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Biomedical subjects

K R Trott

Publications and source records attributed to K R Trott.

At least 55 records · Page 3Linked to original sources
PubMed1995

The proliferative capacity of mouse fibrosarcoma cells that survived x-irradiation.

Delayed reproductive death, the appearance of colonies with a reduced cell density (impaired colonies) and the number of giant cells per colony were investigated in murine fibrosarcoma cells after irradiation with 3 to 9 Gy of x-rays. Radiation survivors were replated after reaching confluence, which occurred after 13 to 15 doublings; this procedure was repeated three times. The replating efficiency decreased in a dose-dependent manner, the survivors of 9 Gy achieving only 30% of the plating efficiency of unirradiated cells. After the third replating, i.e. after 40 to 45 doublings, the plating efficiency of the survivors approached that of the controls. The median colony size of the survivors showed a similar dose-dependent decrease, which was pronounced after the first replating but still remained significant after the third replating. The fraction of impaired colonies was increased to more than 30% in 9-Gy survivors, and though abating, the increase was still significant even after the third replating. Evidence of residual damage was also provided by the presence of giant cells. For instance, after 6 Gy irradiation and 13 to 15 doublings, the proportion of colonies with giant cells was 60%, decreasing only to 45% after 40 to 45 doublings. The number of giant cells per colony was 1.4 in colonies arising immediately after 6 Gy, decreasing to 0.9 after the third replating. These results suggest that the proliferative capacity of surviving cells is depressed even longer than their clonogenic capacity.

Animals↗
PubMed1995

Epidermal morphology, cell proliferation and repopulation in mouse skin during daily fractionated irradiation.

In mouse, a 2 cm long field of both legs was irradiated daily with 3 Gy, five fractions per week for up to 3 weeks. Epidermal morphology, the circadian variation of the labelling index, and repopulation were determined at the end of each week. After a decrease of epidermal cellularity in the first week, excessive regeneration led to hyperplasia and hypertrophy, which continued throughout the experimental period while the residual tolerance of the epidermis to top-up irradiation decreased progressively. Although the repopulation rate was accelerated five-fold, it was unable to compensate the effects of more than two-thirds of the given dose. The hypertrophic and hyperplastic response is attributed to pronounced acceleration of abortive proliferation of doomed stem cells.

Animals↗
PubMed1995

The effects of local X-irradiation on the distensibility of the rectum in rats.

Proctometry was performed on female Wistar rats following irradiation of the rectum with single doses of 15, 18 and 22 Gy of X-rays. The results indicated a progressive increase in distensibility until week 29 after irradiation which was attributed to degenerative changes in the intestinal wall. A major factor which determines colorectal pressure is the neuromuscular activity, however, neuromuscular transmission was not affected by irradiation.

Animals↗
PubMed1995

[The effect of x-rays on experimental arthritis in the rat].

AIMS: We investigated the therapeutic efficacy of low doses of X-rays on different in-vivo models of monoarticular arthritis which have been developed for the investigation of anti-inflammatory drugs. MATERIAL AND METHODS: Zymosan or heat-inactivated mycobacterium tuberculosis was injected into 1 knee joint of Wistar rats to produce, via different pathogenetic mechanisms, an acute monoarticular arthritis. Five days later, the amount of joint swelling, bone destruction and cartilage catabolism were measured. Immediately after arthritis induction, the knees were irradiated with a single dose of 5 Gy or with 4 daily fractions of 1 Gy. RESULTS: X-irradiation with daily doses of 1 Gy significantly reduced bone loss and cartilage degradation in Zymosan-induced arthritis and joint swelling in mycobacterium tuberculosis induced arthritis. However, a single high radiation dose significantly increased bone loss in mycobacterium tuberculosis induced arthritis. CONCLUSIONS: These data confirm the hypothesis of an anti-inflammatory effect of low radiation doses which so far has been based only on clinical experience. By using an established model of monoarticular arthritis we have now the opportunity to study the mechanism of the anti-inflammatory radiation effect in comparison to that of anti-inflammatory drugs. This way, we hope to provide a scientific basis for the use of radiotherapy in various painful degenerative joint disorders.

Acute Disease↗
PubMed1995

Radiation-induced impairment of osseous healing: quantitative studies using a standard drilling defect in rat femur.

