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Biomedical subjects

O Dahl

Publications and source records attributed to O Dahl.

At least 73 records · Page 4Linked to original sources

Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study.

Between 1984 and 1987, 61 radically resected patients with carcinoma of the pancreas (n = 47) or the papilla of Vater (n = 14) were randomised either into postoperative adjuvant combination chemotherapy (AMF); 5-fluorouracil 500 mg/m2, doxorubicin 40 mg/m2, mitomycin C 6 mg/m2 (n = 30) once every 3 weeks for six cycles, or into a control group (no adjuvant chemotherapy) (n = 31). The median survival in the treatment group was 23 months compared with 11 months (P = 0.02, median test) in the control group, dependent on a survival benefit in the treatment group during the initial 2 years (P = 0.04 generalised Wilcoxon). The long-term prognosis was the same with an identical survival after 2 years (P = 0.10, power = 0.83). The observed 1, 2, 3 and 5-year survivals in the treatment group were 70, 43, 27 and 4% compared with 45, 32, 30 and 8 in the control group. 1 patient succumbed to sepsis probably attributable to chemotherapy. Cardiotoxicity and nephrotoxicity were recorded in 2 patients. These results suggest that adjuvant chemotherapy does postpone the incidence of recurrence in the first 2 years following radical surgery but increased cure rate was not observed.

Adult↗

[Half-body irradiation. An effective palliative treatment of widespread skeletal metastases].

In a large number of cancer patients, extensive skeletal metastases or myelomatosis induce vast suffering, such as intolerable pain and local complications of neoplastic bone destruction. Analgetic drugs frequently do not yield sufficient palliation. Irradiation of local fields often has to be repeated, because of tumour growth outside previously irradiated volumes. Wide field irradiation of the lower or upper half of the body causes significant relief of pain in most patients. Adequate pretreatment handling of patients, method of irradiation, and follow-up are of marked importance to reduce side effects, and are described as they are carried out at the Department of Oncology, Haukeland Hospital.

Bone Neoplasms↗

[In-hospital day for patients connected with the District Psychiatric Center in Svendborg. A controlled study].

As of 31.12.1990, the employment of bed-days and admissions was calculated for patients who had been connected with a district psychiatric centre for more than three years. A before-and-after comparison revealed a percentage reduction in the employment of bed-days as compared with a control group. This corresponds to the findings in other investigations. In the before-and-after analysis, various reductions are described according to the diagnostic groups. The reduction in bed-day employment consisted mainly of fewer readmissions and reduction in the group of long-term hospitalisations. A reduction also occurred in the group of patients who could characterized as least ill. In this group, a marked percentage reduction in bed-days was observed as compared with the control group and this was probably due to the good and continuous treatment after discharge offered by the district psychiatric centre. This investigation revealed that the employment of bed-days for a patient population receiving district psychiatric treatment after discharge can be reduced. Nevertheless, the most severely ill patients will still require periodic admission to hospital. The value of treatment after discharge of the "Svendborg Model" type does not provide scientifically valid arguments that hospital admission can be avoided where the most severely ill patients are concerned.

Adult↗

Thermochemotherapy with cisplatin or carboplatin in the BT4 rat glioma in vitro and in vivo.

The effect of thermochemotherapy with cisplatin or carboplatin was compared in the BT4-cell line. In vitro: BT4C-cells were treated with different concentrations of cisplatin or carboplatin, with or without simultaneous hyperthermia. In vivo: Inbred BD IX rats with transplanted glioma-like BT4A or glioblastoma-like BT4An tumors on the hind leg were treated with cisplatin (4 mg/kg) or carboplatin (50 mg/kg), with or without local hyperthermia. In vitro the benefit of adding hyperthermia to chemotherapy was similar for cisplatin and carboplatin. For both cisplatin and carboplatin, the difference of treatment effect between thermochemotherapy and chemotherapy alone increased with higher drug concentrations. In vivo hyperthermia clearly enhanced the effect of carboplatin on BT4A tumors. When treating BT4An tumors, thermochemotherapy with cisplatin or carboplatin was equally effective. Both combinations were superior to treatment with hyperthermia alone. Local toxicity and weight loss following thermochemotherapy were comparable when substituting cisplatin with carboplatin.

Animals↗

Solid phase synthesis of oligodeoxyribonucleoside phosphorodithioates from thiophosphoramidites.

Oligonucleoside phosphorodithioates 1 are modified DNA sequences with potential use as antisense oligonucleotides. The preparation of up to 20-mers containing all four bases by solid phase synthesis is described, with details on the preparation of the four monomer units (protected nucleoside thiophosphoramidites 2), the conditions used for the assembly of the strands with up to 19 phosphorodithioate linkages, and the purification and characterisation of the products. Full-length homogeneity of HPLC-purified all-phosphorodithioate products is demonstrated by PAGE, but 31P NMR discloses the presence of phosphorothioate impurities (typically 8-9%), the origin of which is discussed. Oligonucleoside phosphorodithioates are freely soluble in water at neutral or basic pH, and are very stable towards oxidation, hydrolysis, and nuclease cleavage. Their ability to hybridize to complementary DNA has been studied by UV melting point (Tm) measurements. The observed depression of Tm, 0.5-2 degrees C per phosphorodithioate linkage, is higher that the 0.4-0.6 degrees C found for phosphorothioates.

