Renal and hepatic nitrogen metabolism during NH4Cl ingestion in protein-deprived rats

PURPOSE: We assessed the morphodynamic features of cavernous arteries and helicine arterioles by power Doppler sonography in vasculogenic and nonvasculogenic impotent men. MATERIALS AND METHODS: A total of 40 impotent patients with and without definite vascular risk factors were studied by penile power Doppler sonography. The test was performed during penile flaccidity, after intracavernous injection of 20 mcg. alprostadil and after subsequent genital and audiovisual sexual stimulation. A second injection and stimulation were given if the erectile response observed after the initial injection was less than the maximum erection seen during sexual activity. Morphodynamic parameters evaluated by power Doppler imaging included vessel course, shape, wall thickness and pulsatility, peak systolic velocity, end diastolic velocity, acceleration time and resistance index. RESULTS: In the nonvasculogenic group all patients who achieved rigid erection showed normal cavernosal artery and helicine arteriole inflow. In these cases the arteriolar picture was characterized by the presence of 3 orders of distal ramifications originating from the cavernous arteries with an acute angle, systolic diastolic flow during penile tumescence and systolic flow alone at full rigidity. In the vasculogenic group patients with normal cavernous artery inflow showed an arteriolar tree that was pathological in 50% and was characterized by a reduced number of ramifications originating perpendicularly from the cavernous arteries and irregular caliber (arteriolar impotence). In the same group patients with reduced cavernous artery inflow also showed normal or pathological arteriolar components (pre-penile arterial impotence and diffused penile arterial impotence). CONCLUSIONS: Power Doppler sonography allows a precise study of the morphodynamics of the cavernous arteries and helicine arterioles. Our preliminary data suggest that the intracavernous arteriolar component may have a significant role in the genesis of some forms of vasculogenic impotence.     

The pharmaco-erection test

Intracavernous administration of vasoactive drugs induces an erection in absence of erotic stimuli; we can use this property in the study of impotent patients, inducing the appearance on an erection to examine it in all its phases (FIC Test). In case of the appearance of a good erection, the test should rule out the presence of a penile arterial disease or of a corpora-veno-occlusive deficiency. When the administration of the drug does not cause complete tumescence, it is very probable that the erectile dysfunction is caused by arterial vascular alterations or by organic disorders of veno-occlusion mechanism, but we cannot exclude for a certainty a psychogenic dysfunction. In fact an excessive noradrenergic autonomic control, as during stress condition, may limit FIC Test response. Therefore we hope that more efficacious molecules will be available in a near future. Nevertheless, we consider the opportunity of enclosing tests in the diagnostic algorithm of impotent patients to reveal an excessive adrenergic tone, such as, for example, psychological tests, study of cavernous potential, or intracavernous catecholamine dosage.     

A quantitative study of daytime sleepiness induced by carbamazepine and add-on vigabatrin in epileptic patients

Improvement in natural erections has been reported in approximately 9% of impotent men using intracavernous injections of vasoactive drugs for erection induction. The mechanisms which may account for this improvement are psychogenic, improved cavernous hemodynamics, prostaglandin-induced angiogenesis, improved cavernous oxygenation, cavernous smooth muscle hypertrophy and/or normal episodic fluctuations in erectile function. A review of the basic science literature on this subject reveals several theoretical explanations for this phenomenon but a review of the clinical literature reveals little convincing evidence that physiologic and/or pharmacologic factors are responsible for improvement in natural erections with intracavernous injection therapy. Furthermore, the prevalence of a placebo effect from impotence therapy exceeds the reported rate of improvement in natural or spontaneous erections. The most plausible explanations for spontaneous improvement in erections during or after intracavernous injection therapy are psychogenic and episodic variations in erectile function, rather than physiologic or pharmacologic factors. However, intracavernous injection therapy started soon after radical prostatectomy may have a protective effect in preserving normal cavernous physiology and erectile function in men being treated for prostate cancer.     

