Immune responses in four patients with Bloom syndrome.
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Adolescent↗
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Results for “Telangiectasis”
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Cerebellar hemorrhage associated with capillary telangiectasia and venous angioma: a case report.
We report a case of recurrent cerebellar hemorrhage from a capillary telangiectasia associated with a venous angioma. Based on the findings in this case and a review of the literature, we concluded that the hemorrhage was from the telangiectasia and not from the associated venous angioma. The association between capillary telangiectasias and cavernous malformations and the established association of the latter with venous angiomas are reviewed. This case illustrates the complex interrelationship between these histologically distinct malformations and its influence on their potential to hemorrhage.
Adult↗
Bladder toxicity due to cyclophosphamide. Experimental induction and treatment.
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Animals↗
Radiation therapy of penile cancer.
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Adult↗
Nifedipine and telangiectasias.
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Humans↗
Sister-chromatid exchange induction by metabolically activated retinoids in human diploid fibroblast cultures.
13-cis-Retinoic acid, retinyl-mthyl-ether, retinyl-phenyl-ether, retinyl-thio-ether and axerophthene each induced dose-dependent sister-chromatid exchanges (SCE) in human diploid fibroblasts. The functional relationship between retinoid concentration and SCE rate was similar in each of the 5 retinoids tested. The relationship reached a plateau at concentrations exceeding 8 micrograms/ml. alpha-Naphthoflavone (ANF), an inhibitor of P448-dependent mono-oxygenase, prevented the retinoid-induced increase of the SCE rate, but had no inhibitory effect in the presence of 4-nitroquinoline-1-oxide, an ultimate carcinogen. ANF did not reduce the spontaneously increased SCE rate in fibroblasts of patients with Bloom's syndrome. Retinoids failed to induce SCE in V79 Chinese hamster cells, which lack mono-oxygenase. Thus, we conclude that the retinoid-induced SCE rate increases independently of structural changes in the molecular side-chain ad that a metabolic activation of retinoids is required for SCE induction by cytochrome P448-dependent mono-oxygenase.
Abnormalities, Multiple↗
Analysis of late effects data using dose-response models: application to human skin telangiectasia data.
The clinical data for skin telangiectasia from previous prospective studies at the Radiotherapy Department in Gothenborg are reanalyzed using two dose-response models - the general formulations of the well known linear-quadratic (LQ) and NSD isoeffect models. Assuming that essentially no repopulation appears in the vessel endothelium for overall treatment times up to 68 days, the alpha/beta-value of 2.75 Gy is obtained for the LQ-model. The time factor is found not to be significant by the NSD-model for the treatment times used (less than or equal to 68 days) at the 95% level of confidence. The estimated value of the exponent of the number of fractions, A, is 0.321. The obtained values of the alpha/beta-ratio and of A show high sensitivity of the vessel endothelium to changes in the dose per fraction. Our results show that within the interval of the number of fractions used, 10-35 fractions, the NSD-model gives predictions comparable to those of the LQ-model. For number of fractions smaller than 5, a high discrepancy occurs between the two models, the NSD-model predicting higher values of the isoeffective total dose. The maximal deviation between the models appears for N = 1; 25% and 27% at the 5 and 50% level of effect, respectively. For large N and especially at low effect probabilities the NSD-model again predicts higher isoeffective doses: the dose predicted by the NSD-model for a regimen with 40 fractions and for 5% probability of telangiectasia is 7.5%, higher than that predicted by the LQ-model. Based on the estimated dose-response curves, considering the telangiectasia as the decisive late tissue effect, the requirement for the combined uncertainty in the dose delivery is estimated between 3 and 4.5%.
Dose-Response Relationship, Radiation↗
The progression rate of late radiation effects in normal tissue and its impact on dose-response relationships.
