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Biomedical subjects

P Ekman

Publications and source records attributed to P Ekman.

At least 55 records · Page 3Linked to original sources
PubMed1997

Predicting pelvic lymph node involvement in patients with localized prostate cancer.

Pelvic lymph node dissection is a routine staging procedure in localized prostate cancer. It provides prognostic information, it influences the design of the subsequent therapeutic strategy and it provides information necessary to compare the results of various therapeutic strategies. It is not considered a curative procedure. Thanks to improved diagnostic means, the unexpected finding of positive lymph nodes has decreased from 30% 15 years ago to below 10%. Hence, today the procedure is unnecessary in over 90% of the cases. Improvements in staging by imaging techniques, including CT scan, MRI, ultrasound, and ileopelvic scintigraphy, have so far been unsuccessful because of low specificity and sensitivity. Using a combination of tumor grade and stage plus serum prostate-specific antigen (PSA) levels, a good indication of the likelihood of positive pelvic nodes can be obtained. A review of the literature indicates that for clinically localized tumors, i.e. stages T1a to T2b, lymph node dissection can be omitted provided serum PSA levels are < 10 ng/ml and the tumor is well to moderately well differentiated (Gleason grade < 7). Using these cutoff values, approximately 25% of our patients can be saved a pelvic lymph node dissection at the price of approximately 3% missed cases.

Biomarkers, Tumor↗
PubMed1996

[Treatment of benign prostatic hyperplasia with Proscar (finasteride). Results of a 10-year Scandinavian study].

707 patients with moderate prostatic hyperplasia were recruited to a two-year Scandinavian multicenter study. The study was randomized, prospective and double-blind. Half of the patients were treated with finasteride (5 mg daily) and the controls were given placebo. The patients were monitored with regard to symptoms, urinary flow rate and prostate volume. In addition, various laboratory examinations were performed. A statistically significant difference was found between the groups with regard to symptom improvement and increase in urinary flow rate in favour of finasteride. Finasteride reduced prostate volume and stopped further growth, leading to a difference of 30% in prostate volume between the two groups after two years of treatment. Thus, finasteride was able to stop the continuous growth of the prostate in the elderly male. The proportion of patients with adverse clinical experiences was similar in both treatment groups. However, the finasteride-treated group contained more patients with sexual dysfunction. We conclude that finasteride is an alternative to vigilant waiting for patients with moderate symptoms of benign prostatic hyperplasia.

Aged↗
PubMed1996

[Finanseride in symtomatic benign prostatic hyeprtrophy. A 2-year placebo-controlled study].

The efficacy and safety of treatment with finasteride 5 mg daily for 24 months was assessed in this multicentre double blind placebo-controlled study including 707 patients with moderately symptomatic benign prostatic hyperplasia. Efficacy parameters were changes in voiding- and bladder storage symptoms assessed by a validated symptom score, changes in maximum urinary flow rate and changes in the prostate volume. In the finasteride patients, symptom score improved during the whole study with a significant difference between active treatment and placebo after 24 months (p < 0.01). Maximum flow rate increased in finasteride treated patients resulting in a difference between these and the placebo treated patients of 1.8 ml/s after 24 months (p < 0.01). Prostate volume was reduced by 19% in the finasteride treated patients versus an increase of 12% in the placebo treated patient group (p < 0.01). Finasteride was well tolerated. Patients receiving placebo progressed in symptoms after 16 months. Finasteride can halt the natural progression of moderately symptomatic BPH over a 24 month period.

Aged↗
PubMed1996

A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma.

PURPOSE: We compared the efficacy and toxicity of long-term mitomycin C versus bacillus Calmette-Guerin (BCG) instillation in patients at high risk for recurrence and progression of superficial bladder carcinoma. MATERIALS AND METHODS: Our randomized comparison study included 261 patients with primary dysplasia, or stage Tis, stage T1, grade 3 and multiple recurrent stage Ta/T1, grade 1 or 2 disease. Mitomycin C (40 mg.) or Pasteur strain BCG (120 mg.) was instilled weekly for 6 weeks, then monthly for up to 1 year and every 3 months during year 2. RESULTS: After a median followup of 39 months 49% of the patients given BCG and 34% given mitomycin C were disease-free (p < 0.03), compared to 48 and 35%, respectively, of those with stage Ta or T1 disease, and 54 and 33%, respectively, of those with dysplasia or stage Tis tumor. Tumor progressed in 13% of patients, with no statistically significant difference observed regarding progression between the mitomycin C and BCG groups. Side effects were more common after BCG instillation, with 5 cases of severe side effects compared to 1 in the mitomycin C group. Treatment was stopped due to toxicity in 10% of the patients. CONCLUSIONS: The majority of patients tolerated long-term intravesical therapy well. BCG instillation was hampered by more frequent side effects. BCG was superior regarding recurrence prophylaxis, since patients given BCG had fewer recurrences and a significantly longer time to treatment failure compared to those treated with mitomycin C. No statistically significant difference was observed regarding progression.

