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Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 37 records · Page 2Linked to original sources
PubMed1992

Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC). METHODS: Brain stem function was investigated by auditory brain stem responses (ABR). RESULTS: Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction. CONCLUSIONS: The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.

Adult↗
PubMed1992

Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas.

BACKGROUND AND METHODS: A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology, tumor size, and the TNM classification. RESULTS: The investigation showed a significant difference between the volume-weighted mean nuclear volume (nuclear vv) of oral leukoplakia (n = 29) and oral squamous cell carcinomas (P = 0.001). The value of the parameters as prognostic indicators of survival and recurrence was tested with Kaplan-Meier plots and Cox multiple hazard regression analysis. Tumor size, T-stage, stereologically estimated nuclear vv, and mean nuclear profile area were all of significant prognostic value in single factor analysis with reference to both survival and recurrence. The histologic parameters of mitotic activity, morphologic nuclear dedifferentiation, and histologic mean malignancy score and the DNA ploidy level had no prognostic value. A prognostic index based on the results of the Cox analysis that included T-stage and nuclear vv was correlated highly with survival (P = 0.00001) and recurrence (P = 0.002). CONCLUSION: These findings may contribute to optimal and individualized therapy.

Adult↗
PubMed1992

Effect of etoposide, carmustine, vincristine, 5-fluorouracil, or methotrexate on radiobiologically oxic and hypoxic cells in a C3H mouse mammary carcinoma in situ.

The effect of etoposide (VP16), carmustine (BCNU), vincristine (VCR), methotrexate (MTX), and 5-fluorouracil (5-FU) on the oxic and hypoxic cells in a C3H mammary carcinoma in CDF1 mice was investigated using an in situ local-tumor-control (TCD50) assay. The surviving fraction (SF) was calculated from the size of the radiation dose needed to inactivate the surviving tumor cells in drug-treated tumors relative to untreated controls. Preferential drug cytotoxicity towards oxic and hypoxic cells was evaluated from the difference in the response to irradiation under ambient and clamped conditions, respectively. Three drugs caused a significant (P less than 0.05) reduction in the survival of hypoxic cells, the SFs being 0.31 (VP-16), 0.13 (BCNU) and 0.16 (VCR). VCR was also toxic towards oxic cells (SF, 0.17), whereas VP16 and BCNU had no significant effect on these cells (SF, 0.5 and 0.76, respectively). Two drugs produced significant killing of cells in the oxic compartment: 5-FU (SF, 0.10) and MTX (SF, 0.22); these two drugs had no effect on hypoxic cells (SF, 0.78 and 1.11, respectively).

Animals↗
PubMed1992

BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma.

The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity.

Animals↗
PubMed1992

Fractionation sensitivity and latency of late radiation injury to the mouse urinary bladder.

Transurethral bladder filling is a functional, non-invasive, in vivo assay of early and late radiation injury to the mouse bladder. Fractionated irradiations using single doses or 2, 3, 5, or 10 dose fractions in an overall time of 4 or 4.5 days, with a range of total doses, were given to the bladder of 12-14 week-old C3D2F1/Bom mice. In 372 mice, bladder volume at an intravesical pressure of 20 mmHg was measured before irradiation and at regular intervals thereafter. The endpoint for late bladder injury was a volume of less than 50% of the median pretreatment volume in all animals, occurring more than 30 days after irradiation. This endpoint was reached after a latent period ranging between 35 and 401 days. Fractionation and latency parameters were estimated using a mixture model. There was a highly statistically significant dose-dependency of the latent period (p < 10(-8)). The alpha/beta ratio was estimated at 5.8 Gy [95% confidence limits (3.6; 8.8) Gy] for 250 kVp X-rays. Thus late radiation injury in the mouse urinary bladder is one of the least sensitive late endpoints with respect to change in dose per fraction. Introducing early bladder injury as a variable in the model improved the fit significantly (p = 0.03), but the alpha/beta ratio remained unchanged. Thus the hypothesis that late bladder injury may be, at least in part, consequent upon early injury did not explain the relatively high alpha/beta ratio for this late endpoint.

Animals↗
PubMed1992

Education in radiation oncology in Europe.

