Search PubMed⌕ Search

Biomedical subjects

O S Nielsen

Publications and source records attributed to O S Nielsen.

At least 19 recordsLinked to original sources
PubMed1992

Influence of dose on regeneration of murine hematopoietic stem cells after total body irradiation and 5-fluorouracil.

The regeneration of murine bone marrow stem cells after treatment with 5-fluorouracil (5-FU) and total body irradiation (TBI) was investigated by means of the spleen colony assay. 5-FU was given intraperitoneally in doses ranging from 75 to 225 mg/kg body weight. TBI was administrated as a single fraction in the dose range 0.75-3.50 Gy. The frequency of stem cells declined rapidly and reached a minimum (nadir) on day 1-2 after either of the 2 treatments. Their number returned to near-pretreatment values by day 7-10. Increasing the dose of either 5-FU or TBI resulted in a lower nadir in stem cell survival and a higher regeneration rate of the stem cells. The maximal regeneration rate corresponded to a doubling time of 19 h. The time to complete regeneration was constant and neither influenced by the treatment modality nor by the dose. Both this work and previous studies on cyclophosphamide and combined 5-FU and TBI may indicate that the regeneration rate of bone marrow stem cells after a cytotoxic assault is influenced primarily by the stem cell surviving the treatment rather than the treatment modality.

Animals↗
PubMed1991

Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer.

Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m2. In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (mean t1/2 gamma, 21.6 +/- 7.9 h; range, 10.6-69 h; n = 110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (mean t1/2 gamma, 18.1 +/- 4.8 h; range, 8.2-38.4 h; n = 105). Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (mean t1/2 gamma, 13 +/- 4.6 h; range, 2.7-29 h; n = 104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC = 9.44 x c2 + 62.5 x c24 + 157.7 (r = 0.953).

Breast Neoplasms↗
PubMed1991

A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement.

Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirubicin. A similar correlation was observed when the metabolite epirubicinol was also considered. The decrease in leucocyte count as expressed by the logarithmic ratio between nadir WBC and initial WBC was linearly correlated with the AUC of either epirubicin alone (r = -0.55, P less than 0.001) or epirubicin and epirubicinol together (r = -0.63, P less than 0.001). As a relationship between the concentration of epirubicin in a single plasma sample taken at 6 h following i.v. administration and the AUC of the drug has been established, a log-linear relationship between the expected decrease in leucocytes and the concentration at 6 h after administration could be calculated. The proposed model is expressed as the equation: log WBCnadir = log WBCinitial -0.0073 x c6 (ng/ml)-0.14.

Bone Marrow↗
PubMed1991

Sensitization to hyperthermia induced in a normal tissue by step-down heating.

The effect of step-down heating was investigated in the skin of the CDF1 mouse foot. Step-down heating was induced with a 44.7 degrees C/10 min pretreatment followed by a test treatment at a lower temperature for variable time. Step-up heating, that is, a test treatment followed by a 44.7 degrees C/10 min treatment, and single heating were used as controls. The normal tissue reaction was scored at five levels of damage (from slight redness and oedema to loss of a toe or greater reaction), and the heating time to induce each level in 50% of the animals, RD50, was used as the endpoint. The effect of step-down heating was quantified by the step-down ratio, calculated as the ratio of test heating times to obtain the endpoint. A significant reduction of the RD50 was seen at all score levels when the 44.7 degrees C/10 min was given in a step-down heating schedule, and the effect increased with decreasing test treatment temperature. In contrast, the heat sensitivity was only marginally influenced by step-up heating. An analysis of the time-temperature relationship demonstrated a log-linear relationship between temperature and RD50 for single heating in the range 42.2-44.7 degrees C and for step-down heating in the range 41.7-44.7 degrees C. The curve for step-down heating showed a lesser slope indicating a decrease of the activation energy. The kinetics of the SDH effect were investigated by inserting an interval between a primary 44.7 degrees C/10 min treatment and a test treatment performed at 42.2 degrees C. The effect of step-down heating was maximal with no interval between the priming treatment and the test treatment. As the interval was increased to 1.5 hr the step-down sensitization disappeared, and with even longer intervals thermotolerance developed. From a clinical point of view, the present data indicate that step-down heating may increase the extent of both reversible and irreversible heat damage in the normal tissue.

