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Wolfgang Dörr

Publications and source records attributed to Wolfgang Dörr.

At least 19 recordsLinked to original sources
PubMed2007

Effects of systemic or topical administration of sodium selenite on early radiation effects in mouse oral mucosa.

PURPOSE: To quantify the effect of sodium selenite (selenium) on radiation-induced oral mucositis (mouse) after subcutaneous or topical administration. MATERIAL AND METHODS: Mucosal ulceration of the lower epithelium of mouse tongue was analyzed. Selenium (5 mug) was applied subcutaneously (s.c.) or locally, 60 min or 30 min prior to irradiation, respectively. In combination with single-dose irradiation, a single selenium application was given. With daily fractionated irradiation (3 Gy/fraction) for 1 week (days 0-4), selenium was administered at all 5 days of irradiation. With ten fractions over 2 weeks, selenium was applied in week 1, week 2, or both. All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. RESULTS: In a single-dose control experiment, the ED(50) (dose after which ulcer induction is expected in 50% of the mice) was 12.9 +/- 1.6 Gy. Selenium increased the ED(50) to 17.7 +/- 2.6 Gy (s.c.; p = 0.0003) and 16.3 +/- 3.0 Gy (local; p = 0.0104). The ED(50) for test irradiation after 5 x 3 Gy was 7.4 +/- 2.2 Gy. Subcutaneous administration of selenium resulted in an ED(50) of 11.5 +/- 2.0 Gy (p = 0.0015), local application yielded an ED(50) of 10.0 +/- 2.1 Gy (p = 0.0284). The ED(50) for test irradiation after 10 x 3 Gy/2 weeks was 8.0 +/- 1.7 Gy. Subcutaneous or local administration of selenium in week 1 yielded a significant increase in ED(50) to 10.5 +/- 1.0 Gy (p = 0.0069) and 10.7 +/- 1.0 Gy (p = 0.0039), respectively. By clear contrast, selenium administration in week 2 had no significant effect. Administration in both weeks resulted in an ED(50) of 9.1 +/- 2.0 Gy (s.c.; p = 0.2747) and 9.7 +/- 1.4 Gy (local; p = 0.0541). CONCLUSION: Administration of sodium selenite during clinically relevant fractionated irradiation protocols has a significant effect during the initial treatment phase, i.e., week 1 in the mouse. Therefore, in clinical radiotherapy, the latent time to manifestation of confluent mucositis may be significantly prolonged, and hence the burden for the patient clearly reduced by selenium.

Administration, Topical↗
PubMed2006

Effect of post-exposure administration of keratinocyte growth factor (Palifermin) on radiation effects in oral mucosa in mice.

Oral mucositis is a severe component of the acute radiation syndrome. The present study was initiated to determine the potential of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) to ameliorate oral mucositis in a mouse model after a single radiation exposure. A 3 x 3 mm(2 )area in the center of the lower tongue surface of C3H/Neu mice was irradiated with graded single doses of 25 kV X-rays. Acute mucosal ulceration was used as the quantal end-point for dose-response analyses. Palifermin was applied at a dose of 15 mg/kg on days 0, 1, 2, 3, 4 or 5. For comparison, three injections of 5 or 15 mg/kg on days 1-3 were administered. The ED(50) (dose at which ulceration is expected in 50% of the animals) for irradiation alone was 11.6 +/- 1.2 Gy. Mean latent time was 9.4 +/- 0.2 days; mean ulcer duration was 2.8 +/- 0.2 days. Single injections of rHuKGF did not result in a significant increase in isoeffective radiation doses at any of the administration days. However, the latent time to ulceration was significantly shortened by 1-2 days in all protocols. Repeated administration of rHuKGF (15 mg/kg) resulted a significant increase in ED50 to 16.8 +/- 4.0 Gy (P = 0.0047); the mean latent time was 4.4 +/- 0.9 days. Three injections of 5 mg/kg of Palifermin on days 1-3 yielded an ED50 of 19.4 +/- 1.7 Gy. In this protocol, mean latent time was 6.6 +/- 0.6 days. In conclusion, Palifermin has a potential to reduce the mucositis burden in patients after a single radiation exposure. Repeated injections are required. For three injections, a negative dose-effect of rHuKGF was observed. The optimum dose, number and timing of the administration require further investigation.

