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Biomedical subjects

P Iversen

Publications and source records attributed to P Iversen.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vivo evaluation of a morpholino antisense oligomer directed against tumor necrosis factor-alpha.

Morpholino antisense oligomers directed against the cytokine tumor necrosis factor (TNF-alpha) can specifically inhibit production of TNF-alpha by macrophages in vitro. To evaluate the efficacy of morpholino antisense in vivo, we characterized a mouse model of increased pulmonary TNF-alpha production and inflammation in response to aerosolized endotoxin. Pretreatment of mice by intranasal (i.n.) insufflation of oligomers (30 microl of 100 microM/ml) 12 hours prior to lipopolysaccharide (LPS) exposure resulted in specific and consistent inhibition of TNF-alpha production by the oligomer MAS-2, whereas no effect was observed with a sequence-scrambled control (% inhibition 31.5 +/- 3.5 vs. 1.3 +/- 8.0, respectively, p < 0.005). Dose-response analysis showed similar efficacy for MAS-2 at 25-100 microM/ml and diminished effects with lower concentrations. Inhibition of TNF-alpha did not alter the increase in neutrophils seen in bronchoalveolar lavage (BAL) fluid, a result consistent with observations using i.n. administration of neutralizing anti-TNF-alpha antibody or TNF receptor knockout mice. The results establish that morpholino oligomers directed against cytokine targets can function in vivo. Additional studies of other targets and administration protocols to improve efficacy are warranted.

Administration, Intranasal↗
PubMed2000

The association between implicit theories of personality and the attributional process.

The influence of implicit theories of personality (entity vs. incremental theorists; see Dweck, Chiu and Hong, 1995) on the stages of the Sequential Operations Model of attribution (Gilbert, Pelham, and Krull, 1988) was investigated. Two hundred eighty Norwegian participants were given a Norwegian translation of the implicit personality theories measure. Participants then read two essays, one advocating the pro-life position and the other advocating the pro-choice position on the abortion issue. The essay positions were ostensibly assigned rather than freely chosen by the author. After each essay, participants were asked to rate the essay position and the true attitude of the author. Entity and incremental theorists showed no differences in their ratings of the essay position; however, entity theorists made significantly stronger correspondent inferences about the author's attitude than did incremental theorists. These results support the contention that entity theorists engage in less attributional correction than incremental theorists.

Adult↗
PubMed2000

Photoactivation of vascular iNOS and elevation of cGMP in vivo: possible mechanism for photovasorelaxation and inhibition of restenosis in an atherosclerotic rabbit models.

Recently, intravascular low-power red laser light (LPRLL) therapy has been proposed for the prevention of postangioplasty restenosis due to the observed inhibition of experimental neointimal formation. The objective of this study was to determine the impact of endoluminal LPRLL on vascular levels of inducible nitric oxide synthase (iNOS) and cyclic guanosine monophosphate (cGMP) to help define the mechanism of this effect. Eight atherosclerotic male adult New Zealand White rabbits weighing 4-6 kg were used in these studies. The iliac arteries were treated in separate zones with: (1) balloon inflation only; (2) laser illumination only; and (3) balloon inflation + laser illumination. An uninjured zone of the iliac artery served as a control. Laser irradiation (630 nm) was delivered to the vessel wall via a Cold laser Illuminator (Cook, Inc., Bloomington, IN), with a 3 mm-diameter balloon. Experiments demonstrated that vascular cGMP levels obtained immediately following treatment in the balloon only group was the lowest (0.29 +/- 0.05 pmol/mg protein) and significantly lower compared with the uninjured controls (1.01 +/- 0.07 pmol/ mg protein) (P < 0.001). In the laser only treated group cGMP levels were significantly increased (2.87 +/- 0.12 pmol/mg protein) compared with the uninjured control (P < 0.001) and the balloon only group (P < 0.001). Vascular cGMP levels in the balloon + laser group (2.09 +/0.07 pmol/mg protein) was also increased compared to the balloon only (P < 0.001) and control (P < 0.001) groups. Qualitative analysis of Western blot demonstrated that laser illumination induces iNOS. In contrast balloon dilatation did not induce iNOS. Balloon + laser treatment, however, tended to restore the expression of iNOS. Our study demonstrated that intravascular low dose laser irradiation induces iNOS and elevates vascular cGMP in an in vivo atherosclerotic rabbit model.

