Oral phentolamine as treatment for erectile dysfunction

PURPOSE: For most patients with erectile dysfunction oral agents are a preferred treatment option. Oral or buccal phentolamine has been shown to produce full erections in impotent subsets of study populations. We evaluate the efficacy of oral phentolamine. MATERIALS AND METHODS: After a comprehensive evaluation 44 patients with recent onset (less than 3 years) of erectile dysfunction and a high likelihood of organogenic etiology underwent a prospective, double-blind and placebo controlled trial with oral phentolamine after placebo. RESULTS: After placebo 4 of the 44 patients who reported full erections were excluded from study. Of the 40 patients in the double-blind phase full erections were achieved by 2 of 10 with placebo, and 3 of 10 with 20 mg., 5 of 10 with 40 mg. and 4 of 10 with 60 mg. phentolamine. There were no serious complications observed during the study, and only a single minor side effect occurred in 1 patient after 60 mg. phentolamine. CONCLUSIONS: Our results indicate that oral phentolamine may be of benefit for the treatment of erectile dysfunction. Further studies are required to corroborate our findings.     

A therapeutic taxonomy of treatments for erectile dysfunction: an evolutionary imperative

AIM OF THE STUDY: A functional classification of treatments for erectile dysfunction is important but none exists at present. Advances in the understanding of the mechanisms of drug action and of the mechanisms of penile erection suggest that there is now a rational basis for a therapeutic classification, with the expectation that a logical diagnostic classification will follow. METHODS: The currently available treatments for erectile function and the known relevant basic science were reviewed and assessed. From this, and analysis of classification systems in other fields, a classification was proposed and evaluated with respect to existing treatments. RESULTS: The treatments for erectile dysfunction were classified into five major classes by their mode of action: (I) Central Initiators, (II) Peripheral Initiators, (III) Central Conditioners, (IV) Peripheral Conditioners and (V) Other. Drugs in these classes are further subdivided by the routes of administration and the mechanisms of specificity. CONCLUSIONS: It is possible to analyze all known treatments using this classification. The principles of this scheme should be sufficiently clear as to enable knowledgeable specialists to arrive at similar conclusions about a drug. The classification proposed is general enough such that most new drugs should fall within a class. However, it should be modified if necessary, if new therapeutic agents can not be appropriately classified. It is our conclusion that with such endeavours the specialty itself and national regulatory bodies will find it easier to define and control how to apply new drugs, how to evaluate new drugs, and how to establish reasonable equivalences among agents and in whom these drugs and devices should be used.     

Pathophysiology of erectile dysfunction

During the past decade, our knowledge of the hemodynamics, functional anatomy, neurophysiology, and neuropharmacology of erectile function has evolved substantially. The change of smooth muscle tone has emerged as a key factor in erection and detumescence. However, future studies are needed to elucidate the cellular and molecular basis of erectile physiology. With insight into normal physiology we will understand the pathologic process and be able to treat it.     

Causes and treatment of erectile dysfunction

Erectile dysfunction (ED), more commonly known as impotence, is, along with men's health in general, a neglected subject. In this article, the author highlights reasons why ED may occur, the treatments available and why professionals should encourage men to discuss this problem.     

Pharmacological therapy of erectile dysfunction

Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-producing beta cells. Approximately 10%-20% of patients may benefit from adjuvant immunotherapy upon diagnosis of the disease in order to protect residual beta-cell function. It has been suggested that this subgroup of patients differs from others by virtue of the presence of residual pancreatic inflammation and beta-cell function. In this study we have investigated to what extent technetium-99m-labelled human polyclonal immunoglobulins (99mTc-HIG) accumulate in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter, with a view to ascertaining whether HIG scintigraphy is useful for the identification of IDDM patients with residual pancreatic inflammation. Patients with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1 year later, and ten age- and sex-matched normal subjects were also studied. Gamma camera imaging and target to background ratio, analysed blind by three independent readers, were used to quantify the radioactivity in the pancreatic region and findings were correlated with metabolic, immunological and clinical parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher than the mean +2SD of normal subjects). One year after diagnosis, pancreatic accumulation of HIG was still detectable in most IDDM patients who were positive at the time of diagnosis. Six out of seven patients with positive scintigraphy had a partial clinical remission. These results indicate that HIG scintigraphy at the time of onset of diabetes identifies a subset of patients with residual beta-cell function who may benefit from adjuvant immunotherapy.     

