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Biomedical subjects

E Wespes

Publications and source records attributed to E Wespes.

At least 19 recordsLinked to original sources

[Erectile dysfunction, physiologic approach, diagnosis and therapy].

Erectile dysfunction is defined as the consistent or recurrent inability to obtain and/or maintain a penile erection sufficient for sexual activity. Erection is a vascular phenomenon under a psychoneurological control and situated in an hormonal environment. A variety of treatment options are available to the clinician including medical, psychological and surgical treatments. The choice of therapy should be based on careful matching of the patient's needs and preferences with the available treatment options.

Algorithms↗

Erectile dysfunction is associated with a high prevalence of hyperlipidemia and coronary heart disease risk.

OBJECTIVES: Erectile dysfunction (ED) is frequently of vascular origin. An association between ED and ischemic heart disease has been suggested as a consequence of endothelial disease of penile and coronary arteries. The role of serum lipid levels has been demonstrated in coronary heart disease (CHD), but the relationship with ED is poorly documented. We evaluated undiagnosed hyperlipidemia in ED patients and their coronary heart disease risk. METHODS: We prospectively compared a group of patients with ED to matched non-ED patients. Risk factors for ED and CHD were noticed and a serum lipid work up (total cholesterol [TC], triglycerides [TG], HDL-cholesterol [HDL-C], LDL-cholesterol [LDL-C] and TC/HDL-C ratio) was measured. We compared the prevalence of hyperlipidemia in the two groups and its impact as predictor of ED. We calculated the risk to develop CHD in patients with or without ED based upon commonly accepted variables of the Framingham Heart study. RESULTS: 215 patients had ED (mean age 57.6+/-9.6 years) and 100 no ED (mean age 59.7+/-8.3 years). The prevalence of hypercholesterolemia (TC >200 mg/dl or 5.17 mmol/l) was 70.6% vs. 52% in ED and non-ED groups respectively (p=0.06). After exclusion of confounding factors, logistic regression analyses showed HDL-C and TC/HDL-C ratio as significant predictors of ED (p=0.011 and 0.000 respectively). Increased 10-year CHD risk was found in 56.6% in the ED group compared to 32.6% in the control group (p<0.05). The median risk was 12.18% vs. 9.07% respectively with a significant age-related risk (p<001). CONCLUSIONS: Hyperlipidemia is common in ED patients. HDL-C and TC/HDL-C ratio are predictors of ED. These patients have a high risk of later developing CHD. Erectile dysfunction might therefore serve as sentinel event for coronary heart disease.

Adult↗

The ageing penis.

Epidemiological reports have demonstrated the determinant role that age plays in the pathophysiological mechanism of an erection. The atherosclerosis of the penis and its ischaemia that occurs with ageing impacts directly on the intracavernous structures and the erectile physiologic function. The effects of testosterone on libido and sexual behaviour are well established but its function in the erectile mechanism remains unclear. In the animals, testosterone deficiency seems to provoke a decrease in smooth muscle content and nitric oxide (NO) production. In human, testosterone seems to affect the central system rather than the peripheral mechanism of an erection. The role of ischaemia and the decrease in testosterone in the mechanism of erectile dysfunction are reviewed.

Aging↗

Smooth muscle pathology and erectile dysfunction.

Penile erection is a vascular phenomenon that results from smooth muscle relaxation, arterial dilation and venous restriction. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction of smooth muscle cells has been demonstrated in relation with this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance. Chronic ischemia is, therefore, associated with fibrosis but also with nitric oxide (NO)-cyclic guanosine monophosphate. The sensitivity of the alpha-adrenoceptors on the smooth muscle cells increases with aging. All those modifications can explain the prevalence of erectile dysfunction with aging. Low oxygen tension in prostanoid production may also play a role in the mechanism of ischemia-induced cavernosal fibrosis; however, intracavernous injections of prostaglandin E(1) do not seem to modify the intracavernous structures by reducing muscular atrophy. The effects of androgen on libido and sexual behavior are well established, but their role in the human erectile mechanism remains unclear. Several studies performed on animals have demonstrated impacts directly on both the physiological function and the trabecular structure of the corpora cavernosa in rats, dogs and rabbits. However, in humans, no study seems to demonstrate a role of testosterone on muscular atrophy or penile neurologic control. Testosterone treatment alters the human behavior but not penile physiologic processes. Further studies are necessary to explain the real role of testosterone not only on the peripheral mechanism of erection but also on the central control.