The progression of late skin telangiectasia after radiotherapy has been studied prospectively in patients for 1, 2 and 5 fractions per week and various dose levels. The degree of telangiectasia was scored on an arbitrary scale. Skin telangiectasia was found to be a continuously progressing endpoint both in the individual patient and in terms of the number of patients who achieved a certain degree of damage. The rate of progression was dose-dependent. Dose-response analysis were performed at 3, 5 and 9 years follow-up for various endpoints: telangiectasia score greater than or equal to 1, score greater than or equal to 2 and score greater than or equal to 3. Iso-effective doses (ED50S) for score greater than or equal to 1 at 3 years, score greater than or equal to 2 at 5 years and score greater than or equal to 3 at 9 years were very similar. In an iso-effect analysis it is therefore worthwhile and time-saving to include the minimal detectable damage in the endpoint (e.g. using score greater than or equal to 1), even if this mild damage is of no clinical significance, and the dose in the endpoint (e.g. using score greater than or equal to 1), even if this mild damage is of no clinical significance, and the dose response become somewhat less steep than for more severe damage. The fact that the progression rate is dose-dependent has impact on dose-response analysis. Dose-response analysis for score greater than or equal to 3 at various follow-up times showed a very flat curve at 3 years compared to 5 and 9 years. The steepness of the dose-response curves was similar at 5 and 9 years. A minimum follow-up of 5 years is therefore necessary for reliable estimation of the late complication rates in a comparison of two dosage schedules using this endpoint. The implication of the continuous progression of telangiectasia is that the dose-response curves are shifted to the left with follow-up. The ED50 is dramatically reduced between 3 and 5 years. The ED50 is also significantly reduced between 5 and 9 years' follow-up, in spite of no change in the steepness of the dose-response curve during this period. Consequently, the time of response is the most fundamental parameter in any iso-effect analysis with progressive endpoints and the late complication rates always have to be specified at a fixed time of follow-up.
Dose-Response Relationship, Radiation↗
Latent-time estimation for late cutaneous and subcutaneous radiation reactions in a single-follow-up clinical study.
In this paper, an analysis of the fractionation sensitivity and latency of subcutaneous fibrosis and telangiectasia in a clinical series is presented. The series comprised 163 breast cancer patients who, from 1978 to 1980, received postmastectomy irradiation delivered in 12 fractions, with 2 fractions per week over a period of 37 to 46 days. The total dose was specified either as a maximum absorbed dose of 51.36 Gy, or as a minimum target dose of 36.6 Gy specified at the level of the mid-axilla. From 1981 to 1982, 66 patients received a minimum target dose of 40.92 Gy in 22 fractions administered as 5 fractions per week over 29 to 35 days. Late complications were evaluated prospectively at a single follow-up after a minimum observation time of 16 months. The clinical endpoints analyzed were subcutaneous fibrosis and telangiectasia. The data were analyzed using a mixture model that incorporates both dose fractionation and latency effects. The length of time to expression of 90% of the ultimate frequency of moderate or severe complications was 3.2 years (95% confidence limits (c.l.) [2.3,3.9] years) and 4.7 years (95% c.l. [4.0,4.8] years) for fibrosis and telangiectasia respectively, while the alpha/beta ratios were 1.9 Gy (95% c.l. [0.8,3.0] Gy) and 3.7 Gy (95% c.l. [0.2,47] Gy), respectively. For subcutaneous fibrosis the time to reach a specific grade of reaction increases with the grade, thus being consistent with the clinical impression that fibrosis progresses in severity over time. If latency and censoring effects are unaccounted for, serious underestimates of the ultimate frequency of radiation complications in groups with incomplete follow-up may result.
Breast Neoplasms↗
Repair capacity and kinetics of human skin during fractionated radiotherapy: erythema, desquamation, and telangiectasia after 3 and 5 year's follow-up.
Prospective clinical fractionation studies on acute and late reactions in skin have been going on since 1972 at the Radiotherapy Department in Gothenburg. The clinical assay consisted of breast cancer patients irradiated postoperatively to the internal mammary nodes from unilateral or bilateral fields exposed to various dose schedules. 750 fields in 450 patients have been analysed. Schedules with 1, 2 or 5 fractions per week and 2 or 3 fractions per day were evaluated with erythema, desquamation and telangiectasia as endpoints. For some schedules a dose-response relationship was established in a limited dose range, but often there was only one dose group per schedule. These data are suited to analysis by the method of direct analysis of quantal response. This was used in the present analysis, along with the linear quadratic (LQ) model and its generalization, the incomplete repair (IR) model. The repair capacity was similar for erythema and desquamation, with alpha/beta ratios between 7.5 and 11.2 Gy. Unexpectedly, there was more significant time factor during radiotherapy courses up to 6 weeks for erythema and desquamation, but the repair capacity was changed after 4 weeks for both endpoints, and alpha/beta increased to between 18.3 and 34.5 Gy. The repair capacity for late telangiectasia differed significantly from that for erythema and desquamation, with alpha/beta values between 2.8 and 4.3 Gy. There was a significant time factor for telangiectasia with characteristic doubling time of about 16 days, when an exponential function for time was used. Concerning the repair kinetics in skin, there were insufficient data to obtain precise estimates, but there was a suggestion of two components of repair. This was inferred from higher-than-predicted recovery with 15-min intervals, when the data were fitted with the monoexponential model. The monoexponential fit gave t1/2 between 1.1 and 1.3 h for acute effects and 3.5 h for late effects. Recovery after 15-min fractionation intervals, if it resulted from a fast repair component, would be consistent with a half-time of 0.3-0.4 h. The time factor and the relative long half-time for repair for late effects have important implications for multiple-fraction-per-day treatment, and imply that interfraction intervals of 4 h or less, as commonly used, will be insufficient. Instead, intervals of 6 h or longer are recommended. Using accelerated fractionation with a significant reduction in overall treatment time a dose reduction is still necessary to take into account the time factor for late effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Breast Neoplasms↗
Fractionation sensitivity and latency of telangiectasia after postmastectomy radiotherapy: a graded-response analysis.
