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Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 253 records · Page 14Linked to original sources
PubMed1985

A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanoma.

Thirty-five tumors in 14 patients with metastatic or recurrent malignant melanoma were randomized to high dose per fraction radiotherapy at either 9 Gy X 3 or 5 Gy X 8 twice weekly. Complete and persistent regression was found in 24/35 (69%) and partial response in 10/35 of the tumors. The overall response rate was 97%. No difference was observed between the two treatment regimens. Acute and late radiation damage to normal tissue was acceptable and of the same magnitude in both schedules.

Erythema↗
PubMed1984

Lateral cervical facetectomy. The surgical pathology of radicular brachialgia.

In 113 patients with radicular brachialgia and neuropathy without spinal cord affection surgical treatment consisted in facetectomy and exposure of the extrathecal part of the cervical root from the axilla to the lateral border of the root canal. In 27 patients disc herniation, and in 43 uncovertebral exostosis, was detected. In 59 patients a thick, fibrous periradicular cuff tightened the exposed root. The surgical pathology of radicular brachialgia is discussed. A total of 70 patients recovered.

Adult↗
PubMed1984

The carpal tunnel syndrome and amyloidosis. A clinical and histological study.

Twenty-six non-randomized patients with carpal tunnel syndrome are presented. It is documented that three out of four patients may be diagnosed pre-operatively by five or more clinical parameters. All patients were screened for amyloidosis in biopsies from the carpal tunnel. One patient presented amyloid deposits in the transversal carpal ligament. The importance of macro- and microscopic findings in the carpal tunnel inclusive local amyloidosis for the pathogenesis of the carpal tunnel is discussed. It is concluded that provided systemic amyloidosis is not suspected, screening for amyloidosis may have diagnostic interest, however without therapeutic consequences and therefore unnecessary.

Adult↗
PubMed1984

A phase I clinical study of Nimorazole as a hypoxic radiosensitizer.

Nimorazole, a 5-Nitromidazole compound has been shown in animal studies to have similar radiosensitizing properties to misonidazole at clinically acceptable dose levels. The drug is well absorbed in humans after oral administration with peak plasma levels occurring around 90 min after ingestion (range 35-135 min) and a plasma half life between 2 and 4.8 hours. Total doses of Nimorazole up to 60 grams given in daily doses with conventional radiation therapy have demonstrated a significant lack of side effects, in particular no demonstrable neurotoxicity.

Adult↗
PubMed1984

Dose-response relationship for radiation therapy of recurrent, residual, and primarily inoperable colorectal cancer.

One hundred and thirteen patients with advanced locoregional recurrent (77), residual (18) or primarily inoperable (18) colorectal carcinoma were treated with radiotherapy. Eighty-five patients had locoregional disease only and 28 had both local disease and distant metastases. The treatment was given with varying dose levels (23-73 Gy) in daily fractions of approximately 2 Gy in 3-8 weeks. This dose variation allowed an evaluation of the dose-response relationship for radiation treatment of this tumour. A good subjective response was obtained in 63%. This effect showed no dose-response relationship except for doses greater than or equal to 56 Gy, where all patients received relief of symptoms. Eighty-two per cent of evaluable patients achieved an objective response (PR 53%, CR 29%). The frequency and duration of the complete responses showed a marked dose-response relationship. Thus, at doses greater than or equal to 56 Gy, a 2-year actuarial complete response rate of 40% was found compared with 7, 4 and 0% at doses of 46-55 Gy, 36-45 Gy and less than or equal to 35 Gy, respectively. The dose-response relationship for local control also influenced the survival rate, although a number of patients died from distant metastases even when local control was obtained. However, with regard to locoregional disease, the 2-year survival was 53% for patients with complete tumour regression but only 8% for patients without complete tumour regression.

Adult↗
PubMed1984

Isotherm mapping in hyperthermia using subtraction X-ray computed tomography.

The prospects for the use of X-ray computed tomography (CT) for isotherm mapping were investigated. The spatial distribution of CT changes was obtained by digital subtraction of images taken before and during heating of a 200 mm diameter cylindrical 4% agar phantom. Due to a rather unfavourable signal-to-noise ratio, the noise level in the resulting image had to be reduced by low-pass filtering using the 2-dimensional Fast Fourier Transform followed by spatial averaging. The resulting isotherms showed a resolution of 0.5 degree C at a spatial resolution of 4.2 mm. Isotherms so obtained are presented and the possibility of using the method in clinical hyperthermia is discussed.

Humans↗
PubMed1984

Formula to estimate the thermal enhancement ratio of a single simultaneous hyperthermia and radiation treatment.