Erectile Dysfunction↗

Male andropause: myth, reality, and treatment.

A progressive decrease in androgen production is common in aging men. The physiological causes for this phenomenon seem to be multifactorial. The magnitude of the decline in testosterone with age and the prevalence of older men with low testosterone levels have not been well established. The extent to which an age-dependent decline in androgen levels leads to health problems that might affect or alter the quality of life remains under debate. In men older than middle age, total testosterone levels may be misleading because of an increase in sex hormone-binding globulin levels. The mechanism of the age-associated decrease of the endocrine testicular function is also essentially due to primary testicular failure, but important changes occur at the hypothalamopituitary level. The most prominent endocrinological alterations with aging are related to the sex steroids, but others, such as growth hormone, melatonin cortisol, and thyroxine, are also affected. The clinical picture of andropause syndrome is characterized by diminished sexual desire and erectile capacity, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density that results in osteoporosis, and increase in visceral fat and obesity. Current medical treatments for androgen supplementation include oral tablets, intramuscular injections, and scrotal and nonscrotal patches. Unfortunately, none of these preparations mimic the circadian rhythm, even if some of them may approximate the circadian rhythm by dose adjustments. Moreover, the androgen supplementation could have adverse effects on different organs, namely, the liver, lipid profile, cardiovascular disease, prostate, sleep disorders, and emotional behavior. Clinical response is a better guide to dose requirements, regardless of serum testosterone levels. This important field must be actively investigated by the medical, behavioral, and social sciences.

Climacteric↗

Intracavernous injection as an option for aging men with erectile dysfunction.

Sexuality remains a vital aspect of life in spite of aging. Advances in impotence research and increased knowledge of the pathophysiology of erection have completely changed the treatment of erectile dysfunction. Before oral therapy, intracavernous injection was considered as the first-line therapy for impotent patients. However, the new simple oral treatment raises the question as to whether intracavernous injection therapy is still a useful tool for treatment of aging men with erectile dysfunction. The efficacy and safety of oral therapy and intracavernous injection are reviewed.

Administration, Oral↗

Complete phalloplasty using the free radial forearm flap for correcting micropenis associated with vesical exstrophy.

PURPOSE: We present a new surgical technique for reconstructing the penis in a man with micropenis associated with vesical exstrophy. MATERIALS AND METHODS: A free radial forearm flap was used to create a penis of normal length and diameter. The flap was wrapped around the native micropenis. A penile prosthesis was then inserted in the flap to provide erection. RESULTS: The flap was well vascularized and no skin damage was observed 6 years after reconstruction. The patient achieved sexual intercourse on a regular basis. He is satisfied with the result. CONCLUSIONS: Free transfer of the radial forearm flap may be done in select men with micropenis associated with vesical exstrophy for penile reconstruction. An inflatable prosthesis may be inserted in the flap to provide erection. The results of this technique have remained stable in the long term. This method provides a new tool for phalloplasty in these difficult cases.

Adult↗

Erectile dysfunction in the ageing man.

