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Biomedical subjects

L Dewit

Publications and source records attributed to L Dewit.

At least 37 records · Page 2Linked to original sources
PubMed1987

Early and late damage in the mouse rectum after irradiation and cis-diamminedichloroplatinum(II).

The effects of radiation and cis-diamminedichloroplatinum(II) (c-DDP) in the mouse rectum were assessed using two functional endpoints (anal discharge/diarrhoea and body weight changes), one lethal endpoint (obstructive rectal stenosis) and a microscopic endpoint (semiquantitative histological scoring). After irradiation, anal discharge, diarrhoea and lethal rectal stenosis were found to be the result of submucosal fibrosis with a secondary mucosal ulcer due to mechanical damage by the faeces. Weight loss at both early and late times after irradiation seemed to be related to epithelial cellular depletion. c-DDP, when given in combination with X-rays, did not enhance the incidence of late anal discharge, diarrhoea or rectal stenosis. Using an arbitrary semiquantitative scale for measuring the degree and extent of late rectal injury, c-DDP sometimes seemed to postpone the expression of radiation damage in the rectum. This effect, however, might also be the result only of interexperimental variation. An increase by c-DDP in the early body weight loss after irradiation was also observed which could be explained by an additive effect in the rectal epithelium.

Animals↗
PubMed1987

Late effects in the mouse small intestine after a clinically relevant multifractionated radiation treatment.

Late radiation effects were investigated in the mouse small intestine after a daily fractionated radiation treatment. Mice were given 14 X 3 Gy in 2 weeks over a partial abdominal irradiation field. There was evidence for late injury in the intestinal epithelium, the submucosa, and the subserosa. Late damage in the epithelium was shown histologically by a reduced crypt number and villus atrophy at 3 and 6 months but not at 24 h after the end of treatment. The reduction in crypt number was significant in the ileum at 3 and 6 months after irradiation: 100 +/- 4 and 98 +/- 5 (SEM) per circumference, respectively, versus 132 +/- 3 and 146 +/- 6 in age-matched controls (P less than 0.01, t test). The mitotic activity in the crypts of the irradiated animals was significantly increased at all investigated times, suggesting a prolonged but insufficient compensatory response to maintain the mucosal integrity. The repercussion on intestinal epithelial function was, at least in part, reflected by a progressively reduced body weight gain up to 5 g at 3 months after treatment. The ability of the surviving crypt stem cells to form microcolonies after irradiation, however, was not impaired. Evidence for injury in the submucosa was provided from macroscopic and histological examination. Macroscopically, at 6 months after treatment, narrowed and rigid bowel segments surrounded by fibrotic adhesions were observed, causing partial intestinal obstruction. In addition, sometimes focal areas of hemorrhage and infarction in small bowel segments were present. Histologically, diffuse and pronounced submucosal edema without increased fibrosis was seen, together with markedly dilated small blood vessels in focal areas of macroscopic intestinal infarction. The intestinal perfusion, as assessed by 86Rb extraction, was significantly but transiently reduced at 3 months after irradiation. These data suggest mainly late effects in the small intestine after this daily fractionated irradiation treatment. The reduced number of epithelial cells and the submucosal edema are possibly mediated by radiation injury in the intestinal microvasculature.

Animals↗
PubMed1987

Modification by cis-diamminedichloroplatinum (II) of the radiation dose-response curve for intestinal crypt cells in mice.

The effect of cis-diamminedichloroplatinum (II) (c-DDP) on the shape of the radiation dose-response curve for mouse duodenal crypt cells was investigated. A priming X-ray dose was followed 18 h later by graded test doses (single doses or five equal fractions at 3-h intervals) with or without c-DDP. Curves were fitted by a linear quadratic (LQ) relationship. The drug modified the dose-response curve by enhancing both the alpha and the beta terms. Repair kinetics were analyzed in split-dose experiments. c-DDP caused a minor, nonsignificant decrease in the rate of repair after irradiation. The survival ratio after split-dose irradiation, when the same X-ray doses were given, was actually slightly increased by the drug. This paradoxical effect can be explained by the fact that c-DDP mainly increased the beta term in the LQ relationship. There was no significant increase in crypt cell survival when split-drug doses were given alone at increasing intervals, suggesting no cellular repair after c-DDP treatment. The data are discussed in the light of the recently proposed "lethal and potentially lethal" (LPL) unified repair model of Curtis.

