Racial/Ethnic differences in inflammation levels among older adults 56+: an examination of sociodemographic differences across inflammation measure.

OBJECTIVE: Chronic inflammation is a key biological risk factor for many widespread adult health conditions. This study examines racial/ethnic differences in inflammation across several inflammatory markers, including selected cytokines that are identified as important for aging and age-related health outcomes. METHODS: Data came from the 2016 Venous Blood Collection Subsample of the Health and Retirement Study. Using logistic regression models, we compared high-risk categories of C-reactive protein and cytokine markers (IL-6, IL-10, IL-1RA, TNFR1, and TGF-Beta), across race/ethnicity and whether these differences persisted among men and women. RESULTS: The findings provided evidence of significant race/ethnic differences in inflammatory measures, but the patterns differed across marker types. CONCLUSIONS: These findings emphasize that race/ethnic differences are not consistently captured across markers of inflammation and that researchers should proceed with caution when using individual markers of inflammation in an effort to not overlook potential racial/ethnic differences in biological risk.

Surveillance imaging for sporadic renal angiomyolipoma less than 40 mm: lessons learnt and recommendations from the experience of a large district general hospital.

Introduction Sporadic renal angiomyolipomas, although benign in natural can cause life-threatening spontaneous haemorrhage. Surveillance of smaller lesions is recommended but there is no guidance on the surveillance interval or modality. Our aim was to study our sporadic angiomyolipoma population to determine the growth rate, factors that were associated with a higher growth rate and design a surveillance programme. Materials and methods All sporadic renal angiomyolipomas diagnosed between September 2009 and March 2015 were included. Patients with a diagnosis of tuberous sclerosis were excluded. Results A total of 217 sporadic renal angiomyolipomas were diagnosed. The median follow-up was 24 months (range 10-118 months). The median size at diagnosis was 9.00 mm with a mean growth rate of 0.13 mm/year (standard deviation 0.88). One hundred and fifty angiomyolipomas (69%) were shown to have negative or zero growth. In the remaining 67, 59 had a growth rate of less than 2.00 mm/year. Size of angiomyolipoma, tumour burden and age were not associated with a higher growth rate on multivariate analysis. Conclusion The majority of sporadic angiomyolipomas are small and do not grow. Our practice is to perform surveillance for those greater than 20 mm, with five-yearly ultrasound scans for 21-29 mm, and two-yearly surveillance for 30-39 mm tumours.

Blocking extracellular activation of myostatin as a strategy for treating muscle wasting.

Many growth factors are intimately bound to the extracellular matrix, with regulated processing and release leading to cellular stimulation. Myostatin and GDF11 are closely related members of the TGFß family whose activation requires two proteolytic cleavages to release the growth factor from the prodomain. Specific modulation of myostatin and GDF11 activity by targeting growth factor-receptor interactions has traditionally been challenging. Here we demonstrate that a novel strategy for blocking myostatin and GDF11, inhibition of growth factor release, specifically and potently inhibits signaling both in vitro and in vivo. We developed human monoclonal antibodies that selectively bind the myostatin and GDF11 precursor forms, including a subset that inhibit myostatin proteolytic activation and prevent muscle atrophy in vivo. The most potent myostatin activation-blocking antibodies promoted robust muscle growth and resulted in significant gains in muscle performance in healthy mice. Altogether, we show that blocking the extracellular activation of growth factors is a potent method for preventing signaling, serving as proof of concept for a novel therapeutic strategy that can be applied to other members of the TGFß family of growth factors.

Interactions in the aetiology, presentation and management of synchronous and metachronous adenocarcinoma of the prostate and rectum.

Adenocarcinoma of the prostate and rectum are common male pelvic cancers and may present synchronously or metachronously due to their anatomic proximity. The treatment of rectal or prostate cancer (in particular surgery and/or radiotherapy) may alter the presentation, incidence and management should a metachronous tumour develop. This review focuses on the interaction between prostatic and rectal cancer diagnosis and management. We have restricted the scope of this large topic to general considerations, management of rectal cancer after prostate cancer treatment and vice versa, management of synchronous disease and cancer follow-up issues.

