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Biomedical subjects

B E Persson

Publications and source records attributed to B E Persson.

At least 19 recordsLinked to original sources

Optimizing the therapeutic approach of transurethral alprostadil.

OBJECTIVE: To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 microg and 500 microg, MUSE, Vivus Inc., Menlo Park, CA, USA, and Astra Läkemedel AB, Södertälje, Sweden) and the need for dose titration in a general population with erectile dysfunction. PATIENTS AND METHODS: In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 microg of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 microg) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. RESULTS: The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 microg for 1% of participants, 250 ++microg for 27%, 500 microg for 32%, 1000 microg for 6%, and finally 1000 microg plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients (> 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 microg). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 microg than with 250 microg (P < 0.05) during the first 4 weeks. However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. CONCLUSION: Recommending 500 microg as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 microg, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 microg.

Adult↗

Monoclonal antibodies against human prostasomes.

BACKGROUND: The prostasomes are secreted into the gland ducts of the human prostate. At ejaculation, these native prostasomes are expelled with the secretions of the prostate and appear in the seminal plasma as seminal prostasomes, where they facilitate sperm function in various ways. We have designed methods for producing monoclonal anti-prostasome antibodies to be used for immunohistochemistry and sequencing analyses of the prostasomes. METHODS: The immunogen applied was purified seminal prostasomes placed on small pieces of nitrocellulose membranes (prostasome blots) and deposited into the spleen of mice for immunization. For screening, both seminal and native prostasomes were used. RESULTS: We obtained antibodies which detected native prostasomes both in prostatic secretions and in paraffin sections of the prostate. The immunostaining demonstrated that all prostate epithelial cells contained prostasomes. They were located in the apical parts of the secretory cells and in the gland ducts, while the nuclei and the corpora amylacea were unstained. CONCLUSIONS: Using the methods described, monoclonal antibodies against native prostasomes were produced. In addition to their usefulness in structural and functional studies of prostasomes, specific monoclonal antibodies can be used to characterize prostasomes by sequencing analyses.

Animals↗

Allopurinol treatment results in elevated prostate-specific antigen levels in prostatic fluid and serum of patients with non-bacterial prostatitis.

Non-bacterial prostatitis is a common problem in young men. It is a disease which is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed including identified and non-identified microorganisms, stone formation and psychological factors. It was shown in an earlier study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) took place to a varying extent in the prostatic ducts and this reflux was related to prostatic pain and urate concentration in expressed prostatic secretion (EPS). Allopurinol treatment lowered the urate concentration in EPS and relieved the subjective discomfort. This study reports serum (S) levels of prostate-specific antigen (PSA) in patients with non-bacterial prostatitis and the way in which S-PSA was affected by allopurinol treatment. It is also shown that the S-PSA level is age dependent. A correlation existed between the S-PSA concentration and EPS content of white blood cells. Patients with high EPS urate concentrations corresponded to low S-PSA levels and allopurinol treatment resulted in elevated S-PSA levels. PSA in EPS was also increased by allopurinol treatment. Hence, an increased release of PSA from the prostate gland was noted upon allopurinol treatment. The mechanism of the allopurinol-induced release is obscure. It might be explained by an induction of PSA synthesis via an allopurinol effect on the genome but an increased leakage of the prostatic cells elicited by allopurinol could no be ruled out.

Adult↗

Evidence for a mechanistic association between nonbacterial prostatitis and levels of urate and creatinine in expressed prostatic secretion.

PURPOSE: Chronic prostatitis is a common disease of the late teenage years, which affects patients for many years. In the majority of cases etiology is unknown but in some cases prostatitis is clearly caused by microorganisms that result from overuse of antibiotic drugs. We attempt to gain further knowledge about the etiology of the disease. MATERIALS AND METHODS: We studied 56 patients with nonbacterial prostatitis in regard to whether urine reflux into the prostatic ducts was responsible for increased concentrations of creatinine, urate and white blood cells in expressed prostatic secretion. The patients were interviewed using a standard questionnaire. RESULTS: A relationship was demonstrated between pain estimated in accordance with a scoring scale, and expressed prostatic secretion contents of white blood cells, urate and creatinine. CONCLUSIONS: These results provide further support of the role of reflux into the prostatic ducts as an underlying mechanism initiating a chemical inflammatory reaction. Urate appears to be the chemical agent eliciting this inflammatory response.

Creatinine↗

Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study.

