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Biomedical subjects

A M Olsson

Publications and source records attributed to A M Olsson.

At least 19 recordsLinked to original sources

Efficacy and safety of sildenafil citrate for the treatment of erectile dysfunction in men with cardiovascular disease.

Men with cardiovascular disease (CVD) are more likely to have erectile dysfunction (ED) than the general population, as both conditions share risk factors and some drugs used to treat CVD may induce ED as a side-effect. This study was undertaken to assess the efficacy and safety of sildenafil citrate for the treatment of ED in men with CVD who were receiving treatment with beta-blockers and/or angiotensin-converting enzyme inhibitors and/or calcium-channel blockers, but not nitrates. Treatment with sildenafil was associated with significant increases in the mean end-of-treatment scores for the questions from the International Index of Erectile Function that assess the ability to achieve and maintain erections (p = 0.0001). Furthermore, 71% of patients taking sildenafil reported improved erections compared with 24% taking placebo (p = 0.0001). This study also showed that sildenafil was well tolerated in patients with CVD and ED. Besides flushing, no treatment-related cardiovascular adverse events were noted for sildenafil.

Adrenergic beta-Antagonists↗

Gonadal and sexual function in men treated for childhood cancer.

BACKGROUND: Insofar as a majority of children with malignant diseases are cured, the late effects of treatment are of major importance. PROCEDURE: A retrospective study was conducted of gonadal and sexual function of 77 adult male survivors of childhood malignancies treated and cured at a single center from 1970 to 1989 and followed for a median of 13 years. The study included an interview, physical examination, sperm test, and hormonal analyses. RESULTS: One-third of the patients were treated for hematological malignancies, one-third for CNS tumors, and one-third for other malignancies. Eleven patients required androgen substitution after treatment for tumors of the pituitary-hypothalamic region or acute lymphoblastic leukemia including testicular irradiation and/or orchiectomy. In three patients the testicles were removed. The other eight had small testicles, and those providing sperm samples had azoospermia, and sexual function was disturbed in most of them. Most of the remaining 66 patients had small testicles. Normozoospermia was found in 63%, oligozoospermia in 20%, and azoospermia in 17%. Although there was a highly significant correlation between testicular volume and sperm test, 25% of patients with testicles of <10 ml had normozoospermia. Sexual function was normal in 46 patients, and they were married at a frequency comparable to the normal population. Twenty-one patients had no signs of gonadal dysfunction. CONCLUSIONS: Patients treated for tumors in the hypothalamic-pituitary region or treated with testicular irradiation or with high doses of alkylating agents had severe gonadal and sexual dysfunction. Most of the other patients had good prospects for preserved gonadal and sexual function.

Adolescent↗

Sildenafil citrate (Viagra) is effective and well tolerated for treating erectile dysfunction of psychogenic or mixed aetiology.

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double-blind, fixed-dose study to placebo (n = 95) or sildenafil 10 mg (n = 90), 25 mg (n = 85), or 50 mg (n = 81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p < 0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p < 0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p < 0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p < 0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment-related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well-tolerated treatment for ED of psychogenic or mixed aetiology with once-daily dosing.

Adolescent↗

Separation of selected peptides by capillary electroendoosmotic chromatography using 3 microns reversed-phase bonded silica and mixed-mode phases.