Androgen regulation of stage-dependent cyclin D2 expression in Sertoli cells suggests a role in modulating androgen action on spermatogenesis.

Regulation of spermatogenesis involves stage-dependent androgen action on Sertoli cells, but the pathways involved are unclear. We assessed if cyclin D2 could play a role. In rats, Sertoli cell nuclear, stage-dependent immunoexpression of cyclin D2 switched on after Day 10 and persisted through Day 35, but disappeared by adulthood. However, ethane dimethane sulfonate (EDS)-induced testosterone withdrawal in adult rats for 6 days induced stage-dependent cyclin D2 immunoexpression in Sertoli cells, with highest expression at stages IX-XII and nondetectable at stages VI-VIII (opposite that for androgen receptor [AR] immunoexpression). In EDS-treated rats, a single injection of testosterone but not of estrogen reversed this change in 4 h, and testosterone administration from the time of EDS treatment prevented expression of cyclin D2 in Sertoli cells. The EDS-induced changes in cyclin D2 immunoexpression were matched by changes in expression of Ccnd2 (cyclin D2) mRNA in isolated stage-dissected tubules. Treatment of adult rats with flutamide induced stage-dependent cyclin D2 immunoexpression in Sertoli cells within 18 h, and confocal microscopy revealed that immunoexpression of AR and cyclin D2 were mutually exclusive within individual seminiferous tubules in these animals. Sertoli cell-selective ablation of the AR in mice using Cre/loxP technology also resulted in stage-dependent Sertoli cell cyclin D2 immunoexpression. Downstream from cyclin D2 action is retinoblastoma 1 (RB1), a tumor suppressor protein, immunoexpression of which paralleled stage-dependent AR expression in Sertoli cells; RB1 stage specificity disappeared after EDS treatment. These results point to a non-cell cycle role for cyclin D2 and RB1 in mature Sertoli cells in the stage-dependent mechanisms regulated by AR expression and androgen action.

The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer.

Regulation by hypoxia may underlie the expression of vascular endothelial growth factor in bladder cancer. We have compared the distribution of vascular endothelial growth factor mRNA with a hypoxia marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor mRNA was analysed by in situ hybridisation and CA IX by immunochemistry in 22 cases of bladder cancer. The relationship of microvessels to the distribution of CA IX was determined. In a separate series of 49 superficial tumours, CA IX immunostaining was compared with clinico-pathological outcome. In superficial and invasive disease there was overlap in the expression of vascular endothelial growth factor and CA IX, CA IX being more widespread. Both were expressed predominantly on the luminal surface, and surrounding areas of necrosis (invasive tumours). Expression of both factors was greater in superficial disease. Expression was absent within approximately 80 microm of microvessels. Unlike vascular endothelial growth factor, CA IX did not predict outcome in superficial disease. Differential responses to reoxygenation provide one explanation: vascular endothelial growth factor mRNA declined rapidly, while CA IX expression was sustained for >72 h. Expression of vascular endothelial growth factor mRNA in bladder tumours is consistent with hypoxic regulation and suggests differential regulation in superficial vs invasive disease. The expression of CA IX on the luminal surface justifies investigation of its utility as a therapeutic target/prognostic indicator.

Development and validation of a new monoclonal antibody to mammalian aromatase.