Ambulatory treatment of erectile dysfunction

To evaluate whether low DHEA-S levels are predictors of cortical origin, benignity and hormonal activity in incidentally detected adrenal masses, thirty-five patients with adrenal incidentalomas were studied. All patients were operated on and the diagnosis was histologically confirmed. Basal endocrine workup included plasma determination of cortisol before and after dexamethasone (1 mg overnight), plasma ACTH (08:00 h), 17-OH-progesterone, testosterone and potassium, standing plasma renin activity and aldosterone, supine and standing plasma noradrenaline and adrenaline. If necessary, we performed dexamethasone suppression tests at low (2 mg) and high (8 mg) doses, or the loperamide test (16 mg os) for evaluation of glucocorticoid activity and the glucagon test (1 mg i.v.) for exploring adrenal medulla function. Plasma DHEA-S was measured in all patients and the results were compared to those obtained in controls matched for age, sex and menopausal status. Suppression of DHEA-S was found in 11 out of 35 patients (31.5%). However, this hormonal finding occurred in 50% of the extracortical adrenal lesions, while in proven cortical adenomas (no. = 19) it was detected in only 5 patients (26.3%). Sensitivity, specificity, diagnostic accuracy and positive predictive value of low DHEA-S in indicating a cortical origin of the mass were 0.27, 0.0, 0.25, and 0.80. In malignancies (no. = 6) low DHEA-S levels were found in 1 out of 2 metastases and never in cortical carcinomas. Sensitivity, specificity, diagnostic accuracy and positive predictive value of low DHEA-S in indicating a benign form were 0.34, 0.83, 0.42, and 0.91. Six out of 19 patients with cortical adenomas showed signs of hypothalamic-pituitary adrenal (HPA)-axis dysfunction. Low DHEA-S levels were found in 50% of adenomas with HPA-axis abnormality and in 15.3% of adenomas without hormonal activity. Sensitivity, specificity, diagnostic accuracy, and positive predictive value of low DHEA-S levels in indicating hormonal activity of the mass were 0.50, 0.84, 0.73, and 0.60. Our data indicate that the association between low DHEA-S levels and adrenal incidentalomas is frequent. Low DHEA-S appears to be a poor predictor of hormonal activity with low sensitivity and specificity in respect of cortical origin and benignity of the mass. In conclusion, our results show that DHEA-S measurement does not offer relevant clinical information in the management of adrenal incidentalomas.     

New developments in self-injection therapy for erectile dysfunction

The photostimulation of nerve cells using a caged compound is very useful because it is non-invasive and non-destructive compared with standard electrophysiological techniques. There are no methods, however, for continuously measuring the photo-uncaged 'free' compound concentration at high temporal and spatial resolutions which can detect how much uncaged compound has been applied to cells. Here, we used an electrochemical detection method for the real-time measurement of photo-uncaged glutamate. In this way, we were able to determine the amount of uncaged glutamate and investigate neural activities by tracing [Ca]i while simultaneously employing photostimulation and on-line glutamate measurement. The combination of an on-line sensor and laser-photostimulation with [Ca]i measurement could be a powerful tool with which to investigate synaptic connections and activities.     

Evaluation of erectile dysfunction and sleep-related erections

Significant advances in this past decade have improved our understanding of erectile physiology. A variety of tests are available for diagnosing impotence. SRE testing provides objective physiological information that is useful for indexing erectile capability and formulating a rational treatment plan. As such, SRE testing is a powerful noninvasive tool for assessing dysfunction. Nonetheless, in making a final diagnosis, the skillful clinician relies on more than one assessment parameter and on clinical acumen.     