Most studies have shown an increase in the prevalence of erectile dysfunction with ageing. Penile erection is a vascular phenomenon resulting from smooth muscle relaxation, arterial dilatation and venous restriction. The atherosclerosis of the penis that occurs with ageing causes a decrease in penile oxygen tension. This change in oxygen tension impacts directly upon both the physiologic function and the trabecular structure of the corpora cavernosa. Chronic ischaemia of the penis is associated with fibrosis of smooth muscle fibres and with endothelial and neuronal NO/cGMP pathways. The effects of androgens on libido and sexual behaviour are well established but their role in the erectile mechanism remains unclear. The histologic and haemodynamic causes responsible for the erectile decline in the ageing man are reviewed.

Age Factors↗

Does prostaglandin E1 therapy modify the intracavernous musculature?

PURPOSE: Intracavernous injection of prostaglandin E1 in patients with erectile dysfunction has become widespread. However, to our knowledge long-term side effects on the penile smooth muscles in man have not been documented. We evaluated the histological changes of intracavernous smooth muscle after long-term treatment with prostaglandin E1. MATERIALS AND METHODS: A total of 10 patients with a mean age of 56.5 years (range 46 to 69) underwent biopsy of the corpora before (5) and after (10 in both corpora) prostaglandin E1 treatment. Between 150 and 250 injections during 3 years were performed, and the dosage varied from 5 to 20 microg. Only 1 patient injected prostaglandin E1 on both sides. Staining with hematoxylin and eosin, and immunohistochemical staining with actin anti-actin of intracavernous smooth muscle and its quantification with computerized image analysis were performed. RESULTS: No histological difference was observed with classic staining. A reduction was noted in the percentage of intracavernous smooth muscle after treatment in 2 of 5 patients on the side of injection (before 35% and 41%, and after 19% and 30%, respectively) but there was no difference with the other corpus cavernosum. No difference was observed in the percentage of intracavernous smooth muscle between both corpora in the 5 patients with biopsies performed only after treatment. CONCLUSIONS: Prostaglandin E1 does not seem to alter intracavernous structures.

Aged↗

Improving the prognostic value of histopathological grading and clinical staging in renal cell carcinomas by means of computer-assisted microscopy.

The present work aims to refine prognosis in cases of renal cell carcinoma (RCC) by integrating a variety of parameters with the prognostic information provided by histopathological grading and clinical staging, carried out on a series of 97 RCCs. To this end, Feulgen-stained RCC cell nuclei were characterized by means of 38 variables describing nuclear DNA ploidy levels and morphology. All of these data were subjected to a principal components analysis. On the basis of this multivariate analysis, Fuhrman grade II was subdivided into grades II- and II+, and Fuhrman grade III into grade III- and III+. The same kind of subcategorization was performed in the case of the T2 and T3 clinical stages. The results show that the classification into grade II- and III- RCCs correspond to a more favourable prognosis than grade II+ and III+, to which shorter survival periods were attributable. Similar results were obtained for the subcategorization of the T2 and T3 clinical stages. Very simple biological characterizations of these grade- or stage-related RCC groups were obtained by means of a decision tree approach applied to the cytometry-generated variables. The resulting classification rules were validated on a new series of 18 patients and enabled very accurate predictions of survival.

Adult↗

[New treatments for impotence].

The development of new oral drugs and the poor results of the reconstructive vascular surgery has modified the therapeutical approach of the impotent patient. The doctor has to be aware of these changes in the management of impotence.

3',5'-Cyclic-GMP Phosphodiesterases↗

Corporeal veno-occlusive dysfunction: a distal arterial pathology?