The outcome of an inventory among 22 European countries with respect to the radiotherapy facilities and the training of new radiation oncologists in each country is described. The radiotherapeutic profession, which mostly prescribes also cytostatics or hormones, has become well-regulated in the last 20 years. Most radiation oncologists are also involved in the diagnostic work-up and follow-up of the cancer patient. The numbers of radiotherapists and other staff, treatment capacities, and patients are given. The training for radiation oncologists is mostly taken at the university centers, but the curricula are rather diverse.

Europe↗
PubMed1992

Effect of carboxyhemoglobin on tumor oxygen unloading capacity in patients with squamous cell carcinoma of the head and neck.

Hemoglobin and blood gas parameters, with special attention to the influence of carboxyhemoglobin, were studied in 115 head and neck cancer patients undergoing radiotherapy. In 712 weekly blood samples, the values of total hemoglobin, carboxyhemoglobin (CO-Hb), and p50 were measured and the total oxygen content in the arterial and tumor venous blood was estimated. The difference between these values express the tumor oxygen unloading capacity (t-OUC). CO-Hb ranged from 0-12% and showed a significant inverse relationship with t-OUC. This was caused by a reduced amount of effective hemoglobin combined with a left shift of the oxyhemoglobin dissociation curve (reduced p50). Overall, the tumor oxygen utilization decreased from 70% to 52% as a function of an increase in CO-Hb from 0 to 12%.

Adult↗
PubMed1992

Improving the radiation response in a C3H mouse mammary carcinoma by normobaric oxygen or carbogen breathing.

The limited therapeutic benefit from nitroimidazoles has renewed the interest in normobaric oxygen as a hypoxic cell radiosensitizer. In this experimental study we have tried to modify the oxygenation of a C3H mammary carcinoma by flushing tumor-bearing mice with oxygen or carbogen for 5 min before and during treatment. The response to these treatments was evaluated by the changes in radiation-induced tumor control (TCD50) and by the changes in tumor hypoxic fraction (HF). Irradiation was given either as a large, single dose or as five equal, daily fractions. High levels of oxygen in the inspired air were found to decrease the TCD50 significantly. The enhancement ratios were in the range of 1.2-1.4 (p less than 0.05) for both single dose and fractionated irradiation, which suggests that hypoxic cells may be important even when reoxygenation is believed to be complete between fractions. The change in TCD50 corresponded to a decrease in the fraction of clonogenic hypoxic cells from 12% to 3-4% (p less than 0.05). Tumor blood flow was not significantly influenced by the gas treatment. This study thus shows that normobaric oxygen/carbogen inhalation may significantly improve the local tumor control by reducing the diffusion related hypoxia within tumors.

Administration, Inhalation↗
PubMed1992

Influence of carboxyhemoglobin level on tumor growth, blood flow, and radiation response in an experimental model.

Carboxyhemoglobin (HbCO) is formed when carbon monoxide is bound to hemoglobin. High levels of HbCO are known to reduce the amount of oxygen that can be carried to the tissues. This experimental study focuses on the influence of HbCO on the growth, blood flow, and radiation response of an experimental mouse tumor. The study was designed to mimic the clinical situation where heavy smokers are undergoing radiotherapy while having a high HbCO level. The tumor was a C3H mammary carcinoma grown in the feet of CDF1 mice. Chronic exposure to carbon monoxide, resulting in 10% HbCO, increased the tumor volume doubling time from 2.5 to 3.5 days (p less than 0.05). The acute exposure to carbon monoxide prior to and during irradiation significantly raised the radiation dose required to control the tumor locally. The TCD50 increased from 54 Gy in air breathing mice (HbCO 0-2%) to 57 Gy (HbCO 7-9%) and 61 Gy (HbCO 20-23%). This increase corresponded to an increase in the fraction of clonogenic hypoxic tumor cells from 0.12 in air breathing animals to 0.21 and 0.41, respectively. The tumor blood flow, determined by the 86RbCl extraction technique, decreased to 63% (n.s.) and 50% (p less than 0.05) for low and high HbCO levels, respectively.

Animals↗
PubMed1992

Biochemical and physiological changes induced by nicotinamide in a C3H mouse mammary carcinoma and CDF1 mice.