Acclimatization↗
PubMed1991

Preoperative and postoperative irradiation of soft tissue sarcomas: effect of radiation field size.

For the treatment of soft tissue sarcomas it has frequently been staged but not quantitatively demonstrated, that the volume irradiated is smaller when irradiation is given preoperatively as compared to postoperatively. In this study the field size used for preoperative irradiation was compared with that necessary in the same patient had the radiation been given postoperatively. Twenty-six patients with soft tissue sarcomas of the extremity, groin, and shoulder girdle who had received preoperative irradiation were resimulated following surgery to determine the size of the postoperative field. The simulation was performed by a physician not involved in the preoperative treatment planning. Preoperatively a radial margin of 5 cm around the tumor was used for low and intermediate grade and 7 cm for high grade sarcomas. Postoperatively the same margins were used but around the surgical field. Twelve patients underwent a wide resection and 14 patients a resection followed by vascularized tissue transfer to the surgical bed. The median follow-up was 22 months (range 13-46). No local recurrences and two cases of distant metastasis were observed. Independently of surgical procedure and tumor grade, the size of the preoperative radiation field and number of joints included in the field were significantly smaller than that of postoperative radiation (p less than 0.001). In two patients preoperatively and four patients postoperatively, the radiation field involved the whole circumference of the limb. Provided that equivalent radiation time-dose-fraction parameters are used and that the complication rate is proportional to the radiation field size, late complications may be less after preoperative irradiation than after post-operative irradiation.

Adolescent↗
PubMed1991

An assessment of combined tumour markers in patients with seminoma: placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD) and beta human chorionic gonadotrophin (beta HCG).

We have assessed the tumour markers placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD), and human chorionic gonadotrophin (beta HCG) using 2,000 serum samples from 286 patients with seminoma. The ROC curves show that no one marker performs adequately for the detection of disease either at initial staging or during follow-up. We used a Markov model heuristically to devise strategies, in which marker results were assessed in combination, which might be useful in clinical practice. We found that the best strategy was to consider a test result abnormal only if either the beta HCG was greater than 6 Ul-1 or the LD was greater than 400 U l-1 and the PLAP level was greater than 60 U l-1. This will detect about 50% of patients with disease and the false-positive rate is 2%. In practical terms this means that PLAP need only be estimated in patients whose beta HCG is less than 6 IU l-1 and whose LD is greater than 400 U l-1.

Alkaline Phosphatase↗
PubMed1991

Bone metastases: pathophysiology and management policy.

The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response.

Bone Neoplasms↗
PubMed1991

Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group.

From December 1980 to January 1984, all patients with stage I nonseminomatous testicular cancer in Denmark entered a randomized trial comparing surveillance only with radiotherapy after orchiectomy. One hundred fifty patients were assessable for the final analysis. Relapse occurred in 23 patients in the surveillance group and in 11 patients in the radiotherapy group. Radiotherapy completely prevented retroperitoneal relapse; 14 retroperitoneal relapses occurred in the surveillance-only group. All relapsing patients in the surveillance-only group are without evidence of disease with a median observation time after chemotherapy of 67 months. Two of the patients with relapse in the radiotherapy group died with disease; the others are alive without evidence of disease, with a median observation time after relapse treatment of 72 months. In the surveillance group, four relapses occurred later than 2 years after orchiectomy; only one such late relapse occurred in the radiotherapy group. Four of the retroperitoneal relapses occurred without concomitant increase in the serum marker levels (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]). It is concluded that surveillance only should replace radiotherapy after orchiectomy as standard treatment for clinical stage I nonseminomatous testicular cancer. Improved methods for control of retroperitoneal relapses, especially of embryonal carcinomas, are needed.

Adolescent↗
PubMed1990

Is placental alkaline phosphatase (PLAP) a useful marker for seminoma?

