| 1. |
- Agardh, Carl-David, et al.
(författare)
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Influence of treatment with diethylstilbestrol for carcinoma of prostate on platelet aggregation and plasma lipoproteins
- 1986
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 28:6, s. 469-471
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of prostatic carcinoma with estrogens is accompanied by an increased risk for thromboembolic and cardiovascular complications. The underlying mechanisms are still unknown. Patients treated with diethylstilbestrol (DES) were compared with patients given no estrogen treatment regarding factors (platelet aggregation in vitro and plasma lipoproteins) that have been suggested to contribute to increased thrombogenesis and cardiovascular risk. The results do not show any increase in in vitro platelet aggregation in patients treated with DES compared with those given no treatment. This indicates that hyperaggregability does not contribute to the increased incidence in thromboembolic events seen in DES-treated patients. This is in contrast to the increased platelet aggregation previously described in patients treated with polyestradiolphosphate + etinylestradiol. The changes in plasma lipoproteins observed during DES-treatment are generally considered beneficial from an atherogenic point of view and do not appear to cause the elevated incidence of cardiovascular disease in these patients.
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| 2. |
- Andersson, Karl-Erik
(författare)
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Bladder activation: afferent mechanisms.
- 2002
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Ingår i: Urology. - 1527-9995. ; 59:5 Suppl 1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- The major function of the lower urinary tract is to store and periodically evacuate urine from the bladder. This requires coordination of the smooth muscles of the bladder and urethra, and of the striated muscles of the outflow region and pelvic floor by a complex neural control system. Lumbosacral afferent fibers (pelvic afferents), but also afferents in the hypogastric and pudendal nerves, are of major importance for the regulation of the mechanisms for continence and micturition. In the bladder, afferent nerves have been identified suburothelially as well as in the detrusor muscle. Suburothelially, they form a plexus that lies immediately beneath the epithelial lining. This plexus is particularly dense in the bladder neck and the trigone. The most important afferents for the micturition process are myelinated Adelta-fibers and unmyelinated C-fibers. Immunocytochemical and tracing studies have revealed that numerous peptides, including substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalins, and cholecystokinin are localized either alone, or in combination, in afferent pathways of the bladder and urethra. The receptors on these nerves include: vanilloid receptors, purinoceptors, tachykinin, and prostanoid receptors. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been proposed that in the bladder, distention causes release of ATP from the urothelium. ATP, in turn, can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, it is most likely that a cascade of inhibitory and stimulatory transmitters/mediators, as well as ATP, are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling.
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| 3. |
- Andersson, Karl-Erik
(författare)
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Introduction
- 2003
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Ingår i: Urology. - 1527-9995. ; 62:5 Suppl 2, s. 1-2
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Andersson, Karl-Erik
(författare)
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New pharmacologic targets for the treatment of the overactive bladder: an update.
- 2004
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 63:3 Suppl 1, s. 32-41
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Tidskriftsartikel (refereegranskat)abstract
- Although currently available antimuscarinic agents are the standard of care for overactive bladder (OAB), they are limited by certain side effects, particularly dry mouth and constipation. Research aimed at discovering new therapies for OAB has resulted in the identification of some promising drugs. Investigations of pharmacologic targets in the central nervous system (CNS) have yielded encouraging results with several agents, including tramadol and gabapentin. Further investigation may show that drugs acting at serotonergic and noradrenergic CNS sites are clinically useful as therapies for OAB. Some peripherally acting drugs, such as resiniferatoxin and botulinum toxin, have already been proved to be of clinical value. However, development of other agents that block afferent or efferent nerve impulses in the bladder through activity at vanilloid, purinergic, or opioid-like receptor sites may result in clinically useful drugs.
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| 5. |
- Andersson, Karl-Erik, et al.
(författare)
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Pharmacologic perspective on the physiology of the lower urinary tract
- 2002
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Ingår i: Urology. - : Elsevier. - 0090-4295 .- 1527-9995. ; 60:5 Suppl 1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Myogenic activity, distention of the detrusor, and signals from the urothelium may initiate voiding. In the bladder, afferent nerves have been identified not only in the detrusor, but also suburothelially, where they form a plexus that lies immediately beneath the epithelial lining. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been shown that bladder distention causes release of ATP from the urothelium. In turn, ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably, not only ATP but also a cascade of inhibitory and stimulatory transmitters and mediators are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling. These mechanisms may be targets for future drugs. The central nervous control of micturition involves many transmitter systems, which may be suitable targets for pharmacologic intervention. gamma-Aminobutyric acid, dopamine, enkephalin, serotonin, and noradrenaline receptors and mechanisms are known to influence micturition, and potentially, drugs that affect these systems could be developed for clinical use. However, a selective action on the lower urinary tract may be difficult to obtain. Most drugs currently used for treatment of detrusor overactivity have a peripheral site of action, mainly the efferent (cholinergic) neurotransmission and/or the detrusor muscle itself. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis, as well as in the aging bladder, a noncholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions.
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| 6. |
- Andersson, Karl-Erik
(författare)
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Storage and voiding symptoms: pathophysiologic aspects.
