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Biomedical subjects

A Dritschilo

Publications and source records attributed to A Dritschilo.

At least 127 records · Page 7Linked to original sources

Radiosensitization of human fibroblasts by 3-aminobenzamide: an inhibitor of poly(ADP-ribosylation).

The poly(ADP-ribose) synthetase inhibitor 3-aminobenzamide (3AB) increases the radiosensitivity of normal human fibroblasts in tissue culture in a dose-dependent manner at noncytotoxic concentrations. 3AB was also found to inhibit the repair of potentially lethal damage as well as the recovery occurring when radiation was delivered as fractionated vs single exposures. However, repair as measured by an increased survival when radiation is delivered at low dose rate compared to high dose rate was not effected by 3AB administration.

Benzamides↗

Measurement of blood flow through surgical anastomosis using the radioactive microsphere technique.

Two different radioactive microspheres (141Ce and 46Sc) were used to measure blood flow to an area of the large intestine in dogs before and after a surgical resection was performed with surgical staples. The healing of an anastomosis is theoretically related to the blood flow to the anastomotic site. Blood flow studies were conducted in three dogs using this technique. The average blood flow preoperatively was 0.558 mL/minute per gram and 1.04 mL/minute per gram postoperatively. The standard deviation was +/- 0.16. These results indicate a statistically significant (P less than .05) increase in blood flow at the anastomotic site six days after anastomosis when compared with the blood flow to the same area before any surgical procedures.

Animals↗

[Initial results in the mammographic diagnosis of recurrences following tylectomy and irradiation].

In several institutions lumpectomy combined with in- and external radiation is being used as an alternative to the modified radical mastectomy. The mammographic detection of local recurrence is complicated by the fact that the changes after radiation and surgery interfere with primary and secondary signs of malignancy. The authors report about their preliminary experience in the radiographic detection of recurrence in these patients.

Breast Neoplasms↗

Response of human fibroblasts to low dose rate gamma irradiation.

Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to gamma radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase in the terminal slope (D0) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.

Ataxia Telangiectasia↗

Measure of blood flow by the multiple radioactive microsphere technique in radiated gastrointestinal tissue.

In this study, two different radioactive microspheres were used to measure blood flow of an irradiated segment of small intestine in four dogs before, and 12 days after, irradiation with 2000 rad. The technique and implications are discussed. Using multiple radioactive microspheres, the study demonstrated an increased blood flow in irradiated tissues twelve days after a single dose of 2000 rad. There was also an increase in blood flow to adjoining nonradiated segments of intestine in the same animal. These observations may be of significance in clinical applications of radiation therapy and surgery. A major surgical concern is the impaired healing of irradiated tissue in the immediate postradiation period. The mechanism of this has generally implicated decreases in the perfusion of irradiated tissue. No decrease in blood flow was shown in this study, suggesting that other mechanisms, e.g., stem cell depletion, should be considered. Further studies of this type are recommended to increase understanding of the blood flow in irradiated tissue.

Animals↗

Sonography of the breast: findings following conservative surgery and irradiation for early carcinoma.

A dedicated-waterpath ultrasound breast scanner was used to examine 25 patients who had early breast carcinomas that were treated with conservative surgery (lumpectomy, tylectomy) and irradiation. Sonographic findings following such therapy included asymmetry in breast size, skin deformity and thickening, nipple retraction and/or distortion, and thickening of the Cooper ligaments. Disruption of the central echogenic cone of fibroglandular tissue, and general architectural distortion and internal asymmetry when the breasts were compared were also present in a large percentage of patients. The single case of recurrent carcinoma revealed only enlargement of the treated breast when the breasts were compared; no other pertinent sonographic findings were evident. The significance of sonography in the evaluation of the breast after conservative therapy for carcinoma remains to be determined. However, many of the sonographic findings in this group of patients are similar to those of the secondary signs of carcinoma. Knowledge of the sonographic changes of the conservatively treated breast therefore assumes importance for the sonographer.

Brachytherapy↗

Clinical trial of the effect of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) (NSC 296961) on the toxicity of cyclophosphamide.

S-2-(3-Aminopropylamino)-ethylphosphorothioic acid (WR-2721) is reported to protect normal tissues from the effects of ionizing radiation and possibly alkylating agents as well. The present trial assessed the ability of this compound to modify the clinical toxicity of cyclophosphamide. Patients with advanced cancer first received a dose of 1000 mg/m2 cyclophosphamide intravenously and were observed for toxicity, principally myelosuppression. After the nadir in white blood cell counts and/or platelets had been documented and adequate recovery had occurred, a second course of cyclophosphamide was given, this time preceded by WR-2721 30 min earlier. In this fashion, each patient served as his own control. Doses of WR-2721 ranging from 250 to 1000 mg/m2 were tested. A total of 13 evaluable courses of WR-2721 were given with cyclophosphamide. In no instance did the prior administration of WR-2721 diminish the bone marrow toxicity of cyclophosphamide alone. At the end of the trial two additional patients received the WR-2721 in a split dose, one-half prior to the cyclophosphamide and one-half 6 hr later; again there was no protection. The side effects of WR-2721 included nausea, vomiting, hypotension, sneezing, and swelling of the tongue. We conclude that WR-2721 is a potentially toxic compound that produces no amelioration of cyclophosphamide toxicity in the doses used. Because of the severity of the side effects of WR-2721, principally hypotension, the trial was terminated after 1000 mg/m2 WR-2721 failed to protect against the toxicity of 1000 mg/m2 cyclophosphamide.