Comparative results of goal oriented therapy for erectile dysfunction

PURPOSE: Goal oriented therapy for erectile dysfunction, based on a complete education of the couple, was offered to 460 patients. The short-term and long-term results of the first and second treatments selected were compared. MATERIALS AND METHODS: From September 1991 to March 1995, 460 patients with erectile dysfunction were evaluated and treated prospectively. The success of treatment, selected by the patient or couple, was defined as the ability to achieve and maintain good erections for successful coitus for at least 1 year after the start of therapy. Sexual satisfaction of the couple was required to confirm a successful outcome. RESULTS: The preferred first line of treatment by 322 patients was pharmacotherapy, with intracavernous injections being the second most selected therapy (80% success rate). However, there was a high long-term dropout rate for intracavernous injections. Approximately 70% of the patients were lost to followup or refused further treatment. CONCLUSIONS: Overall, this prospective study showed that goal oriented therapy is initially highly successful. However, the long-term high dropout rate and dissatisfaction of the couple cast doubt about the efficacy of the present treatment options.     

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.     

Use of prostaglandin E1 for treatment of erectile dysfunction

Metastatic tumors to the head and neck are uncommon. We report a case of renal cell carcinoma that presented as an epidermal inclusion cyst on the forehead. The forehead is an exceedingly uncommon site for renal cell metastases. We review the biology of tumor metastases and explore the pathways by which infraclavicular tumors spread to the head and neck. We then discuss the clinical appearance and management of metastatic renal cell carcinoma.     

The epidemiology of erectile dysfunction and its risk factors

The yeast Saccharomyces cerevisiae has at least six species of acid and alkaline phosphatases with different cellular localizations, as well as inorganic phosphate (Pi) transporters. Most of the genes encoding these enzymes are coordinately repressed and derepressed depending on the Pi concentration in the growth medium. The Pi signals are conveyed to these genes through a regulatory circuit consisting of a set of positive and negative regulatory proteins. This phosphatase system is interested as one of the best systems for studying gene regulation in S. cerevisiae due to the simplicity of phenotype determination in genetic analysis. With this methodological advantage, considerable amounts of genetic and molecular evidence in phosphatase regulation have been accumulated in the past twenty-five years. This article summarizes the current progress of research into this subject.     

Serum and salivary testosterone levels in erectile dysfunction]

In this study 66 male patients with erectile dysfunction were investigated. The authors measured the testosterone levels in serum and in saliva, which latter represent with good accuracy the serum levels of free testosterone. The mean serum total testosterone level was 17.6 nmol/L (confidence intervals: 15.5 and 20.2 nmol/L, normal range: 10-50 nmol/L). The mean salivary free testosterone level was 218.5 pmol/L (confidence intervals: 198.3 and 239.9 pmol/L, normal range: 200-1000 pmol/L). Low salivary (free) testosterone levels were found in 36.4% of patients, while only in 10.6% of patients had low serum testosterone levels (p = 0.01, by binomial test). Although there is a relationship between serum and salivary testosterone levels (r = 0.41, p < 0.001), the patients with low salivary (free) testosterone levels have in major part a normal serum total testosterone level. These data indicate that a considerable proportion of patients with erectile dysfunction have androgen deficiency. The serum total testosterone level is not a sensitive indicator to detection of hypogonadism. The androgen substitution therapy has a beneficial effect on erectile dysfunction in a significant part of patients. The measurement of free testosterone level in saliva may have an important role both in the diagnosis of diseases characterized by androgen deficiency and hyperandrogenic status.     

Oral medications in the management of erectile dysfunction

The diagnostic impact and reproducibility of the different methods used within the concept of functional MR-Mammography (FMRM) was assessed by a multi-reader-analysis. By four experienced readers, 100 histologically confirmed cases were evaluated in six different sessions. Per session, one of the following components was analyzed: clinical history (I), static MRM (II), color-coded projection images (III), time-signal curves of contrast enhancement within a large ROI (IV) and the strongest enhancing pixel (V) obtained from the histologically confirmed lesion and the complete FMRM reading (VI). The functional methods (IV-VI) revealed significantly (p < 0.05) higher specificities than the others (I-III). The highest reproducibility between the readers was observed for (IV) phi chi = 0.80, (V) phi chi = 0.76 and FMRM (VI) phi chi = 0.63. These three methods also presented the best ROC-curves and showed the highest complementarity with respect to the false positive classifications in x-ray mammography. FMRM is a reader independent, reproducible method. The analysis of the contrast enhancement time-intensity curves with high temporal resolution allows an improved differentiation of malignant and benign findings.