The femora of adult Wistar rats were locally irradiated with single doses of X rays and 1 day later were wounded by a standardized drilling defect that extended through the diaphyseal cortex into the marrow cavity. Healing of the lesion was followed over 30 weeks to assess the time course of osseous closure. In unirradiated bones healing was complete by week 7. Irradiation with doses up to 15 Gy imparted a dose-dependent delay in the formation of primary callus and its subsequent replacement by more mature bone, while after higher doses healing remained permanently compromised or even suppressed. Using histomorphometry, osseous closure was also measured quantitatively for healing periods of 7, 10, 16 and 30 weeks and the data were expressed as the percentage of responders with < or = 40% fractional closure. The resulting dose-response curves were steep, displaying a large threshold dose and ED50 values between 16.8 to 17.5 Gy (7 to 16 weeks) and 19.4 Gy (30 weeks), respectively.

Animals↗
PubMed1995

The effect of irradiated volume on the chronic radiation damage of the rat large bowel.

PURPOSE: The dependence of the structural and the functional chronic radiation damage in the large bowel of rats was investigated in order to develop criteria for optimising treatment plans. MATERIAL AND METHODS: Rats were locally irradiated to different volumes of their rectum. The resulting chronic damage was determined by clinical observation, by rectoscopy and by histopathology. RESULTS: The structural damage as well as the functional damage depend very much on the dose distribution in the large bowel, however, this influence is different for structural and for functional damage expression. Much less field size effect was seen for the structural damage of ulceration than for the functional damage of rectal obstruction when the length of whole circumference irradiation was reduced or when only half of the circumference was irradiated. CONCLUSIONS: Different criteria are likely to apply for different types of damage even in one particular organ. The volume or the proportion of an organ which receives the target dose is not always a useful criterium for optimizing treatment plans.

Animals↗
PubMed1994

Post-irradiation bladder dysfunction: muscle strip findings.

Strips of rat detrusor muscle were studied in an organ bath 6 months after X-irradiation at doses of 15 and 25 Gy; cystometric studies in these animals had shown a persistent and significant reduction in compliance. The organ bath study demonstrated an increase in the purinergic sensitivity of irradiated detrusor muscle as compared with control. This was significant: p < 0.0145 for the 25 Gy dose group (n = 8) and p < 0.0456 for the 15 Gy group (n = 8) at an alpha,beta-methylene-ATP concentration of 10(-4) M (Mann-Whitney U-Test). There was no difference in sensitivity to cholinergic or noradrenergic stimulation, or to electrical stimulation of the transmural nerves. The finding of purinergic hypersensitivity in irradiated muscle, coupled with ultrastructural evidence of a neural injury, raises the interesting possibility that a denervation supersensitivity phenomenon may contribute to the pathophysiology of post-irradiation bladder dysfunction.

Animals↗
PubMed1994

Tumour stem cells: the biological concept and its application in cancer treatment.

Experiments in different transplantable mouse tumours suggest that a proportion ranging from 0.1% to 100% of all tumour cells in these different tumours meet the functional definition criteria of tumour stem cells, i.e. regrowth of the tumour proceeded by clonal expansion from a single cell with unlimited proliferative potential. It is concluded that the proliferative organization of many or most human tumours may resemble that of the tissue of origin with a small proportion of stem cells and the majority of transit cells, both proliferating or resting. Cell loss and accelerated repopulation are due to regulated changes in the symmetry constraint of stem cell divisions.

Animals↗
PubMed1994

Clonal heterogeneity in the progeny of HeLa cells which survive X-irradiation.

Clones of HeLa cells that had survived 9 Gy X-rays were investigated for plating efficiency, radiosensitivity, the proportion of giant cells, and chromosome numbers. A significant decrease in plating efficiency was observed that persisted for > 20 population doublings. The reduced plating efficiency was associated with an increased proportion of giant cells in the colonies. There was pronounced clonal heterogeneity in the progeny of irradiated surviving cells with respect to plating efficiency, proportion of giant cells, and chromosome numbers. The radiosensitivity of progeny from irradiated cells did not change compared with controls.

Cell Survival↗
PubMed1994

Radiation risks from imaging of intestinal and abdominal inflammation.

Most abdominal imaging procedures involve some radiation dose to the patient. The types of radiation-induced harm from these techniques are described. The dose received from each of these techniques in clinical practice is thought to be below the threshold required to cause developmental abnormalities in pregnancy. According to the present state of knowledge, there is no significant risk of genetic damage to the patient from any of these procedures. Organs vary considerably in their sensitivity to radiation-induced cancer. The effect of radiation on any organ depends on the radiation dose to that particular organ only. The most radiosensitive organs are bone marrow, lung, stomach and large bowel. The macroscopic and microscopic distribution of radiation dose is discussed for all of the various imaging techniques. There is a large dose variation between individual patients and the mean dose received from each procedure is similar for each of the imaging techniques described, the mean radiation dose is low and the decision as to which test to choose depends more on the diagnostic value of each particular procedure.

