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Biomedical subjects

R Wurm

Publications and source records attributed to R Wurm.

At least 19 recordsLinked to original sources
PubMed1998

The efficiency of vertical transmission of Neospora caninum in dairy cattle analysed by serological techniques.

The association of Neospora caninum infections with cattle families was examined in a dairy cattle herd with sporadic abortions using three different serological tests. Cattle seropositive for N. caninum clustered in six families, three of which encountered abortions. In absence of age-related differences in the N. caninum seroprevalence, the family association of N. caninum infection indicated that congenital infection represented the predominant route of transmission in this herd. Fourteen (93%) out of 15 descendants of 10 seropositive cows were seropositive themselves. Only one female calf of a seropositive cow remained seronegative and gave birth to a calf which was tested seronegative again. Only one seronegative cow that had two seronegative descendants also gave birth to one seropositive calf. This was the only indication for potential postnatal transmission that occurred in the herd. The results of this study suggest that the N. caninum-infection can be maintained over several generations at a nearly constant prevalence level, apparently without a need for dispersion by an definitive host.

Abortion, Veterinary↗
PubMed1998

Thymoma: prognostic factors and treatment outcomes.

BACKGROUND: The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy. METHODS: Seventy patients treated at the University Hospital Düsseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test. RESULTS: In univariate analysis, KPS (P < 0.001), histologic type (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy. CONCLUSIONS: Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.

Adolescent↗
PubMed1998

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial.

AIM: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. PATIENTS AND METHODS: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. RESULTS: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). CONCLUSIONS: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.

Adult↗
PubMed1998

Comparison of conventional and virtual simulation for radiation treatment planning of malignant lymphoma.

PURPOSE: The exact coverage of the lymph nodes and optimal shielding of the organs at risk are necessary for patients with Hodgkin's disease or malignant lymphoma to guarantee a high cure rate and a low rate of late effects for normal tissue. The purpose of this study was to compare conventional simulation and blocking with virtual simulation in terms of coverage of the target volume and shielding of the organs at risk in this highly curative patient group. PATIENTS AND METHODS: In 10 patients diagnosed with Hodgkin's disease and 5 patients with a Non-Hodgkin lymphoma radiation treatment planning for a mantle field or para-aortic field with inclusion of the spleen was performed in a conventional manner and with virtual simulation. With conventional technique, irradiation portals were defined during fluoroscopy and shielding of the organs at risk was drawn onto the simulation films, based on the information from previous X-ray films, CT or MRI scans. For virtual simulation, contouring of the target volumes and organs at risk (e.g. the kidneys) and the definition of the irradiation portals were performed with the AcQSim software package on a VoxelQ workstation (Picker Inc.) This was done in a beam's eye view environment on a currently driven CT scan in the treatment position. Both irradiation portals were compared in terms of coverage of the target volume and shielding of the organs at risk. RESULTS: Planning of a mantle field in the conventional way resulted in an incomplete coverage of the right hilus in 4/15 cases and of the left in 1/15 cases, respectively. The spleen and the spleen hilus were not covered completely in 5/15 and 6/15 cases, respectively. The left kidney was adequately shielded in only two thirds (10/15) of the conventionally planned fields. The planning time required for virtual simulation was reduced for the patient, but was increased for the physician because of the more time consuming contouring procedure compared to conventional simulation. CONCLUSIONS: Virtual simulation based on CT scans for radiation treatment planning of malignant lymphoma gives more information about soft tissue structures than conventional treatment planning. Therefore, it allows a more precise coverage of the target volumes and better shielding of the organs at risk. However, the time required for the whole procedure is increased. This is justified because of the often highly curative intention when treating this group of patients.

Feasibility Studies↗
PubMed1997

Direct evidence for uptake of intact liposomes encapsulating silver sulfadiazine by cultured human keratinocytes based on combined transmission electron microscopy and X-ray microanalysis.

Cultured human keratinocytes were exposed to liposomally encapsulated silver sulfadiazine, free silver sulfadiazine, silver sulfadiazine cream, and a corresponding vehicle for 5 min to 24 h. Phagocytosis of intact liposomes by keratinocytes was demonstrated in vitro by combined X-ray microanalysis and electron microscopy. Silver as an active part of the antimicrobial served as an electron-dense marker.

Anti-Infective Agents, Local↗
PubMed1997

[Neospora caninum causes abortions in a cattle herd in North Rhine Westphalia].