The usefulness of placental alkaline phosphatase (PLAP) as a tumour marker was assessed in 1578 serum samples from 236 patients with seminoma. Smoking habits were known for all but 7 patients (22 samples). Smoking was associated with significantly higher mean levels of PLAP in disease-free patients (28.8 [S.E. 2.1] U/l vs. 15.9 [1.3] U/l in non-smokers). Mean PLAP levels were higher in patients with active disease (78.6 [23.5] U/l in non-smokers and 47.2 [18.5] U/l in smokers). The median values showed a similar trend. However, there was considerable overlap between the various groups and differences between mean and median values indicated that PLAP values were distributed asymmetrically. The predictive value of PLAP as a tumour marker was consequently much less than superficial inspection of these values might suggest. In 97 patients on surveillance, only 2 out of 11 patients who relapsed had elevated PLAP at the time of clinically detectable relapse. With the upper limit of normal PLAP quoted by our laboratory (35 U/l), specificity and sensitivity were, respectively, 88% and 45% (all patients) and 96% and 47% (non-smokers). The sensitivity and specificity of PLAP were assessed in more detail for a series of threshold values (normal vs. abnormal) with a graphical method. Only in non-smokers did PLAP seem useful and even in this group the positive predictive value of an "abnormal" test may be low; less than 50% in clinically relevant circumstances. Serum PLAP assay cannot usefully stand alone as a marker for seminoma and its routine estimation contributes little to follow-up.

Adult↗
PubMed1990

Long-term results of carbon dioxide laser treatment of meatal condylomata acuminata.

A group of 74 men who underwent carbon dioxide laser treatment of meatal condylomata were observed for an average of 18 months. The cure rate after 1 treatment of isolated meatal lesions was 78%; the presence of external lesions lowered the rate to 32% and additional external and urethral warts to 25%. Following multiple treatments all but 6 patients were cured; 83% of the recurrences developed within 3 months. One urethral and 6 meatal strictures occurred more than 3 months after treatment; 9 patients had a spraying stream many years after treatment and 2 complained of frequency.

Adult↗
PubMed1990

Ultrasonically guided percutaneous nephrostomy.

Ultrasonically guided percutaneous nephrostomy was planned in 98 patients with a total of 128 nephrostomies. The success rate was over 90%. The catheters were maintained from a 1/2 day to 150 days with a median duration of 13 days. 26% of the patients had the catheter replaced, mainly because of displacement. Two major complications were seen, one perforation of the gallbladder and one case of major haemorrhage resulting in a nephrectomy. Two of the 26 patients infected at the puncture died from sepsis. Among cases with low ureteral obstruction untreated prostatic carcinoma and ureteral tumors were the two only categories in which a palliative nephrostomy was beneficial.

Adult↗
PubMed1990

Time-temperature relationships for L1A2 cells step-down heated from 38 to 45 degrees C in vitro.

The in vitro response of L1A2 cells to a single exposure to one temperature and to step-down heating was investigated. Single heating consisted of heating for a specified time at a constant temperature in the range 38.0-45.0 degrees C, whereas step-down heating involved a pretreatment of either 45.0 degrees C for 10 min or 42.0 degrees C for 90 min. The pretreatments were adjusted to give the same survival level. The survival curves for single heating had an initial shoulder followed by an exponential region, whereas for step-down heating they were strictly exponential and had no shoulder. The time-temperature relationship for cells exposed to single heating showed a biphasic Arrhenius curve with a downward inflection at 40.5 degrees C. Biphasic Arrhenius curves were also observed for step-down heating, but both the 45 degrees C/10 min and the 42 degrees C/90 min pretreatment showed an upward inflection that broke at 42.5 degrees C and 40.5 degrees C, respectively. The downward inflection on the Arrhenius curve for single heating has been attributed to thermotolerance development and the effect of step-down heating to a temporary inhibition of thermotolerance development. However, the present shape of the Arrhenius curves for step-down heating cannot be explained by inhibition of thermotolerance. It is therefore reasonable to assume that step-down heating is more than just the inhibition of thermotolerance, and that step-down heating and thermotolerance are distinct phenomena which act independently.

Animals↗
PubMed1989

[Bone metastasis].

Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumour originates from the breast, prostate or lungs. Even although the prognosis is serious, a proportion of the patients will survive for several years and will thus require active treatment. More than 25% of the patients have no symptoms whereas pain dominates in the remainder. Frequent complications are pathological fractures, hypercalcaemia and spinal cord compression. Normally, the diagnosis can be established from the clinical picture compared with a series of laboratory analyses, x-ray investigations of the skeleton and bone scintigraphy. As treatment is mainly palliative, the purpose is primarily relief of pain, prevention of fractures and ensuring a reasonable functional level. The therapeutic possibilities comprise local treatment in the form of surgery and irradiation and also systemic treatment in the form of chemotherapy, endocrine therapy and possibly diphosphonates. of these, irradiation still plays the most important role. About 80% of the patients respond to treatment and, after 12 months, 50-70% of the surviving patients will still be free from pain. Only few randomized investigations are found in the literature available and the criteria of response are, in general, difficult to interpret. There is, therefore, a great requirement for more clinically controlled investigations which assess the efficacy of the numerous therapeutic possibilities.