PURPOSE: Nonbacterial prostatitis is a common problem in young men. It is a disease that is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed, including identified and unidentified microorganisms, stone formation and psychological factors. We have demonstrated in a previous study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) occurs to a varying extent into the prostatic ducts, and this reflux has been related to prostatic pain and urate concentration in expressed prostatic secretion. MATERIALS AND METHODS: We performed a paralled double-blind controlled study of the objective and subjective effects of allopurinol on patients with nonbacterial prostatitis. Twenty patients received placebo, 18 received 300 mg. allopurinol daily and 16 received 600 mg allopurinol daily for 240 days. All patients began medication at the same time regardless of whether the disease was in an active state. No side effects were noted in the treatment groups. RESULTS: Significant effects were noted on the concentrations of serum urate, urine urate, expressed prostatic secretion urate, expressed prostatic secretion xanthine and subjective discomfort. CONCLUSIONS: Allopurinol has a significant, positive effect on nonbacterial prostatitis. It is safe and worthy of trial for all at least a 3-month period at each episode to relieve the symptoms of nonbacterial prostatitis.

Allopurinol↗

Dye-coupling between term pregnant human myometrial cells before labor: carboxyfluorescein versus lucifer yellow.

Term pregnant human myometrial cells in whole mounts were microinjected by pressure with the fluorescent probes Lucifer Yellow and carboxyfluorescein. Tissues obtained from acute and elective sections displayed weak dye-coupling when injected with Lucifer Yellow. Injection of carboxyfluorescein into cells from the elective sections resulted in a more extensive dye-coupling than that observed with Lucifer Yellow. These results indicate that term pregnant human myometrial cells are metabolically coupled before labor and carboxyfluorescein is superior to Lucifer Yellow in detecting the coupling.

Cell Communication↗

The chloride concentration in the lateral intercellular spaces of MDCK cell monolayers.

We measured the Cl concentration of the lateral intercellular spaces (LIS) of MDCK cell monolayers, grown on glass coverslips, by video fluorescence microscopy. Monolayers were perfused at 37 degrees C either with HEPES-buffered solutions containing 137 mM Cl or bicarbonate/CO2-buffered solutions containing 127 mM Cl. A mixture of two fluorescent dyes conjugated to dextrans (MW 10,000) was microinjected into domes and allowed to diffuse into the nearby LIS. The Cl-sensitive dye, ABQ-dextran, was selected because of its responsiveness at high Cl concentrations; a Cl-insensitive dye, Cl-NERF-dextran, was used as a reference. Both dyes were excited at 325 nm, and ratios of the fluorescence intensity at spectrally distinct emission wavelengths were obtained from two intensified CCD cameras, one for ABQ-dextran the other for Cl-NERF-dextran. LIS Cl concentration was calibrated in situ by treating the monolayer with digitonin or ouabain and varying the perfusate Cl between 0 and 137 mM (HEPES buffer) or between 0 and 127 mM (bicarbonate/CO2 buffer). LIS Cl in HEPES-buffered solutions averaged 176 +/- 19 mM (n = 12), calibrated with digitonin, and 170 +/- 9 mM (n = 12), calibrated with ouabain. LIS Cl in bicarbonate/CO2-buffered solutions averaged 174 +/- 10 mM (n = 7) using the ouabain calibration. The Cl concentration of MDCK cell domes, measured with Cl-sensitive microelectrodes and by microspectrofluorimetry, did not differ significantly. Images of the LIS at 3 focal planes, near the tight junction, midway and basal, failed to reveal any gradients in Cl concentration along the LIS. LIS Cl changed rapidly in response to perfusate Cl with characteristic times of 0.8 +/- 0.1 min (n = 21) for Cl decrease and 0.3 +/- 0.04 min (n = 21) for Cl increase. In conclusion, (i) Cl concentration is higher in the LIS than in the bathing medium, (ii) no gradients of Cl along the depth of LIS are detectable, (iii) junctional Cl permeability is high.

Animals↗

Direct intracellular injections for studying human myometrial gap junctions prior to labor.

Direct intracellular microinjection of a fluorescent dye (Lucifer Yellow) was performed on ex-situ muscle strips from term pregnant women not in labor. The aim was to characterize the intracellular distribution of LY to obtain criteria for an intracellular injection in whole mounts and ultimately to study the gap junctional communication between myometrial cells in those tissues. Fifteen injections performed on biopsies from ten cases showed a well-bordered fusiform shape and were considered to be intracellular. The intercellular spread of the dye into an adjacent cell was observed in three injections (three cases). The average cell dimension was 284 +/- 95 microns for length and 5 +/- 1.5 microns for width (n = 17). The intracellular injection was confirmed by light microscopy of cross sections. It is concluded that limited coupling exists between myometrial cells of women prior to labor.

