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Biomedical subjects

O Dahl

Publications and source records attributed to O Dahl.

139 records · Page 8Linked to original sources

Irradiation and surgery of primarily inoperable rectal adenocarcinoma.

Preoperative irradiation followed by radical surgical removal of the tumor should be attempted in all patients with locally advanced rectal adenocarcinomas, including patients with moderate distant metastases. If the tumor is not operable after half dose of irradiation (3150 rads), the patients should be re-explored for resectability after full irradiation dose. Resectability can only be adequately determined by exploratory laparotomy and an attempt to resect the tumor-bearing segment by anatomic dissection, and not solely by rectal exploration or palpation of the pelvis at laparotomy.

Adenocarcinoma↗

Fluorescein-conjugated lysine monomers for solid phase synthesis of fluorescent peptides and PNA oligomers.

Fluorescein ethyl ester, I, was used to prepare the fluorescent mixed ester/ether 6-O-(carboxymethyl)-fluorescein ethyl ester, III. Conjugation of III to the epsilon-amino group of alpha-N-Boc-L-lysine, via the N-hydroxysuccinimde ester, IV, gave the Boc-protected fluorescein-conjugated lysine monomer V. Removal of the Boc group, followed by reaction with Fmoc chloride, gave the Fmoc-protected monomer, VI (Figure 1). These Boc- and Fmoc-protected fluorescein-conjugated lysines were readily incorporated into peptides and PNA oligomers during solid phase synthesis to give fluorescent products. Mass spectroscopy and UV studies showed that the fluorophore remains unchanged during solid phase synthesis. In contrast to fluorescein, the photophysical properties of these derivatives are pH independent from pH 3 to 8, with a molar absorption coefficient, epsilon max 456, of 2.9 x 10(4) M-1 cm-1 and fluorescence quantum yield, phi f, of 0.18.

Biopolymers↗

Referee: hyperthermia alone or combined with cisplatin in addition to radiotherapy for advanced uterine cervical cancer.

There are two evidence based therapeutic options for locally advanced cervical cancer: Radiotherapy and concurrent chemotherapy (cisplatin alone or combined with other drugs) or radiation and hyperthermia, documented in randomised trials. The weight of evidence is less for the most advanced stages. Combination of all three options are currently tested in several centres with good clinical response and acceptable toxicity. Based on a pragmatic approach we propose to proceed with a trial selecting cisplatin concurrent with radiation therapy as the standard arm to be compared with the same regimen with the addition of hyperthermia once a week.

Antineoplastic Agents↗

Hyperthermia exhibits anti-vascular activity in the s.c. BT4An rat glioma: lack of interaction with the angiogenesis inhibitor batimastat.

We investigated the anti-vascular activity of local hyperthermia (44 degrees C, 60 min) in s.c. BT4An rat gliomas, and the influence on tumour growth of hyperthermia and the anti-angiogenic compound batimastat (30 mg/kg i.p.). Heat-induced vascular damage was assessed in small (82 mm3) and large (171 mm3) tumours using confocal microscopy and immunostaining for von Willebrand factor. The influence of hyperthermia on tumour blood flow was measured using the 86RbCl method. The anti-tumour activity of hyperthermia (one or two fractions a week apart) and batimastat (7 or 14 daily injections) and various combination schedules were examined. Hyperthermia disrupted 25-50% of the vasculature in the BT4An tumours, and the vascular damage was most extensive in the central part of the large tumours. The heated tumours exhibited a 40-60% blood flow reduction, which persisted until the last measurement after 24 h. One fraction of hyperthermia caused a significant growth delay of 4 days, compared with the control group (p = 0.01), but no additional tumour response was produced by a second heating session. Batimastat had no influence on tumour growth and the combination of drug and local heating did not enhance the tumour response, compared with heating alone. It was concluded that hyperthermia at 44 degrees C for 60min exhibits anti-vascular activity and inhibits tumour growth in the BT4An tumour model. Batimastat had no effect on tumour growth.