Base Sequence↗

Thermal enhancement of ACNU and potentiation of thermochemotherapy with ACNU by hypertonic glucose in the BT4An rat glioma.

Hyperthermia increases the cytotoxicity of the nitrosourea BCNU (carmustine). Glucose given before treatment may further increase the value of thermochemotherapy, presumably by lowering tumour pH through blood flow reduction. The water-soluble ACNU (nimustine) is an alternative to other nitrosoureas in the treatment of gliomas. The drug is soluble without use of ethanol, and the eye complications when given intra-arterially are reduced compared with similar use of BCNU. The influence of simultaneous hyperthermia on treatment with ACNU, and the value of glucose administered before thermochemotherapy therefore were investigated in the malignant rat glioma BT4An. BD IX rats with subcutaneous BT4An tumours on the hind leg were treated with ACNU (i.p.), or ACNU and locally applied waterbath hyperthermia (44 degrees C for 45 min), with or without previous glucose (6 g/kg i.p. 2 hours before treatment). ACNU (10 or 20 mg/kg) alone and ACNU (20 mg/kg) after previous glucose did not influence tumour growth, compared to the controls. Simultaneous ACNU (10 mg/kg) and hyperthermia clearly was more effective than treatment with hyperthermia alone. Glucose load before treatment further enhanced the effect of combined ACNU and hyperthermia. Glucose before treatment did not change local toxicity or weight profiles of treatment with ACNU alone, or simultaneous ACNU and hyperthermia. Glucose load therefore represented a therapeutic gain when administered before thermochemotherapy with ACNU.

Animals↗

Venous and neural invasion as predictors of recurrence in rectal adenocarcinoma.

After radical surgery for rectal adenocarcinoma, the presence of venous and neural invasion of tumor cells was correlated with the pattern of treatment failure, local in the pelvis or distant. Of 128 operation specimens, venous and neural invasion was demonstrated in 22 percent and 32 percent, respectively. A significant decrease of the distant recurrence-free 5-year survival (Kaplan-Meier method) was seen when venous invasion was demonstrated (32.9 percent vs. 84.3 percent; P less than 0.0001), whereas more local failures were registered in patients with neural invasion. The local recurrence-free 5-year survival in patients with neural invasion was 64.3 percent, compared with 81.1 percent when neural invasion was not demonstrated (P = 0.03). Their prognostic value was then studied in a Cox regression model including stage and grade. Neural invasion had the strongest association with local recurrences, whereas venous invasion was found to be the third strongest independent predictor of metastasis, after lymph node status and extent of local tumor infiltration. We conclude that examining for the presence of venous and neural invasion gives reliable prediction of recurrences after radical resection of rectal cancer. Recording of tumor recurrence pattern may lead to a better selection of patients for adjuvant therapy after surgery.

Adenocarcinoma↗

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.

Adolescent↗

Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway.

A randomized, multicenter clinical trial was conducted in Western Norway to study the effectiveness of preoperative radiation therapy in operable rectal cancer, given at a dosage of 3150 cGy in 18 fractions, 2 to 3 weeks before radical surgery. Three hundred nine patients were entered into the trial between May 1976 and December 1985. After radiation no tumor was seen in 4.5% of the patients. There was no increased morbidity or mortality at surgery. The 5-year survival for evaluable patients was 57.5% in the control group and 56.7% in the radiotherapy group. For patients operated on for cure the 5-year survival was 60.9% and 64.2% in the control group and radiotherapy group, respectively. Radiation significantly delayed both local and distant recurrences in patients in the radiation group who had curative resection from 13.3 months in controls to 27.1 months. The local recurrence rate in the corresponding groups was 21.1% and 13.7%, respectively. We conclude that higher preoperative radiation doses should be used in new trials as a higher dosage may transform the observed positive effects into a survival benefit.

Adult↗

Retropseudogenes constitute the major part of the human elongation factor 1 alpha gene family.

The elongation factor 1 alpha (EF-1 alpha) is a protein which promotes the GTP-dependent binding of aminoacyl-tRNA to ribosomes in the protein synthesis process. A human gene coding for EF-1 alpha has previously been cloned and sequenced along with a pseudo-gene. Here, we have further analyzed the family of human EF-1 alpha genes. Using an EF-1 alpha cDNA as probe twelve genomic EF-1 alpha-like clones were isolated and analyzed. Four of these were sequenced and found to contain EF-1 alpha retropseudogenes. A Southern blot analysis indicated that the remaining eight clones also contained retropseudogenes. Genomic Southern blot analysis revealed at least twenty loci in the human genome with sequence homology to the EF-1 alpha cDNA. Besides the already described active gene only one potentially active locus was found. The others appeared to be retropseudogenes. EF-1 alpha retropseudogenes were also found to be abundant in the mammalian species mouse and pig, while the chicken contained only one presumably active EF-1 alpha gene.