Subclinical trauma to perineum: a possible etiology of erectile dysfunction in young men

A substantial number of young men with erectile dysfunction have neither systemic disease nor a trauma in their history. We are familiar with impotence after major trauma but it is an unanswered question whether subclinical trauma may also induce arterial degeneration with subsequent erectile dysfunction. In a period of 36 months 129 patients underwent penile arteriography. After excluding those with major surgery, trauma or psychogenic impotence 91 angiograms were reevaluated. Special attention was paid to atherosclerotic and to focal occlusive arterial disease (> 50% stenosis) in the hypogastric-cavernous branch. 12 angiograms showed normal arteries, 59 typical atherosclerotic and 20 focal occlusive arterial disease. The mean age of patients with atherosclerosis was 53 +/- 8 years versus 35 +/- 14 years of those with focal lesions (p < 0.0001). 30% with focal arterial lesions were subject to subclinical trauma. 68% with atherosclerotic disease had clinical relevant atherosclerotic risk factors. Latency between onset of erectile dysfunction and presentation at the impotence clinic was 51 months in patients with focal lesions and 39 months in those with atherosclerotic disease (nonsignificant). We conclude that subclinical trauma of the hypogatric-cavernous arteries can induce focal arterial lesions with significant impairment of perfusion. This pathology may contribute to erectile dysfunction. These patients are significantly younger and they suffer from clinically evident impotence approximately 18 years earlier than patients whose impotence is clearly of atherosclerotic origin. Focal arterial lesions due to subclinical trauma are described for the first time as an etiology of erectile dysfunction. Further studies are needed to confirm these results.     

The value of color-coded duplex ultrasound as standard assessment in erectile dysfunction

Erectile dysfunction has taken on increasing importance in urologic practice. Still open is the question of which tests are mandatory for adequate clinical assessment of erectile dysfunction. One accepted standard modality is the intracavernous pharmacotest with vasoactive agents. In contrast, color duplex sonography is not considered mandatory although it reveals detailed information about penile vessels and functional implications. The question remains whether the information gained by color duplex sonography is relevant for therapy, making it an indispensable standard procedure. Patients with erectile dysfunction were evaluated, without preselection, by extensive history, clinical evaluation, laboratory tests, tumescence and rigidity measurements, intracavernous administration of vasoactive drugs and color duplex sonography. Seventy-nine patients were available for final analysis. Color duplex sonography revealed 39 normal tests, 16 arterial impairments. 19 venous leakages and 5 arteriovenous fistulae. Intracavernous vasoactive agents (pharmacotest) revealed 44 reactions sufficient for intercourse and 35 insufficient responses. In 89% of patients, the diagnoses on color duplex sonography and intracavernous pharmaco-testing were similar. The accuracy of the two methods in diagnosing erectile dysfunction was not statistically different (McNemar's test). In contrast to intracavernous pharmaco-testing, color duplex sonography permitted further etiologic subdivision into arterial disease, venous leakage, arteriovenous fistula and normal result. This was made possible by measuring significantly (P < 0.01) different arterial peak flow velocities, end-diastolic velocities and calculated resistance index. These data did not imply direct clinical consequences. Color duplex sonography and intracavernous pharmacotesting reveal comparable results concerning the diagnosis of an erectile dysfunction. In contrast to pharmacotesting, color duplex sonography reveals details of the nature of the erectile dysfunction. Because this information has no profound implications for the choice of therapeutic procedure, color duplex sonography can not be recommended as a standard procedure in the evaluation of erectile dysfunction.     

Erectile response to intracavernous injection of linsidomine in 38 impotent patients. Comparison with prostaglandin E1

OBJECTIVE: To test the effects of intracavernous injection of Linsidomine, an NO donor, and to compare the results to those obtained after injection of PGE1. MATERIAL AND METHODS: 38 subjects with erectile insufficiency received an intracavernous injection of 10 micrograms of PGE1, followed by an intracavernous injection of 1 mg of linsidomine at least 3 days later. The erectile response after linsidomine was compared to that obtained after PGE1. 21 patients were investigated by Duplex ultrasound after each injection. RESULTS: Linsidomine induced complete rigidity in 4 subjects considered to suffer from psychogenic impotence (versus 11 subjects with PGE1) and 1 subject considered to suffer from arterial disease (versus 8 subjects with PGE1). The maximal systolic velocities recorded after linsidomine were significantly correlated with those measured in the same subject after PGE1. The resistance index was not modified after linsidomine injection. CONCLUSION: Our study confirms the impact of linsidomine on the local mechanisms of erection. It shows that linsidomine is much less effective than PGE1, but nevertheless has a place in the therapeutic armamentarium of impotence.     

