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Biomedical subjects

P Iversen

Publications and source records attributed to P Iversen.

At least 91 records · Page 5Linked to original sources
PubMed1991

In vivo studies with phosphorothioate oligonucleotides: pharmacokinetics prologue.

Phosphorothioate oligonucleotides which contain 35S at each internucleoside linkage have been prepared and employed to evaluate the in vivo pharmacokinetics in mice, rats and rabbits. A single administration of a 27-mer complementary to the rev gene of HIV into adult male rats by either the intravenous or intraperitoneal route reveals a biphasic plasma elimination. An initial half-life of 15-25 min represents distribution out of the plasma compartment and a second half-life of 20-40 h represents elimination from the body. The second half-life is significantly longer than a variety of nucleic acids such as poly-IC and Ampligen and suggests therapy with phosphorothioate oligonucleotides should be possible and practical. Repeated daily injections of the 27-mer provides steady-state concentrations in 6-9 days, confirming the estimated long half-life from single injection studies. Finally, chronic treatment studies indicate that the phosphorothioate oligonucleotides are relatively non-toxic. Hence, pharmacokinetic considerations are not likely to be limiting factors in anti-cancer drug design with phosphorothioate oligonucleotides.

Animals↗
PubMed1991

Long-term results of ultrasonically guided implantation of 125-I seeds combined with external irradiation in localized prostatic cancer.

Transperineal 125-iodine seed implantation guided by transrectal ultrasonography and subsequent external beam irradiation was employed in the treatment of 32 patients with localized prostatic carcinoma (16 poorly differentiated). Follow-up is currently 35-98 months with a median of 65 months. Distant metastases have developed in 18 patients, of whom 11 have died from prostatic cancer. Median change in prostatic volume was a reduction of 35%. Re-biopsy or transurethral resection of the prostate was performed in 25 patients after 1-4 years, revealing still malignant histology in 10 (40%), of whom 8 have developed distant metastases or died from prostatic cancer. Fourteen patients suffered from late complications of which surgical intervention was indicated in five cases. Nine patients are presently free of progression and prostate specific antigen is less than 0.5 ng/ml in 8 of these. The future role of ultrasonically guided implantation in the management of prostatic cancer is discussed.

Adenocarcinoma↗
PubMed1990

Comparability of EORTC and DAPROCA studies in advanced prostatic cancer.

Very often not enough patients are entered and/or the follow-up is insufficient to be able to draw valid conclusions in cancer clinical trials. In this article, we discuss the possibility of pooling the data from two or more trials asking the same or similar questions in order to overcome such problems. How comparable the studies should be for combining their data, in terms of design, patient population, follow-up, and end-points, is discussed in the first part of this paper. Whether these general considerations were completely or partially fulfilled in the two prostatic studies of the EORTC and DAPROCA is the subject of the second part of this article. Problems of interpreting apparently contradictory results, like the superiority of zoladex and flutamide over orchidectomy in terms of time to progression with no clear superiority in terms of overall duration of survival, is also discussed.

Aged↗
PubMed1990

A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate.

In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate.

Aged↗
PubMed1990

Zoladex and flutamide versus orchiectomy in the treatment of advanced prostatic cancer. A combined analysis of two European studies, EORTC 30853 and DAPROCA 86.

A total of 591 patients with advanced prostatic cancer have been randomized to either orchiectomy or treatment with zoladex 3.6 mg as a depot preparation combined with flutamide 250 mg tid in two European studies, EORTC protocol 30853 and DAPROCA 86. Identical design and comparable patient characteristics in the two studies have allowed combined analysis. A small but statistically significant difference in time to objective progression or death from prostatic cancer was found in favor of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchiectomy. Thus, no difference between treatment groups in overall survival was found. As a conclusion, the combined androgen blockade was not superior to orchiectomy in the treatment of patients with advanced prostatic cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Flutamide-induced liver failure.

Two cases of clinically manifest liver failure in patients with metastatic prostatic cancer treated with the non-steroidal antiandrogen flutamide combined with a luteinizing hormone-releasing hormone analogue are described. One patient developed severe hepatic insufficiency with jaundice, ascites and hepatic coma. The condition reversed after discontinuation of flutamide. The other patient only became jaundiced with a biochemical cholestatic pattern. Previous reports of hepatic adverse reactions only include elevated transaminase levels without clinical manifestations. The morphological lesions in the liver biopsy and the clinical condition may be due to a reversible interaction with metabolic processes in the hepatocytes.

Aged↗
PubMed1990

Zoladex plus flutamide vs. orchidectomy for advanced prostatic cancer. Danish Prostatic Cancer Group (DAPROCA).

The study comprised 262 patients with previously untreated advanced carcinoma of the prostate. Patients were randomized either to undergo orchidectomy or to receive combined treatment with Zoladex, 3.6 mg every 4 weeks, plus flutamide, 250 mg t.i.d. At present the median follow-up is 39 months. The objective response to therapy was better in the Zoladex plus flutamide group, but no differences in subjective response, time to disease progression, or survival have been demonstrated between the 2 groups. Adverse effects were more common in the Zoladex plus flutamide group. Thus, 'total androgen blockade' with Zoladex plus flutamide was not clinically superior to orchidectomy in the treatment of patients with advanced prostatic cancer.

Aged↗
PubMed1989

[Severe toxic hepatitis during flutamide (Eulexin) treatment].

