Age-matched cavernous peak systolic velocity: a highly sensitive parameter in the diagnosis of arteriogenic erectile dysfunction.

Recently it has been reported that there is a strict correlation between erectile dysfunction (ED) and cardiovascular diseases, but the importance of such relationship still needs to be addressed. Ultrasonographic peak systolic velocity (PSV), is considered a reliable parameter for the diagnosis of arteriogenic ED. However, the cut-off value of PSV<30 cm/s has sufficient sensitivity only in the diagnosis of advanced arteriogenic ED and it is not representative of peripheral vascular alterations. In the present study, we set up an age-adjustment of PSV - calculated with the formula PSV <6.73+age x 0.7 - that permits a more accurate diagnosis of vascular aetiology in ED patients and may predict the presence of carotid wall alterations. We studied 179 consecutive subjects (mean age 52 years, range 23-79 years), with a history of ED of at least 6 months, by means of penile colour doppler ultrasonography (P-CDU) and common carotid arteries colour doppler ultrasonography (CCA-CDU) between June 2003 and September 2004. Statistical analysis was carried out with the statistical software R. PSV and CCAD values showed a statistically significant negative correlation. Age adjustment further improved this relationship permitting to identify an age-dependent PSV cut-off given by the formula PSV <6.73+age x 0.7. The age-adjusted PSV cut-off allows an accurate interpretation of vascular aetiology in ED patients and predicts the presence of carotid wall alterations, from the intima-media pathologic thickness to the plaque formation, with high values of both sensitivity and specificity.

Molecular analysis of the androgen receptor gene in testicular cancer.

Testicular cancer (TC) is the most common solid tumour in white males aged 20-34 years, and its incidence has doubled over the past 40 years. Some risk factors for TC have been proposed, such as cryptorchidism, infertility and testicular dysgenesis. However, the causes of TC remain still largely unknown. Recently a genetic basis for TC has been proposed, but specific genetic alterations have not been identified. The risk of TC is markedly increased in subjects with androgen insensitivity and some authors have suggested that mutations in the androgen receptor (AR) gene or disorders of CAG and GGC repeats could be related to TC. However, definitive data have not been produced. In this study, we analysed the AR gene for mutations and CAG and GGC triplets in exon 1 in 123 patients affected by TC. In three patients (2.3%) we found a mutation in the AR gene, two of which represent a novel mutation. Evaluation of CAG and GGC repeat numbers showed no difference with respect to controls when these variables were analysed separately. However, when joint distributions of CAG and GGC were considered, we found that the combination CAG=20/GGC=17 was significantly more frequent in TC patients (8.1%) with respect to controls (1.7%, P<0.05). Furthermore, we observed that in TC subjects, differently from controls, the joint analysis of CAG and GGC showed a statistically significant dependence among these variable repeats. In conclusion, our data show for the first time a high prevalence of AR gene mutations in patients affected by TC and suggest that some CAG/GGC combinations might be more frequently associated with an increased risk of TC.

Sertoli cell function in infertile patients with and without microdeletions of the azoospermia factors on the Y chromosome long arm.

Deletions of the azoospermia factors on the Y chromosome long arm are an important cause of male infertility, and they may involve germ cell-specific genes or ubiquitously expressed genes. To date, no clinical or hormonal parameters have yet been found to distinguish patients with and without Yq microdeletions. In particular, Sertoli cell function, as evaluated by inhibin B, has not yet been described. Our hypothesis was that microdeletions involving genes specifically expressed in germ cells should not alter Sertoli cell function. To do this, we have evaluated the testicular hormonal function in infertile patients affected by severe testiculopathies with and without Yq microdeletions, with particular emphasis on Sertoli cell function. We studied 102 well-characterized infertile patients; 27 had Yq microdeletions, and 75 were classified as idiopathic infertiles. Patients with Yq microdeletions had lower FSH and higher inhibin B plasma concentrations with respect to patients without microdeletions, suggesting that Sertoli cell function in Yq-deleted men is only partially altered. Furthermore, patients with deletions involving germ cell-specific genes had higher concentrations of inhibin B with respect to patients with deletions of ubiquitously expressed genes. These results suggested that a specific alteration of germ cells only partially influences Sertoli cell function. Hormonal status of patients without deletions suggested that in such cases the cause that has determined the spermatogenic defect may have damaged both Sertoli and germ cells. Inhibin B production in patients with Yq deletions was about 70% higher than the nondeleted patients, and the functional relationship between FSH and inhibin B was normally preserved. This study elucidated the multifactorial mechanisms underlying spermatogenic defects, where Sertoli cells may be normally functioning or damaged depending on the primary cause that has determined the testicular damage.

Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility.

The androgen receptor (AR) has two polymorphic sites in exon 1, characterized by different numbers of CAG and GGC repeats resulting in variable lengths of polyglutamine and polyglycine stretches. Longer CAG repeats result in a reduced AR transcriptional activity, whereas the role of the GGC triplets is less clear. A relationship between decreased spermatogenesis and moderate expansion in the CAG tract has been found in some studies, but not in others. Furthermore, the joint distribution of CAG and GGC repeats in male infertility has never been reported before. We analysed CAG and GGC repeat lengths in a group of 163 men with idiopathic infertility compared with 115 fertile normozoospermic men. No difference was found between patients and controls in the mean and median values, and in distribution of CAG and GGC, when considered separately. However, the analysis of the joint distribution of CAG and GGC showed that the distribution of particular haplotypes is significantly different between patients and controls. In particular, two CAG/GGC haplotypes seem to increase susceptibility to infertility (CAG = 21/GGC = 18 and CAG >/=21/GGC >/=18, relative risk 2.47 and 1.6), while one haplotype (CAG >/=23/GGC