Animals↗
PubMed1986

Malignant schwannoma with a rhabdomyoblastic component, a so-called triton tumor. A clinicopathologic study.

Triton tumors, malignant schwannomas with a rhabdomyoblastic component, are rare. This article reports the clinical course, therapeutic approach, and histopathologic aspects of three cases. Immunoperoxidase staining for the Schwann's cell marker S-100 protein and for the skeletal muscle proteins desmin, myosin, and myoglobin proved to be useful for diagnosis. The clinical histories of 24 previously reported cases are analyzed, and the therapeutic possibilities are discussed.

Adult↗
PubMed1986

The effects of cis-diamminedichloroplatinum (II) and radiation on the proliferation kinetics of mouse duodenal crypt cells and on a partially synchronized crypt cell population.

The effects of c-DDP and radiation, given alone or in combination, on the proliferation kinetics of mouse duodenal crypt cells were investigated by repeated labelling with 3H-thymidine. Crypt cells surviving a single dose of X-rays or c-DDP alone, appeared to proliferate faster than untreated controls. When both agents were given in combination, the proliferation rate of surviving crypt cells was markedly reduced as a result of a significant increase in the DNA synthesis time. The influence of the proliferation rate of crypt cells on the effects of c-DDP and X rays was analyzed using the crypt microcolony assay. Mice were given single doses or 2 fractions of X rays with 2 different time intervals (4 and 48 hours) either alone or in combination with c-DDP given 30 minutes before the second fraction. The lethal effect of the drug was approximately the same in cells that were in accelerated proliferation after the first irradiation as in unstimulated cells. A tendency for less cell killing by the drug was observed 3.5 hours after the first irradiation. To rule out cell age dependent effects of c-DDP, crypt cell survival was assessed after irradiation was given alone or in combination with the drug on a partially synchronized crypt cell population, obtained by repeated injections of hydroxyurea. A predominant lethal effect of c-DDP was found in cells in the late G1-phase. These findings are important to consider both from a mechanistic point of view as for clinical application of the agents.

Animals↗
PubMed1986

Radiosensitization by cisplatin of RIF1 tumour cells in vitro.

The ability of cis-diamminedichloroplatinum (II) (c-DDP) to enhance radiation-induced cell killing was tested on oxic RIF1 tumour cells in monolayer culture. Marked radiosensitization of the survivors of a 1 h drug treatment was found with all c-DDP doses tested, with enhancement ratios increasing from 1.2 to 2.2 with increasing drug dose. Isobologram analyses showed that the interactions of c-DDP with X-rays were supra-additive. To test whether part of the enhancement was due to a selection of subpopulations, the diploid and tetraploid RIF1 cells, which normally coexist in culture, were separated by unit gravity velocity sedimentation, and by developing diploid and tetraploid clones. Both methods showed that there was little difference in either drug sensitivity or radiation sensitivity between diploid and tetraploid cells. DNA histograms obtained by flow cytometry showed little or no cycle progression during the 1 h drug treatment. These data indicate that the radiosensitization was not the result of the drug exposure leaving cells in a radiosensitive phase. The observed radiosensitization, therefore, appears to have resulted from a true drug/X-ray interaction.

Cell Cycle↗
PubMed1985

Influence of cis-diamminedichloroplatinum (II) on mouse duodenal crypt stem cell survival after multifraction X ray treatment.

The mechanism of interaction of cis-platinum and X rays was investigated in mouse duodenal crypts using the microcolony assay. Mice were exposed to 1, 2, 5, 10, or 15 fractions of X rays, either alone or preceded by a single i.p. injection of cis-platinum, 8 mg/kg, one-half hour before the first fraction. In all fractionation regimens, cisplatinum caused a shift of the X ray survival curve for crypt cells towards lower doses. The vertical distances between the survival curves after X rays and those in combination with cis-platinum were about the same, giving a mean value of 0.89 +/- 0.12 log10 cells. After cis-platinum treatment alone, a crypt cell survival curve was established in the high dose range. The estimated cell kill by 8 mg/kg of cis-platinum, obtained by extrapolation of this curve, was 1 log10 cell number. These data imply independent cell killing mechanisms for cis-platinum and X rays. However, even after correction for cell kill by the drug, cis-platinum tended to inhibit slightly sublethal damage repair after X rays. This was supported by linear quadratic analyses, in which the alpha/beta value after combined treatment was found to be slightly higher than after X rays alone (20 +/- 4 Gy versus 13.0 +/- 1.7 Gy).