Animals↗
PubMed2006

RBE of 25 kV X-rays for the survival and induction of micronuclei in the human mammary epithelial cell line MCF-12A.

The broad application of low energy X-rays below about 50 keV in radiation therapy and diagnostics and especially in mammography substantiates the precise determination of their relative biological effectiveness (RBE). A quality factor of 1 is stated for photons of all energies in the International Commission on Radiological Protection Recommendations. However, the RBE of low-energy X-rays compared to high-energy photons was found to be dependent on photon energy, cell line and endpoints studied, hence varying from less than one up to about four. In the present study, the human mammary epithelial cell line MCF-12A has been chosen due to the implementation of the results in the estimation of risk from mammography procedures. The RBE of 25 kV X-rays (W anode, 0.3 mm Al filter) relative to 200 kV X-rays (W anode, 0.5 mm Cu filter) was determined for clonogenic survival in the dose range 1-10 Gy and micronuclei (MN) induction in the range 0.5-3.5 Gy. The RBE for clonogenic survival was found to be significantly higher than 1 for surviving fractions in the range 0.005<S<0.2. The RBE decreased with increasing survival, with an RBE0.1 at 10% survival of 1.13+/-0.03. The effectiveness of soft X-rays for MN induction was found to be 1.40+/-0.07 for the fraction of binuclear cells (BNC) with MN and 1.44+/-0.17 for the number of MN per BNC. In contrast, the RBE determined from the number of MN per MN-bearing BNC was found to be 1.08+/-0.32. This indicates that the effectiveness of 25 kV X-rays results from an increase in the number of damaged cells, which, however, do not have higher number of MN per cell.

Cell Line↗
PubMed2006

Radiation-induced damage to mouse urothelial barrier.

PURPOSE: To determine changes of the urothelial barrier during the early as well as late radiation response in mouse urinary bladder. MATERIALS AND METHODS: Groups of mice were irradiated with a single dose of 20Gy and sacrificed between days 0 and 360. Urothelial cell numbers were counted, and the fraction of urothelium with a positive immunohistochemical signal for uroplakin-III (UP-III) on the luminal surface of the bladder was defined. Also, cytoplasmic UP-III staining signal in urothelium was quantified using an arbitrary score (0-3). RESULTS: Irradiation resulted in a significant decrease in the number of superficial umbrella cells during the early response phase (days 0-31) as well as during the initial late radiation reaction (days 90, 120). Progressive loss of the UP-III layer on the bladder luminal surface correlated with the decrease in the number of umbrella cells (p=0.002). Also, increased cytoplasmic staining of UP-III in the urothelium was seen after irradiation, correlating negatively with the reduction of the superficial UP-III layer (p<0.0001). CONCLUSION: Irradiation of the urinary bladder results in morphological impairment of the urothelial barrier that is associated with a loss of superficial umbrella cells during the early as well as initial late radiation response phase.

Animals↗
PubMed2006

A prospective study on radiation-induced changes in hearing function.

PURPOSE: To quantitate changes in hearing function after radiotherapy for head-and-neck tumors. METHODS AND MATERIALS: At the Department of Radiotherapy and Radiation Oncology, 32 patients were irradiated for head-and-neck tumors. Three-dimensional treatment planning was applied. Total tumor doses were 30.0-77.6 Gy, local doses to the inner ear (n = 64) ranged from 1.7 to 64.3 Gy. Audiometry was performed before the onset of radiotherapy (RT), at a tumor dose of 40 Gy or at the end of palliative treatment, at the end of curative RT, and 2-6 months post-RT. Assays applied were frequency-specific threshold measurements for air and bone conduction, measurements according to Weber and Rinne, tympanometry and assessment of the stapedius reflex. RESULTS: Age and prior disease significantly decreased, whereas previous or concurrent alcohol consumption significantly increased hearing ability. A significant reduction in hearing ability during RT was found for high frequencies (at 40 Gy) and low frequencies (at end of RT), which persisted after RT. No differences were observed for air or bone conduction. None of the other assays displayed time- or dose-dependent changes. Dose-effect analyses revealed an ED50 (dose at which a 50% incidence is expected) for significant changes in hearing thresholds (15 dB) in the range of 20-25 Gy, with large confidence limits. CONCLUSIONS: Radiation effects on hearing ability were confined to threshold audiogram values, which started during the treatment without reversibility during 6 months postradiotherapy.