Latent time and dose-fractionation characteristics for telangiectasia are estimated in a series of 401 treatment fields in 335 patients treated with postoperative radiotherapy at the Department of Oncology in Gothenburg. To this end an extension of the mixture model to include graded-response data is proposed. In addition, a method for non-parametric estimation of median latent time is presented. Severity of telangiectasia was scored on an arbitrary 4-point scale ranging from no reaction to severe telangiectasia. The estimated number of tissue-rescuing units for the three grades of telangiectasia increased with increasing grade of reaction. The average length of time to expression of 90% of the ultimately expected damage was estimated at 6.6 years, 9.1 years and 14.8 years for grades greater than or equal to 1, greater than or equal to 2 and equal to 3, respectively. Thus increasing grades of telangiectasia occurred at progressively longer follow-up times. A statistically significant correlation was found between the level of tissue injury and the latent period. Patients with a high probability of ultimately expressing a specific grade of telangiectasia had a shorter latent period the higher the level of injury.
Breast Neoplasms↗
Characteristics of dose-response relationships for late radiation effects: an analysis of skin telangiectasia and of head and neck morbidity.
The dose-response characteristics were analysed for late skin telangiectasia in patients for 1, 2 and 5 fractions per week and 3 to 4 dose levels per schedule. Altogether 286 fields were used. Skin telangiectasia was scored on an arbitrary scale and dose-response analysis was performed at 10 year's follow-up for various degrees of telangiectasia, score greater than or equal to 1 to greater than or equal to 4. The following parameters were determined for each schedule and the equivalent single dose-response curves for each endpoint using probit analysis: the ED50, the absolute steepness, measured as the probit width, K, the relative steepness, K/ED50, and the normalised effect gradient, gamma 50. The inverse radiosensitivity, Doeff or Do, was estimated using the Poisson and LQ-models for tissue response. The alpha/beta value was found to be independent of the degree of telangiectasia used as endpoint. The absolute steepness of the dose-incidence curve increased with increasing dose per fraction and was correlated to the degree of damage. The relative steepness was independent of the dose per fraction when the dose-response curve was generated by a fixed dose per fraction, and was less than if generated by a fixed number of fractions. The relative steepness increased with higher degree of damage. Doeff decreased with increasing dose per fraction, and also with higher degree of telangiectasia. The highest steepness determined for telangiectasia score greater than or equal to 4 (partially confluent or more) at 10 years corresponded to K = 0.8 Gy, K/ED50 = 5%, gamma 50 = 7 and Do = 0.7 Gy. The dose-response characteristics found for late skin telangiectasia score greater than or equal to 2 to greater than or equal to 4 were consistent with those determined for necrosis and fatal complications 5 years after radiotherapy to head and neck tumours in our department.
Breast Neoplasms↗
Relationship between early and late normal-tissue injury after postmastectomy radiotherapy.
Factors of importance in the development of telangiectasia were investigated in a series of 229 patients who, between 1978 and 1982, received postmastectomy radiotherapy with two different fractionation schedules. Patients who developed moist desquamation had a statistically significantly increased risk of developing telangiectasia after a specific course of radiotherapy. As an example the estimated incidence of severe telangiectasia after 44 Gy in 22 fractions increases from 27% to 49% in patients who developed grade greater than or equal to 2 moist desquamation as an early radiation reaction. A reanalysis of the Aarhus data with telangiectasia as the endpoint gave an alpha/beta ratio at 2.8 Gy (95% c.l. (-0.1, 8.1) Gy) and a relative biological effectiveness (RBE) of high energy electrons relative to 8 MV photons at 0.89 (95% c.l. (0.85, 0.93)). Patients age or the occurrence of severe erythema did not predispose to telangiectasia. A similar predisposition after moist desquamation was not seen for subcutaneous fibrosis. The RBE of high energy electrons relative to 8 MV photons for this endpoint was estimated at 0.88 (95% c.l. (0.86, 0.91].
Breast Neoplasms↗
Moist desquamation and telangiectasia in patients treated by postmastectomy irradiation.
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Breast Neoplasms↗
Does the interval between fractions matter in the range of 4-8 h in radiotherapy? A study of acute and late human skin reactions.
