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Biomedical subjects

I Turesson

Publications and source records attributed to I Turesson.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1993

Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia.

Several studies indicate that interferon (IFN) treatment, intensive chemotherapy and autologous bone marrow transplantation (ABMT) effectively reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients < or = 55 years, we have combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a status of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After six months of treatment, Ph-analysis was performed. Patients with Ph-positive cells in bone marrow then received 1-3 courses of intensive chemotherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1993, 97 patients were registered in the study. Six months of IFN+HU reduced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotransplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month after ABMT due to interstitial pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The effects of hyperbaric oxygenation on bone-titanium implant interface strength with and without preceding irradiation.

This study investigated the influence of a single 15-Gy dose of irradiation on the capacity of titanium screws to integrate in irradiated bone tissue. The biomechanical force necessary to unscrew the titanium implants 8 weeks after placement was 54% lower for implants in irradiated bone tissue compared to implants in nonirradiated bone tissue. Postirradiation use of hyperbaric oxygen treatment at 2.8 ATA (2-hour daily treatments for 21 days) increased the biomechanical force necessary to unscrew the titanium implants by 44% in irradiated bone and by 22% in nonirradiated bone.

Animals↗
PubMed1993

Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia.

We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.

Adolescent↗
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

Evidence for individual differences in the radiosensitivity of human skin.

Previously published clinical data have been re-analysed to investigate individual differences in the radiosensitivity of human skin. In the clinical studies, acute and late skin reactions were recorded for 254 breast cancer patients receiving radiotherapy to the internal mammary nodes following simple or modified radical mastectomy. Each patient was treated bilaterally with different fractionation schedules to the right and left fields. Patients were assigned prospectively to 10 different treatment groups of 11-35 patients each, with all patients in a group receiving the same pair of fractionation schedules to the right and left fields. In the present study, correlations between the skin reactions in the two treatment fields per patient were investigated. For each of three different endpoints--peak reflectance measure of erythema, peak acute skin reaction score, and a ranking measure of the progression rate of telangiectasia--significant correlations were found between the levels of skin injury to the right and left treatment fields of the patients in most treatment groups. Although there were correlations between the absorbed doses in the right and left fields, statistical analyses indicated that dose effects were not sufficient to explain fully the patient-to-patient differences in skin response. Thus, these data provide evidence for the existence of individual differences in the radiation response of human skin, both for early and late effects. Whether these differences are dominated by heterogeneity in intrinsic cell radiosensitivity or by other factors has yet to be determined. However, there was no clear evidence of a correlation between the acute and late endpoints, suggesting that the individual differences in radiosensitivity are not dominated by a common genetic component expressed equally in all cells.

Breast Neoplasms↗
PubMed1992

Bolus therapy with mitoxantrone and vincristine in combination with high-dose prednisone (NOP-bolus) in resistant multiple myeloma. Nordic Myeloma Study Group (NMSG).

In a phase II study, 58 patients with resistant multiple myeloma (MM) were treated with a combination chemotherapy (NOP-bolus regimen) consisting of mitoxantrone (16 mg/m2 for the first 25 patients and 12 mg/m2 for the subsequent 33), vincristine (2 mg), both as bolus injections on day 1 and prednisone (250 mg/d on d 1-4 and 17-20). In patients greater than 70 years of age, the mitoxantrone dose was reduced to 12 mg/m2 or 8 mg/m2, respectively. The treatment was repeated every 4 weeks. A response (greater than 50% reduction in M component) was obtained in 26% of the patients and a minor response (clinical improvement but less than 50% reduction in M component) in another 21%. Median response duration was 27 wk and median survival for all patients was 25 wk. There were no differences in response rate or duration between patients receiving the high or low mitoxantrone dose, but patients in the low-dose group had fewer serious infections.

Adult↗
PubMed1991

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↗
PubMed1991

Interferon therapy during the plateau phase of multiple myeloma: an update of the Swedish study.