In a cattle herd in North Rhine-Westphalia a series of eight abortions occurred between 15th August and 14th October, 1996. Four of the aborted fetuses were histopathologically, virologically, bacteriologically and parasitologically examined. A multifocal necrotising encephalitis was observed in two fetuses. In addition, the liver of two fetuses and the placenta of one fetus contained infected foci. In three fetuses protozoan stages were detected which were identified as N. caninum by immunohistochemistry. A polymerase chain reaction conducted with histological material revealed N. caninum-DNA in the placenta of an aborted fetus. When seven cows that had aborted were tested for antibodies directed against N. caninum, six animals were positive by immunofluorescence and all seven by immunoblotting. The serological examination of the entire herd revealed a high herd seroprevalence of antibodies directed against N. caninum. Potential modes of infection with N. caninum in the herd are discussed, in particular the possibility of exposure to a point source (definitive host).

Abortion, Veterinary↗
PubMed1996

Normal tissue radiosensitivity--how important is it?

The success of radiotherapy in eradicating tumours depends on the total radiation dose, but what limits this dose is the tolerance of the normal tissues within the treatment volume. Selection of the appropriate dose for all patients is based on a balance between minimising the incidence of severe normal tissue complications and maximizing the probability of local control. In patients treated to the same radical dose, a wide range of reactions is seen; in many clinical situations, radical doses are limited by the minority of patients whose normal tissues are particularly sensitive. Clinical studies of radiotherapy reactions have demonstrated that a large part of the spectrum of normal tissue reactions, perhaps as much as 80%, is due to differences in individual normal tissue sensitivity. This suggests that it might be possible to measure this sensitivity and to change treatment accordingly. The main objective of normal tissue sensitivity testing is to permit dose escalation without increased normal tissue complication rates in patients with more resistant normal tissues. Calculations suggest that the most "resistant' 40% of patients could be dose escalated by 17%-18%, which is likely to be associated with significant gains in local control, perhaps by as much as 34%-36%; this should translate into an increase in overall survival. It should also be possible to identify those relatively few patients who suffer serious normal tissue morbidity with conventional doses. Thus, if successful, predictive testing of normal tissue response should improve the therapeutic ratio of radiotherapy.

Forecasting↗
PubMed1996

Low dose-rate fibroblast radiosensitivity and the prediction of patient response to radiotherapy.

The relationship between cellular radiosensitivity and normal-tissue response to radiotherapy in individual cancer patients has attracted increasing attention over the last few years. Recent work has suggested that a correlation exists between fibroblast sensitivity and normal-tissue reactions. We have examined the radiosensitivity of fibroblasts grown from skin biopsies of four normal individuals and three patients identified as having suffered unexpectedly severe reactions to clinical radiotherapy, called here 'over-reactor' (OR) patients. Clonogenic survival was measured after high (HDR) and low dose-rate (LDR) irradiation. By comparing the two, and LDR Recovery Factor was derived. Potentially-lethal damage repair was examined in 4 cell strains. After HDR the OR strains were indistinguishable from the normals. At LDR the range of sensitivity was expanded. The OR strains fell at the sensitive end of the range and were characterized by a lack of LDR recovery, which clearly distinguished them from the normal strains. Experimental errors were estimated by considering all the data sets together rather than viewing each experiment individually. Duplicate strains from several patients were tested, and the differences between them were found to be within the estimated experimental errors, suggesting that these differences were not biologically significant. The data are consistent with the hypothesis that normal-tissue response is linked to individual cellular radiosensitivity. Our data confirm the importance of using LDR irradiation in clinical investigations of cellular sensitivity.

Adult↗
PubMed1994

Cellular radiosensitivity and DNA damage in primary human fibroblasts.