- 2003
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 62:5 Suppl 2, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- Lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, and postmicturition symptoms. Although often associated with benign prostatic hyperplasia (BPH), they may also occur in women. This observation, the beneficial effects of a-adrenoceptor (AR) antagonists in men with BPH and LUTS, and the frail correlation between LUTS, and prostatic enlargement and/or outflow obstruction have focused interest on the role of extraprostatic alpha-ARs in the pathogenesis of LUTS. It has been suggested that an upregulation of contraction-mediating alpha-ARs and a downregulation of relaxation-mediating beta-ARs can contribute to LUTS generation. However, recent investigations on human bladder tissue could not confirm such a change. Antimuscarinic agents are effective for treatment of the overactive bladder, which is characterized by urge, frequency, urge incontinence, and nocturia (ie, LUTS). This suggests that muscarinic receptors are involved in the pathogenesis of LUTS, and there is recent evidence implicating purinergic receptors. Structural changes in the bladder, such as smooth muscle hypertrophy and connective tissue infiltration, are associated with detrusor overactivity in about 50% to 66% of patients with BPH. However, it is unclear whether this is caused by bladder outlet obstruction because the symptoms may remain in up to 33% of the patients after surgical removal of the obstruction. When outflow obstruction is reversed in rats, there is a subset (20%) that continues to have overactive voiding, despite a reversal of the bladder hypertrophy, suggesting that changes within the central nervous system may be a contributing factor. LUTS can be caused by many, often overlapping, pathophysiologic mechanisms, which may contribute to individual variation in response to treatment.
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| 7. |
- Andersson, Karl-Erik
(författare)
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Summary.
- 2003
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Ingår i: Urology. - 1527-9995. ; 62:5S2, s. 38-39
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Andersson, Karl-Erik
(författare)
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Treatment of the overactive bladder: possible central nervous system drug targets.
- 2002
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Ingår i: Urology. - 1527-9995. ; 59:5 Suppl 1, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- The well-known side effects of antimuscarinic drugs have focused interest on other modalities of treatment of the overactive bladder. To effectively control bladder activity, identification of suitable targets for pharmacologic intervention is necessary. Such targets may be found in the central nervous system (CNS) or peripherally. Several CNS transmitters may modulate voiding, but few drugs with a defined CNS site of action have been developed for treatment of voiding disorders. Drugs affecting gamma-aminobutyric acid, opioid, serotonin, noradrenaline, dopamine, or glutamatergic receptors and mechanisms are known to influence micturition, and potentially such drugs could be developed for clinical use. However, a selective action on the lower urinary tract may be difficult to obtain.
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| 9. |
- Baert, L, et al.
(författare)
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Clinical Fluorescence Diagnosis of Human Bladder-carcinoma Following Low-dose Photofrin Injection
- 1993
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 41:4, s. 322-330
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Tidskriftsartikel (refereegranskat)abstract
- A point-monitoring fluorescence diagnostic system based on a low-energy pulsed laser, fiber transmission optics, and an optical multichannel analyzer was used for diagnosis of patients with bladder malignancies. Twenty-four patients with bladder carcinoma, carcinoma in situ, and/or dysplasia were injected with hematoporphyrin derivative, Photofrin, 0.35 or 0.5 mg/kg body weight, forty-eight hours prior to the investigation. The ratio between the red sensitizer emission and the bluish tissue autofluorescence provided excellent demarcation between papillary tumors and normal bladder wall. Certain cases of dysplasia also could be differentiated from normal mucosa. Benign exophytic lesions such as malakoplakia appeared different from malignant tumors in fluorescence. Flat suspicious bladder mucosa such as seen in infectious diseases or after radiation therapy appeared normal on fluorescence.
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| 10. |
- Becker, Charlotte, et al.
(författare)
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Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater
- 2000
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Ingår i: Urology. - 1527-9995. ; 55:5, s. 694-699
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the clinical value of human glandular kallikrein 2 (hK2) compared with free (f) and total (t) prostate-specific antigen (PSA) in the early detection of prostate cancer (PCa). METHODS: In PCa screening conducted in 1995 to 1996 in Goteborg, Sweden, 5853 of 9811 randomly selected men (aged 50 to 66 years; median 61) accepted PSA testing; those with tPSA levels of 3. 0 ng/mL or greater were offered digital rectal examination, transrectal ultrasound, and sextant biopsies. Serum from 604 of 611 biopsied men (18% with positive digital rectal examinations, tPSA range 3.0 to 220 ng/mL, 144 men with PCa) was analyzed for hK2 (research assay) and tPSA and fPSA (Prostatus). Sera were stored at -20 degrees C for a maximum of 2 weeks for tPSA and fPSA and 3 years for hK2. RESULTS: hK2 levels and hK2 x tPSA/fPSA values were significantly elevated in men with PCa. Receiver operating characteristic data revealed that the area under the curve for hK2 x tPSA/fPSA was significantly greater than that for tPSA and greater, but not significantly greater, than that for percent fPSA. Also, the cancer-detecting sensitivity was significantly improved (P <0.05) using hK2 x tPSA/fPSA compared with tPSA and percent fPSA at specificity levels of 75% to 90%. At 75% specificity, a sensitivity of 74% was obtained compared with 64% or 54% using percent fPSA or tPSA; at 90% specificity, the corresponding sensitivity level was 55%, 41%, and 36%, respectively. CONCLUSIONS: Discrimination of men with and without PCa in a randomly selected population was improved by measuring hK2 in addition to tPSA and fPSA.
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