Adult↗
PubMed2006

Early intestinal changes following abdominal radiotherapy comparison of endpoints.

PURPOSE: To compare tests for intestinal function with clinical scores after abdominal irradiation. PATIENTS AND METHODS: At the Department of Radiotherapy, Erfurt, Germany, intestinal changes were studied in 91 patients receiving abdominal radiotherapy between 1992 and 1996. Conventional fractionation (1.8-2 Gy per fraction, total doses 30.6-62.5 Gy) was applied. Before and at weekly intervals during radiotherapy, the clinical response was scored according to RTOG/EORTC for the upper and lower gastrointestinal (GI) tract. Resorption tests for vitamin B(12) and D-xylose were performed before the onset and immediately after treatment. RESULTS: The clinical response displayed a well-defined dose-effect relationship with grade 1 effects in 5% and 50% of the patients at about 10 Gy and 50 Gy, respectively. For grade 2 reactions, 5%- and 50%-effective doses were 20-30 Gy and 60-80 Gy. Effects in the upper and lower GI tract were highly correlated. Changes in body weight did not show a correlation with other clinical symptoms. Changes in resorption also displayed a significant dose effect. However, no correlation was found with the clinical symptoms in the individual patient. CONCLUSION: In the present study, the clinical manifestation of intestinal side effects according to RTOG/EORTC criteria was reflected by neither the vitamin B(12) nor by the D-xylose resorption test. Hence, these tests cannot be regarded as useful for objective quantitation of intestinal radiation injury.

Abdomen↗
PubMed2006

Amelioration of early radiation effects in oral mucosa (mouse) by intravenous or subcutaneous administration of amifostine.

PURPOSE: To quantify the reduction of radiation-induced oral mucositis by amifostine as a function of administration route. MATERIAL AND METHODS: Mucosal ulceration of lower mouse tongue epithelium was analyzed. Amifostine was injected at 1.8 mg/injection subcutaneously (s.c.) or intravenously (i.v.), 45 min or 10 min prior to irradiation. With single-dose irradiation, a single amifostine injection was given. During daily fractionated irradiation (5 x 3 Gy) for 1 week, amifostine was administered s.c. or i.v. twice (days 0, 3), or s.c. on all irradiation days (days 0-4). With ten fractions over 2 weeks, five s.c. injections were given in week 1 (days 0-4) or week 2 (days 7-11), or both. Two i.v. injections were given either in week 1 (days 0, 3) or week 2 (days 7, 10). All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. RESULTS: In a single-dose control experiment, the ED(50) (dose after which ulcer induction is expected in 50% of the mice) was 11.7 +/- 1.4 Gy. Intravenous application of amifostine increased the ED(50) to 14.0 +/- 1.4 Gy (p = 0.024), while s.c. administration had no significant effect. The ED(50) for test irradiation after 5 x 3 Gy was 5.8 +/- 1.4 Gy. Two s.c. or i.v. amifostine injections yielded ED(50) values of 7.2 +/- 1.1 Gy (p = 0.0984) or 7.6 +/- 1.2 Gy (p = 0.0334); five s.c. injections increased the ED(50) to 8.2 +/- 0.9 Gy (p = 0.0039). The ED(50) after 10 x 3 Gy/2 weeks was 6.6 +/- 1.8 Gy. Subcutaneous or intravenous administration of amifostine in week 1 yielded a significant increase in ED(50) to 9.4 +/- 2.5 Gy (p = 0.0099) and 10.0 +/- 2.2 Gy (p = 0.0014). By contrast, amifostine administration in week 2 had no significant effect. Administration in weeks 1 and 2 resulted in an ED(50) of 10.8 +/- 3.6 Gy (p = 0.0053). CONCLUSION: Amifostine during daily fractionated irradiation is effective only if administered in the initial treatment phase, i.e., week 1 in the mouse. The differences in the effect in weeks 1 and 2 suggest mechanisms of action other than radical scavenging.