Absence of modulating effects of cytokines on antioxidant enzymes in peritoneal mesothelial cells

Erectile dysfunction is a common (affecting 10-20 million men in the USA) and multifactorial disease due to organic and/or psychological factors that strongly impairs the quality of life in man. During the past decade many advances in the understanding of the pathophysiology of erectile dysfunction have been made and new therapeutic strategies have become available. It has been established that an insufficient production of nitric oxide by penile nerve terminals and/or vascular endothelium may result in an impaired erection or complete impotence. Nowadays, intracavernous injection of vasoactive drugs represents a standardized approach for the diagnosis, and the treatment of choice, for erectile dysfunction, but is not widely accepted by the patients. The possibility of treating erectile dysfunction with intraurethral administration of prostaglandin-E1 has recently become available in the USA, and is a therapy more acceptable to the patients. Other noninvasive medical therapies are undergoing evaluation.     

Erectile impotence in multiple sclerosis: a neurophysiological study

Pudendal evoked potentials, motor evoked potentials of the bulbocavernosus muscle to magnetic stimulation and bulbocavernosus reflex were recorded in 34 patients with multiple sclerosis (MS). Responses were delayed in 26, 20 and 3 cases respectively. No relationship was found between neurophysiological abnormalities and the presence or severity of erectile dysfunction, showing that these tests have little diagnostic usefulness in MS patients with impotence. Nocturnal penile tumescence was assessed in 14 cases: the test result was normal in 10 patients, including 3 severely paraplegic subjects.     

Pharmacokinetics of prostaglandin E1 and its main metabolites after intracavernous injection and short-term infusion of prostaglandin E1 in patients with erectile dysfunction

PURPOSE: Alprostadil (prostaglandin E1) is the preferred monotherapy for intracavernous injection in the diagnosis and treatment of erectile dysfunction. Our study was designed to evaluate whether there is a difference in the pharmacokinetics of prostaglandin E1 and its main metabolites after intracavernous injection or short-term intravenous infusion. In addition, we also investigated the influence of the erectile response on prostaglandin E1 kinetics after intracavernous injection. MATERIALS AND METHODS: A total of 24 patients with erectile dysfunction received, in a randomized order at an interval of 5 hours, an intracavernous injection or a 30-minute intravenous infusion of 20 microg. of alprostadil alfadex (prostaglandin E1). Venous blood samples were obtained 5 minutes before and at various times after the applications. We used highly sensitive gas chromatography/double-mass spectrometry method to measure prostaglandin E1 and its metabolites in plasma. RESULTS: We demonstrated the presence of relevant systemic blood levels of prostaglandin E1 and its metabolites immediately after intracavernous injection. We found significantly lower systemic prostaglandin E1 concentrations between 7 and 20 minutes after intracavernous injection in patients with an erectile response compared with those without. CONCLUSIONS: We found significant systemic concentrations of prostaglandin E1 and its metabolites after intracavernous injection. The systemic presence did not lead to significant changes in vital signs.     

