumen by a plug of lymphohistiocytic cells and fibrin. In an intermediate phase (stage III), the occluding plug is replaced by proliferating subendothelial cells accompanied by the occurrence of dilated capillaries in the adventitia of the occluded vessel. The late phase (stage IV) shows fibrosis and shrinkage of the affected vessels. We investigated sections of paraffin-embedded specimens of 18 patients by immunohistochemistry using a panel of antibodies to detect endothelial cells, macrophages, T cells, smooth muscle-specific actin, and intermediate filaments (vimentin, desmin). We found that the cells involved in subendothelial proliferation were vimentin and actin positive (smooth-muscle-specific), but desmin negative and thus displayed the phenotype characteristic of smooth muscle cells, which was confirmed by ultrastructural studies. CD3+, UCHL-1+, and HLA-DR+ cells constituted a significant proportion of the inflammatory infiltrate in the early stages. The endothelial cells in the dilated capillaries of the adventitia were strongly HLA-DR positive. In later stages, endothelial cells and leukocytes were scarce. The data confirm the hypothesis that Sneddon's syndrome starts as an inflammatory and possibly immunologically mediated disorder, leading to a migration and proliferation of smooth cells of small arteries, resulting in a partial or complete narrowing of the vessel lumen.

Arterial Occlusive Diseases↗

Mechanism of allergic cross-reactions. V. High incidence of unanticipated cross-stimulation by natural allergens of rat basophilic leukemia cells sensitized with monoclonal IgE antibodies.

The incidence of cross-stimulations by natural allergens was investigated using RBL-2H3 cells sensitized with five different mouse monoclonal anti-DNP IgEs and four mercury-induced rat monoclonal IgEs. Cells sensitized with 3 of the 5 monoclonal anti-DNP IgEs (clones SPE-7, SRT-1, LB4) responded by serotonin release upon stimulation by natural allergens such as Dermatophagoides pteronyssinus, horse dander and mugwort extracts. Serotonin release could be inhibited by monovalent DNP-lysine, indicating the involvement of DNP-binding sites of IgEs. Two of the clones (LO-DNP-30 and LA2) were negative on all tests with allergens. All but one (Hg32) of the mercury-induced rat IgE monoclonal antibodies tested positive with DNP-BSA, and with at least one of the six allergen extracts. IgE clone Hg12 mediated serotonin release with 5 of the 6 allergens tested.

Allergens↗

[Eosinophilic cellulitis (Wells syndrome) with involvement of para-articular muscles and fascia].

A 62-year-old woman developed eosinophilic cellulitis of her right arm, accompanied by systemic signs (fever, leucocytosis) and massive restriction of the motility of her right shoulder joint. Sonography and computed tomography revealed massive cutaneous and subcutaneous oedema, and accumulations of fluid around the deep muscular fasciae, interstices and (less severe) within the joint. High-dose systemic corticosteroid treatment led to rapid clearing of the skin lesions, and joint motility was restored several weeks later. This is the first case of eosinophilic cellulitis in which involvement of deep structures adjacent to joints has been demonstrated by modern imaging techniques.

Administration, Oral↗

Kinetics of radiation-induced apoptosis in the cerebellum of 14-day-old rats after acute or during continuous exposure.

We have studied, by histological methods, cytological progression, frequency and distribution of apoptosis in the external granular layer of the cerebellum after whole-body irradiation of 14-day-old rats by gamma-rays from 60 Co. After acute exposure to 0.25, 0.5, 1.5 and 3 Gy (18 cGy/min), the duration of the apoptotic process gradually increased with dose from 6-9 h after 0.25 Gy, to > 24 h after 3 Gy. Up to 1 Gy, maximal frequency was found 6 h after exposures, and at this postirradiation time a linear increase in apoptosis with dose was observed. No effect of dose-rate on apoptosis induction could be demonstrated 6 h after delivering 1 Gy at dose-rates from 2.2 to 18 cGy/min. Continuous irradiation at 1.8 cGy/h induced a gradual increase of apoptosis that remained at a plateau value of about 3% from 15 to 29 h (controls 0.12%, SD = 0.07) and then gradually decreased to 1% at 53 h. At this time the mitotic index was similar to that measured in controls. Apoptosis occurring 3 h after acute irradiation, confined to proliferative cells, was only observed for doses of 1.5 and 3 Gy.

Animals↗

Buschke-Loewenstein tumour infiltrating pelvic organs.

We report a 42-year-old HIV-negative patient with a 12-year history of exceptionally extensive genital warts and coexisting verrucous carcinoma of the anogenital region (Buschke-Loewenstein tumour). Masses of both tumour and viral papillomas infiltrated the external genitalia, perineum and buttocks, pelvic diaphragm and parts of the lesser pelvis, as well as the urethra, prostate and parts of the urinary bladder, necessitating repeated surgical intervention and plastic reconstruction. Adjuvant interferon-alpha therapy was given without any lasting effects. Human papillomavirus type 6 was detected by DNA in situ hybridization and Southern blot analysis.