Animals↗
PubMed1985

Concurrent cis-diamminedichloroplatinum(II) and radiation treatment for melanoma metastases: a pilot study.

Thirteen evaluable patients with 25 melanoma metastases were treated by radiotherapy, 6 X 6 Gy in 6 weeks (one fraction per week) and concomitant weekly cis-platinum infusion, 20, 30 or 40 mg/m2. Acute systemic toxicity was mainly gastro-intestinal, grade 1 to 3 (WHO-criteria) in all patients, and bone marrow toxicity grade 1-2 in four patients, not distinctly drug-dose related. Acute local skin reaction did not appear to be enhanced. Symptomatic bowel spasms occurred in 2 of 4 patients treated on an iliac-inguinal field, both having received a high drug dose (40 mg/m2). Late severe and disabling subcutaneous fibrosis was encountered in 2 of 8 patients with a minimal follow-up of 6 months, suggesting that cis-platinum concurrently given, enhances late radiation damage to connective tissue, although possible contribution of other factors cannot be ruled out. Initial response was observed in nine patients, but sustained local control (longer than 6 months) was obtained in only 3 of 8 patients. Concentrations of total platinum, measured in tumour at the time of first irradiation, approach the minimal concentration assumed to be required for radiosensitizing effects of cis-platinum.

Anemia↗
PubMed1985

Dose and time effects of cis-diamminedichloroplatinum(II) and radiation on mouse duodenal crypts.

The effect of cis-platinum and radiation on mouse duodenal crypts was assessed using the microcolony assay. The diameters of regenerating crypts were measured at various times after X-rays and cis-platinum given either alone or in combination. It appeared that the appropriate time of assay after any of these treatments was 88 h. When 10 mg/kg of cis-platinum was administered 24 h before, 0.5 h before or 10 min after radiation, the X-ray survival curve for crypt stem cells was shifted towards lower doses, with a Dose Effect Factor (DEF) of 1.2-1.3. When the drug was given one week before X-rays, no effect on the survival curve was observed. The slope of the X-ray survival curve was not modified by cis-platinum. When the drug was given within 6 h time of X-rays, the increased killing of crypt cells by cis-platinum was the same irrespective of the sequence of administration. These data suggest that cis-platinum and radiation kill crypt cells by independent cellular mechanisms. A survival curve for crypt cells was also obtained after graded doses of cis-platinum alone. It was characterised by a D0 of 3.18 +/- 0.40 mg/kg (1 S.E.) and an extrapolation number N of 2.9 X 10(4). When the drug treatment was combined with a single dose of X-rays, this survival curve was shifted towards lower drug doses without a significant change in the slope (D0 = 2.87 +/- 0.37 mg/kg). This suggests that independent killing of crypt cells by the two agents occurred over a wide range of drug doses.

Animals↗
PubMed1985

Differences in the acute intestinal syndrome after partial and total abdominal irradiation in mice.

The acute intestinal syndrome in mice was analysed after partial (PAI) and total abdominal irradiation (TAI). The LD50/15 was significantly higher after PAI (16.3 Gy) than after TAI (14.3 Gy). The dose-response curve for maximal weight loss also showed a shift of 1.8-2 Gy to higher doses after PAI compared with TAI. The X-ray survival curve for duodenal crypt cells was shifted by only 0.6 Gy for PAI and TAI. In order to assess the possible role of radiation-induced leucopenia and the influence of irradiating the spleen (shielded with PAI), lethality, weight loss and blood leucocyte counts were compared after PAI and TAI in splenectomized and non-splenectomized mice. No major difference in leucopenia was found between the different treatment groups, whereas the differences in lethality and weight loss between PAI and TAI remained the same. Shielding the spleen in the partial abdominal field therefore did not contribute to the difference in LD50/15. These findings imply that the increased LD50/15 after PAI compared with TAI was mainly due to shielding of a small part of the bowel (about 13 per cent of the abdominal area).