Amifostine↗
PubMed2006

Effects of selenium on radiation responses of tumor cells and tissue.

PURPOSE: This review summarizes information about modulation of radiation effects in tumor cells and tissues by selenium. RESULTS: In vitro, clonogenic survival to ionizing radiation was found to be reduced, depending on selenite concentration and duration of administration, by a factor of 1.5-4.4. In experimental animal tumors, a positive effect of selenium was observed with chemotherapy. The only available study in combination with irradiation did not show any benefit of selenium with clinically relevant radiotherapy protocols in R1H tumors. None of the investigations demonstrated a negative effect on the tumor response to therapy. CONCLUSION: The only study with fractionated irradiation was performed in a rat R1H tumor, which does not show accelerated repopulation. Therefore, interaction of selenium with such repopulation processes, potentially resulting in increased tumor tolerance, could not be detected. For local administration of normal tissues with selenium, potential tumor effects may be of less importance, but these may be relevant for systemic administration. Therefore, well-designed studies with relevant tumor models and endpoints, and with clinically relevant fractionation protocols are recommended.

Animals↗
PubMed2006

Radiation induced late damage to the barrier function of small blood vessels in mouse bladder.

PURPOSE: We identified changes in vascular barrier function in relation to collagen deposition during the late radiation response of mouse bladders. In this study albumin leakage was assessed as a marker of blood vessel barrier disruption. MATERIALS AND METHODS: Female C3H/Neu mice were irradiated with a single dose of 20 Gy and sacrificed for (immuno) histological studies after 90, 120, 180, 240 and 360 days. The fractional area of subepithelial tissue with extravascular albumin signal was defined. Moreover, the amount of collagen was determined after Masson's trichrome staining on an arbitrary score of 0 to 3. RESULTS: Subepithelial albumin infiltration due to leakage from the blood vessels was seen in irradiated animals during the entire late phase. It was most pronounced at days 120 and 180 after treatment (vs control p <0.0001). Similarly an increase in collagen deposition in the bladder wall was seen during the whole late radiation phase but with increasing values toward the end of the experiment (day 360 vs control p <0.0001). CONCLUSIONS: Irradiation of the bladder results in late damage to the barrier function of small subepithelial blood vessels, causing pronounced albumin leakage at the early steps of the chronic radiation reaction, clearly preceding excessive collagen deposition in the bladder wall. Current data suggest a vascular component in the development of late radiation induced changes in the bladder.

Animals↗
PubMed2006

Radiation induced inflammatory changes in the mouse bladder: the role of cyclooxygenase-2.

PURPOSE: We assessed the effect of irradiation on COX-2 expression in blood vessels of the mouse bladder wall during the early and late radiation response phases. Vasodilatation was quantified as an additional marker of inflammation related to COX-2 activity. MATERIALS AND METHODS: Female C3H/Neu mice were irradiated with a single dose of 20 Gy. The intensity of the COX-2 immunohistochemical staining signal was assessed using an arbitrary semiquantitative score of 0 to 3. To evaluate vasodilatation the percent of the bladder wall covered by the lumen of the blood vessels, depicted as vascular area, was determined. RESULTS: Constitutive COX-2 expression was found in the tunica intima and media of bladder blood vessels. During the early response significant biphasic changes were detected in the COX-2 staining signal as well as in the vascular area with peak values on days 4 and 16 after irradiation. A significant association was found between vascular area and COX-2 expression in blood vessels during the early radiation response (p <0.0001). No changes in COX-2 expression were observed during the late phase, that is between days 90 and 360 after irradiation. Minor vasodilatation seen during the late phase did not correlate with COX-2 activity. CONCLUSIONS: Irradiation resulted in pronounced COX-2 dependent inflammatory changes in the bladder wall during the early but not during the late radiation reaction. Therefore, a potential effect of COX-2 inhibition on early radiation side effects in the bladder can be proposed.

Animals↗
PubMed2005

Effects of radiotherapy on olfactory function.

