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Biomedical subjects

H J Kirkeby

Publications and source records attributed to H J Kirkeby.

At least 19 recordsLinked to original sources

Conditional stimulation of the dorsal penile/clitoral nerve may increase cystometric capacity in patients with spinal cord injury.

AIMS: To investigate the feasibility of conditional short duration electrical stimulation of the penile/clitoral nerve as treatment for detrusor hyperreflexia, the present study was initiated. METHODS: Ten patients with spinal cord injury, 4 women and 6 men, with lesions at different levels above the sacral micturition center had a standard cystometry performed. During a subsequent cystometry, conditional short duration electrical stimulation of the penile/clitoral nerve was performed as treatment for one or more detrusor hyperreflexic contractions. RESULTS: In all patients, at least one contraction (mean, 7.8; range, 1-16 contractions) was inhibited by the stimulations. The mean cystometric capacity was increased significantly by conditional electrical stimulation, from 210 mL in the control cystometries to 349 mL in the stimulation cystometries (P=0.016). The maximal detrusor pressure during the first contraction in the control cystometries was mean 51 cm H(2)O, whereas the maximal pressure of the first contraction in the stimulation cystometries was reduced to mean 33 cm H(2)O (P=0.045). CONCLUSIONS: The authors conclude that repeated conditional short duration electrical stimulation significantly increased cystometric capacity in patients with spinal cord injury. The increase was caused mainly by an inhibition of detrusor contractions. The need for a reliable technique for chronic bladder activity monitoring is emphasized, as it is a prerequisite for clinical application of this treatment modality.

Adult↗

Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies.

OBJECTIVES: To determine the efficacy and safety of fixed-dose oral sildenafil in patients with erectile dysfunction (ED) of various etiologies. METHODS: In a 12-week, double-blind, randomized, placebo-controlled, fixed-dose study, 514 men (mean age 56 years) with ED were randomized to receive 25, 50, or 100 mg of sildenafil or placebo. The primary etiology of ED was determined to be organic in 32% of men, psychogenic in 25%, or mixed in 43%. Sildenafil or placebo was taken in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of the IIEF, a global efficacy question, event log data, and a partner questionnaire. RESULTS: Sildenafil significantly increased patients' ability to achieve and maintain erections (P <0.0001), with efficacy increasing with increasing dose. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction, and overall sexual satisfaction (P <0.0001). The proportion of subjects who felt that treatment with sildenafil improved their erections was significantly greater (67% to 86%) than that with placebo treatment (24%, P <0.0001). The proportion of successful attempts at sexual intercourse also increased significantly with sildenafil treatment (P <0.001). Partner responses corroborated patient reports. Sildenafil was well tolerated at the three doses studied. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for ED of various etiologies.

Administration, Oral↗

Treatment of penile curvature--a retrospective study of 175 patients operated with plication of the tunica albuginea or with the Nesbit procedure.

OBJECTIVE: To evaluate the outcome and complications after operative correction of sexually disabling penile angulation. PATIENTS AND METHODS: Between January 1 1987 and December 31 1991, 175 patients underwent operative correction of penile angulation due to Peyronie's disease (57 patients) or congenital curvature (118 patients). Thirty two patients were treated by plication of the tunica albuginea and 143 by the Nesbit procedure. Post-operatively 91% of the patients were seen in the out-patient clinic after 3-5 months. A questionnaire sent to all patients 6-60 months after surgery was returned by 74% of the patients, and the present results are based on the most recent information obtained. RESULTS: In the plication group good or acceptable results were obtained in 12 of 32 patients (38%) after the first operation, and in a further nine patients (22%) after a second operation. In the Nesbit group 126 of 143 patients (88%) obtained good or acceptable results after the first operation and a further seven patients (5%) reported success after a second operation. The failures in the Nesbit group were due mainly to post-operative erectile dysfunction in patients with Peyronie's disease, in contrast to the plication group where failures were primarily due to recurrence of angulation. CONCLUSION: Operative correction of penile curvature is a reasonably safe procedure, but should not be performed solely for cosmetic reasons. In the present retrospective study the results were better after the Nesbit procedure compared with plication of the tunica albuginea. However, a review of the literature does not give support to one operative technique over the other. This can only be clarified by performing a prospective randomized trial.