PURPOSE: Alteration of intracavernous smooth muscle cells has been demonstrated in patients with pure venous leakage. This modification seems correlated with reduction of intracavernous oxygen tension. However, Doppler imaging of the cavernous arteries in these patients is normal. To understand the ischemic factor we studied the endothelium of the terminal arteries with computerized image analysis and immunohistochemical staining with 2 types of lectin in patients with venous leakage and those with normal erections. Lectins are glycoproteins that can be used as histological markers to monitor functional and pathological changes. MATERIALS AND METHODS: Four patients 44 to 59 years old with normal erections who were operated on for penile cancer and 11 patients 27 to 62 years old with pure venous leakage (flow to maintain erection greater than 15 ml. per minute and cavernous flow velocity greater than 35 cm. per second) were included in the study. Immunohistochemical staining with 2 lectins, wheat germ agglutinin and Ulex europeaus agglutinin I, was performed and analyzed with computerized image analysis. The labeling index which relates to the percentage of staining indicates the distribution of the endothelial cells, and mean optical density which relates to the staining intensity indicates the function of these cells. RESULTS: Mean labeling index values for the 2 lectins were similar in both groups (p >0.05). Mean optical density values for the 2 lectins were significantly greater for the patients with normal erections (p <0.01). Therefore, the distribution of the endothelial cells was the same while their function was different in patients with corporeal veno-occlusive dysfunction. CONCLUSIONS: Staining with wheat germ agglutinin and Ulex europeaus agglutinin I lectin types allowed us to detect alteration in the glyco-histochemistry of the endothelial cells of the small arteries, and venous leakage could be the first step in vasculogenic impotence.

Adult↗

The chromatin pattern of cell nuclei is of prognostic value for renal cell carcinomas.

Using a series of 105 renal cell carcinomas (RCCs) we investigated whether features quantitatively describing the appearance of Feulgen-stained nuclei and, more particularly, of their chromatin (on the basis of computer-assisted microscopy) can contribute any significant prognostic information. Thirty morphonuclear and 8 nuclear DNA content-related variables were thus generated. The actual prognostic values of this set of cytometric variables was compared (by means of discriminant statistical analysis) to conventional diagnostic and/or prognostic markers including histopathological grades, tumour invasion levels and the presence or absence of metastases. We obtained complete clinical follow-ups for 49 of the 105 RCC patients under study, making it possible to define a subset of patients with a bad prognosis (i.e., who died in the 12 months following nephrectomy) and a subset of patients with a good prognosis (i.e., who survived at least 24 months following nephrectomy). An original method of data analysis related to artificial intelligence (decision tree induction) enabled a strong prognostic model to be set up. In the case of 10 new patients, this model identified all the dead patients as having a bad survival status, with a total of 8 correct predictions. Another prognostic model similarly generated enabled the correct predictions to be confirmed.

Adult↗

Prognostic value of stem cell line identification for renal cell carcinomas.

OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight variables were used to characterize DNA ploidy levels. They included DNA index and seven others characterizing the presence of specific stem cell lines in each of the 95 RCCs under study. All these variables were determined by means of computer-assisted microscopy applied to Feulgen-stained nuclei. The actual information contributed by each of the eight variables was determined by means of univariate statistical analyses. RESULTS: The results showed that in the DNA ploidy-related eight variables, the presence of at least 4% aneuploid nuclei with > 5C DNA content was associated with the most significant prognostic value in RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study clearly showed that stem cell line characterization, and particularly the presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs with significant prognostic value. This kind of marker may help the identification of patients who will develop metastases after surgery and for whom adjuvant therapy might thus be indicated.

Adult↗

[Sildenafil].

Sildenafil is an innovative molecule, effective in most cases of erectile dysfunction, acting by inhibition of type 5 phosphodiesterase in the corpus cavernosum. Its impressive success attests its efficacy and the frequency of erectile dysfunction in man. The authors review the clinical data and call for caution in its prescription requiring a thorough check-up of the cardiovascular system taking into account its potentially letal interactions with nitrates.

3',5'-Cyclic-GMP Phosphodiesterases↗

Objective measurement of the different collagen types in the corpus cavernosum of potent and impotent men: an immunohistochemical staining with computerized-image analysis.