Effects of hyperchloremia on blood oxygen binding in healthy calves

Three different levels of hyperchloremia were induced in healthy Friesian calves to study the effects of chloride on blood oxygen transport. By infusion, the calves received either 5 ml/kg of 0.9% NaCl (low-level hyperchloremia; group A), 5 ml/kg of 7.5% NaCl (moderate hyperchloremia; group B), or 7.5 ml/kg of 7.5% NaCl (high-level hyperchloremia; group C). Blood was sampled from the jugular vein and the brachial artery. Chloride concentration, hemoglobin content, arterial and venous pH, PCO2, and PO2 were determined. At each time point (0, 15, 30, 60, and 120 min), the whole blood oxygen equilibrium curve (OEC) was measured under standard conditions. In groups B and C, hyperchloremia was accompanied by a sustained rightward shift of the OEC, as indicated by the significant increase in the standard PO2 at 50% hemoglobin saturation. Infusion of hypertonic saline also induced relative acidosis. The arterial and venous OEC were calculated, with body temperature, pH, and PCO2 values in arterial and venous blood taken into account. The degree of blood desaturation between the arterial and the venous compartments [O2 exchange fraction (OEF%)] and the amount of oxygen released at tissue level by 100 ml of bovine blood (OEF vol%) were calculated from the arterial and venous OEC combined with the PO2 and hemoglobin concentration. The chloride-induced rightward shift of the OEC was reinforced by the relative acidosis, but the altered PO2 values combined with the lower hemoglobin concentration explained the absence of any significant difference in OEF (% and vol%). We conclude that infusion of hypertonic saline induces hyperchloremia and acidemia, which can explain the OEC rightward shift observed in arterial and peripheral venous blood.     

The role of nitric oxide in vivo feline erection under hypoxia

Previous in vitro studies have demonstrated that the cavernous relaxation under hypoxia does not involve the endothelium dependent mechanism. However, the mechanism of nitric oxide pathway under hypoxia are not fully evaluated or understood yet in vivo. The changes of intracavernous pressure to various vasoactive substances were monitored in 45 mature male cats in vivo under normoxia and hypoxia (pH: 7.03, PO2: 25.52 mmHg, PCO2: 84.66 mmHg). L-arginine and SNAP (s-nitroso-n-acetyl-penicillamine) produced cavernous relaxation under normoxia, but not under hypoxia (n = 19, P < 0.01). The L-arginine-induced relaxations were inhibited by L-NAME (N omega-nitro-1-arginine-methyl-ester) or methylene blue under normoxia (n = 19, P < 0.01). The cavernous relaxation was 58% suppressed under hypoxia compared to normoxia with 10(-3) M/0.2 ml of acetylcholine (n = 22, P < 0.01). Moreover, L-NAME attenuated the acetylcholine-induced relaxation under normoxia, but not under hypoxia (n = 22, P < 0.05). Epinephrine suppressed the acetylcholine-induced relaxation in both conditions (n = 10, P < 0.01), while indomethacin significantly potentiated the acetylcholine-induced relaxation under normoxia compared to hypoxia (n = 6, P < 0.05). However, none of these substances responded in severe hypoxia (PO2 < 15 mmHg, n = 3). These results suggest that erectile and contractile responses are attenuated under hypoxia. The endothelium derived relaxation via nitric oxide does not play a role in cavernous relaxation under definitive hypoxia with acidosis like in ischemic priapism (PO2 < 30 mmHg, pH < 7.25).     

Preload and incident angle independent index of left ventricular contractility determined by continuous wave Doppler echocardiography

BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated blood and conventionally stored blood on oxygen consumption in acutely anemic dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1 hour they were transfused to a hematocrit of 18% with control or phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin P50 measurements allowed calculation of oxygen consumption during anemia, and posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with phosphoenolpyruvate-treated blood allowed greater O2 consumption than control (8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or venous PO2 or pH; there were marked differences in HOA, measured by posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation. CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen consumption at a similar hematocrit when compared with untreated banked blood.     