BACKGROUND AND PURPOSE: Changes in olfactory function have been reported in patients receiving significant doses of radiation to the olfactory epithelium. Aim of this study was to investigate severity and time course of changes in olfactory function in patients irradiated for tumours of the head and neck region. MATERIAL AND METHODS: Forty-four patients receiving radiotherapy (RT) for tumours in the area of the head and neck participated (16 women, 28 men; age 11-81 y; mean 55 y). Olfactory function was measured before and bi-weekly during RT for 6 weeks. A subgroup (25 patients) was followed for 12 months. Patients were divided into two groups according to the dose to the olfactory epithelium. Twenty-two patients ('OLF group') had radiation doses to the olfactory epithelium between 23.7 and 79.5 Gy (median 62.2 Gy). In the 22 patients of the 'non-OLF group' the dose applied to the olfactory epithelium was significantly lower (2.9-11.1 Gy, median 5.9 Gy). Total tumour dose (30-76.8 Gy), age, sex distribution, and baseline chemosensory function were not significantly different between groups. Testing was performed for odour identification, odour discrimination, and olfactory thresholds. RESULTS: Odour discrimination, but not odour identification or odour threshold, was significantly decreased 2-6 weeks after begin of therapy in the OLF group. In addition, a significant effect of the radiation dose was observed for odour discrimination. More than 6 months after therapy, OLF group patients had significantly lower odour identification scores compared to the non-OLF group. CONCLUSION: As indicated through the non-significant change of olfactory thresholds, the olfactory epithelium is relatively resistant against effects of radiation. It is hypothesized that RT has additional effects on the olfactory bulb/orbitofrontal cortex responsible for the observed changes of suprathreshold olfactory function.

Adolescent↗
PubMed2005

Reduction of radiochemotherapy-induced early oral mucositis by recombinant human keratinocyte growth factor (palifermin): experimental studies in mice.

PURPOSE: To study the effect of recombinant human keratinocyte growth factor (rHuKGF or palifermin) on oral mucositis induced by radiochemotherapy in a mouse model. METHODS AND MATERIALS: Cis-diamminedichloroplatinum (cisplatin) and/or 5-fluorouracil were given before single dose irradiation, combined with palifermin before or after the treatment, or both. Daily fractionated irradiation for 2 weeks was followed by graded test doses. With additional chemotherapy in Week 1, palifermin was given before radiotherapy and at the end of the first week, or additionally at the end of Week 2. Radiochemotherapy in Week 2 was combined with palifermin at the end of Weeks 1 and 2, Weeks 1, 2, and 3, or additionally before radiotherapy. Ulceration of mouse tongue mucosa was analyzed as the endpoint. RESULTS: The dose associated with ulcer induction in 50% of the mice (ED(50)) for single-dose irradiation was 11.5 +/- 0.7 Gy. Palifermin increased the ED(50) to about 19 Gy in all protocols tested. Similar values were observed when chemotherapy was added before irradiation. With fractionated irradiation, palifermin increased the ED(50) for test irradiation from 5.7 +/- 1.5 Gy to 12-15 Gy, depending on the administration protocol. With chemotherapy in Week 1, two palifermin injections had no significant effect, but a third injection increased the ED(50) to 13 Gy. With chemotherapy in Week 2, all palifermin protocols resulted in ED(50) values of 13-14 Gy. CONCLUSION: A marked increase in oral mucosal radiation tolerance by palifermin was found, which was preserved in combinations with chemotherapy using cisplatin and/or 5-fluorouracil.

Animals↗
PubMed2005

Effects of keratinocyte growth factor (palifermin) administration protocols on oral mucositis (mouse) induced by fractionated irradiation.