Angioplasty, Balloon↗
PubMed2000

The need for hospital care of patients with clinically localized prostate cancer managed by noncurative intent: a population based registry study.

PURPOSE: We studied the need for hospital care of patients 74 years old or younger with clinically localized prostate cancer managed by deferred endocrine therapy. MATERIALS AND METHODS: Our series included all cases of newly diagnosed, clinically localized prostate cancer reported to the Danish Cancer Registry from 1977 to 1992. Information on the number of hospitalizations and operations performed from 1977 to 1994 was obtained from the Danish Hospital Discharge Registry. RESULTS: Our study included 4,790 men 37 to 74 years old with clinically localized prostate cancer. During the year of diagnosis and once a year of the following 9 years patients were hospitalized an average of 2.2 and 1 times and remained hospitalized an average of 22 and 10 days, and prostate cancer accounted for approximately 80% and 67% of hospitalizations the year of diagnosis and once a year subsequently. Nearly 90% of patients underwent transurethral prostatic resection within the year of diagnosis and in 30% repeat resection was necessary. A third of the patients underwent orchiectomy during the study period. Median time from the diagnosis to orchiectomy was 23 months. The estimated probability of surviving 5 and 10 years without orchiectomy was 39% and 17%, respectively. CONCLUSIONS: Patients diagnosed with clinically localized prostate cancer managed expectantly had a substantial need for hospital care in the years after the diagnosis. When evaluating outcome and quality of life after treatment of localized prostate cancer, the cost and impact of associated morbidity must be considered as well as patient survival.

Adult↗
PubMed2000

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup.

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.

Androgen Antagonists↗
PubMed1999

Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells.

Epidemiologic and animal studies have linked pancreatic cancer growth with fat intake, especially unsaturated fats. Arachidonic acid release from membrane phospholipids is essential for tumor cell proliferation. Lipoxygenases (LOX) constitute one pathway for arachidonate metabolism, but their role in pancreatic cancer growth is unknown. The expression of 5-LOX and 12-LOX as well as their effects on cell proliferation was investigated in four human pancreatic cancer cell lines (PANC-1, MiaPaca2, Capan2, and ASPC-1). Expression of 5-LOX and 12-LOX mRNA was measured by nested RT-PCR. Effects of LOX inhibitors and specific LOX antisense oligonucleotides on pancreatic cancer cell proliferation were measured by (3)H-thymidine incorporation. Our results showed that (1) 5-LOX and 12-LOX were expressed in all pancreatic cancer cell lines tested, while they were not detectable in normal human pancreatic ductal cells; (2) both LOX inhibitors and LOX antisense markedly inhibited cell proliferation in a concentration-dependent and time-dependent manner; (3) the 5-LOX and 12-LOX metabolites 5-HETE and 12-HETE as well as arachidonic and linoleic acids directly stimulated pancreatic cancer cell proliferation; (4) LOX inhibitor-induced growth inhibition was reversed by 5-HETE and 12-HETE. The current studies indicate that both 5-LOX and 12-LOX expression is upregulated in human pancreatic cancer cells and LOX plays a critical role in pancreatic cancer cell proliferation. LOX inhibitors may be valuable for the treatment of pancreatic cancer.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1999

Morbidity in patients with clinically localized prostate cancer managed with non-curative intent. A population-based case-control study.