Abdomen↗
PubMed1984

A modified radiotherapy technique in the treatment of medulloblastoma.

Craniospinal irradiation is a standard treatment technique in patients who receive surgery for medulloblastoma. In most centers megavoltage photon irradiation is used, resulting in significant irradiation exposure to critical organs. In order to overcome this difficulty, we recently modified the technique applied in our center, by using high energy electrons (20 MeV) for irradiation of the spinal cord. The reliability of this technique was checked by performing dosimetry in a specially constructed wax phantom. Attention was focused upon dose variations at the junction of fields. Furthermore, the influence of vertebrae on the absorbed dose distribution of high energy electrons is presented. This technique seems to be safe and reliable in selected patients (children and teenagers).

Adolescent↗
PubMed1984

Low grade astrocytoma in children treated by surgery and radiation therapy.

Results of treatment of low grade astrocytoma by surgery and postoperative irradiation in 35 children under 15 were retrospectively analysed. The actuarial overall 5 and 10 year survival was 94 and 82 per cent, the actuarial relapse-free survival 87 and 70 per cent, respectively. The male patients fared better, although not significantly, than the females. No significant difference in relapse rate was found between cystic and solid tumors. The cystic processes had a more indolent course, but a fatal outcome was noted in one case (after 21 years). No relapse occurred in totally removed tumors (10 cases), which throws doubt on the need for postoperative irradiation in this subgroup. In the subtotally resected processes (24 cases) radiation therapy seemed to be beneficial, as in 3 of 4 local recurrences geographic misses of tumour remains probably existed. No dose response relationship was apparent. The performance status was severely impaired in 11 per cent (3/27 patients). Growth retardation was observed in 2 patients.

Actuarial Analysis↗
PubMed1984

Radiation treatment planning for the localized prostatic carcinoma: methods and rationale.

External radiation therapy is an effective treatment modality for the locally confined prostatic carcinoma. The incidence of radiation induced morbidity varies among the different published series. It is definitely related to the treatment technique used. A number of examples are shown, and their validity discussed. The treatment set up needs to be individualized, determined by, among other factors, local tumor extent and the irradiated volume of critical organs within the treatment volume.

Adenocarcinoma↗
PubMed1983

Acute side effects and late complications after radiotherapy of localized carcinoma of the prostate.

In the last two decades, many authors have treated prostatic carcinoma by radiation therapy. Accumulated data have been updated, after 10 and 15 years of follow-up. In stage A and B, the reported survival and local control rates after irradiation (20, 22, 30, 34, 35, 39, 42) are as good as in selected patients treated by radical prostatectomy (9, 18, 23). In stage C, the results after irradiation (20, 22, 30, 42) are better than after radical surgery (23, 43). However, patients are nonrandomly selected and the methods of statistical analysis differ. Therefore, a valid comparison cannot be made. The therapeutic ratio is determined by survival and local control, and also by therapy related complications. It is therefore of interest to find out from radiotherapy series if their incidence is related to the treatment technique. Unfortunately, relatively few studies accurately describe treatment technique and complications. Gastro-intestinal radiation injury becomes significant when the dose at the posterior rectal wall is 65-76 Gy and the length of the treated rectum is at least 10 cm. A hot spot of 80-84 Gy needs to be only 2 to 3 cm to increase the risk of late bowel stenosis. Genito-urinary complications are influenced by local extension of the tumor and by previous surgical manipulations. A dose at the prostatic area exceeding 70 Gy should be avoided, as it does not improve local control (22, 35) and apparently increases the risk of late urethral stricture and penile/scrotal edema (12, 39). The dose at the anterior bladder wall correlates with other types of genito-urinary complications. Therefore, the anterior bladder wall should not receive a dose higher than 65 Gy. Incidence of impaired potency after irradiation is usually 30 to 40%, which is much less than after radical surgery. As many data in the literature dealing with radiation treatment of the prostate are still inadequate a more standardized reporting is recommended to make comparison of effectiveness and side effects possible.

Adenocarcinoma↗