A case of severe toxic hepatitis in a patient with metastatic prostatic cancer treated for three months with flutamide (Eulexin) combined with an LHRH analogue, goserelin (Zoladex) is described. The patient developed severe liver failure with jaundice, ascites and severe encephalopathy. The condition reversed after discontinuation of flutamide. Less severe, but otherwise similar, adverse reactions have been reported in the literature, and the importance of considering the drug as a potential hepatotoxin is stressed.

Anilides↗
PubMed1989

Ultrasonically guided 125iodine seed implantation with external radiation in management of localized prostatic carcinoma.

Thirty-three patients with localized prostatic carcinoma (16 poorly differentiated) were treated with transperineal 125Iodine seed implantation (160 Gy) guided by transrectal ultrasonography and subsequent external beam irradiation (47.4 Gy). The observation time was six to sixty-eight months with a median follow-up of thirty-five months. Median change in prostatic volume was a reduction of 35 percent. Re-biopsy or transurethral resection of the prostate was performed in 25 patients after one to two years, revealing still malignant histology in 12 (48%). Development of distant metastases occurred in 14 patients (44%), and 8 have died of prostatic cancer. Fourteen patients suffered from late complications of which surgical intervention was indicated in 3 cases.

Aged↗
PubMed1989

LHRH analogue as a depot preparation (Zoladex) in the treatment of advanced carcinoma of the prostate followed by orchiectomy as a second line therapy--a phase II study.

An LHRH agonist, Zoladex, was employed as a monthly depot in 56 previously untreated patients with advanced carcinoma of the prostate. Of 53 evaluable patients, 27 achieved partial remission and 7 were stable. Median duration of response was 10 months. A favorable subjective response was attained in 68% of the patients. During treatment, serum testosterone was in the castrate range in all patients except five. Possible explanations for this escape phenomenon are discussed. No toxicity was observed and treatment was well tolerated in all patients. Thirty-two patients underwent bilateral orchiectomy following treatment failure of Zoladex. In one patient partial remission according to protocol criteria was recorded. Treatment with LHRH agonists seems safe and may serve as an alternative to conventional hormonal treatment of advanced carcinoma of the prostate.

Aged↗
PubMed1988

Chromatographic and spectral investigations on the in vivo metabolites of 6-nitrobenzo[a]pyrene.

6-Nitrobenzo[a]pyrene (6-NBaP) occurs in the environment, is mutagenic in the Ames assay in the presence of added S9 and is carcinogenic to male but not female mouse liver when injected intraperitoneally (i.p.) into mice. In order to understand what kinds of active metabolites could have been produced in vivo, both male and female mice were injected i.p. with 6-NBaP in dimethyl sulfoxide. Twenty-four hours after injection, urine, feces, blood, liver and spleen (non-target tissue) were examined for metabolites by chromatographic and high-resolution mass spectral means. On the basis of the mass spectral fragmentation patterns of synthetic and metabolic standards, it was observed that both male and female animals excreted ring-hydroxylated metabolites of 6-NBaP in the urine to differing extents. Male animals additionally excreted 6-aminobenzo[a]pyrene and the significance of this observation is discussed.

Aging↗
PubMed1988

Sensitivity of 131I-hippuran diuresis renography and pressure flow study (Whitaker test) in upper urinary tract obstruction.

Diuresis renography and pressure flow studies were performed in 14 patients with unilateral hydronephrosis. Based upon the results of intravenous pyelography, typical symptomatology, and the outcome of surgical treatment, all patients were found to have upper urinary tract obstruction. It was therefore possible to calculate the sensitivity of the two tests. Obstruction was found at the pressure flow studies in 7 of 14 patients (50%), while an obstructive pattern was found at diuresis renography in 12 of 13 patients (92%). Due to a very low glomerular filtration rate, diuresis renography was equivocal in 1 case. Based upon these results, diuresis renography seems to be superior to pressure flow studies in cases with upper urinary tract obstruction.

Adult↗
PubMed1988

Thyroid hormone turnover in patients with small cell carcinoma of the lung.

Patients with small cell carcinoma of the lung often present with symptoms suggestive of hyperthyroidism i.e. weight loss without anorexia. Consequently [125I]T4 and [131I]T3 turnover was studied using simultaneously iv bolus injection and noncompartmental analysis in 6 patients with untreated small cell carcinoma of the lung and 14 normal subjects of comparable ages. Both T4 and T3 production rates were enhanced, T4 production being in median 135 nmol.day-1.70 kg-1 (range 111-200) in patients with small cell carcinoma of the lung vs 98 nmol.day-1.70 kg-1 (range 69-134) in controls (P less than 0.01), and T3 production being 46 nmol.day-1.70 kg-1 (range 33-65) vs 31 nmol.day-1.70 kg-1 (range 24-45) (P less than 0.01). The mean transit time was shortened for both T4 and T3, T4 mean transit time being 5.9 days (3.9-8.0 days) vs 8.3 days (6.1-11.2 days) in controls (P less than 0.01), and T3 mean transit time being 0.74 days (0.36-0.98 days) vs 1.03 days (0.81-1.45 days) in controls (P less than 0.01). Serum total and free T4 and T3 levels were unchanged. Basal serum TSH levels and the TSH response to iv TRH were also normal. Thyroid-stimulating immunoglobulins were only present in the serum in 1 of 6 patients. Thus, thyroid hormone production seemed under pituitary regulation. The peripheral effect of thyroid hormones was evaluated measuring serum sex hormone binding globulin levels, which were increased to in median 270% (77-310%) (P less than 0.01) of that in controls, suggesting some degree of hyperthyroidism in liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