We have continued our investigation into the mechanism by which nicotinamide can enhance radiation damage in tumors, using a C3H mouse mammary carcinoma grown in CDF1 mice. Biochemical analysis of tumor extracts showed that nicotinamide (1000 mg/kg; i.p.) increased the ATP/Pi and ATP/ADP + AMP ratios. This change in metabolic activity was consistent with nicotinamide increasing tumor oxygenation. Moreover, the greatest effect occurred 0.5-2.5 hr after drug injection, a time at which radiosensitization by nicotinamide in this tumor had previously been shown to be maximal. These changes were observed without any apparent modification in tumor blood perfusion, measured using the 86-RbCl uptake procedure, and occurred despite nicotinamide producing a 50% decrease in mean arterial blood pressure, estimated directly by a carotid cannulation technique.

Adenosine Diphosphate↗
PubMed1992

Relationship between the hydralazine-induced changes in murine tumor blood supply and mouse blood pressure.

The relationship between hydralazine-induced changes in blood pressure and tumor blood flow was investigated in restrained but non-anesthetized CDF1 mice bearing C3H/Tif foot tumors. Mean arterial blood pressure measurements were made using the procedure of carotid cannulation, and tumor blood flow was estimated using laser Doppler flowmetry. Hydralazine doses from 0.1 to 5.0 mg/kg were tested. Following hydralazine administration the maximum changes in blood pressure and blood flow were apparent within 10-15 min and were maintained for at least 30 min after injection. Blood pressure decreased with increasing hydralazine dose, achieving a maximum reduction of 50% at 2.5 mg/kg. Tumor blood flow was found to be increased by 30% at the lowest hydralazine dose (0.1 mg/kg), even though blood pressure was decreased by 10% at this dose. At hydralazine doses producing a 15% or greater blood pressure drop, blood flow decreased, reaching an 80-90% reduction between 2.5 and 5.0 mg/kg.

Animals↗
PubMed1992

Interaction of misonidazole, hyperthermia, and irradiation in a C3H mammary carcinoma and its surrounding skin in vivo.

The interaction of irradiation, Misonidazole (MISO), and hyperthermia was studied in a C3H mouse mammary carcinoma and its surrounding skin in vivo. MISO (0.5-1.0 mg/g) was injected 30 min before irradiation. Hyperthermia (41.5 degrees-43.5 degrees C for 60 min) was given either simultaneously, 0.5 hr, or 4 hr after X rays. The results were evaluated as the radiation dose to achieve tumor control (TCD50) or moist desquamation of the skin (DD50) in half of the treated animals. A therapeutic gain was found when the enhancement in tumors were greater than that found in skin. The combination of simultaneous heat and irradiation caused great enhancement in radiation response, but with no therapeutic gain. A slightly lower enhancement of the damage in both tissues was found with a 30 min interval between irradiation and hyperthermia, whereas heat 4 hr after X rays gave a small, but significant therapeutic gain. MISO significantly enhanced the response in tumors but not in skin. Combined trimodality treatment with MISO, irradiation, and hyperthermia resulted in enhancement ratios up to 15, dependent on temperature, radiation-heat interval, and to a lesser extent the MISO dose. The enhancement was for all schedules most pronounced in the tumors, resulting in an improved therapeutic effect. The combination of MISO and hyperthermia may be a valuable addition to radiotherapy, especially if heat and irradiation can be applied with close interval and with one of the modalities given selectively to the tumor.

Animals↗
PubMed1992

Time to loco-regional recurrence after resection of Dukes' B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis.

Factors influencing time to loco-regional recurrence were identified in a multivariate regression analysis of data from a series of 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. A number of clinical and pathological characteristics were prospectively collected and recorded. In addition, carcinoembryonic antigen (CEA) was measured within 1 week before surgery. The endpoint used was recurrence below the level of the umbilicus. All patients were followed for at least 5 years or until time of death. The two Dukes' stages B and C were analysed in two separate analyses using the Cox proportional hazards model. In patients with Dukes' B tumours, an increased risk of loco-regional recurrence was associated with perineural invasion, tumour located less than 10 cm from the anal verge, patient aged above 70 years, and small tumour size. In patients with Dukes' C tumours, the necessity to resect neighbour organs, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and large tumour size were all associated with a poor loco-regional outcome. Postoperative radiotherapy was not a significant prognosticator for loco-regional control. An update of the 5-year results of the randomised study of post-operative radiotherapy (50 Gy with 2 Gy per fraction in an overall treatment time of 7 weeks) showed no survival benefit from adjuvant radiotherapy in either Dukes' category and no statistically significant improvement in the 5-year loco-regional control rate. However, when the comparison was restricted to a group of high-risk patients there was a statistically significant benefit from radiotherapy with respect to loco-regional control (P = 0.03) but not with respect to survival (P = 0.23). The potential advantage, in terms of the required number of patients, of restricting clinical trials of intensified loco-regional therapies to the high-risk patients, is illustrated.