Adjuvants, Immunologic↗
PubMed1996

Finasteride in the treatment of benign prostatic hyperplasia.

Finasteride is an enzyme inhibitor which blocks the conversion of testosterone by 5 alpha-reductase to dihydrotestosterone, the active androgenic metabolite in the prostate. In a double-blind, placebo-controlled study, 707 patients with moderately symptomatic BPH were treated for 2 years. The study confirmed that treatment significantly improved symptoms, reduced prostate size and increased urine flow rate. Side effects were usually mild. The authors find that finasteride can reverse the natural progression of BPH.

Aged↗
PubMed1995

Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group.

OBJECTIVES: To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months. METHODS: This was a multicenter, double-blind, placebo-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Scandinavian countries. Following enrollment and a 4-week single-blind placebo run-in period, patients were randomized to receive finasteride 5 mg once daily or placebo for 24 months. Urinary symptoms, urinary flow rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically. RESULTS: In finasteride-treated patients the total symptom score improved throughout the study, with a significant difference between the two groups at 24 months (P < or = 0.01), whereas in placebo-treated patients, there was an initial improvement in the symptom score but no change from baseline at 24 months. The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P < or = 0.01). The mean change in prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P < 0.01). Finasteride was generally well tolerated throughout the 2-year study period. CONCLUSIONS: The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study. These results demonstrate that finasteride can reverse the natural progression of BPH.

Aged↗
PubMed1995

Endocrine therapy for benign prostatic hyperplasia in the 90's.

Endocrine therapy by means of castration for benign prostatic hyperplasia was introduced already in the middle of the 19th century. The technique was never popularized and was abandoned following the introduction of safe surgical techniques. In the second half of this century, small series of various endocrine treatments have been reported, mainly using progestational agents. The hormone dependency of the prostate is unique, since testosterone itself is not very active on the prostate cells but has to be converted to 5 alpha-dihydrotestosterone, which is almost ten times as effective an androgen in the prostate cell. By blocking this conversion, highly specific antiandrogenic effect will be obtained in the prostate but not in other organs of the body. The first 5 alpha-reductase inhibitor, finasteride, has proven effective in reducing prostate DHT. In large clinical trials, it has shown to reduce prostate size, improve urinary flow and reduce symptom score, statistically significantly better than placebo. The effect is sustained over at least 3 years. In a double-blind, randomized, placebo-controlled study over 2 years, patients were similarly improved in the finasteride group, whereas they deteriorated in the placebo group. This indicates that finasteride is able to halt the progression of the natural course of benign prostatic hyperplasia. Benign prostatic hyperplasia, generally believed to be a stromal disease, is potentially dependent on estrogens for its development. By blocking aromatization of testosterone to estrogen in the prostate cells, a hypothetical beneficial effect on the disease process should be gained. Results from phase II-studies have been promising. However, in placebo-controlled studies, aromatase inhibitors did not perform better than placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗
PubMed1995

Protein kinase C phosphorylates two of the four known syndecan cytoplasmic domains in vitro.

The transmembrane heparan sulfate proteoglycans of the syndecan family are implicated to participate in several cellular reactions which are dependent on protein kinase C. We have used an in vitro assay to assess whether any of the Peptides corresponding to the complete cytoplasmic domains of rat syndecans 1 through 4 were used as substrates for the enzyme. The syndecan-2 (fibroglycan) and syndecan-3 (N-syndecan) peptides were both found to be phosphorylated by protein kinase C with Kms of 15 +/- 3 microM and 85 +/- 25 microM, respectively, while the syndecan-1 and -4 peptides were not phosphorylated under the conditions used. The sites of in vitro phosphorylation for syndecans-2 and -3 were localized to ser-197 and ser-339, respectively. Thus, among 13 available sites (serines and threonines) in the four peptides, two were selectively modified by the enzyme. The specificity and the kinetics of the reactions indicate that the cytoplasmic domains of syndecan-2 and -3 are likely to be physiological substrates for protein kinase C.