The retention behaviour and selectivity of selected basic, neutral and acidic peptides have been studied by capillary electroendoosmotic chromatography (CEC) with Hypersil C8, C18, Hypersil mixed-mode, and Spherisorb C18/SCX columns, 250 (335) mm x 100 microns, packed with 3 microns particles, and eluted with mobile phases composed of acetonitrile-triethylamine-phosphoric acid (TEAP) at pH 3.0 using a Hewlett-Packard Model HP3DCE capillary electrophoresis system. The selected peptides were desmopressin (D), two analogues (A and B) of desmopressin, oxytocin (O) and carbetocin (C). The peptides eluted either before or after the electroendoosmotic flow (EOF) marker, depending on the concentration of acetonitrile used and the buffer ionic strength. The retention and selectivity of these peptides under CEC conditions were compared to their behaviour in free zone capillary electrophoresis (CZE), where the separation mode was based on the electrophoretic migration of the analytes due to their charge and Stokes radius properties. In addition, their retention behaviour in RP-HPLC was also examined. As a result, it can be concluded that the elution process of this group of synthetic peptides in CEC with a TEAP buffer at pH 3.0 is mediated by a combination of both electrophoretic migration processes and retention mechanisms involving hydrophobic as well as silanophilic interactions. This CEC method when operated with these 3 microns reversed-phase and mixed-mode sorbents with peptides is thus a hybrid of two well-known analytical methods, namely CZE and RP-HPLC. However, the retention behaviour and selectivity of the selected peptides differs significantly in the CEC mode compared to the RP-HPLC or CZE modes. Therefore this CEC method with these peptides represents an orthogonal analytical separation procedure that is complimentary to both of these alternative techniques.

Chromatography↗

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer.

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Biomarkers, Tumor↗

The bacterial flora of the genitourinary tract in healthy fertile men.

The clinical significance of microorganisms in semen is unclear, as they may signify contamination rather than infection. Specimens from six locations in 97 healthy men scheduled for vasectomy were analyzed. Totally 1033 strains, aerobic or anaerobic, were isolated. Of 61 intraoperatively obtained vas deferens cultures, only one was positive. Of the 97 semen samples, 83% contained bacteria, 140 aerobes and 113 anaerobes; 44% of the strains found in semen and 58% of those in prostatic secretion were also identified in the urethra. The finding that 71% of the strains colonizing the coronal sulcus were present in the urethra indicates that the distal part of the urethra is colonized by a bacterial flora similar to that in the sulcus. The urethral flora may then contaminate semen and prostatic secretion. Presence of multiple bacterial species in semen was not associated with abnormal sperm function.

Adult↗

Microsurgical correction of posttesticular obstruction. Peroperative findings and postoperative semen quality.

Exploration for microsurgical reconstruction of the vas deferens or its epididymal junction was performed in 47 consecutively treated men. Epididymovasostomy was planned in 27 cases. Malformation was found in five and Young's syndrome in nine, and most of the others had a history of urogenital infections. Reconstruction was accomplished in 17 cases. Nine were azoospermic preoperatively. Four (three with Young's syndrome/malformation) remained so, whereas patency was demonstrated in four and one did not supply a semen specimen postoperatively. Eight had severe unexplained oligozoospermia preoperatively, and in four of them the sperm counts normalized postoperatively while the other four remained oligozoospermic. In no case did preoperative oligozoospermia progress to azoospermia postoperatively. Complete normalization of all spermiogram parameters occurred in only two cases after epididymovasostomy. Of the 20 who underwent reversal of vasectomy, 17 provided semen for postoperative testing. 16/17 specimens contained spermatozoa, but spermiograms, including penetration tests, were completely normal in only three cases. This study indicates a discrepancy between good patency and good semen quality. Our study also suggests that some men with unexplained severe oligozoospermia are as likely to benefit from epididymovasostomy as are azoospermic men.

Adult↗

Stereoselective high-performance liquid chromatographic assay of (+/-)-delmopinol in plasma using solid-phase extraction, a chiral derivatizing agent and electrochemical detection.