The biosynthesis of oestrogens from androgens is catalysed by the aromatase complex, an essential component of which is the aromatase cytochrome P450 (P450 arom) protein. Expression of a functional P450 arom is essential for normal fertility in males and females and the sequence of the protein is highly conserved. We have raised a new monoclonal antibody against a conserved peptide and validated it on fixed tissue sections of the rat, common marmoset (Callthrix jacchus) and human. The monoclonal antibody was used successfully for Western analysis and specifically reacted with a 55 kDa protein in microsomal extracts. On sections of ovaries in all three species, expression in follicles was specific to the mural granulosa cells of antral follicles and was present in corpora lutea. In the human and marmoset, staining of luteal cells was markedly heterogeneous and did not appear to vary consistently with the stage of the cycle. The intensity of immunostaining was elevated in corpora lutea from pregnant rats and following human chorionic gonadotropin rescue in the human. In the testis, the highest levels of expression were observed in the Leydig cells within the interstitium. In adult rat and marmoset, and possibly also in the human, some P450 arom was associated with the cytoplasm surrounding elongate spermatids but other germ cells were immunonegative. In conclusion, a new monoclonal antibody specific for P450 arom recognises the protein in rodent, primate and human. Its ability to work on fixed tissue sections will facilitate identification of individual cells expressing P450 arom within complex tissues.

Relationship between expression of sex steroid receptors and structure of the seminal vesicles after neonatal treatment of rats with potent or weak estrogens.

In this study we evaluated the effect of manipulating the estrogen and androgen environment of the neonatal male rat on subsequent immunoexpression of sex steroid receptors in the seminal vesicles (SVs) at age 18 days. The aim was to establish to what extent such changes were associated with and predictive of changes in SV structure/composition. Treatments were either diethylstilbestrol (DES; 10, 1, or 0.1 microg/injection), ethinyl estradiol (EE; 10 microg/injection), tamoxifen (2 mg/kg/day), flutamide (50 mg/kg), a gonadotropin-releasing hormone antagonist (GnRHa; 10 mg/kg), genistein (4 mg/kg/day), octylphenol (2 mg/injection), or bisphenol A (0.5 mg/injection). Compared with controls, treatment with DES (10 microg) induced loss of epithelial and stromal androgen receptor (AR) immunoexpression coincident with induction of stromal progesterone receptor (PR) immunoexpression and upregulation of stromal immunoexpression of estrogen receptor-alpha (ERalpha). These changes were associated with gross distortion (increase) of the normal stromal:epithelial tissue proportions in the SVs. DES (1 microg) and EE induced similar but less pronounced changes, and DES (0.1 microg) had no noticeable effect. Tamoxifen and flutamide induced PR and slightly upregulated ERalpha immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs. The latter was also evident in GnRHa-treated males, but otherwise this treatment had no effect on AR and PR immunoexpression. None of the foregoing treatments had any detectable effect on the immunoexpression of ERss in stromal or epithelial cells. The major treatment-induced changes in immunoexpression of AR, PR, and ERalpha and lack of change in ERss were confirmed by Western blots of SV protein extracts. None of the three weak (environmental) estrogens tested caused any detectable change in sex steroid receptor immunoexpression or SV tissue composition. We conclude that treatment-induced loss of AR is a prerequisite for altered stromal:epithelial proportions in the SVs and that such loss is always associated with induction of PR and upregulation of ERalpha; the latter two changes are insufficient on their own to bring about such a change. Nevertheless, induction of PR expression was always associated with altered SV development and is a potentially useful marker because it is not normally expressed in male reproductive tissues.

Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man.

The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and hisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin-releasing hormone antagonist (GnRHa) or the anti-oestrogen tamoxifen or the anti-androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor-alpha (ERalpha) and ERbeta were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERbeta occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERbeta but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high-dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high-dose DES (iv and v) can be largely prevented by co-administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.

Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.