BACKGROUND AND PURPOSE: Aim of this study was to assess the impact of the administration protocol of palifermin on amelioration of oral mucositis after fractionated irradiation. MATERIALS AND METHODS: Mouse tongue ulceration was analysed as the clinically relevant endpoint. Daily fractionated irradiation (5 x 3 Gy/week, days 0 to +4, +7 to +11, with a weekend gap on days +5 and +6) was followed by graded test doses on day +14, i.e. after a second weekend gap. Palifermin (5 mg/kg) was injected subcutaneously. In the first series of experiments, the effect of three daily injections (days -3, -2 and -1) was compared with a single administration either on day -2 or -1; all animals received a further injection on day +4. In the second series, a single or three injections were given in the weekend gap between fractionated irradiation (days +5 to +6), with an additional administration on day +11. In a final protocol, single weekly injections of palifermin were given either on days -3, +4 and +11, days +4, +11 and +18, or on days -3, +4, +11 and +18. RESULTS: The ED50 (dose after which ulcer induction is expected in 50% of the mice) to single dose irradiation was 11.5+/-0.7 Gy. The ED50 for test irradiation after 10 x 3 Gy was 5.7+/-1.6 Gy. Palifermin administration before the start of fractionated irradiation and on day +4 increased the ED50 to 10-12 Gy, administration over the first weekend and on day +11 to 11-15 Gy. Administration over three consecutive weekends, starting on day -3 or day +4, increased the ED50 to 13.0+/-0.1 and 14.9+/-0.3 Gy. Single weekly KGF administrations over four weekends, including the weekend prior to and after completion of radiotherapy, showed no further increase in ED50. CONCLUSIONS: A single palifermin injection during the weekend gap before or during fractionated irradiation is as effective as three applications. Onset of the palifermin treatment during the first weekend gap between fractionated irradiation is more effective than during the weekend before radiotherapy. The effect of palifermin on oral mucositis can be increased by three weekly injections, while four injections do not yield a further increase in ED50.

Animals↗
PubMed2005

Radiation induced lung reactions in breast cancer therapy. Modulating factors and consequential effects.

BACKGROUND AND PURPOSE: Radiologic reactions in lung, usually subclinical, are a frequent side effect of radiotherapy for breast cancer. This study was initiated to identify effects of age and tamoxifen on radiation pneumonitis and consequent fibrosis. PATIENTS AND METHODS: Retrospectively, 451 patients irradiated postoperatively between 1992 and 1995 at the Department of Radiotherapy of Carl-Thiem-Klinikum (Cottbus, Germany) were analyzed. The median age was 58 years. After mastectomy (n = 296), 25 x 2.0 Gy were applied; breast-conserving surgery (n = 155) was followed by 30 x 2.0 Gy. In 221 patients, adjuvant tamoxifen was given. Follow-up included thorax radiography after 15 weeks and 1 year. In patients with reversible observations in standard chest radiography from 15 weeks to 1 year, CT or high-resolution (HR-)CT scans were analyzed after 4-7 years. RESULTS: Clinical symptoms of pneumonitis were seen in 25 patients (5.5%), all with radiologic changes. Early radiologic changes were detected in 134 patients (29.7%). Age (> 58 years; p = 0.0127) and tamoxifen (p = 0.0001) were found as significant parameters of early pneumopathy. Late radiologic changes were seen in 94/425 patients (22.1%), all after a positive early reaction (p = 0.001). CONCLUSION: A low incidence of clinically symptomatic pneumonitis was observed, while the vast majority of patients presented with early radiologic changes. Higher age and tamoxifen treatment significantly increased the incidence of early pneumopathy. Local fibrotic responses must be expected in all patients with early reactions, indicating a strong consequential component of the late reaction.

Adult↗
PubMed2005

Reduction of oral mucositis by palifermin (rHuKGF): dose-effect of rHuKGF.