Quantitative measurements of the collagen types (I, II, and IV) in the corpora cavernosa of potent and impotent men were carried out to investigate whether quantitative immunohistochemistry might contribute additional information as to the cause of erectile dysfunction. The study group consisted of 22 men with various etiologies of impotence and 4 normal, potent men. The quantitative immunohistochemistry measurements were performed by means of a cell-image processor. Three variables for each of the three types of collagen were studied, namely, the mean optical density (MOD), which relates to histochemical staining intensity; the labeling index (LI), which is positively related to the percentage of immunostaining; and the quick score (QS) index, which takes into account both LI and MOD values. None of the quantitative parameters taken individually (monovariate statistical analyses) made it possible to obtain any statistically significant difference between the types of collagen of the group under study. The mean QS value recorded for collagen type IV was significantly lower than that noted for collagen type I in the psychogenic (P = 0.019), arteriogenic (P = 0.012), and venogenic (P = 0.001) groups, whereas the MOD value was significantly lower in the normal (P = 0.043), arteriogenic (P = 0.013), and venogenic (P = 0.001) groups but not in the psycogenic group. The mean MOD of collagen type III was intermediate between that of the other types. In contrast, the mean LI value recorded for collagen type IV was significantly lower only in the venogenic (P = 0.032) and psychogenic (P = 0.049) groups as compared with the other groups. No objective qualitative change in the collagen types was observed that could be correlated to the etiology of erectile dysfunction. The significant difference seen in the quantitative parameters with regard to collagen type IV and the observed increase in the type I/III collagen ratio might attest to the notion that the response of the erectile tissue to ischemia is similar to that of other organs. The net effect of these changes is a restricted capacity for corporal expansion and alteration of the veno-occlusive mechanism.

Adult↗

Biochemical alterations of the tunica albuginea in impotence.

PURPOSE: The objectives of this study were to quantify the immunohistochemical stainings of collagen types I, III and IV, and investigate the value of glycohistochemical staining with 3 lectin types specific to a particular glycan structure, Arachis hypogaea, Triticum vulgare and concanavalin A, as a method of defining possible changes in the collagen structure of the tunica albuginea in potent and impotent patients. MATERIALS AND METHODS: The study involved 4 normal men, 4 with pure venous leakage and 4 with pure arterial disease. Collagen types I, III and IV, and lectins Arachis hypogaea, Triticum vulgare and concanavalin A were studied using a cell image processor. The labeling index relates to the percentage of staining and mean optical density relates to the staining intensity. RESULTS: Mean labeling index values for the 3 types of collagen and lectins were similar (p > 0.05). Mean optical density value relating to collagen type I was significantly higher in the arteriogenic group than in the other groups (p < 0.05), while mean optical density value of collagen type IV was significantly higher in the venogenic group than in the 2 other groups (p < 0.05). Mean optical density values relating to the 3 lectin types were similar in the 3 clinical groups (p > 0.05). CONCLUSIONS: An alteration in the distribution and structure of the various collagen types and lectins in the tunica albuginea of impotent patients has been shown that may interfere with normal function and lead to impotence.

Adult↗

Corporeal veno-occlusive dysfunction: predominantly intracavernous muscular pathology.

PURPOSE: We investigated whether a relationship exists between the flow to maintain an erection obtained at cavernosometry and the alteration of intracavernous structures in impotent patients with corporeal veno-occlusive dysfunction and normal arterial inflow. MATERIALS AND METHODS: Computerized histomorphometric analysis of smooth muscle and elastic fibers, and endothelial cells was compared to the flow necessary to maintain erection after intracavernous vasoactive drug injection in 18 patients with corporeal veno-occlusive dysfunction. RESULTS: A significant correlation between percentage of smooth muscle fibers and flow to maintain erection was observed, while no correlation was noted with elastic fibers and endothelial cells. CONCLUSIONS: Corporeal veno-occlusive dysfunction seems to be due mainly to smooth muscular alterations. According to this observation treatment of impotent patients with this abnormality should not be restricted to the penile veins but should also include the intracavernous structures, predominantly the muscular component.

Adult↗