An experimental model composed of a C3H mammary carcinoma and its surrounding skin has been exposed to simultaneous radiation and hyperthermia given with different combinations of heating time and temperature. Based on the thermal enhancement ratio (TER) values obtained in the temperature range 41.5 to 43.5 degrees C, a linear relationship between TER and the heating time was achieved at each temperature. The slopes of the curves drawn at each temperature were found to have a log-linear relationship with the treatment temperature. With these relationships it was possible to make a formula expressing the TER as a function of treatment temperature and time. This formula gives a crude but probably acceptable estimate of the TER following a single simultaneous radiation and heat treatment. Although subject to several limitations, the formula represents an attempt to describe a heat dose concept for the radiosensitizing effect of hyperthermia. This may be useful to establish the tolerance level of a given radiation treatment when combined with hyperthermia.

Animals↗
PubMed1983

The importance of thermotolerance for the clinical treatment with hyperthermia.

Thermotolerance (i.e. a temporary heat resistance following a prior heat treatment) is a general phenomenon occurring in both normal tissues and tumours. Besides affecting a fractionated heat treatment, thermotolerance may also influence the effect of fractionated combined heat and radiation. The importance of thermotolerance for fractionated clinical hyperthermia is discussed on the basis of a series of in vitro experiments in L1A2 cells and in vivo studies of a C3H mouse mammary carcinoma. If maximal tumour interaction is wanted, thermotolerance should be avoided, but it would be preferable in normal tissues in order to reduce the amount of damage. Unfortunately, there is a considerable variation in the kinetics and magnitude of thermotolerance between different tissues, and it is currently not possible to predict how thermotolerance will develop in a given tumour or normal tissue. However, both the magnitude and the kinetics appear to depend on the heat damage induced by the priming heat treatment. Thus, in a given tissue, thermotolerance will develop later, but will reach a higher maximum by a larger priming heat treatment. It follows that if a homogeneous temperature cannot be applied to a given tissue, different parts will develop thermotolerance at different kinetic patterns. Therefore, at the time of subsequent heat treatment, the tissue may express different heat sensitivities in different areas. With the current knowledge, the best way to overcome the problems of thermotolerance when heat is given alone or sequentially with radiotherapy will be by application of a single or few, but large heat fractions given with an interval that allows thermotolerance to develop and decay before the next hyperthermic treatment is given. With a simultaneous heat and radiation treatment which optimally requires heating in association with all radiation fractions, the fractionation interval should also be long, which is complicated by the fact that such long fractionation intervals may not result in an optimal radiation treatment.

Cell Line↗
PubMed1983

Studies of the pharmacokinetic properties of nimorazole.

The pharmacokinetics of the hypoxic radio-sensitizer nimorazole were studied in 19 individuals after single oral doses of between 0.5-3.5 g. HPLC measurements showed, after a rapid absorption, a linear relationship between peak plasma concentration and given dose. Mean elimination half life was 3.1 h. A tendency to a dose-dependent variation in the apparent volume of distribution, total body clearance and elimination half life suggest non-linear pharmacokinetics of nimorazole. Tumour concentrations measured in 5 patients gave tumour/plasma ratios between 0.8-1.3. No toxicity was observed. The results indicate that nimorazole may have potential as a clinically useful hypoxic radiosensitizer.

Adult↗
PubMed1983

Microcolony survival assay for jejunal crypt cells exposed to radiation alone and combined with cancer chemotherapeutic agents--methodological problems.

The effect of radiation alone or in combination with cyclophosphamide (CTX), methotrexate (MTX) and 5-fluorouracil (5-FU) on the jejunal crypt cells in C3D2F1/Bom mice was studied using the microcolony survival assay. In determination of survival curves, two sections per mouse and six mice per datum point were used in order to obtain a constant coefficient of variance of D0 (approximately 5 per cent). When CTX (250 mg/kg), MTX (150mg/kg), and 5-FU (150 mg/kg) were injected intraperitoneally 15 min before irradiation, the regeneration time for the surviving crypts increased. Thus, following radiation alone the regeneration time was 90 hours and when combined with the drugs, 96, 102, and 120 hours, respectively. At these hours the crypts were of an equivalent size. Scoring the crypt number at the regeneration times was found to be necessary, since the use of a constant assay time underestimated the crypt survival following the drug-radiation combinations. Neither was a constant assay time followed by a correction for different crypt sizes found sufficient to replace the use of different regeneration times. All three drugs significantly enhanced the radiation effect without changing the D0. The DEF values for CTX, MTX, and 5-FU were 1 . 05, 1 . 08 and 1 . 13, respectively.

Animals↗
PubMed1983

Influence of thermotolerance on the interaction between hyperthermia and radiation in a solid tumour in vivo.