Amino Acid Sequence↗
PubMed1994

Nonrandom numerical aberrations of chromosomes 7, 9, and 10 in DNA-diploid bladder cancer.

Double-target in situ hybridization technique (ISH) was applied to 37 cases of bladder cancer to detect numerical aberrations of chromosomes 7, 9, 10, and 11 by centromeric DNA probes. Of 33 evaluable cases, 29 (88%) demonstrated chromosome aberrations. In 17 cases with diploid pattern as measured by flow-cytometric DNA analysis (FCM), 15 (88%) demonstrated chromosome aberrations. Of these, trisomy 7, monosomy 9, and trisomy 10 were detected in three, three, and one case, respectively, as a single chromosome aberration. In 14 (88%) of 16 cases with an aneuploid DNA pattern, chromosome aberrations for two or more chromosomes were demonstrated. A significant correlation was observed between grade of chromosome aberrations and tumor grade (p < 0.01, Fisher's test), between number of spots for chromosome 7 and peak value in FCM (p = 0.015, by Spearman rank order test). In eight cases, chromosome aberrations in the tumor were compared with the corresponding pattern in the grossly normal and histologically benign mucosa. Trisomy 10 and monosomy 9 were detected as chromosome numerical aberrations in the histologically normal mucosa, consistent with aberrations in the corresponding patients. We conclude that trisomy 7, monosomy 9, and trisomy 10 may be early events in the evolution of bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1994

D-amino acid residues as substrate specificity determinants for casein kinase II.

A set of diastereomeric peptides RRRDDDSDDD each with a corresponding D-amino acid residue successively in every position (except the arginines) was tested as substrates for casein kinase II. It was found that the D-serine containing peptide was not detectably phosphorylated. The replacements at the positions +1, -1 and +2 decreased the kII values more than 60, 30 and 20 times, respectively. The effect of the L/D replacements decreased with increased distance from the serine. The D-amino acid scan used herein seems to be a helpful complementary tool for studies of substrate specificity determinants for different protein kinases.

Amino Acid Sequence↗
PubMed1994

Strong evidence for universals in facial expressions: a reply to Russell's mistaken critique.

J. A. Russell (1994) misrepresents what universality means, misinterprets the evidence from past studies, and fails to consider or report findings that disagree with his position. New data are introduced that decisively answer the central question that Russell raises about the use of a forced-choice format in many of the past studies. This article also shows that his many other qualms about other aspects of the design of the studies of literate cultures have no merit. Russell's critique of the preliterate cultures is inaccurate; he does not fully disclose what those who studied preliterate subjects did or what they concluded that they had found. Taking account of all of Russell's qualms, my analysis shows that the evidence from both literate and preliterate cultures is overwhelming in support of universals in facial expressions.

Cross-Cultural Comparison↗
PubMed1994

Iodine-125 brachytherapy for clinically localized prostate cancer: a 5-year follow-up of outcome and complications.

Thirty-seven patients with clinically localized prostate cancer of all grades were treated by suprapubic digitally guided implantation of 125I seeds. The median age at the time of diagnosis was 68 years. The mean follow-up period was 62 +/- 19 months. At last follow-up 18 patients were clinically free of disease; 11 deaths occurred: 9 from prostate cancer and 2 from another disease. Complications occurred in 24 patients most commonly urgency and proctitis, attributable to the treatment. Four patients had severe late rectal complications, and 2 patients died of sepsis secondary to rectal fistulae. Digitally directed retropubic implantation of 125I appears inferior to other treatments of clinically confined prostate cancer both regarding outcome as well as complication rate.

Aged↗
PubMed1994

Pharmacological treatment of benign prostatic hyperplasia with finasteride: a clinical review.

Finasteride acts by blocking the conversion of testosterone to 5 alpha-dihydrotestosterone, the active androgen metabolite in the human prostate. In large, double-blind, placebo-controlled phase III studies recruiting over 1600 patients, it was shown that the administration of Finasteride, either 5 or 1 mg a day, reduced the size of the prostate by a mean of 22%, following 6 months of therapy. Despite this reduction in prostate size, urinary flow rate only improved by a mean of 1.7 ml per second and symptom score improved only marginally, but statistically significantly different from placebo. Long-term results in small series of patients have indicated a further improvement beyond 1 year. After 3 years flow was improved by 60%. The future role for Finasteride therapy is emerging, but it appears as if patients with mild to moderate symptoms would be a group who could benefit the most. Whether or not Finasteride can stop the long-term natural course of benign prostatic hyperplasia has still to be demonstrated.