A multicentre clinical trial was carried out in order to evaluate the effect of interferon (IFN) in patients with multiple myeloma. Patients (n = 120) who had shown response to conventional intermittent melphalan-prednisone induction therapy, and achieved a plateau phase, were randomized at that point to receive either interferon alfa-2b in a dose of 5 million units (MU) three times per week or no therapy. This report presents the results of an interim analysis, performed when the patients had been followed for a median of 20 months. The duration of the plateau phase was significantly longer in the IFN arm (59 weeks), compared to the no therapy arm (26 weeks). A total of 34 deaths have occurred, 13 in the IFN arm and 21 in the no therapy arm. In spite of the high median age of the patients studied (70 years), most patients were able to tolerate a full or only slightly reduced IFN dose.

Aged↗
PubMed1991

Primary radiotherapy for glottic laryngeal carcinoma stage I and II. A retrospective study with special regard to failure patterns.

A retrospective study has been made of 302 patients with vocal cord carcinoma stage I and II treated between 1963 and 1983, emphasizing treatment failure patterns. The primary treatment modalities were radiotherapy for 266 patients and surgery for 36 patients. The minimum follow-up was 4 years. After primary radiotherapy there were 63 local recurrences and 7 neck lymph node recurrences, all appearing outside the target volume. The actuarial loco-regional recurrence-free rates at 5 years were 78% for T1, 76% for T2a (normal cord mobility) and 60% for T2b (impaired cord mobility) tumors. The actuarial regional lymph node recurrence-free rates at 5 years were 99, 100 and 93% for T1, T2a and T2b tumors respectively. The actuarial corrected survivals at 5 years were 95, 96 and 79% for T1, T2a and T2b tumors with primary radiotherapy and salvage surgery for recurrence. Salvage surgery was less successful in T2b compared to T1 and T2a tumors. In conclusion, after primary radiotherapy with salvage surgery the loco-regional control rate was high and very similar for glottic cancer T1 and T2a but less satisfactory for T2b tumors. Regional lymph node metastases were not a large problem in any of the subgroups. More effective radiotherapy with higher dose levels or an altered fractionation might increase the local control rate for T2 tumors with impaired cord mobility.

Adult↗
PubMed1991

Changes in the basal cell density in pig skin after single radiation doses with different dose rates.

Radiation-induced changes in the basal cell density (BCD) and the labelling index (LI) in the epidermis of pig skin were used to compare the effect of high and low dose rate irradiation. Single doses of 6, 12 and 24 Gy were applied at 1.5 and 0.02 Gy/min with two equal 137Cs sources. Punch biopsies were taken daily for 40 days. The linear BCD was calculated from histological sections. The LI was determined by an in vitro H3-thymidine labelling technique. We found a degenerative phase in the basal cell layer with a linear cell loss of 2% per day, independent of the dose and dose rate. The time and level of the minimum BCD were dose and dose rate dependent. The LI data indicated an increased proliferation rate after a 25% reduction in BCD, i.e. before the nadir was reached. From the BCD data an iso-effective dose factor of 1.8 was estimated for the two dose rates used, which was consistent with that determined from macroscopic scoring. The BCD can be used as an endpoint for comparison of different radiotherapy modalities and gives, together with the LI, further information on the time-course of the proliferation changes in the tissue.

Animals↗
PubMed1990

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↗
PubMed1990

Time-dose factors in radiotherapy: a review of the human data.

The values for alpha/beta (fractionation sensitivity, or recovery capacity) for early and late reactions in human normal tissues are consistent with results from experimental animals. For breast treatments direct analysis indicates that for early reactions alpha/beta is in the range 7 to 11 Gy, while for late effects it is in the range 2 to 4 Gy. Data on recovery kinetics in human tissues is limited but these indicate that recovery may be slower in humans than in rodents. For early skin reactions the halftime of recovery is about 1 h, while for late telangiectasia it is more than 3 h. alpha/beta values for human tumors are more variable than in rodents: some are high (head and neck, lung, skin, cervix) and similar to those for early reacting normal tissues. Others are low, including melanomas, where alpha/beta was estimated at 0.6 (-1.1, 2.5) Gy, and liposarcomas, where direct analysis of cases surveyed from the literature suggested that alpha/beta = 0.4 (-1.4, 5.4) Gy. Repopulation kinetics is faster in the mucosa of the soft palate and faucial pillars (1.8 Gy/day) than in head and neck tumors (up to 1 Gy/day).

Animals↗
PubMed1990

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation.

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterised by alpha/beta values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5 Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2 Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal-tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore necessary to verify further the presented scaling between fraction size and dose rate.

Animals↗