Cell Communication↗

Proinsulin levels in newborn siblings of type 1 (insulin-dependent) diabetic children and their mothers.

Elevated proinsulin levels have been observed in healthy first degree relatives of Type 1 (insulin-dependent) diabetic patients. This elevation could reflect a sequele after a previous attack on the beta-cells not necessarily leading to diabetes, or represent a family trait related to the development of diabetes. When cord plasma levels of proinsulin, insulin and C-peptide from 14 newborn siblings of Type 1 diabetic patients were compared with 21 newborn control siblings unrelated to diabetic subjects, no differences were observed. Neither were any differences observed between their mothers at delivery when comparing the same parameters. In cord plasma the proinsulin levels (median and range) were higher than those in plasma from 35 adult fasting women unrelated to diabetic subjects (10, 5-83 pmol/l vs 4, 2-33 pmol/l; p < 0.001) whereas the C-peptide levels (median and range) were lower (0.20, 0.11-0.56 nmol/l vs 0.37, 0.21-0.69 nmol/l; p < 0.001). No differences in insulin levels using a highly specific insulin assay were observed. The results suggest that newborn children have high proinsulin and low C-peptide levels unrelated to heredity of diabetes and that the previously described elevated proinsulin level observed in older first degree relatives of diabetic subjects occurs later in life.

Adult↗

Uridine, xanthine and urate concentrations in prostatic fluid and seminal plasma of patients with prostatitis.

The etiology of prostatitis is not fully understood and several causative factors have been considered in the past. In this study we analyzed the expressed prostatic secretion (EPS) and seminal plasma with regard to uridine, xanthine, urate, creatinine and zinc from patients with prostatitis (the diagnosis was based on symptoms for at least 1 year), together with creatinine, urate and zinc in the serum. In 8 of the patients, a direct comparison of these constituents was performed between EPS and seminal plasma. EPS contained low concentrations of uridine and xanthine and high concentrations of creatinine and zinc as opposed to seminal plasma that displayed a reverse pattern. The mean urate concentration in seminal plasma, exceeding that of EPS by 78%, was rather close to the mean value found in serum but no significant correlation was seen between urate in serum and urate in seminal plasma or EPS. Urate in EPS correlated significantly to xanthine in EPS and such a relationship was also observed between urate and creatinine in EPS. In seminal plasma, urate and xanthine were likewise correlated with each other. On division of the patients into a high-score symptom group and a low-score group, no intergroup differences were found in EPS and seminal plasma constituents. Hence, we found high concentrations especially of uridine and xanthine in seminal plasma, compared with other body fluids, and evidence of a backflow of urine mixing with the prostatic fluid of these patients was seen. We suggest that crystal formation of these metabolites may occur under certain conditions and could constitute a first step in the development of prostatitis-vesiculitis-epididymitis in some cases.

Adult↗

Tubuloglomerular feedback and chloride activity in the juxtaglomerular interstitium in Amphiuma.

Fresh-water animals excrete large volumes of dilute urine. The pronounced dilution of the tubular fluid starts in the early distal tubule. In this paper the reabsorptive capacity of the diluting segment is discussed, with special attention to the maximal salt concentration of the reabsorbed fluid. Earlier studies have shown a reabsorption-dependent chloride concentration on the basolateral side of the epithelium (juxtaglomerular interstitium, JGI) at the site of the juxtaglomerular apparatus. In the present study measurements were made of chloride activities in the immediate vicinity of the basolateral side of the tubular epithelial cells at high and low tubular perfusion rates. Extremely high chloride activities (2451 +/- 625 mM (SE), n = 7) were found in the JGI at maximal reabsorption, while more plasma-like values were noted at zero tubular flow. The flow-dependent salt reabsorption may be a powerful signal for tubuloglomerular feedback from the tubular lumen to the effector cells.

Animals↗

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.

Chorionic Gonadotropin↗

Effect of bumetanide on tubuloglomerular feedback in Necturus maculosus.