To compare the morbidity in patients with newly diagnosed clinically localized prostate cancer managed conservatively with the morbidity in a randomly selected age-matched background population with no history of prostate cancer. Patients younger than 75 y at diagnosis with newly diagnosed clinically localized prostate cancer reported to the Danish Cancer Registry in the period 1977-1992. Morbidity in patients and age-matched controls was extracted from The Danish Hospital Discharge Registry. Admissions were stratified by discharge diagnosis. Overall 4744 patients were hospitalized for 251,695 days within the first 10 y following diagnosis compared with 74,563 days in 4774 age-matched controls. The patients were admitted 6.7 (6.4-7.1) times more often than controls in the year following diagnosis, and 2.7 (2.6-2.8) times more often in the following 9 y. Excess morbidity declined over time. When prostate cancer-related admissions were excluded, the relative risk of admission was reduced to 1.35 (1.3-1.4) and 0.86 (0.83-0.89), respectively. The estimated costs associated with deferred therapy in patients with clinically localized prostate cancer exceeded the estimated cost in age-matched controls by approximately US$88 million, equivalent to an average extra cost per patient of approximately US$18,500. Patients with clinically localized prostate cancer managed conservatively had a significantly higher morbidity than age-matched controls due to admissions associated with prostate cancer. In future comparisons of treatment strategies, morbidity following treatment and impact on quality of life have to be included when evaluating the outcome.

Journal Article↗
PubMed1999

Quality of life issues relating to endocrine treatment options.

Recent interest has focused on the use of hormone therapy in prostate cancer for both the management of patients with non-metastatic disease and as a neoadjuvant or adjuvant to curative therapies. This has resulted in patients with fewer symptoms being treated for longer periods of time. Endocrine treatments for prostate cancer, such as castration, combined androgen blockade and non-steroidal antiandrogen monotherapy, have shown similar results in terms of time to progression and survival. The main difference between these treatments is their impact on patients' quality of life. Instruments for measuring health-related quality of life should assess both overall and disease-specific quality of life. Data from two large studies of bicalutamide monotherapy show that this non-steroidal antiandrogen is associated with significant health-related quality of life advantages in the treatment of patients with locally advanced (M0) disease compared with castration, suggesting that this treatment may benefit patients with early disease. Bicalutamide was favoured in 8 out of 9 evaluable quality of life dimensions, and this was statistically significant for sexual interest and physical capacity. Endocrine treatments with minimal adverse effects on quality of life will be increasingly favoured for patients with non-metastatic disease who are being treated for longer periods of time.

Androgen Antagonists↗
PubMed1999

Mortality of patients with clinically localized prostate cancer treated with observation for 10 years or longer: a population based registry study.

PURPOSE: We studied the outcome in patients with early and probably organ confined prostate cancer who were considered candidates for curative therapy and treated expectantly. MATERIALS AND METHODS: The study included 2,570 patients with newly diagnosed prostate cancer reported to the Danish Cancer Registry from 1943 to 1986 and surviving for 10 years or longer. Mortality and causes of death were analyzed and stratified by stage, age and time of diagnosis. Excess mortality was calculated from life expectancy tables for the general population. RESULTS: An overall excess mortality (standard mortality ratio 1.58, 95% confidence interval [95% CI] 1.51 to 1.65) was found. Young age and advanced clinical stage at diagnosis entailed a higher risk of death from prostate cancer. Overall 42.7 and 19.1% of the patients who died had prostate cancer as the direct or contributing cause of death, respectively. Of the annual deaths 13% were attributable to prostate cancer. In 1,326 patients 55 to 64 and 65 to 74 years old with clinically localized prostate cancer at diagnosis the excess mortality was still significant (standard mortality ratio 1.72, 95% CI 1.54 to 1.93 and 1.50, 95% CI 1.39 to 1.62, respectively). Prostate cancer was the primary or contributing cause of death in 42.9% of the younger group and 21.5% of the older group. In these patients 15% of the annual deaths were related to prostate cancer. CONCLUSIONS: Patients with clinically localized prostate cancer for 10 years or longer, who were likely candidates for curative therapy when diagnosed, had significant excess mortality when treated expectantly.

Adult↗
PubMed1998

[Radical prostatectomy for localized prostatic cancer].

Curatively intended surgical management of clinically localized prostate cancer has recently been introduced in Denmark. This literature review covers results of preoperative evaluation, impact of stage and grade on outcome, and the results following radical prostatectomy.

Denmark↗
PubMed1998

[Localized prostatic cancer. Survival and loss of life expectancy].

Computerized linkage between the Danish Cancer Registry and the Central Personal Registry was established. A total of 1459 men aged 55-74 years with newly diagnosed clinically localized prostate cancer in the period 1983-1987 were identified. Routine treatment in this period was observation and endocrine therapy in case of progression. Survival analysis demonstrated a significant excess mortality and a substantial loss of life expectancy.