Androgens are important for the structural and functional integrity of the testis and the prostate and this may in part be mediated by the aromatisation of testosterone to oestradiol. The aim of the present study was to establish an in vivo model that would allow the identification of genes, the expression of which was regulated acutely by androgen and/or oestrogen in the male reproductive system. In rats in which the Leydig cells were ablated by administration of ethane dimethane sulfonate (EDS) 6 days earlier, testosterone esters (T) were administered from day 0 (To), and additional animals were administered either T, 17beta-oestradiol benzoate (EB) or diethylstilbestrol (DES) for 1 or 4 h on day 6 after EDS-treatment. Nuclear immunoexpression of the androgen receptor (AR) was reduced or absent from the testis but unaffected in the ventral prostate following these treatments. ERbeta immunoexpression in these tissues was unchanged. Northern blot analysis showed that EB and DES as well as T administration 4 h earlier could modulate mRNA expression of two androgen-responsive genes, C3 and SGP-2, in the prostate. The co-administration of T or EB with the AR antagonist, flutamide, or with the ER antagonist, ICI 182,780 (ICI), did not block the suppression of SGP-2 mRNA expression by T or EB. In contrast, the upregulation of C3 mRNA expression by T was successfully antagonised by both flutamide and by ICI. A preliminary evaluation of the expression of three Sertoli cell and five germ cell mRNAs revealed that their expression was not steroid regulated. Our results support the hypothesis that the action of testosterone in the male reproductive system may in part be mediated by its conversion to oestradiol. This in vivo model should prove of value in future studies to identify androgen and oestrogen regulated genes in the male reproductive system.

Suppression of androgen action and the induction of gross abnormalities of the reproductive tract in male rats treated neonatally with diethylstilbestrol.

This study evaluated whether androgen action is altered in rats treated neonatally with diethylstilbestrol (DES) at a dose that induced reproductive tract abnormalities. Rats were treated on alternate days 2-12 with 10 microg DES and studied on Day 18. DES-induced abnormalities included a 70% reduction in testis weight, distension and overgrowth of the rete, distension and reduction in epithelial height of the efferent ducts, underdevelopment of the epididymal duct epithelium, reduction in epithelial height in the vas deferens, and convolution of the extra-epididymal vas. In DES-treated rats, androgen receptor (AR) immunoexpression was virtually absent from all affected tissues and the testis, whereas AR expression in controls was intense in epithelial and stromal cells. The DES-induced change in AR immunoexpression was confirmed by Western analysis for the testis. In rats treated neonatally with 1 microg DES, reproductive abnormalities were absent or minor, except for a 38% reduction in testis weight; loss of AR immunoexpression also did not occur in these rats. Treatment-induced changes in AR expression were paralleled by changes in Leydig cell volume per testis (91% reduction in the 10-microg DES group; no change in the 1-microg DES group). To test whether suppression of androgen production or action alone could induce comparable reproductive abnormalities to 10 microg DES, rats were treated neonatally with either a potent gonadotropin-releasing hormone antagonist (GnRHa) or with flutamide (50 mg/kg/day). These treatments reduced testis weight (68% for GnRHa, 40% for flutamide), and generally retarded development of the reproductive tract but failed to induce the abnormalities induced by 10 microg DES. GnRHa and flutamide caused no detectable change in AR immunoexpression in target tissues, with the exception of minor changes in the testes of flutamide-treated males. GnRHa treatment caused a reduction (83%) in Leydig cell volume comparable to that caused by 10 microg DES. Immunoexpression of estrogen receptor alpha (ER alpha) in the efferent ducts and of ER beta in all tissues studied were unaffected by any of the above treatments. Neonatal coadministration of testosterone esters (TE; 200 microg) with 10 microg DES prevented most of the morphological abnormalities induced by 10 microg DES treatment alone, though testis weight was still subnormal (46% reduction in DES + TE vs 72% in DES alone and 49% with TE alone) and some lumenal distension was still evident in the efferent ducts. Coadministration of TE with DES prevented DES-induced loss of AR immunoexpression (confirmed for testis by Western blot analysis). It is concluded that 1) reproductive tract abnormalities induced in the neonatal male rat by a high (10 microg) dose of DES are associated with reduced AR expression and Leydig cell volume; 2) these changes are largely absent with a lower dose of DES (1 microg); 3) treatments that interfere with androgen production (GnRHa) or action (flutamide) alone failed to induce reproductive tract abnormalities or alter AR expression as did 10 microg DES; 4) a grossly altered androgen:estrogen balance (low androgen + high estrogen) may underlie the reproductive tract abnormalities, other than reduced testis weight, induced by high doses of DES.