Adult↗
PubMed1992

Early and late changes in the normal mouse bladder reservoir function due to irradiation and cis-DDP.

Early and late changes in the reservoir function of the mouse bladder were investigated after radiation alone or a combination of radiation and cisplatinum (cis-DDP). Bladder function was investigated by repeated cystometries. Treatments consisted of either single fraction radiation (5-10-15-25-30 Gy) or 20 Gy in combination with cis-DDP (6 mg kg-1; i.p.) administered at various time intervals from 14 days before until 14 days after radiation. At two selected time intervals (15 min and 4 h before) radiation was given at different dose levels (5-10-15-20 Gy). Within 30 days after irradiation a dose-dependent early response was noticed both in the radiation alone group and the group where cis-DDP was administered 15 min before radiation. The dose-response curve showed a slight but non-significant shift to the left in the combined treatment group (dose effect factor (DEF) = 1.18). Investigation of the early change in bladder reservoir function in the animals treated with 20 Gy alone or a combination of 20 Gy plus cis-DDP at various intervals in relation to irradiation demonstrated a significant increase in response when cis-DDP was administered 24 h and 15 min before and 4 h, 72 h and 336 h after 20 Gy (P less than 0.05). The reversible nature of the early damage was demonstrated. Late response was irreversible and significantly increased in most groups were cis-DDP was administered from 168 h before until 72 h after compared to radiation alone. Comparing groups treated with radiation alone with groups where cis-DDP was administered 15 min and 4 h before radiation revealed DEF values up to 1.45 (P less than 0.05), reflecting the significantly larger response in combined treatment groups. Survival was significantly decreased in all combined treatment groups compared to groups treated with radiation only and likewise survival was decreased in the group treated by cis-DDP alone compared to control (no treatment at all).

Animals↗
PubMed1992

Malignant parotid tumors in 110 consecutive patients: treatment results and prognosis.

The UICC 1987 classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients. All of the patients had malignant parotid tumors which had been diagnosed and treated during the period from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumors were seen in 28% of the patients, mucoepidermoid tumors in 18%, adenoid cystic tumors in 15%, acinic tumors in 13%, undifferentiated tumors in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival rate was 52%, and significant differences of survival were found between: 1. patients with disease stages I through IV (I: 85%; II: 69%; III: 43%; IV: 14%); 2. those with local tumor extension (34%) and without local tumor extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); and 4. those with low- or intermediate-grade malignant tumors (69% combined) and those with high-grade malignant tumors (30%). After primary treatment, 45% of the patients were cured, and, additionally, 22% were salvaged after local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumor) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors.

Adolescent↗
PubMed1992

Cisplatin and hyperthermia treatment of a C3H mammary carcinoma in vivo. Importance of sequence, interval, drug dose, and temperature.

The effect of combining cisplatin and hyperthermia was investigated in a C3H mammary carcinoma in vivo, using a regrowth delay assay. Cisplatin (6 mg/kg) was given i.p. at intervals ranging from 24 h before to 24 h after a 43.5 degrees C/60 min treatment. A supra-additive effect was obtained by giving cisplatin 15 min before heat, whereas an additive effect was obtained at all other intervals. The importance of cisplatin dose and heating temperature were investigated by giving variable cisplatin doses (2-8 mg/kg) 4 h or 15 min before a 60 min heating at temperatures in the range 40.5-43.5 degrees C. Linear relationships between length of regrowth delay and cisplatin dose were obtained both for cisplatin alone and for the combined treatment. The effect of the combined treatment could therefore be quantitated by a ratio (ER) between the slopes of dose-response curves. The ER values for cisplatin give 4 h before a 60 min heating at 42.5 or 43.5 degrees C were not significantly different from 1 (p greater than 0.5). In contrast, significant ER values were obtained above 40.5 degrees C (p less than 0.05) for cisplatin given 15 min before heat. The data demonstrates the possibility of achieving chemosensitization at clinically relevant temperatures.

Animals↗