Corpus cavernosum electromyography (CC-EMG): a new technique in the diagnostic work-up of impotence

We have studied cavernous electrical activity in 42 subjects, healthy volunteer controls and groups of impotent patients using a nonspecific electromyographic device (PICO-MENFIS) and a specific one, the SPACE-recorder 7500 designed to achieve electric recordings from the corpora cavernosa. In all of the patients, we detected under basal conditions a mean amplitude of 583 +/- 323 microV, a mean duration of 4.9 +/- 7 s, a mean polyphasicity of 3.5 +/- 1.4. It should be emphasized that a significant reduction of potential amplitudes was recorded after pharmacological stimulation in both the controls and the impotent patients. The healthy controls showed amplitudes significantly higher than the impotent patients after radical cystectomy (715 +/- 141 microV versus 381 +/- 227 microV, p < 0.01). The patients after a "nerve-sparing" radical cystectomy with a mean amplitude similar to the controls (500-700 microV) reacted well to the intracavernous drugs in a high percentage of cases. In our experience, CC-EMG seems to be a reliable method which can pinpoint directly lesions to the cavernous smooth muscle and penile autonomic nerves. It has also been able to assess the effects of stress, anxiety and pain on the erectile mechanisms.     

Penile angiography in impotence: local experience

Vasculogenic causes of impotence and especially venous leakage are now considered to be significantly worthwhile to be evaluated in the light of new developments and changes in the treatment of erectile dysfunction. The investigations of cavernosography and penile arteriography are gaining importance. In 32 months, from August 1990 to March 1993, 126 cavernosograms and 11 bilateral internal pudendal arteriograms have been performed on patients from Toa Payoh Hospital. Smooth muscle relaxants are helpful in both procedures. Nearly three-quarters of the cavernosograms showed deep venous leakage. The use of arteriograms is still very restricted. The many variations of the arterial supply to the penis pose problems in the interpretation of the arteriograms and hence, recognition of the numerous variations besides the knowledge of the normal basic vascular anatomy is of paramount importance.     

Contribution of PO2, P50, and Hb to changes in arteriovenous O2 content during exercise in heart failure

Arteriovenous O2 content (a-vCO2) differences increase during exercise in normal subjects through several mechanisms including PO2, O2 pressure at which hemoglobin (Hb) is half saturated with O2 (P50), and Hb concentration changes. The present study was undertaken to evaluate how much these biochemical changes are relevant to a-vCO2 difference through exercise in patients with heart failure. Twenty-seven patients with congestive heart failure [10 patients in functional class A (peak exercise O2 uptake >20 ml x kg-1 x min-1), 9 in class B (20-15 ml x kg-1 x min-1), and 8 in class C (15-10 ml x kg-1 x min-1)] underwent a cardiopulmonary exercise test with once-per-minute simultaneous blood sampling from the pulmonary and systemic arteries for determination of Hb, PO2, PCO2, pH, O2 content (CO2), Hb saturation and lactic acid (pulmonary artery only), and calculation of P50. Analysis of data was done at six exercise stages: the first at rest, the last at peak exercise, and the second to the fifth at one-, two-, three-, and four-fifths of O2 consumption increase. a-vCO2 difference at peak exercise was 14.3 +/- 2.1, 16.9 +/- 2.4, and 14.7 +/- 2.1 (SD) ml/dl in class A, B, and C patients, respectively. The contribution of Hb, P50, and PO2 changes to the increments of a-vCO2 difference during exercise was 21, 17, and 63%, respectively; the only interclass difference observed was for P50, which plays a greater role in a-vCO2 difference in class A. Hb changes act mainly at the arterial site, whereas P50 and PO2 act at the venous site. Hb increase was constant through the test, venous P50 increase was greater above anaerobic threshold, and venous PO2 reduction was most remarkable at the onset of exercise; in class C patients, no venous PO2 change was recorded in the second half of exercise. Thus a-vCO2 difference increase during exercise is notable in patients with heart failure but unrelated to the severity of the syndrome. Hb, P50, and, to the greatest degree, PO2 changes participate in the increment of a-vCO2 difference. In class C patients, the lack of PO2 reduction in the second half of exercise suggests the achievement of a "whole body critical venous PO2."     