Adolescent↗

[Penile vein resection. Treatment of patients with erectile dysfunction caused by venous leakage].

In the period February 1991 to February 1992, 12 patients underwent penile vein resection as described by Tom Lue for erectile dysfunction caused by venous leakage. The median age of the patients was 43.7 years (range 23 to 46 years). Two patients had haematoma and two had penile oedema postoperatively. Both conditions resolved spontaneously within two weeks. At the first follow up six weeks postoperatively, 10 patients were able to have normal intercourse. After six month this number had declined to eight. After a follow-up period of 18 to 30 months only four patients were able to have intercourse. One of these needed self injection with papaverin/phentolamine. Because of the poor results, penile vein resection as described by Tom Lue cannot be recommended as a routine procedure in patients with erectile dysfunction caused by venous leakage. However the operation may be relevant in younger patients with penile venous leakage, where there are no concomitant causes of the erectile failure.

Adult↗

Comparison of the effects of prostanoids on human penile circumflex veins and corpus cavernosum tissue.

The mechanical effects of the prostaglandins PGE1, PGE2, PGF2 alpha and PGI2 were investigated in human isolated penile circumflex veins (CV) and corpus cavernosum (CC) tissue. PGE1 did not affect resting tension, while the compound produced relaxation of both CC and CV preparations after precontraction with noradrenaline (NA) 3 x 10(-6)M. PGE2 produced contraction in CC and CV preparations. After precontraction with NA, however, relaxation was induced in both tissues. PGF2 alpha induced contraction in CC and CV preparations, while no relaxant responses were seen in preparations precontracted with NA. PGI2 produced no mechanical effects in unstimulated CV preparations, whereas dose-related contraction was induced in CC tissue strips. After precontraction with NA, PGI2 showed no effect in 2 of 6 CC preparations, while relaxation was seen in 4. In CV preparations precontracted with NA, PGI2 produced relaxation. Local synthesis of prostanoids may influence resting tension and modulate NA-induced responses not only in human penile CC but also in CV smooth muscle.

Adolescent↗

Role of the L-arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins.

In human penile corpus cavernosum strips, pre-contracted by noradrenaline, electrical stimulation of nerves evoked non-adrenergic, non-cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10(-6) M, NG-nitro-L-arginine (L-NNA) 10(-7)-10(-4) M, and oxyhaemoglobin 10(-5) M, but not by methylene blue (MB) 10(-5) M. Acetylcholine-induced relaxations were also inhibited by L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M, but were unaffected by pyrogallol 10(-4) M, MB 10(-5) M, and tetrodotoxin 10(-6) M. MB 5 x 10(-4)-10(-4) M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10(-7)-10(-4) M and sodium nitroprusside 10(-9)-10(-4) M caused concentration-dependent relaxations. The NO-induced relaxations were inhibited by oxyhaemoglobin 10(-5) M, and the concentration-response curve for sodium nitroprusside was shifted to the right by MB 10(-5) M. The response to sodium nitroprusside was unaffected by L-NNA 10(-4) M, oxyhaemoglobin 10(-5) M, and pyrogallol 10(-4) M. In circumflex veins, pre-contracted by noradrenaline, no NANC-mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium-dependent relaxations, which were insensitive to L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M. NO and sodium nitroprusside caused concentration-dependent relaxations; the concentration-response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10(-5) M. Removal of the endothelium left the NO- and sodium nitroprusside-induced relaxations unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

A hydrodynamic model of rabbit corpus cavernosum pressure responses to vasodilators.

The intracavernosal pressure changes induced by 3 vasodilating drugs, diazoxide, glyceryltrinitrate and verapamil were investigated during autologous extracorporeal penile blood perfusion in an experimental rabbit model. In order to separate the arterial and venous components the experiments were performed with both intact and interrupted penile arterial inflow. The major hemodynamic effect of these drugs was an increased outflow resistance from the corpora cavernosa, probably effected through relaxation of the corporal smooth muscle. However, the intracorporeal pressure responses only reflected a part of the drug-induced smooth muscle relaxation. A theory is presented, according to which the corpora cavernosa are 'accumulating' smooth muscle relaxation, without direct reflection in an increased cavernosal pressure. At the moment when sufficient smooth muscle relaxation is achieved, a sudden increase in cavernosal pressure will appear and lead to an erection. This concept was generated through an approximation of corpora cavernosa to an elastic cylinder following the elastic law of Laplace in combination with the hydrodynamic law of Poiseuilles.