Bone Neoplasms↗
PubMed1989

Palliative irradiation of bone metastases.

Painful bone metastases is a common feature in patients with advanced cancer. The application of radiotherapy is often used as palliative treatment. A review of available data from the literature reveals that irrespective of the primary diagnosis palliation is achieved in 70-100% of cases. The biological basis of pain and the effects of radiotherapy is discussed. Treatment schedules for patients with single-bone lesions are reviewed. It is concluded that single-shot treatment in doses ranging from 5 to 8 Gy is as effective as multi-fractionated treatment. In addition, the possible role of radiotherapy in relation to patients with multiple lesions, and the use of combined surgery and radiotherapy in patients with impending and manifest fractures are discussed. It is concluded that the literature does not allow a definitive conclusion concerning an optimal use of radiotherapy.

Bone Neoplasms↗
PubMed1989

Thermotolerance in the mouse foot estimated at various levels of normal tissue damage.

The effect of fractionated 43.7 degrees C water bath heating on the skin of CDF1 mice was investigated. The normal tissue damage was scored at five levels (from slight redness and oedema to loss of a toe or greater damage) according to an arbitrary score system. The heating time to induce a given level of damage in half of the treated animals (RD50) was used as an end point. The feet were exposed either to a single treatment at 43.7 degrees C for different time periods or to a priming treatment of 30 min. at 43.7 degrees C followed at different intervals by a second graded heat treatment at 43.7 degrees C. In all treatment schedules, the score level increased proportionally with heating time, and the score system offered a good description of the acute skin damage following hyperthermia. The priming heat treatment induced thermotolerance with a time course independent of the score level chosen to estimate the heat response. The thermotolerance developed rapidly, reached a maximum within a 24 hr. interval, and then decayed slowly. The degree of thermotolerance was calculated by means of two previously described formulas for the thermotolerance ratio (TTR). The kinetics of thermotolerance in the skin of mice was independent of the TTR formula, whereas the degree of thermotolerance depended on both the score level and the TTR formula used.

Adaptation, Physiological↗
PubMed1989

Infected renal cyst simulating acute abdomen. Case report.

Renal cysts are rarely infected. The diagnosis should not represent a problem with the current techniques: however the condition can simulate acute abdomen in which case resection of the cyst roof and drainage is recommended.

Abdomen, Acute↗
PubMed1988

Effect of combined 5-fluorouracil and radiation on murine hematopoietic tissue.

The interaction of 5-fluorouracil (5-FU) and radiation in hematopoietic tissue was assessed as the survival of hematopoietic stem cells (CFUs) by means of the spleen colony assay. 5-FU was given intraperitoneally in the dose range 50-500 mg/kg body weight. In this dose range, stem cell survival decreased exponentially as a function of 5-FU dose. After 150 mg/kg of 5-FU alone (i.e. the maximum tolerated dose, MTD), the stem cell survival rapidly decreased, reaching a minimum after 1-2 days. The decrease was followed by a regeneration phase with a doubling time of about 28 h, with return to pretreatment values on day 7, and with an overshoot of survival on day 10-28. A similar regeneration was observed after 0.75 Gy radiation alone, but there was no evidence of an overshoot of stem cell number. 5-FU given 15 min before whole-body irradiation resulted in a pronounced reduction in stem cell survival due to an increase in the slope of the radiation survival curve by a factor of 2.1. After combined 5-FU and radiation, the survival rapidly decreased to a minimum at day 1, and it showed only a slight increase within the next 7 days. After this delay, the stem cells regenerated with a doubling time of about 30 h, reaching pretreatment values on day 15. The delayed stem cell regeneration was not seen following 3.5 Gy radiation alone or 225 mg/kg 5-FU alone, which resulted in the same nadir of CFUs survival as found after the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