Adult↗

[Pyoderma gangraenosum: differential diagnosis in ulcus cruris and postoperative exacerbating processes].

A case of pyoderma gangrenosum that was initially misdiagnosed as postthrombotic ulcers is described. Surgical debridement triggered postoperative exacerbation. Dermatologic examination was then initiated and the diagnosis pyoderma gangrenosum was established. No underlying illness was detectable. Immunosuppressive therapy stopped disease activity promptly and as previously reported low-dose cyclosporine was also effective in our exceptionally therapy resistant case. Pyoderma gangrenosum should be considered as a rare, but important differential diagnosis of leg ulcers and postoperative progressive exacerbation. Timely diagnosis based on clinical suspicion is pertinent for correct therapy and to avoid iatrogenic deterioration of the disease.

Diagnosis, Differential↗

[Occurrence of swimmer's itch in Tyrol].

Cercariae from trematodes of birds are capable of penetrating human skin causing a dermatitis, called swimmer's itch. In 1992, after a hot dry summer there was a marked increase in the incidence of cercarial dermatitis in Austria. Although the increased incidence of this complaint can be quite worrisome for the population, the occurrence of swimmer's itch can, in fact, generally be seen as harmless. Cercarial dermatitis responds well to treatment with topical antihistamines or cortisone; even without medication the skin rash heals within 2-3 weeks. The effectiveness of various preventive measures (such as protective sun cream or patting the skin dry) is controversial. The use of molluscicides is definitely contraindicated due to the inoffensive nature of this dermatitis. While it is usually easy to recognize swimmer's itch when there is an increased incidence, the diagnosis is often missed when it occurs sporadically, due to its unspecific characteristics.

Adolescent↗

Specific skin manifestations in acute leukemia with monocytic differentiation. A morphologic and immunohistochemical study of 11 cases.

BACKGROUND: Monocytic differentiation is present in the myelomonocytic (M4) and monocytic (M5) type of acute myeloblastic leukemia. Infiltration of the skin in acute myelomonocytic leukemia occurs in 10-20% of patients, the skin lesions occasionally being the first symptom, even preceding monocytosis. METHODS: Eleven patients with myelomonocytic (n = 2) and monocytic leukemia (n = 9) were studied who had skin manifestations. RESULTS AND CONCLUSIONS: Clinically, all patients showed disseminated papules or nodules that corresponded histologically to nodular or diffuse infiltrates of monocytoid cells, occasionally displaying a whorled pattern. The currently available antibodies for paraffin-embedded sections (lysozyme, elastase, leukocyte common antigen (CD45), MT1 (CD43), Leu-M1 (CD15), LN2 (CD74), MB2, MB1 (CD45RA), LN1 (w75), Mac387, L26 (CD20), UCHL1 (CDR0), MT2 (CD45RA), and KP-1 (CD68)) and chloracetate-esterase are not more helpful in diagnosis than are the histologic findings. By contrast, the antibodies used on frozen sections (Leu-4 (CD3), Leu-3a (CD4), BA1 (CD24), B4 (CD19), Leu-M5 (CD11c), Vim12 (CD11b), VimD5 (CD15), KiM6 (CD68), KIM7 (CD68), My7 (CD13), and My9 (CD33) allow the definition of a reaction pattern that is diagnostic for acute myeloid leukemia with monocytic differentiation.

Adult↗

Effects of adequate versus inadequate treatment of cutaneous manifestations of Lyme borreliosis on the incidence of late complications and late serologic status.

Eighty-two patients who were treated at the Department of Dermatology, Innsbruck, Austria, from 1980 to 1987 for cutaneous manifestations of Lyme disease were subjected to a clinical follow-up investigation aimed at detecting dermatologic, neurologic, and internal late complications of borreliosis. Only 54 of these patients had received adequate antibiotic treatment according to current standards. Also, their sera were investigated for the presence of immunoglobulin G (IgG) and IgM Borrelia burgdorferi antibodies by an indirect immunofluorescence assay, three different enzyme-linked immunosorbent assays, and immunoblotting. As a control, the sera of 126 healthy blood donors were investigated with the same assays. Results showed no unambiguous clinical late complications of Lyme borreliosis, even in inadequately treated or untreated patients. Seropositivity varied considerably according to the assay used; the indirect immunofluorescence assay yielded the highest scores. The proportion of seropositive results (immunofluorescence assay) was 59% in patients with erythema chronicum migrans, 69% in those with lymphocytoma cutis, and 100% in those with acrodermatitis chronica atrophicans (overall 63%); in contrast, only 31% of the blood donor control group were found to be seropositive. Seropositivity did not correlate with adequacy of treatment, interval between onset of symptoms and treatment, time span since treatment, age of patients, and presence of antinuclear antibodies. Immunoblot pattern showed high incidence of antibodies against the 29/31-kD (outer surface proteins OspA and OspB) and 55/58-kD antigens in general and against the 41-kD protein (flagellin) in patients with acrodermatitis chronica atrophicans only.

Adult↗