A non-invasive technique was developed to measure single-nephron glomerular blood flow (SNGBF) in Necturus maculosus. Erythrocytes labelled with rhodamine, a fluorescent dye, were injected systemically and the frequency at which labelled cells entered an arteriole was measured. Frequency was converted to flow by measuring the concentration of labelled erythrocytes in whole blood. Dependence of SNGBF on flow rate in early distal tubules was used to assess tubuloglomerular feedback (TGF). SNGBF decreased with increasing flow in the early distal tubule in a pattern typical of TGF; SNGBF decreased 25% at the highest flow rates. SNGBF increased when bumetanide was added to the perfusate, but the TGF response to flow rate persisted. IC50 (concentration that produces half-maximal inhibition) was 2.4 x 10(-10), 9.8 x 10(-10) and 1.2 x 10(-9) M bumetanide at distal perfusion rates of 5, 10 and 20 nl min-1 respectively. These results are consistent with modulation of SNGBF according to the rate of luminal entry of NaCl into early distal tubule cells. This transport rate depends on the luminal concentration of NaCl, which is tubular flow rate-dependent; NaCl and bumetanide compete.

Animals↗

A clinical study of CA-50 as a tumour marker for monitoring of colorectal cancer.

Using a radioimmunoassay we have determined serum levels of the carcinoma-associated antigen CA-50 in 266 patients with colorectal cancer. Elevated CA-50 levels were found in Dukes' A (15%), Dukes' B (43%), Dukes' C (31%) and Dukes' D (65%). Patients who had developed a recurrence had 66% elevated levels. 25% of resected patients with no evidence of disease also had elevated CA-50 levels. From 139 patients operated on for a Dukes' A-C, a rise in CA-50 levels from the pre- to the 6-9 month post-operative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On follow-up, a recurrence later developed in all these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. A rise in CA-50 levels after resection of a Dukes' A-C is indicative of a recurrence and may precede any clinical evidence of disease by several months or years. Data is also presented from 552 cases with colorectal cancer analysed with a immunoradiometric assay.

Antigens, Neoplasm↗

CA-50 as a tumour marker for monitoring colorectal cancer: antigen rises in patients postoperatively precede clinical manifestations of recurrence.

Using a monoclonal antibody-based radioimmunoassay inhibition method we have determined preoperative serum levels of the carcinoma-associated carbohydrate antigen CA-50 in 266 patients with primary colorectal cancer. CA-50 levels exceeding the mean value for blood donor sera by more than 2 standard deviations (greater than or equal to 17 U/ml) were found in 47% of these patients, with 15%, 43% and 31% being elevated in patients with Dukes' A, Dukes' B and Dukes' C cancer, respectively, and 63% and 66% being elevated in patients with more advanced localized or disseminated cancer. Only 5% of patients with benign colorectal disease had elevated CA-50 level and these were patients with ulcerative colitis of a duration of more than 10 years. Among patients who had developed a recurrence after operation for a primary Dukes' A-C colorectal cancer 66% had elevated levels, and 25% of resected patients with no clinical evidence of disease at corresponding times after operation also had CA-50 levels above the normal concentrations. From 139 patients operated for a Dukes' A-C colorectal cancer a definitive rise in CA-50 levels from the pre- to a 6-9 months postoperative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On prolonged follow-up a clinically manifest recurrence later developed in all of these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. Our findings suggest that a rise in CA-50 levels after resection of a Dukes' A-C primary colorectal cancer is indicative of a recurrence and may precede any clinical evidence of disease by many months or years. Thus CA-50 may be a clinically useful tool for monitoring of patients with colorectal cancer.

Adenocarcinoma↗

Juxtaglomerular interstitial hypertonicity in Amphiuma: tubular origin-TGF signal.

One of the mechanisms mediating renal vascular autoregulation in mammals senses tubular flow rate-dependent changes in luminal NaCl concentrations and signals renal arterioles to change diameter. A similar mechanism operates in the salamander, Amphiuma means. To trace the signal, we measured chloride activity in juxtaglomerular interstitial spaces in Amphiuma during perfusion of the early distal tubule belonging to the same nephron. Interstitial Cl- activity exceeded systemic levels and increased when perfusion rate in the adjacent early distal tubule was increased, reaching values more than five times isotonic. Bumetanide, which inhibits NaCl transport by the early distal tubule, eliminated the hypertonicity. Regions of the interstitial space not a part of the juxtaglomerular apparatus (JGA) were not hypertonic. The Cl- concentration was 80% greater than isotonic in the JGA of nephrons studied under free-flow conditions. Single-nephron blood flow, measured by counting the flux of erythrocytes labeled with a fluorescent molecule, showed typical feedback inhibition with maximum sensitivity to the same rates of tubular perfusion that caused the maximum change in JGA interstitial hypertonicity. Juxtaglomerular interstitial hypertonicity could be an important part of the signal for renal autoregulation.

Animals↗