An enantioselective HPLC bioanalytical method for (+/-)-delmopinol was established in order to elucidate the pharmacokinetic behaviour of this chiral drug. (+/-)-Delmopinol and (+/-)-M1652, a structurally related compound used as internal standard, were extracted from plasma by a solid-phase extraction procedure using CN cartridges. The enantiomers were derivatized with a chiral derivatizing agent (R,R)-O,O'-di-p-toluoyl tartaric acid anhydride yielding diastereomeric derivatives which were separated on a reversed-phase column with acetonitrile-0.1 M ammonium acetate buffer (65:35, v/v) pH 5.7 as mobile phase. The resolution values of the diastereomeric derivatives of (-)- and (+)-M1652 and of the derivatives of (-)- and (+)-delmopinol were 1.03 and 1.46, respectively. The limit of quantitation was approximately 3 pmol (1 ng)/enantiomer per 0.5 ml plasma using electrochemical detection (+0.75 V versus Pd/PdO reference electrode). The effectiveness of the derivatization was > 98% and the total recovery of (+/-)-delmopinol and of (+/-)-M1652 from plasma or serum was found to be approximately 50%. The assay was applied to enantioselective pharmacokinetic investigations in humans, rats and dogs but showing here only one concentration time curve of the (+)- and (-)-delmopinol in a human subject after administering (+/-)-delmopinol in form of an aqueous mouth wash solution for 60 s.

Anhydrides↗

Conventional and controlled release diltiazem. Bioavailability in healthy volunteers and anti-anginal effects in combination with metoprolol in stable angina pectoris.

Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmacokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in anti-anginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.

Adult↗

[A clinical eye].

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Clinical Competence↗

Improved electrophoretic method for the analysis of dystrophin in human muscle.

A new simplified electrophoretic and Western blotting technique for the study of dystrophin in muscle biopsy material is presented and compared with immune histochemistry. The method is based on separation of dystrophin in a linear SDS-PAGE pore gradient of 4-8% acrylamide in ultra-thin, horizontal gels on plastic film support followed by horizontal electrotransfer for Western blotting. The advantages of this procedure are short separation and transfer times at high field strength, high resolution, short staining procedures and small requirements of chemicals. Samples from the same gel can be cut and examined with different antibodies. Final results are obtained in one day. Examination of patients with various types of muscular dystrophies verified the essential absence of dystrophin in DMD patients, and showed considerable dystrophin heterogeneity in patients with BMD. A girl with severe symptoms of dystrophy revealed unexpected dystrophin abnormalities. The results also indicated that SDS-PAGE with Western blotting and immune histochemistry are complementary, diagnostic, and research instruments, and that the reactivity of commercial antibodies may differ in these two techniques.

Adult↗

Early clinical stages of nonseminomatous testis cancer. Evaluation of the primary treatment and follow-up procedures of the SWENOTECA project.

During a 5-year period, 588 consecutive patients with nonseminomatous testicular germ cell cancer were included by 16 hospitals into the Swedish-Norwegian Testicular Cancer Project (SWENOTECA). A total of 370 (63%) had early clinical stages (CS1, CS1Mk+ and CS2A), and 345 (93%) of these patients underwent pathological staging (PS) by retroperitoneal lymph node dissection (RPLND). The overall clinical staging accuracy was 75%, with no significant difference between hospitals with low, medium or high patient accrual rate. Addition of bipedal lymphography did not improve the clinical staging accuracy compared to evaluation of the retroperitoneum by CT alone. Tumor serum markers before and close monitoring of the levels after orchiectomy gave valuable information regarding risk of retroperitoneal metastases. After a median follow-up period of 5 years 30 (13.8%) of 217 patients with PS1 disease relapsed, only 3 of them later than 18 months from the RPLND. Short orchiectomy to RPLND time interval, vascular invasion and absence of teratoma elements in the primary tumour were significant predictors of relapse in PS1 cases according to multivariate analysis. Unilateral RPLND was not associated with higher relapse rate than a bilateral procedure, but significantly reduced the risk of dry ejaculation after RPLND. None out of 122 PS2 patients who received adjuvant cisplatin-based chemotherapy after RPLND relapsed, despite the fact that 37 of them had only undergone a unilateral RPLND. Repeated CT examinations and most routine blood tests except serum alpha foeto protein (AFP), beta subunit of human chorionic gonadotropin (HCG) and lactate dehydrogenase (LD) may safely be omitted in the follow-up period for patients who have been pathologically staged with RPLND, provided that effective adjuvant chemotherapy has been given to the PS2 patients.

Antineoplastic Combined Chemotherapy Protocols↗