Clinical guidelines panel on erectile dysfunction: summary report on the treatment of organic erectile dysfunction. The American Urological Association

PURPOSE: The American Urological Association convened the Clinical Guidelines Panel on Erectile Dysfunction to analyze the literature regarding available methods for treating organic erectile dysfunction and to make practice recommendations based on the treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles from 1979 through 1994 on treatment of organic erectile dysfunction and meta-analyzed outcomes data for oral drug therapy (yohimbine), vacuum constriction devices, vasoactive drug injection therapy, penile prosthesis implantation and venous and arterial surgery. RESULTS: Estimated probabilities of desirable outcomes are relatively high for vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis therapy. However, patients must be aware of potential complications. The outcomes data for yohimbine clearly indicate a therapy with marginal efficacy. For venous and arterial surgery, based on reported outcomes, chances of success do not appear high enough to justify routine use of such surgery. CONCLUSIONS: For the standard patient, defined as a man with acquired organic erectile dysfunction and no evidence of hypogonadism or hyperprolactinemia, the panel recommends 3 treatment alternatives: vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis implantation. Based on the data to date, yohimbine does not appear to be effective for organic erectile dysfunction and, thus, it should not be recommended as treatment for the standard patient. Venous surgery and arterial surgery in men with arteriolosclerotic disease are considered investigational and should be performed only in a research setting with long-term followup available.     

Sexual dysfunction in diabetes mellitus]

Erectile dysfunction or impotence is a very common complication in diabetic male patients; the prevalence of which may be more than that of retinopathy. The cause of diabetic impotence has been thought to be neuropathy or angiopathy or both of them. The diagnosis of diabetic impotence is based on the exclusion of other causes of impotence including psychological, iatrogenic, endocrinological impotence. The treatment options for diabetic impotence such as vacuum device, intracavernous self-injection or surgical procedures are available and useful at present. In this article, other sexual dysfunction; retrograde ejaculation and female sexual dysfunction in diabetes mellitus are also discussed.     

The responses of Verreaux''s sifakas to anti-predator alarm calls given by sympatric ring-tailed lemurs

Erectile dysfunction has an incidence of 2-9% and it is seen often in general practice. But the more recent treatment methods such as intracavernous drug injections and vacuum constriction devices are not known by general practitioners and normally used drug treatment has no efficacy. The management of impotence of the general practitioner should concentrate upon internistic conditions like diabetes, hypertension, hypercholesteremia and different drugs causing impotence. The symptomatic treatment of erectile dysfunction has to be done by a specialist, who is able to offer all therapeutic options.     

Combined pretemporal and endovascular approach to the cavernous sinus for the treatment of carotid-cavernous dural fistulae: technical case report

OBJECTIVE AND IMPORTANCE: The endovascular treatment of carotid-cavernous dural fistulae is becoming the prominent treatment modality for these lesions. The intractability of these lesions and their tendency to recur, especially after previous endovascular treatment sessions, exhausts the available routes and tends to present a difficulty in accessing the cavernous sinus. To avoid the risks associated with a direct surgical approach, an alternative, less invasive route to the cavernous sinus using a pretemporal extradural approach is combined with a direct endovascular approach. CLINICAL PRESENTATION: A 38-year-old woman presented with a history of right visual and ocular symptoms related to a Type D cavernous carotid dural fistula, which was fed by internal carotid and external carotid branches. The fistula was initially treated with embolization of the external carotid arterial supply. After a transient improvement, the patient's visual acuity worsened. A follow-up angiogram showed the major supply from the intracavernous internal carotid branches and draining through the inferior ophthalmic vein. The transvenous route was not accessible. An attempt to cannulate the intracavernous branches was not successful. The combined pretemporal and endovascular approach was then used. INTERVENTION: The pretemporal extradural region of the superior orbital fissure was exposed. Using microsurgical techniques and Doppler flow guidance, the anterior cavernous sinus was cannulated through the orbital venous drainage channels. Using intraoperative angiography, thrombogenic coils were deployed at the level of the fistula. Intraoperative angiography confirmed complete obliteration of the fistula. CONCLUSION: The combined pretemporal (extradural) and endovascular approach to the cavernous sinus is a less invasive alternative for the treatment of intractable carotid-cavernous dural fistulae.