Accelerated radiotherapy has the potential to increase local control of rapidly growing tumours. To determine the necessary time interval for complete repair of sublethal damage in normal tissue in a clinical situation, we have compared the acute and late skin reactions with 8 and 24 h between fractions, using the same dose per fraction and total dose. Forty-nine breast cancer patients participated in this study, and received bilateral parasternal irradiation to 50 Gy with 2 Gy per fraction as part of their adjuvant postoperative radiotherapy. The time interval between daily fractions was always 8 h on the left field and 24 h on the right, and the total treatment time was 2.5 and 5 weeks, respectively. The acute endpoint was erythema, measured by reflectance spectrophotometry and an acute reaction score for erythema and desquamation. The late endpoint was telangiectasia, scored on an arbitrary scale. The results have also been compared with those in a previously treated group of patients with 4 and 24 h between fractions. The degree of acute reactions was decreased with an 8-h interval compared with 24 h between fractions with the peak acute score as endpoint; no difference was seen with the peak reflectance measurements. The maximal expression occurs approximately 1 week earlier with the accelerated schedule, possibly as a consequence of the reduction of the treatment time. The pattern of the acute reaction for 8 h between fractions is similar to that for 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Relationship between the in vitro radiosensitivity of skin fibroblasts and the expression of subcutaneous fibrosis, telangiectasia, and skin erythema after radiotherapy.
OBJECTIVE: To investigate if the occurrence of subcutaneous fibrosis after radiotherapy in an unselected group of breast cancer patients is related to cellular radiosensitivity of skin fibroblasts as measured in a clonogenic assay. MATERIALS AND METHODS: An in vitro colony-forming assay of normal fibroblast radiosensitivity was applied to primary skin biopsies from 31 breast cancer patients who received post-mastectomy radiotherapy with large doses per fraction (2.7-3.9 Gy) more than 10 years earlier. Three clinical normal-tissue endpoints were assessed. Two late endpoints, subcutaneous fibrosis and telangiectasia, were evaluated in three treatment fields by a single experienced clinician. In addition, skin erythema had been assessed at the end of treatment by members of the staff and junior staff. From previous analyses of normal tissue response, individual clinical radiosensitivity could be assessed as "excess risk' of each of the three reactions. This was defined as the difference between the actual observed response in the patient and the expected response estimated from individual treatment characteristics in a linear quadratic (LQ) mixture model and, for the two late endpoints, with correction for the follow-up time. This clinical radioresponsiveness was compared with the in vitro radiosensitivity of the skin fibroblasts. To this end, the fractions of colony-forming cells after graded single doses were fitted by an LQ survival curve using non-linear regression from which the surviving fraction at 3.5 Gy (SF3.5) was estimated. Assessment at 3.5 Gy was chosen to reflect the fraction size during clinical radiotherapy. RESULTS: A statistically significant variability of in vitro radiosensitivity between patients could be detected for both SF2 (P = 0.0095) and SF3.5 (P = 0.0008). A significant correlation was observed between SF3.5 and excess risk of fibrosis (rs = -0.46, P = 0.009) while no association was found between fibroblast radiosensitivity and either the occurrence of severe skin telangiectasia or the acute endpoint skin erythema. CONCLUSION: These results suggest that variability in the occurrence of subcutaneous fibrosis, but not telangiectasia or erythema, after radiotherapy is partly accounted for by differences in cellular radiosensitivity of normal skin fibroblasts.
Adult↗
Pulsed dye laser treatment of telangiectases with and without subtherapeutic sclerotherapy. Clinical and histologic examination in the rabbit ear vein model.
The treatment of leg telangiectases with the carbon dioxide or argon laser results in a low success rate and an unacceptable risk of scarring. Sclerotherapy is effective; however, pigmentation and telangiectatic matting induced by extravasation of RBCs and excessive posttreatment inflammation are common. We conducted a clinical and histologic study of therapy with the 585 nm pulsed dye laser alone and in combination with subtherapeutic sclerotherapy in the rabbit ear vein model. The pulsed dye laser alone was effective when 10 joule/cm2 was used. In combination with immediate injection of the sclerosant, effective endosclerosis occurred with all tested laser energies (8 to 10 joule/cm2).
Animals↗
Clinical association of autoantibodies to fibrillarin with diffuse scleroderma and disseminated telangiectasia.
Circulating autoantibodies against a variety of nuclear and nucleolar antigens are characteristic serologic findings in systemic scleroderma. Some of these antibodies correlate with clinical subsets of the disease. We describe three patients with systemic scleroderma and high autoantibody titers against U3 ribonucleoprotein-associated fibrillarin, a recently identified 34 kD nucleolar protein. These patients showed a progressive course with multiple organ and diffuse skin involvement with disseminated telangiectasia.
Adult↗