PURPOSE: To evaluate the relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts to decide whether the initial or residual DNA damage levels are the more predictive of normal tissue cellular radiosensitivity. METHODS AND MATERIALS: Five primary human nonsyndromic and two primary ataxia telangiectasia fibroblast strains grown in monolayer were studied. Cell survival was assessed by clonogenic assay. Irradiation was given at high dose rate (HDR) 1-2 Gy/min. DNA damage was measured in stationary phase cells and expressed as fraction released from the well by pulsed-field gel electrophoresis (PFGE). For initial damage, cells were embedded in agarose and irradiated at HDR on ice. Residual DNA damage was measured in monolayer by allowing a 4-h repair period after HDR irradiation. RESULTS: Following HDR irradiation, cell survival varied between SF2 0.025 to 0.23. Measurement of initial DNA damage demonstrated linear induction up to 30 Gy, with small differences in the slope of the dose-response curve between strains. No correlation between cell survival and initial damage was found. Residual damage increased linearly up to 80 Gy with a variation in slope by a factor of 3.2. Cell survival correlated with the slope of the dose-response curves for residual damage of the different strains (p = 0.003). CONCLUSION: The relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts of differing radiosensitivity is closest with the amount of DNA damage remaining after repair. If assays of DNA damage are to be used as predictors of normal tissue response to radiation, residual DNA damage provides the most likely correlation with cell survival.

Cell Survival↗
PubMed1994

The relationship between cellular radiation sensitivity and tissue response may provide the basis for individualising radiotherapy schedules.

There is a wide variation in normal tissue reactions to radiotherapy and in many situations the severity of these reactions limits radiotherapy dose. Clinical fractionation studies carried out in Gothenburg have demonstrated that a large part of the spectrum of normal tissue reactions is due to differences in individual normal tissue sensitivity. If this variation in normal tissue reactions is due to differences in intrinsic cellular radiosensitivity, it should be possible to predict tissue response based on measurement of cellular sensitivity. Here we report the initial results of a study aimed at establishing whether a direct relationship exists between cellular radiosensitivity and tissue response. Ten fibroblasts strains, including four duplicates, were established from a group of patients in the Gothenburg fractionation trials who had received radiotherapy following mastectomy. Skin doses were measured and both acute and late skin changes were observed following radiotherapy. Right and left parasternal areas were treated with different dose fractionation schedules. Clonogenic assays were used to assess intrinsic cellular radiosensitivity, and all experiments were carried out without prior knowledge of the clinical response, or which strains were duplicates. Irradiation was carried out using 60Co gamma-rays at high dose-rate (HDR) of 1-2 Gy/min and low dose-rate (LDR) of 1 cGy/min. A spectrum of sensitivity was seen, with SF2 values of 0.17-0.28 at HDR and 0.25-0.34 at LDR, and values of D0.01 of 5.07-6.38 Gy at HDR and 6.43-8.12 Gy at LDR. Comparison of the in vitro results with the clinical normal tissue effects shows a correlation between cellular sensitivity and late tissue reactions, which is highly significant with p = 0.02. A correlation between cellular sensitivity and acute effects was noted in the left-sided parasternal fields, but not the right. This is thought to be coincidental, and without biological significance. Our results suggest that cellular sensitivity might form the basis for the development of an assay system capable of predicting late normal tissue effects to curative radiotherapy, which might allow dose escalation in some patients. Increased local control and cure, with unchanged or improved normal tissue complications, could result from such individualised radiotherapy prescriptions.

Breast Neoplasms↗
PubMed1994

Cellular sensitivity and low dose-rate recovery in Fanconi anaemia fibroblasts.

Fanconi anaemia (FA) is a rare inherited condition characterized by developmental abnormalities and progressive bone marrow failure, which requires bone marrow transplantation for successful treatment. This involves the use of alkylating agents and total body or thoraco-abdominal irradiation. Both chemical clastogens and irradiation cause increased chromosome damage in FA cells compared with controls. In some studies FA fibroblasts have been found to be more radiosensitive than normal. From these data it has been inferred that patients with FA might be more sensitive than normal to radiotherapy. However, increased radiosensitivity of FA fibroblasts has not been a uniform finding. The radiosensitivity of fibroblasts from two FA patients was studied at high and low dose-rate (LDR), and their sensitivity compared with normal strains. Both FA strains fell at the sensitive end of the range, but both demonstrated marked dose-rate sparing, with D0.01 recovery factors of 1.23 and 1.27, similar to the normal strains. These recovery factors are inconsistent with the suggestion that FA patients are recovery deficient. The data indicate that at least some FA strains are capable of LDR recovery, and imply that these patients would probably have a clinical benefit from fractionated or low dose-rate total body irradiation.

Cell Survival↗
PubMed1992

Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity.