Abdomen↗
PubMed1994

[Problems of radiotherapy in Germany after the recent events in Hamburg].

BACKGROUND: During the 3rd Symposium on "Experimental Radiotherapy and Clinical Radiobiology" (Hamburg, March 1994) the consequences of the recent events in the Department of Radiotherapy of the University-Hospital in Hamburg for daily radiotherapy practice in Germany were discussed. The following topics were covered: information of the patient, choice of therapy, development of new treatment modalities, ethics committee, follow-up and role of radiobiology. DISCUSSION AND RESULTS: Information of the patient: Due to the insecure juridical situation in Germany there is a tendency to inform patients excessively, which is rather confusing for them. Adequate information of patients is a difficult task for physicians considering their daily workload. Choice of therapy: Unfortunately in Germany radiotherapists are often not initially involved in planning of the overall treatment strategy for individual cancer patients. The recent events in Hamburg led to a decreased referral of cancer patients for radiotherapy. This might even hold for tumor entities where radiotherapy is an essential part of therapy. Another problem is that dose might be reduced inadequately. This would reduce complications but also significantly increase local failure. Development of new treatment modalities: There are no special juridical problems with the conduction of clinical studies for optimization of radiation treatments. Ethics committee: Ethics committees are not only meant to safeguard patients but also protect physicians and institutions from the consequences of questionable research. FOLLOW-UP: Only radio-oncologists are adequately trained for follow-up after radiation treatment. Nevertheless, because of administrative, financial, legal and political problems many patients in Germany are not regularly seen by the radiation oncologist after end of radiation treatment. Always when new treatment strategies are established, careful follow-up is of special concern. Role of radiobiology: The main obligation of clinical radiobiology is to introduce radiobiological knowledge into clinical practice. This may be best promoted by a period of radiobiological research during residency. However, close collaboration between radiotherapists and radiobiologists is only possible at very few centres in Germany, because the institutes of radiobiology are dismantled systemically.

Aftercare↗
PubMed1994

The importance of the timing of a gap in radiotherapy of squamous cell carcinomas of the head and neck.

AIM: This paper analyses whether the timing of interruptions during radiotherapy of squamous cell carcinomas of the head and neck influences treatment results. PATIENTS AND METHODS: Hundred and ninety-two patients irradiated with curative intent between 1975 and 1985 (63% after surgery and 37 as primary treatment) were analysed with regard to the occurrence, timing, duration and causes of treatment interruptions. In a multivariate analysis, these factors as well as stage, site, extent of surgery etc. were related to 5-year survival rates. RESULTS: Interruptions of the prescribed course of radiotherapy decreased the survival rate from 61% to 28%. No adverse effect of a break was seen if it occurred during the first 3 weeks whereas survival dropped to 18 to 25% with a break later in the course of radiotherapy. CONCLUSION: Timing of treatment interruption in squamous cell carcinomas is a crucial factor determining the chances of tumor cure. The detrimental effect of treatment interruptions increases as treatment progresses. This finding supports the hypothesis that tumor clonogen repopulation accelerates towards the end of radiotherapy of squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1994

Modification of late radiation damage in the rectum of rats by deproteinized calf blood serum (ActoHorm) and pentoxifylline (PTX).

PURPOSE: Prevention and treatment of radiation-induced late rectal ulcer using deproteinized calf blood serum (ActoHorm) or pentoxifylline. MATERIALS AND METHODS: Rectal ulcers were induced in Wistar rats using single X-ray doses of 20, 22 and 24 Gy. ActoHorm or pentoxifylline were given at various times after irradiation. The induced rectal damage was assessed by clinical examination, rectoscopy and histology of the post-mortem specimens. RESULTS: Neither ActoHorm nor pentoxifylline affected the incidence or latency or had any pronounced effect on healing of late rectal ulcers. Histological examination showed increased regenerative activity of the mucosal epithelium in all ActoHorm treated animals. CONCLUSION: Neither ActoHorm nor pentoxifylline prevented the development of radiation-induced rectal ulcers. The stimulation of mucosal epithelium with ActoHorm might, however, be effective in healing of superficial erosions of the intestinal mucosa.

Actihaemyl↗