Adult↗

The value of "routine tests" in the staging evaluation of gynecologic malignancies: a cost effectiveness analysis.

The value of tests employed in the clinical staging of patients with carcinomas of the cervix and endometrium has been examined in a retrospective review of 739 consecutive patients seen at Tufts-New England Medical Center. The yield of positive results of the barium enema (0%) and proctosigmoidoscopy (0.8%) in carcinoma of the cervix suggests that some of these studies may be omitted in asymptomatic patients with early disease on pelvic examinations. Similarly, for carcinoma of the endometrium, the yields from barium enema (0.9%) cytoscopy (0.9%) and proctosigmoidoscopy (0.6) are low. It is concluded that optimal patient care (with respect to morbidity and costs) may be provided without routinely performing these studies in staging asymptomatic patients with cervical and endometrial carcinomas.

Barium Sulfate↗

Potentiation of radiation injury by interferon.

Interferon (IFN) is being tested clinically in the treatment of a wide range of human malignancies. Patients undergoing cancer treatment may require radiotherapy in conjunction with IFN administration. This study examined the effect of purified preparations of IFN on the radiation response of mouse Swiss 3T3 cells in culture. Cells were exposed to 10 U/ml of mouse IFN or human IFN 2 hours prior to radiation. The IFN was left in the medium for the duration of the experiment. Marked enhancement of radiation response was observed in the presence of mouse IFN as compared to human IFN or no IFN treatment. The difference in radiation response was due to a reduction in the shoulder portion of the survival curve with no change in the slope of the exponential portion. Since human IFN was inactive in these experiments, the data suggest that the potentiation of radiation damage is specific for mouse IFN. The reduction in the shoulder in the presence of mouse IFN suggests the inhibition of the ability of cells to accumulate sublethal radiation injury. Split-dose experiments to test for sublethal radiation injury repair capacity failed to demonstrate an IFN effect. We conclude from these studies that IFN potentiates radiation injury. In clinical situations in which IFN is used, careful monitoring of dosage and timing of irradiation may be required to avoid excessive tissue damage. Moreover, treatment strategies may be directed to time radiation and IFN to obtain an improved therapeutic ratio.

Animals↗

Utility of interferons in clinical radiotherapy.

Interferons are being tested in the treatment of a wide range of malignancies. Clinical experience has indicated that interferons may have relatively few side effects compared to other commonly used antineoplastic agents. In addition, they have shown activity as radiation response modifiers in various experimental systems. Thus, as natural biological compounds, interferons may prove to be superior to other radiation response modifiers now on clinical trial in radiotherapy. In this paper radiation-interferon interactions are reviewed and the evaluation of the usefulness of interferons as an adjuvant in radiotherapy is discussed.

Animals↗

Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes.

To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients.

Dose-Response Relationship, Radiation↗

Tolerance of brain to multiple courses of radiation therapy. I. Clinical experiences.

Patients with recurrent brain tumours years after initial radiation therapy pose a difficult management decision. Should retreatment be performed with irradiation, which carries a risk of necrosis, or should retreatment be with less effective agents but without unnecessary risks? We present the results of retreatment of 32 patients at the Mayo Clinic and the Joint Center for Radiation Therapy. Clinical improvement was seen in all retreated patients. The median survival was 36 months after completion of the second course of irradiation. Eight patients (25%) were alive, free of disease, from 22 to 315 months after retreatment. Of the 11 patients alive at the time of analysis, eight were experiencing productive lives and three were suffering from severe neurological damage. Evidence of brain necrosis was observed in two patients (6%); however, only 10/21 patients underwent autopsy examinations. Reirradiation of patients with late recurrences of brain tumours may offer neurological improvement and prolonged survival without excessive risk of necrosis.

Adolescent↗

Radiation and chemical injury in the bone marrow.

Hematopoietic system toxicity is a major limiting factor in the use of aggressive combined modality therapy in the treatment of malignant disease. In this review, the known drug-x-ray interactions using tissue culture systems are extended to the bone marrow compartment. Two hypotheses prevail for late bone marrow failure: (1) stromal damage to the vasculature with subsequent fibrosis and (2) irreversible stem cell depletion in the irradiated site. Clinical extensions of the experimental data for bone marrow kinetics in the animal model have not proven successful to date. The future strategies for therapy of malignancies in which both radiation and chemotherapy are employed may require dose modification or treatment planning to limit bone marrow toxicity.

Animals↗

A FORTRAN program for the optimization of radiotherapy treatment planning using the complication probability factor (CPF).

The complication probability factor (CPF) is an objective function, based directly on radiobiological principles and clinical data, for the optimization of radiotherapy treatment planning; it measures the likelihood that a given radiation dose distribution will lead to serious complications in the patient as a result of damage to healthy tissue. A computerized search can be made for that treatment plan which delivers an acceptable tumoricidal dose, yet minimizes the CPF as averaged over the total volume of healthy tissue irradiated. The CPF FORTRAN program, run on a PDP 11/55 in conjunction with a commercially available radiotherapy treatment planning package, is described in detail.

Computers↗