Blotting, Southern↗

Preoperative radiotherapy in operable rectal cancer.

The effect of preoperative radiotherapy (31.5 Gy in 3.5 weeks) in operable rectal cancer was examined with respect to resectability and prognosis after two surgical procedures, abdominoperineal resection, or low anterior resection. Preoperative radiation did not influence the surgeon's selection of low anterior resection, which was similar (40 percent) in each group. Radiation improved five-year survival probability and decreased the incidence of local recurrence significantly after low anterior resection. In contrast, no improvement of treatment results was found in patients treated by abdominoperineal resection after radiotherapy.

Adenocarcinoma↗

The role of venous and neural invasion on survival in rectal adenocarcinoma.

A total of 254 rectal adenocarcinomas were examined for the presence of venous and neural invasion. Both the incidence of venous and neural invasion increased with Astler-Coller's stage, except for stage C1 related to neural invasion. Both prognostic factors predicted significantly reduced actuarial survival rates in patients with node-negative tumors. Thus, examination for the presence of venous and neural invasion can add information to conventional staging in node-negative tumors for assessing prognosis after radical surgery for rectal adenocarcinoma.

Actuarial Analysis↗

A cerebral glioma model for experimental therapy and in vivo invasion studies in syngeneic BD IX rats.

An in vivo glioma model was developed in syngeneic BD IX rats. The BT4An tumor was derived from serial in vivo passages of the BT4A tumor, originally induced from transformed fetal rat brain cells after transplacental exposure to ethylnitrosourea. The cell line was characterized for the presence of neuroglial differentiation markers, chromosome content and cell cycle distribution as determined by flowcytometry. A standardized method for i.c. tumor induction was developed, and the tumors were investigated by light and electron microscopy and for evidence of blood-brain barrier disruption. Tumor cell ability for phagocytosis was studied, as this property may be important for the invasion pattern of the tumors. We conclude that the model seems suitable for both in vivo therapy and invasion studies. The tumor had 100% tumor take, yielded a predictable symptom-free life span after inoculation, had a characteristic histological picture of an aggressive glioma, and the blood-brain barrier within the tumor was in part disrupted. Compared to the parent cell line, there was loss of neuroglial differentiation markers, the chromosomal distribution was changed, and the ability for phagocytosis was practically lost.

Animals↗

Tumour shrinkage and down staging after preoperative radiation of rectal adenocarcinomas.

In order to analyse the influence of low radiation doses on human rectal adenocarcinomas, gross and microscopical changes after preoperative radiation were compared to controls treated with immediate surgery in a randomised, prospective trial. The X-ray doses given were 31.5 Gy in 3.5 weeks, and the interval between radiation and operation was 2 to 3 weeks. A total of 138 patients having preoperative radiotherapy and 131 controls were analysed. The overall tumour size was reduced after radiation. Complete tumour regression was obtained in six (4.4%) patients. All of these tumours were exophytic and mobile at the initial examination and all were either well or moderately well differentiated. A significant downstaging was found after preoperative radiation. The incidence of positive lymph nodes was 27.5% in the resected specimens in controls and 18.4% after radiation (p less than 0.05). The total number of recurrences was reduced after radiation in stage C2 tumours, but not in the other stages. Preoperative radiation did not influence the histological grade of the tumours. There was no difference between the two randomised groups with respect to 5-year survival or disease-free survival in any histopathological stage.

Adenocarcinoma↗

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.

Chorionic Gonadotropin↗

Physicochemical and structural studies of triamterene.

It has been shown by several physicochemical techniques that the existence of different crystal forms of triamterene, as well as the crystalline products from different solvents with distinct differences in melting points, does not necessarily imply polymorphic crystal forms. The crystalline structure for triamterene is reported herein, revealing a N,N-dimethylformamide molecule and a water molecule within the crystal lattice. Triamterene crystallizes in a face-centered orthorhombic space group, Fdd2 (#43), when grown from aqueous solutions of dimethylformamide (N,N-DMF). In addition, the asymmetric unit contains a partially occupied molecule which is situated on a crystallographic twofold axis. Weak hydrogen bonding occurs between atoms O(1) and N(7), with a distance of 2.66 A, O(1) and N(5) with a distance of 2.96 A, O(2) and N(1), at two different symmetry sites of 2.99 A, and N(2) and N(7), with a distance of 2.91 A. The different solvated crystalline triamterene specimens have different melting points depending on organic solvation, water, or both.

Chemical Phenomena↗

Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group.

From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.

Adolescent↗

Hyperthermia improves local tumour control in locally advanced breast cancer.

We report three patients with advanced breast cancer who received hyperthermia (43 degrees C over 1 h, weekly x 4) and radiotherapy as palliative treatment for chest-wall recurrence. The case reports demonstrate situations where hyperthermia may be beneficial. These include tumours where radiotherapy alone is not expected to achieve control, such as large fungating tumours, and in previously irradiated areas. In these patients, hyperthermia with radiation achieves better local control of the tumour and delays the need for systemic chemotherapy. This may improve the quality of palliation.

Aged↗