The influence of thermotolerance (i.e. a temporary resistance to a subsequent heat treatment induced by prior heating) on the response of a C3H mouse mammary carcinoma to combined water-bath hyperthermia and radiation was investigated. Prior heating at 43.5 C for 30 min induced thermotolerance which was at a maximum 16 h later and had completely disappeared after 120 h. Prior heating reduced tumour response to simultaneous heat and radiation given 16 h later, as evidenced by a reduction from 5.1 to 3.3 in the thermal enhancement ratio (TER). The effect was lost by 120 h. This indicates that development of thermotolerance reduces the degree of thermal radiosensitisation. However, although the time course was the same, the prior heating effect on the combined treatment was smaller than on the resistance to heat alone. With sequential treatment, the tumours were treated with X rays (28 Gy) followed four hours later by a two-dose heat treatment at 43.5 degrees C, the first for 30 min and the second after an interval of 0, 16 or 120 h. With this treatment thermotolerance fully manifested itself. It was necessary to increase the duration of heating when applied 16 h after prior heating by a factor of 5.4 to cause a TER of 2.0, a value not significantly different from the expected value of 5.2, i.e., the thermotolerance ratio for heat alone.

Adaptation, Physiological↗
PubMed1983

Cerebral circulation after head injury. Part 4: Functional anatomy and boundary-zone flow deprivation in the first week of traumatic coma.

A considerable body of evidence suggests that posttraumatic disturbances of the cerebral circulation contribute to poor neurological outcome after blunt head injury, especially when regional cerebral blood flow (rCBF) falls to the ischemic range (below 17 ml/100 gm/min). Cerebral infarction concentrated in the arterial boundary regions has been described in patients who died. Since arterial boundary zones are the cortical areas most susceptible to cerebral ischemia, the authors have investigated the relationship between neurological outcome and the anatomic pattern of rCBF values in the acute phase. The bolus-injection xenon-133 washout technique was used to measure rCBF in 35 regions of the hemisphere during the 1st week after head injury. Eighty-eight hemispheres were studied in 80 patients whose Glasgow Coma Scale (GCS) score was less than 8 on admission to the neurosurgical department. A characteristic pattern of rCBF was found in patients who later died of neurological complications, or who survived in a persistent vegetative state, with low flows in regions conforming to the arterial boundary zones. These patients also had lower average global cerebral blood flow (CBF), GCS scores, and cerebral perfusion pressure compared with those who recovered, with or without neurological deficits; the latter group had an rCBF pattern similar to that of normal individuals. There was little change in the GCS score between the time of hospital admission and CBF measurement, suggesting that the major neurological injury had occurred prior to admission. It was not possible to determine whether boundary-zone ischemia preceded neurological deterioration, but the rCBF pattern of boundary-zone flow deprivation was clearly related to poor neurological outcome. These observations suggest that elevated intracranial pressure and arterial hypotension were important etiological factors. Measures to protect regional cerebral perfusion should be instituted as early as possible after injury, preferably before the patient reaches the hospital.

Arteries↗
PubMed1982

Postoperative radiotherapy in rectosigmoid cancer Dukes' B and C: interim report from a randomized multicentre study.

The design, and complications seen during the first 2 years, of a randomized trial of postoperative radiotherapy for rectosigmoid cancer Dukes' B and C are presented and discussed. It is concluded that the present complication rate-below 10% in 221 patients-permits continuation of the intake, which is planned to include 550 patients, to demonstrate a possible increase in crude 5-year survival by 15% (60-75% in Dukes' B and 25-40% in Dukes' C), on the basis of a 0·01 significance level and a probability that the experiment will be successful of 0·90.

Clinical Trials as Topic↗
PubMed1982

Importance of preheating temperature and time for the induction of thermotolerance in a solid tumour in vivo.

The importance of the priming heat treatment temperature and heating time for the degree and kinetics of thermotolerance was investigated in a C3H mammary carcinoma inoculated into the feet of CDF1 mice. A single heat treatment in the range 41.5-44.5 degrees C resulted in a linear relationship between heating time and tumour growth time (i.e. the time for tumours to reach a volume five times that of the first treatment day). An Arrhenius plot showed an inflection point at 42.5 degrees C with activation energies of 635 and 1508 kJ/mol, respectively, above and below 42.5 degrees C. The degree and kinetics of thermotolerance were independent of the preheating temperature, if the heating time was adjusted to give the same level of heat damage. A pretreatment at these temperatures with a tumour growth time of approximately 10 days, equivalent to 30 min at 43.5 degrees C, resulted in maximal thermotolerance at a 16-h interval with a thermotolerance ratio (TTRmax) of approximately 5.2. Preheating of the tumours at 43.5 degrees C for 3.5, 7.5, 15, 30, or 45 min, showed that if the preheating time was increased, both the TTRmax and the time interval necessary to develop TTRmax increased, both being linear functions of the duration of the preheating time. Maximal thermotolerance was obtained at intervals of 2, 4, 8, 16, and 28 h with TTRmax of 1.6, 2.2, 3.7, 5.2, and 7.7, respectively.

Animals↗