Aged↗
PubMed1998

Clinically favorable effects of raloxifene on bone mineral density and serum lipids: population assessment via bivariate analysis.

Introduction: Raloxifene is a nonsteroidal benzothiophene derivative that is classified as a selective estrogen receptor modulator (SERM). It has clinical promise because of its actions as an estrogen-agonist on bone and serum lipids and an estrogen-antagonist on the breast and uterus.Objectives: To determine the percentage of women who respond to raloxifene therapy with regard to bone mineral density (BMD) and serum low density lipoprotein cholesterol (LDL-C) concentration in a large population of healthy postmenopausal women.Methods: Pooled 24-month interim data from two multicenter, placebo-controlled, double-blind phase III studies were used in this analysis. The study population included 1145 healthy women, 45-60 years of age and 2-8 years postmenopausal, randomized to receive either placebo, raloxifene (RLX) 30 mg/day, RLX 60 mg/day, or RLX 150 mg/day. Changes in BMD, measured by dual x-ray absorptiometry, and serum LDL-C concentration, measured by enzymatic assay, were analyzed simultaneously by plotting the median percentage change (baseline to endpoint) in BMD of the lumbar spine and total hip on the y-axis against the corresponding median percentage change in serum LDL-C on the x-axis for each subject in the placebo group and each of the raloxifene groups. The data localized to one of four quadrants on the plot, the upper-left quadrant representing clinically favorable shifts (increased BMD and decreased LDL-C) and the lower-right quadrant representing clinically unfavorable shifts (decreased BMD and increased LDL-C). The bivariate mean, 50th and 95th percentile ellipses, and the percentage of patients improving in one, both, or neither of the measured parameters are displayed.Results: At the end of 24 months, the bivariate mean and the 50th and 95th percentile ellipses of the placebo group for lumbar spine BMD and LDL-C were shifted to the clinically unfavorable quadrant of the plot, reflecting a decrease in BMD and an increase in LDL-C. In contrast, the bivariate mean for all raloxifene groups had shifted to the clinically favorable quadrant of the plot, reflecting an increase in BMD and a decrease in LDL-C. There was a statistically significant difference (Hotelling-Lawley test, P <.001) in the bivariate mean for all doses of raloxifene compared to placebo. Only 19.1% of subjects in the placebo group exhibited improvement in both lumbar spine BMD and LDL-C, whereas 43.5%, 47.4%, and 49.8% of subjects in the RLX 30, RLX 60, and RLX 150 group, respectively, exhibited improvement in both of these variables. Furthermore, 35.9% of subjects in the placebo group exhibited no improvement in either lumbar spine BMD or LDL-C, whereas only 13.7%, 10.1%, and 11.6% of subjects in the RLX 30, RLX 60, and RLX 150 groups, respectively, exhibited no improvement in either of these variables. Similar results were obtained comparing total hip BMD and LDL-C.Conclusions: Compared with placebo, raloxifene has beneficial effects on BMD and LDL-C in a large sample of healthy postmenopausal women. Thus, insofar as these intermediate endpoints predict disease outcomes, long-term therapy with raloxifene may be beneficial in the prevention of osteoporosis and cardiovascular diseases.

Journal Article↗
PubMed1998

Prostate cancer in Denmark: a 50-year population-based study.

OBJECTIVES: To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period. METHODS: A population-based register study was performed of all new cases of PC recorded in the Danish Cancer Registry from 1943 to 1992. RESULTS: The age-standardized incidence rate for PC increased from 11.5/100,000 in 1943 to 1947 to 30.9/100,000 in 1988 to 1992. Age-specific incidence rates increased in all age groups over 50 years of age. Mortality rates increased from 13.5/100,000 in 1953 to 1957 to 17.8/100,000 in 1988 to 1992. No major changes in the distribution of age, stage at the time of diagnosis, or in diagnostic procedures were found, indicating that the observed change in incidence rates was not caused by attempted early detection or changes in diagnostic strategy. CONCLUSIONS: Our data suggest that the increased PC incidence observed during the period of cancer registration in Denmark represents a true increase in the number of patients with clinical PC.

Age Distribution↗