Angiogenesis Inhibitors↗

Potentiation of combined BCNU and hyperthermia by pH reduction in vitro and hypertonic glucose in vivo in the BT4 rat glioma.

In vitro studies have shown enhanced cell killing of BCNU and hyperthermia at acutely lowered pH. In animals hypertonic glucose i.p. has repeatedly been demonstrated to reduce intratumoral pH. Effect of hyperthermia (43 degrees C for 45 min), or BCNU (3.33 micrograms/ml or both on BT4C cells were investigated in vitro, with pH 7.5, 7.0 and 6.5 in the medium during treatment. The effect of elevated glucose concentration in the medium (20 mmol/l) during treatment with hyperthermia, or BCNU, or both, was also investigated at pH 7.5. BD IX rats with transplanted BT4A or BT4An tumours on the hind foot were treated with BCNU i.p., locally applied water bath hyperthermia (44 degrees C for 45 min) or both, with or without previous glucose (6 g/kg i.p. 2 h before treatment). In vitro: low pH markedly increased cell killing by combined BCNU and hyperthermia, but pH had only a minor influence on treatment with BCNU or hyperthermia alone. Increased glucose concentration in the medium did not influence the effect of BCNU alone, hyperthermia alone, or BCNU and hyperthermia. In vivo: glucose reduced the effect of BCNU alone on BT4A tumours, but did not influence the treatment results with hyperthermia alone. However, glucose enhanced the effect of combined BCNU and hyperthermias. The effect on BT4An tumours of BCNU or hyperthermia alone were not affected by glucose, but glucose markedly enhanced the tumour effect of combined BCNU and hyperthermia. Hyperglycaemia seems to be a promising method to increase the benefit of combined hyperthermia and BCNU. However, glucose-induced altered tumour circulation could hamper the potential benefit by decreased drug uptake.

Animals↗

Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology.

The ESHO protocol 3-85 is a multicentre randomized trial investigating the value of hyperthermia as an adjuvant to radiotherapy in treatment of malignant melanoma. A total of 134 metastatic of recurrent malignant melanoma lesions in 70 patients were randomized to receive radiotherapy alone (3 fractions in 8 days) or each fraction followed by hyperthermia (aimed for 43 degrees C for 60 min). Radiation was given with high voltage photons or electrons. Tumours were stratified according to institution and size (above or below 4 cm) and randomly assigned to a total radiation dose of either 24 or 27 Gy to be given with or without hyperthermia. The endpoint was persistent complete response in the treated area. A number of 128 tumours in 68 patients were evaluable, with an observation time between 3 and 72 months. Sixty-five tumours were randomized to radiation alone and 63 to radiation + heat. Sixty received 24 Gy and 68 tumours received 27 Gy, respectively. Size was < or = 4 cm in 81 and > 4 cm in 47 tumours. Overall the 2-year actuarial local tumour control was 37%. Univariate analysis showed prognostic influence of hyperthermia (rad alone 28% versus rad + heat 46%, p = 0.008) and radiation dose (24 Gy 25% versus 27 Gy 56%, p = 0.02), but not of tumour size (small 42% versus large 29%, p = 0.21). A Cox multivariate regression analysis showed the most important prognostic parameters to be: hyperthermia (odds ratio: 1.73 (1.07-2.78), p = 0.02), tumour size (odds ratio: 0.91 (0.85-0.99), p = 0.05) and radiation dose (odds ratio: 1.17 (1.01-1.36), p = 0.05). Analysis of the heating quality showed a significant relationship between the extent of heating and local tumour response. Addition of heat did not significantly increase the acute or late radiation reactions. The overall 5-year survival rate of the patients was 19%, but 38% in patients if all known disease was controlled, compared to 8% in the patients with persistent active disease.

Adult↗

Effect of hypertonic glucose in thermotolerant rat BT4An gliomas treated with combined hyperthermia and BCNU in vivo.