Animals↗

Effects of vasoactive intestinal peptide, peptide histidine methionine, and neuropeptide Y on intracavernous pressure in the rabbit.

In anesthesized white rabbits blood was extracorporeally circulated from the left carotid artery into the penile corporeal bodies with a constant flow rate. Corpus cavernosum pressure (CCP) responses to intracavernous injections of drugs were recorded in animals with aortic nonocclusion and aortic occlusion, respectively. Vasoactive intestinal polypeptide (VIP, 1 microgram, 5 micrograms, and 20 micrograms), dissolved in 0.5 mL volumes, induced no significant increases in CCP compared with equivalent volumes of solvent, but the peptide increased the time interval until return of CCP to steady state level. Peptide histidine methionine induced a significant increase in the maximal CCP obtained in nonocclusion, and the time interval until return of CCP to steady state levels was increased in both aortic nonocclusion and occlusion. Neuropeptide Y produced an increase in the maximal CCP in animals with aortic occlusion, and a minor increase in the time interval until return of CCP values to steady state levels in both aortic nonocclusion and occlusion. Thus, all the peptides tested were capable of influencing the smooth muscle tissues involved in penile outflow regulation.

Animals↗

Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) in human penile corpus cavernosum tissue and circumflex veins: localization and in vitro effects.

Localization and functional effects of vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), two peptides derived from a common precursor molecule, were investigated in isolated preparations from human penile corpus cavernosum (CC) and circumflex vein (CV). VIP- and PHM-immunoreactivity (IR) was demonstrated in both CC and CV. The concentrations of VIP-IR and PHM-IR in CC tissue were 54.4 +/- 15.3, and 42.0 +/- 7.5 pmol g-1 wet weight respectively with a VIP/PHM ratio of 1.5 +/- 0.4 (mean +/- SEM). The corresponding values for CV tissues were 28.0 +/- 7.7 and 9.6 +/- 2.6 pmol g-1 wet weight with a VIP/PHM ratio of 3.1 +/- 0.4. CC and CV displayed VIP- and PHM-IR confined to nerve fibres in close relation to bundles of smooth muscle cells and blood vessels in both tissues. In vitro, VIP and PHM had no effects in unstimulated tissue preparations. Both peptides concentration-dependently (10(-9)-10(-6) M) relaxed CC and CV preparations precontracted with 3 x 10(-6) M noradrenaline. In CC the maximum relaxant effect of VIP and PHM was 22 +/- 11% and 9 +/- 9% and in CV the corresponding values were 82 +/- 8% and 93 +/- 3% respectively. The present study supports the hypothesis of VIP and PHM as neurotransmitters and/or neuromodulators in the nervous control of penile erection.

Adolescent↗

Functional effects, binding sites and immunolocalization of endothelin-1 in isolated penile tissues from man and rabbit.

Functional effects of endothelin-1 (ET-1) were investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and human penile circumflex veins (CV). In all preparations, ET-1 induced slowly developing, concentration-dependent contractions. The threshold concentration of ET-1 in CV was approximately 10 and 112 times lower than the threshold concentrations in human and rabbit CC, respectively. Furthermore, the contractions in CV reached a defined maximum at 10(-7) M ET-1 (-log EC50 = 9.12 +/- 0.17), whereas no maximum was obtained in CC preparations within the concentration range used (less than or equal to 3 x 10(-7) M). Pretreatment with the Ca++ channel blocker nimodipine partly reduced the ET-1-induced contractions in human and rabbit CC, but had no significant effect on CV preparations. In a Ca(++)-free medium containing the chelator ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetra-acetic acid, the contractions induced by ET-1 were reduced, but not abolished, in all preparations. The contractions induced by ET-1 are thus mediated mainly by influx of Ca++, although there seem to exist differences in the relative contribution of L-type Ca++ channels in CC and CV. Furthermore, additional mechanisms beside Ca++ influx are likely to be involved in both tissues. A high density of [125I]ET-1 binding sites was observed throughout the stroma and in the muscle layer of the deep penile artery in both human and rabbit CC. In the human CV, numerous binding sites were observed, but no clear difference between the various structures of the vessel wall could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Urethral pressure and pressure variations in healthy fertile and postmenopausal women with reference to the female sex hormones.