Age-, cell- and region-specific immunoexpression of estrogen receptor alpha (but not estrogen receptor beta) during postnatal development of the epididymis and vas deferens of the rat and disruption of this pattern by neonatal treatment with diethylstilbestrol.

This study in rats sought to 1) characterize immunoexpression of estrogen receptor alpha (ERalpha) and ERss in the efferent ducts, epididymis, and vas deferens during postnatal development; 2) establish whether ER expression changed after neonatal treatment with diethylstilbestrol (DES); and 3) determine whether ER changes coincided with abnormal epididymal/vas development. Rats were administered 10 microg DES or vehicle on days 2, 4, 6, 8, 10, and 12 and were sampled on days 10, 18, 25, 35, and 90+. At all ages, ERalpha was immunoexpressed intensely in the efferent ducts. On day 10, immunoexpression of ERalpha was absent from the epididymis and vas, but was detectable on day 18 in epithelial cells in the caput, corpus, and proximal cauda. Epithelial expression of ERalpha was absent from the distal cauda and in the proximal and distal vas was confined to a band of periductal stromal cells. Thus, on day 18, the site of ERalpha expression delineated the epididymis-vas boundary. On days 25-35, epithelial expression of ERalpha was absent, but stromal expression persisted in the vas and distal cauda. In adults, immunoexpression of ERalpha in the epididymis and vas was absent. In contrast, ERbeta was immunoexpressed in epithelial cells and some stromal cells in the efferent ducts, epididymis, and vas at all ages. In the vas, stromal expression of ERalpha and ERbeta was in different layers. DES treatment caused 1) underdevelopment of the epididymal duct and reduced epithelial height in epididymis and vas; 2) coiling of the extraepididymal vas; 3) thickening of the periductal actin-free stromal layer in the distal cauda and vas; and 4) reduced cell proliferation on day 18 in the epididymis and vas, based on incorporation of bromodeoxyuridine, especially in the epithelium. These changes coincided with abnormalities in cell- and region-specific immunoexpression of ERalpha, but not ERbeta. Thus, in DES-treated rats on day 18, epithelial expression of ERalpha occurred in all regions of the epididymis and vas instead of being confined to the caput, corpus, and proximal cauda as in controls. Similarly, stromal ERalpha expression in the vas of DES-treated rats was not confined to a periductal layer as in controls, but occurred diffusely in the muscle layer. It is suggested that 1) estrogens play a role in peripubertal development of the epididymis and vas; 2) the cellular site of expression of ERalpha either plays a role in or reflects demarcation of the epididymal/vas boundary; and 3) blurring of this boundary in DES-treated rats coincides with altered ERalpha immunoexpression.

Induction of progesterone receptor immunoexpression in stromal tissue throughout the male reproductive tract after neonatal oestrogen treatment of rats.