The influence of hypertonic glucose i.p. on development of thermotolerance and thermochemosensitivity with BCNU in thermotolerant tumours, and on intratumoural pH alterations in previously unheated and thermotolerant tumours, was investigated in BT4An tumours grown on the hind foot of BD IX rats. Thermotolerance was induced with local waterbath hyperthermia (44 degrees C/45 min) 24 h before start of test treatment. Hypertonic glucose immediately after priming hyperthermia did not inhibit development of thermotolerance, despite a significant reduction of pH by glucose. The pH reduction was less in thermotolerant tumours. Glucose administered before treatment of thermotolerant tumours did not change the growth rate of tumours treated with hyperthermia (44 degrees C/45 min), BCNU (20 or 25 mg/kg i.p.) or thermochemotherapy with a low or high dose BCNU (10 or 20 mg/kg), in contrast to previous results, where glucose enhanced thermochemosensitivity of non-thermotolerant tumours.

Animals↗

Quality assurance for radiofrequency regional hyperthermia.

Today most treatments with regional hyperthermia are applied using radiofrequency systems with 'focus' steering by amplitude and phase control. This paper deals with quality assurance procedures developed to ensure controlled and safe treatments in such systems. Our results show how the deviations between requested and observed phase and amplitude vary with frequency, and how these deviations depend on both the geometry of the object (phantom) inside the system and the power level applied. The results also indicate that the investigated systems' internal quality assurance procedures were inadequate and that additional procedures should be applied. Since the system parameters depend on patient and treatment specific conditions it is concluded that there is a need for QA measurements before or during treatment. This paper deals specifically with the commercial BSD-2000 system from BSD Medical Corp. in Salt Lake City, Utah, as installed in Bergen, but the procedure outlined can be applied to other phase and amplitude-controlled RF-RHT systems with only minimal adjustments.

Calibration↗

Testicular carcinoma. A curable malignancy.

The progress in the management of testicular germ cell tumours is reviewed. A marked improvement of the treatment results has been obtained in non-seminomas, especially by the use of cis-platinum based chemotherapy. At present long term survival can be expected in 85 per cent of all non-seminomas and in 95 per cent of all seminomas after adequate treatment. The natural history of the disease, symptomatology, diagnostic procedures, staging and different treatment modalities, as surgery, radiation therapy, chemotherapy and their combination, are discussed.

Combined Modality Therapy↗

Timing of combined hyperthermia and 1,3-bis(2-chloroethyl)-1-nitrosourea or cis-diamminedichloroplatinum in BD IX rats with BT4A tumours.

Groups of 7-10 evaluable BD IX rats with the neurogenic BT4A tumour on the right hind leg were treated with waterbath hyperthermia (44 degrees C, 60 min) in combination with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) 20 mg/kg or cis-diamminedichloroplatinum (cis-DDP) 3 mg/kg i.p. at different sequences and timing within +/- 24 hr. Tumour responses were evaluated by tumour doubling time and clinical criteria, toxicity by toxic deaths, weight loss, and local skin reactions. With both BCNU and cis-DDP, tumour response was markedly dependent on timing; the greatest effects were obtained giving hyperthermia just after the drug. Local side effects were not different in the timing groups, but cis-DDP general toxicity was most severe when cis-DDP was given just before hyperthermia.

Animals↗

Enhanced effect of combined hyperthermia and chemotherapy (bleomycin, BCNU) in a neurogenic rat tumour (BT4A) in vivo.

The neurogenic rat tumour BT4A was serially transplanted to the dorsum of the right hind leg of BD IX rats. The tumours were treated with water bath heating at 44.0 degrees C for one hour alone or combined with bleomycin or BCNU, both given intraperitoneally at a dose of 20 mg/kg. Bleomycin alone had no effect on tumour growth. Hyperthermia or BCNU alone both caused a transient growth delay before regrowth. Combination of hyperthermia and bleomycin caused a significantly enhanced effect with 8 partial regressions in 9 tumours. BCNU and hyperthermia resulted in 9 complete and one partial regressions of 10 treated tumours. Eight of these were cured. We conclude that the antitumour effects as well as the side effects caused by the combination of local hyperthermia and systemic administration of BCNU and bleomycin deserve further investigation.

Animals↗