PURPOSE: The aim of the present study was to determine the dose effect of palifermin (recombinant human keratinocyte growth factor, rHuKGF) for reduction of the response of oral mucosa to fractionated radiotherapy in a mouse model. MATERIAL AND METHODS: Ulceration (confluent mucositis) of mouse tongue epithelium was analysed as the clinically relevant endpoint. Palifermin at doses from 1 - 30 mg/kg was administered before the onset (day -3), at the end of the first (day +4) or the second week of irradiation (day +11) with 5 x 3 Gy/week. Each protocol was terminated by graded radiation test (top-up) doses. In a further experiment, optimally effective doses were given on days -3 and +4, or -3, +4 and +11. RESULTS: Single dose irradiation of mouse mucosa yielded an ED50 (dose inducing ulcer in 50% of the mice) of 10.7 +/- 1.0 Gy. With fractionated irradiation for 1 week an ED50 for test irradiation (day +7) of 5.1 +/- 1.9 Gy was observed. After 2 weeks (day +14), the ED50 was 7.3 +/- 1.9 Gy. Palifermin significantly increased the ED50 values in all protocols tested. Maximally effective doses for single injections were 15.0 mg/kg (day -3, +11) or 22.5 mg/kg (day +4), which yielded ED50 values of 12.1 +/- 1.3 Gy, 13.7 +/- 1.5 Gy and 14.4 +/- 1.3 Gy, respectively. Higher palifermin doses did not further increase the ED50. Repeated injections on days -3 and +4 did not increase the ED50 beyond the value obtained with injections on day +4 alone. An additional injection on day +11 increased the ED50 further to 15.1 +/- 0.1 Gy. CONCLUSIONS: A significant palifermin dose-effect was seen at doses below 15 mg/kg. However, a significant increase in oral mucosal radiation tolerance by palifermin over untreated control tissue was observed already with low doses of 1 mg/kg. This indicates that in clinical studies with palifermin, the dose of the growth factor may be of minor relevance over a wide dose range.

Animals↗
PubMed2004

Changes in the effect of dose fractionation during daily fractionated irradiation: studies in mouse oral mucosa.

PURPOSE: The aim of the present study was to quantify the fractionation effect in mouse oral mucosa during a daily fractionated protocol. METHODS AND MATERIALS: Irradiation of the snout of C3H mice was performed with 5 x 3 Gy/week. In the first experiment, graded test doses were applied to the lower tongue on Days 4, 7, 11, 14, or 18. Subsequently, a split-dose experiment was performed on the same days with 1, 2, 3, or 5 fractions (graded doses). RESULTS: The ED50 (dose expected to induce ulcer in 50% of the mice) for untreated mucosa was 10.7 +/- 1.0 Gy. Fractionated irradiation with 5 x 3 Gy/week yielded an ED50 for top-up irradiation of 6.5 +/- 1.8 Gy, 6.8 +/- 0.9 Gy, 5.3 +/- 2.1 Gy, 7.3 +/- 1.9 Gy, and 7.5 +/- 1.3 Gy on Days 4, 7, 11, 14, and 18. The ED50 values for split-dose irradiation on Day 4 increased from 6.24 +/- 1.48 Gy (1 fraction) to 9.96 +/- 1.47 Gy (5 fractions). Similarly, an increase from 4.04 +/- 1.56 Gy to 10.07 +/- 1.9 Gy was found on Day 11, and from 5.84 +/- 2.37 Gy to 9.81 +/- 2.29 Gy on Day 18. After the weekend breaks, values between 6.22 +/- 1.60 Gy (1 fraction) and 4.7 +/- 1.95 Gy (5 fractions) were observed on Day 7, and between 5.62 +/- 1.36 Gy and 5.98 +/- 2.01 Gy on Day 14. CONCLUSIONS: These results indicate that the fractionation effect in oral mucosa is consistently lost over the weekends and restored during the treatment weeks.

Animals↗
PubMed2004

[Early loss of teeth after treatment for childhood leukemia].

BACKGROUND: Only few reports of effects of radiotherapy in childhood on the dental apparatus are available in the literature. The basis for early loss of teeth appears to be a reduction of the root surface area after radiation exposure. These effects in the periodontium are a consequence of combined radiochemotherapy usually applied for treatment of childhood neoplasia. Chemotherapy alone also results in changes of periodontal development. CASE REPORT: A 33-year-old patient is reported, who, at the age of 11 years, received high-dose chemotherapy and radiotherapy of neuroaxis and cranium for acute lymphatic leukemia with relapse. The patient consulted the Implant Section of the Department of Oral and Maxillofacial Surgery because of severe dental changes and tooth loss despite adequate dental care and oral hygiene. Radiation doses given to the superior maxilla and mandible at the age of 11 were estimated to be in the range of 8-25 Gy. CONCLUSION: Intense, life-long dental care and follow-up of patients cured from malignant disease in childhood must hence be postulated in order to minimize dental treatment sequelae by supportive measures, but also to initiate timely adequate dental and prosthetic management.

Adult↗