Oestrogen exposure of the male during fetal/neonatal life can fundamentally alter the structure and function of the reproductive system, though how is unknown. This study examined whether such treatment was able to induce a 'female' characteristic, namely immunoexpression of progesterone receptor (PR), in the reproductive system of the male. Rats were treated on postnatal days 2, 4, 6, 8, 10 and 12 with either 10, 1 or 0.1 microg diethystilbestrol (DES) or with the vehicle (20 microl corn oil). Groups of control and treated rats were killed on days 18, 25, 35 and 90 (= adults) and tissues fixed in Bouins for immunolocalisation studies using antisera to PR (recognises A and B forms) and oestrogen receptor-beta (ER beta). PR immunoexpression was absent from all tissues studied in control rats at all ages with the exception of the parasympathetic ganglia of the prostate. In rats treated with 10 microg DES, intense immunoexpression of PR was detected in the nuclei of stromal, but not epithelial, cells of the caput and cauda epididymis, the vas deferens, seminal vesicles and at the base of the dorsolateral prostatic complex (DLPC) at day 18, but was absent from the ventral prostate and from the testis. DES induction of PR immunoexpression was evident after a single injection (on day 3) and at 18-35 days the intensity of immunoexpression was DES dose-dependent; rats treated neonatally with 0.1 microg DES showed no detectable PR immunoexpression at any age. These findings were confirmed by Western analysis which indicated that most of the PR induced was probably the B form. Co-localisation studies, using confocal microscopy, demonstrated that PR and ER beta frequently co-localised to the same stromal cells in the DLPC, epididymis and seminal vesicles of DES-treated rats at day 18, whereas epithelial cells, which also expressed ER beta, did not express PR. In the tissues studied, only occasional stromal cells expressed ER alpha in comparison to the more widespread expression of ER beta, although epithelial cell expression of ER alpha was also detected in the epididymis on day 18 (but not on day 10). In DES-treated rats, immunoexpression of PR in the reproductive tract decreased progressively in intensity from days 18-35 and was non-detectable in adulthood. In conclusion, these findings are interpreted as evidence that neonatal oestrogen treatment exerts pervasive 'reprogramming' effects throughout the reproductive system of the developing male as indicated by the induction of PR immunoexpression. This induction was restricted to stromal tissue even though both stromal and epithelial cells at most sites expressed ER beta and/or ER alpha.

Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels.

This study investigated whether neonatal exposure of male rats to estrogenic compounds altered pubertal spermatogenesis (days 18 and 25) and whether the changes observed resulted in long-term changes in testis size, mating, or fertility (days 90-100). Rats were treated neonatally with a range of doses (0.01-10 microg) of diethylstilbestrol (DES; administered on alternate days from days 2-12), a high dose of octylphenol (OP; 2 mg administered daily from days 2-12) or bisphenol A (Bis-A; 0.5 mg administered daily from days 2-12), or vehicle, while maintained on a standard soy-containing diet. The effect on the same parameters of rearing control animals on a soy-free diet was also assessed as was the effect of administering such animals genistein (4 mg/kg/day daily from days 2-18). Testis weight, seminiferous tubule lumen formation, the germ cell apoptotic index (apoptotic/viable germ cell nuclear volume), and spermatocyte nuclear volume per unit Sertoli cell nuclear volume were used to characterize pubertal spermatogenesis. Compared with (soy-fed) controls, DES administration caused dose-dependent retardation of pubertal spermatogenesis on day 18, as evidenced by decreases in testis weight, lumen formation, and spermatocyte nuclear volume per unit Sertoli cell and elevation of the germ cell apoptotic index. However, the two lowest doses of DES (0.1 and 0.01 microg) significantly increased spermatocyte nuclear volume per unit Sertoli cell. Similarly, treatment with either OP or Bis-A significantly advanced this and some of the other aspects of pubertal spermatogenesis. Maintenance of control animals on a soy-free diet also significantly advanced lumen formation and spermatocyte nuclear volume per unit Sertoli cell compared with controls fed a soy-containing diet. Administration of genistein reversed the stimulatory effects of a soy-free diet and significantly retarded most measures of pubertal spermatogenesis. In general, plasma FSH levels in the treatment groups changed in parallel to the spermatogenic changes (reduced when pubertal spermatogenesis retarded, increased when pubertal spermatogenesis advanced). By day 25, although the changes in FSH levels largely persisted, all of the stimulatory effects on spermatogenesis seen on day 18 in the various treatment groups were no longer evident. In adulthood, testis weight was decreased dose dependently in rats treated neonatally with DES, but only the lowest dose group (0.01 microg) showed evidence of mating (3 of 6) and normal fertility (3 litters). Animals treated neonatally with OP or Bis-A had normal or increased (Bis-A) testis weights and exhibited reasonably normal mating/fertility. Animals fed a soy-free diet had significantly larger testes than controls fed a soy-containing diet, and this difference was confirmed in a much larger study of more than 24 litters, which also showed a significant decrease in plasma FSH levels and a significant increase in body weight in the males kept on a soy-free diet. Neonatal treatment with genistein did not alter adult testis weight, and although most males exhibited normal mating and fertility, a minority did not mate or were infertile. It is concluded that 1) neonatal exposure of rats to low levels of estrogens can advance the first wave of spermatogenesis at puberty, although it is unclear whether this is due to direct effects of the estrogen or to associated elevation of FSH levels; 2) the effect of high doses of OP and Bis-A on these processes is essentially benign; and 3) the presence or absence of soy or genistein in the diet has significant short-term (pubertal spermatogenesis) and long-term (body weight, testis size, FSH levels, and possibly mating) effects on males.