Clinical Trials, Phase III as Topic↗
PubMed1994

Venous shunting as a complication to penile revascularization--a case report.

As a serious complication to arterial penile revascularisation arterio-venous shunting was observed in a 60 years old male. The patient suffered bilateral obstruction of his pudendal arteries. Following revascularization using the left inferior epigastric artery he obtained good pulsation in the penis but no return of sexual function. Instead his general condition deteriorated. A follow-up angiogram revealed shunting of the contrast from the epigastric artery, via the penis, to the venous system. Venous ligation was carried out. The patient's general condition returned to normal status and he can now obtain rigid erections. Reconstructive arterial surgery for erectile dysfunction should never be carried out unless venous leak has been ruled out as a complicating factor.

Follow-Up Studies↗
PubMed1994

Deletion mapping of chromosome 8p in prostate cancer by fluorescence in situ hybridization.

Double-target fluorescence in situ hybridization (FISH) was applied to 42 cases of prostate cancer and seven cases of histologically proven benign prostate hyperplasia for the detection of structural aberrations of chromosome 8. Cosmid probes for two chromosome 8p loci (LPL/8p22 and D8S7/8p23) were used in 34 specimens of malignant tumors obtained by the touch biopsy technique. Deletion was defined as when the number of cosmid signals was lower than the number of centromere signals in more than 35% of all nuclei observed. In total, thirty of the 42 (71%) specimens demonstrated any type of 8p deletion. Out of the 34 cases in which deletion mapping could be evaluated, distal deletion (D8S7) was detected in 17 (50%), of which 10 also showed deletion of LPL. Deletion of LPL was detected in 18 cases (53%), of which 8 (24%) retained the D8S7 (interstitial deletion). When the deletion pattern was graded as (1) no deletion (2) partial deletion (either D8S7 or LPL deleted) and (3) both deletions, the degree of deletion was well correlated with the tumor grade (P = 0.0009) and with stage (P = 0.0072, Fisher's Exact test). These data support the hypothesis that tumor suppressor gene(s) may be located in the chromosomal region 8p22, hence 8p deletions may play a crucial role in the pathogenesis of prostate cancer.

Chromosome Deletion↗
PubMed1993

Endothelial cells release casein kinase II--like activity capable of phosphorylating fibrinogen in response to thrombin.

Rat liver endothelial cells cultivated in the absence of serum and activated with thrombin released up to 10% of the total protein kinase activity into the cell medium using casein or fibrinogen as the phosphate acceptor protein. The activity was partly inhibited by heparin, indicating that it was of the casein kinase II type. The release of kinase started directly after the addition of thrombin (2 NIH U/ml) to the media with two maxima; one after about 10 min and the second after around 30 min. The phosphorylating activity of media from cells incubated for longer times was less dependent on thrombin-induction which probably indicated the start of destruction of the cells. The results reported suggest that phosphorylation of fibrinogen could occur in the blood under acute phase conditions.

Animals↗
PubMed1993

Protein kinase assay using tritiated peptide substrates and ferric adsorbent paper for phosphopeptide binding.

The recently described synthesis of ferric adsorbent paper has made possible the modification of protein kinase assays. The adsorbent contains ferric chelate groups, which are responsible for the binding of phosphopeptide via phosphate group. The selective adsorption of phosphopeptide contra nonphosphorylated peptide allows the use of tritium-labeled peptides and unlabeled ATP as substrates. The binding of the reaction product to the adsorbent was complete and was not affected by the amino acid sequence of the peptide. The conditions required for the separation of the produced phosphopeptide from the initial peptide have been worked out as well. The firmly bound phosphopeptide should be released from the ferric adsorbent paper prior to liquid scintillation counting. Using 0.1 m NH4HCO3 solution (pH 8.0), the elution of phosphopeptides was almost complete. The modified protein kinase assay proposed herein is rapid and allows handling of multiple samples simultaneously. In addition, the ferric paper method avoids the use of 32P-isotope, replacing it with 3H which has lower radiation energy and a much longer half-life.

Adsorption↗