The impact of female sex hormones on the rhythmic urethral pressure variations (UPV) was analysed based on data from one hour urethral pressure recordings from 10 healthy fertile female volunteers measured three times during the menstrual cycle and from 12 healthy postmenopausal women measured twice within two months. The mean maximum urethral pressure (mMUP) and the mean maximum urethral closure pressure (mMUCP) had a median value of 66.5 (Interquartile 58.0-86.0) and 60.0 (49.0-80.0) cm.H2O respectively in the healthy fertile females. The postmenopausal women had a significantly lower mMUP and mMUCP of 55.5 (48.5-58.5) and 43.5 (35.5-47.0) cm.H2O) respectively. Rhythmic UPV was recorded inhealthy fertile and postmenopausal women. Frequency analysis of the UPV revealed a frequency spectrum from 0.0015 to 0.035 Hz on top of which were respiration fluctuations and vascular pulsations. The UPV amplitude was related to the mMUP and increased with increasing mMUP. The parameters analysed were stable during the menstrual cycle and during menopause. Thus no difference in the UPV frequencies or amplitudes was observed between the healthy fertile and the postmenopausal women. The investigation shows that the pressure variation in urethra apparently is not modulated by female sex hormones.

Adult↗

Neuropeptide Y (NPY) in human penile corpus cavernosum tissue and circumflex veins--occurrence and in vitro effects.

The concentration and distribution of neuropeptide Y (NPY) within the penile corpus cavernosum (CC) and in penile circumflex veins (CV) from healthy potent males was investigated by immunochemistry and immunohistochemistry. The concentrations were assessed to 28.6 pmol/gm. (CC) and 15.8 pmol/gm. (CV) respectively. Gel filtration on CC tissue extracts demonstrated a single peak of NPY-immunoreactivity (NPY-IR) similar to synthetic human NPY. The NPY-IR was confined to nerve fibers seemingly innervating smooth muscle cells. In vitro myographic examinations demonstrated contractile activation by NPY in 2/8 CC strips and in 5/8 CV strips. The mean contractile force was 1.17 +/- 0.62 mN (18.3 +/- 15.8% of the K(+)-induced contraction) and 2.42 +/- 0.42 mN (31 +/- 12%) respectively. NPY 10(-7) and 10(-6) M displayed a potentiating effect on the response to NA 10(-9) in one of six CC and four of six CV preparations. It is suggested that NPY could add to the contractile effect of NA in detumescence and in maintenance of the resting state; contribution of NPY to the veno-occlusive mechanism at initiation of erection is another putative physiological function.

Adult↗

[Infusion cavernosography and erectile dysfunction].

Infusion cavernosography with the object of quantitating the rate of venous drainage from the penis and localization of possible abnormities in drainage was employed as a routine investigation in examination of erectile dysfunction in 46 patients. "Infusion to obtain erection" (IOE) and "infusion to maintain erection" (IME) were determined. In five patients, IOE was found to be greater than 180 ml/minute which was considered to be diagnostic of venous leakage. Infusion cavernosography could be assessed in 31 patients. Filling of the glans with the radio-opaque medium was found before rigidity was obtained in 27 whereas, in 19 filling of the glans occurred after rigidity was obtained. No localizing fistulae were demonstrated. It is concluded that routine employment of infusion cavernosography in investigation of impotence is unnecessary. Filling of the glans with the radio-opaque medium in infusion cavernosography does not appear to be a sign of a cavernoso-spongious fistula but rather a physiological phenomenon.

Erectile Dysfunction↗

[Priapism. New diagnostic and therapeutic methods].

Priapism (P) may develop from unknown causes or may occur secondary to other disease or as a side effect of medication. The occurrence of pharmacologically induced erection by intracavernous injection of drugs has resulted in a number of cases of iatrogenic priapism. Priapism may be ischaemic or non-ischaemic and determination of the acid-base status in the cavernous blood may be of value in the choice of treatment. The non-ischaemic cases should be treated primarily by aspiration of blood, possibly followed by intracavernous injection of a vaso-constrictive agent, eg 15 micrograms adrenaline or noradrenaline, repeated if necessary. Cases which do not respond to this and severe ischaemic cases should be treated with glando-cavernous anastomosis.

Humans↗