Rectal examination and urethral catheterization by medical students and house officers: taught but not used.

OBJECTIVE: To assess the acquisition of skills in digital rectal examination (DRE) and urethral catheterization by medical students and house officers associated with a UK medical school, and to determine their confidence in these techniques. Subjects and methods Questionnaires were sent to all final-year medical students at Oxford Medical School immediately before their final examinations. Similar questionnaires were sent to all pre-registration house officers who had graduated from Oxford in the previous year. RESULTS: Responses were received from 71% of the students and 84% of the graduates; 88% of the students and 94% of the graduates had been taught how to perform a DRE as a medical student, but 42% of medical students had performed fewer than five DREs before qualification. Their findings were rarely checked by a doctor. Of the students, 44% had never felt a clinically malignant prostate gland and 41% were 'not at all confident' in their ability to give an opinion based on their findings on a DRE. House officers performed DRE regularly (53% >/= 50 DREs) but rarely received additional instruction, and exposure to pathology remained limited. House officers' findings on DRE were rarely confirmed by a more senior doctor. Most respondents had been taught how to perform male urethral catheterization as a medical student (92% of students, 89% of house officers) but 48% of students had performed fewer than two catheterizations on qualification and 68% of house officers had received no additional instruction; however, 69% of house officers were 'very confident' in their ability to perform male urethral catheterization. CONCLUSIONS: The DRE is a critical skill in assessing the prostate; students conduct few DREs, lack confidence and are exposed to minimal pathology. Legitimate concerns over students carrying out intimate examinations may be mitigating against the acquisition of skills. Possible solutions are explored. House officers perform DREs regularly, but with no additional instruction they may continue to lack confidence. Students lack experience in male urethral catheterization and rarely receive postgraduate instruction. House officers' confidence in their ability to perform male urethral catheterization may be misplaced.

Urology and the Internet: an evaluation of internet use by urology patients and of information available on urological topics.

OBJECTIVE: To determine the use of the Internet by urological patients for obtaining information about their disease, and to conduct an evaluation of urological websites to determine the quality of information available. PATIENTS AND METHODS: Questionnaires about Internet use were completed by 180 patients attending a general urological outpatient clinic and by 143 patients attending a prostate cancer outpatient clinic. The Internet evaluation was conducted by reviewing 50 websites listed by the Hotbottrade mark search engine for two urological topics, prostate cancer and testicular cancer, and recording details such as authorship, information content, references and information scores. RESULTS: Of the patients actively seeking further information about their health, 19% of the general urological outpatient group and 24% of the prostate cancer group used the Internet to obtain this information. Most websites were either academic or biomedical (62%), provided conventional information (95%), and were not referenced (71%). The information score (range 10-100) was 44.3 for testicular cancer and 50.7 for prostate cancer; the difference in scores was not significant. CONCLUSION: The use of the Internet by patients is increasing, with > 20% of urology patients using the Internet to obtain further information about their health. Most Internet websites for urological topics provide conventional and good quality information. Urologists should be aware of the need to familiarize themselves with urological websites. Patients can then be directed to high-quality sites to allow them to educate themselves and to help them avoid misleading or unconventional websites.

Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.

The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0.01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad. The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozole-treated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the brain and the hypothalamo-pituitary axis are considerably more susceptible than is the testis to the effects of an aromatase inhibitor. Anastrozole treatment has resulted in a model of brain oestrogen insufficiency.