The success of radiotherapy depends on the total radiation dose, which is limited by the tolerance of surrounding normal tissues. Since there is substantial variation among patients in normal-tissue radiosensitivity, we have tested the hypothesis that in-vitro cellular radiosensitivity is correlated with in-vitro normal-tissue responses. We exposed skin fibroblast cell lines from six radiation-treated patients to various doses of radiation and measured the proportions surviving. There was a strong relation between fibroblast sensitivity in vitro and normal-tissue reactions, especially acute effects. Assessment of radiosensitivity could lead to improved tumour cure rates by enabling radiation doses to be tailored to the individual.

Breast Neoplasms↗
PubMed1992

The prognostic value of DNA content measured by image cytometry in soft tissue sarcomas.

Nuclear DNA content in soft tissue sarcoma was determined by image cytometry using archival, paraffin embedded material. In a retrospective study 138 specimens of 81 patients have been analysed. The ploidy level was correlated to clinical outcome regarding tumor volume and histological grading, the most important prognostic parameters. Ploidy has a significant prognostic value and correlates well with histological grading (p = 0.01). Tumour volume was found to be an independent prognostic factor (p = greater than 0.1) [chi 2 test]. The DNA content of the primary tumour and of multiple local recurrences remained similar.

Adolescent↗
PubMed1991

[Therapy of multiple myeloma by allogeneic bone marrow transplantation].

Multiple myeloma of IgG kappa type was diagnosed in a 42-year-old man with bone pains, dyspnoea on exertion and increasing drowsiness. Six chemotherapy cycles extending over 14 weeks and consisting of 15 mg/m2 melphalan intravenously on day 1 and 60 mg/m2 prednisolone orally on days 1-4 produced a partial remission. As the HLA-identical sister of the patient was willing to donate bone marrow, an allogeneic marrow transplantation was planned. After 7 days' conditioning treatment (hyperfractionated whole-body irradiation with 12 Gy, chemotherapy with 70 mg/m2 melphalan and 60 mg/kg cyclophosphamide), 4.2 x 10(8) nucleated cells of donor marrow were infused per kg recipient body-weight through a central venous catheter. Despite prophylaxis with short-course methotrexate and cyclosporin, an acute graft-versus-host reaction of grade II-III occurred on day 26, though it settled almost completely after treatment with daily 2 mg/kg prednisone and monoclonal interleukin-2 receptor antibodies (B-B10, daily 10 mg). On day 100 after the marrow transplantation, marrow puncture showed the picture of complete remission with normal regeneration of haemopoietic cells. Allogeneic marrow transplantation may therefore be considered as a new and promising mode of treatment for younger patients with multiple myelomas.

Acute Disease↗
PubMed1989

Insurmountable beta receptor blockade by ICI 147,798 in rabbits.

In rabbits, the characteristics of cardiac beta-1 receptor blockade produced by ICI 147,798, a novel beta receptor blocking agent with diuretic properties, were evaluated and compared with those of propranolol. In conscious rabbits, i.v. injections of 0.31, 1.0 and 3.1 mg/kg of ICI 147,798 and 1.0 mg/kg of propranolol caused significant bradycardia. ICI 147,798 produced a dose-dependent shift to the right of the dose-response (chronotropic) curve of isoproterenol with suppression of the maximal tachycardia, an effect characteristic of insurmountable beta receptor blockade. Propranolol also produced a shift to the right of the dose-response curve of isoproterenol without affecting the maximal tachycardia. ICI 147,798-induced antagonism was specific for beta adrenoceptors as it failed to modify the effects of acetylcholine, angiotensin II, phenylephrine, adenosine, histamine and prostaglandin E2 on mean arterial pressure and heart rate. In rabbits with prior autonomic blockade, ICI 147,798, like propranolol, failed to inhibit the positive chronotropic effects of theophylline which are mediated by postreceptor mechanisms. In reserpinized rabbits, ICI 147,798 was found to have no intrinsic sympathomimetic activity. Unlike the effects of propranolol, which were attenuated by first-pass through the hepatic vascular bed, the effects of ICI 147,798 were unaffected suggesting an absence of first-pass metabolism. The effects of propranolol (1.0 mg/kg i.v.) were not detectable at 24 hr after injection, whereas significant beta receptor blocking activity was still present at 24 hr after ICI 147,798 (1.0 mg/kg i.v.). The results suggest that ICI 147,798 is a specific, long-acting, insurmountable beta-1 receptor blocking agent without intrinsic sympathomimetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