Urodynamic findings in men operated on for an undescended testicle

OBJECTIVE: To test the hypothesis that men with a history of undescended testicle have voiding problems similar to those in rodents exposed to excessive amounts of oestrogens during development, although the role of oestrogen in the failure of the human testicle to descend remains controversial. PATIENTS AND METHODS: Thirteen men (mean age 45 years) previously operated on for an undescended testicle (testis-retention, TR group) and 12 age-matched men operated on for inguinal hernia or appendicitis (control group) participated in a urodynamic examination, transrectal ultrasonography (TRUS) of the prostate, and blood tests for hormones and prostate-specific protein. They also completed a questionnaire on urinary symptoms. RESULTS: The free maximum flow rate was significantly lower and the detrusor pressure at maximum flow (P(det)Q(max)) slightly higher in the TR than the control group. Three men in the TR group (and none of the controls) had bladder outlet obstruction (BOO), whereas voiding was not obstructed among 11 control men (and five men in the TR group). The hormone concentrations of the groups did not differ significantly but the prostates were significantly smaller in the TR group. The testosterone concentrations and the ratio between 17beta-oestradiol (E2) and free testosterone (E2/fT) influenced prostate size significantly. An exploratory analysis suggested that E2/fT may influence the maximum detrusor pressure and P(det)Q(max). CONCLUSION: Men born with an undescended testicle had smaller prostates but more often had BOO than did the controls. The results suggest that an imbalance between the actions of oestrogen and testosterone may influence the initiation and continuance of BOO among cryptorchid men.     

Testosterone concentrations in human seminal plasma and saliva and its correlation with non-protein-bound and total testosterone levels in serum

A sensitive, specific and precise non-chromatographic method for the radio-immunoassay of testosterone in human seminal plasma and saliva from adult and pubertal males is described, and the values compared to total and non-protein-bound testosterone levels in serum. There was a significant correlation between salivary and serum-free levels of testosterone (r = 0.75, P < 0.001, n = 67) whilst the correlation of serum levels of total testosterone with free as well as with salivary testosterone levels was weaker (r = 0.63 and 0.64, respectively). The salivary and serum levels of free testosterone showed better correlation with the stage of puberty than did the serum levels of total testosterone. Further evidence for a correlation between salivary and serum levels of free testosterone was obtained following oral administration of testosterone undecanoate, as this treatment increased the mean concentration of serum total testosterone after 3 h by 82%, but increased salivary and serum levels of free testosterone by only 30% and 20%, respectively. The coefficient of correlation between serum levels of total testosterone and seminal plasma testosterone was 0.73 ( P < 0.001), whilst the correlation between levels of serum-free testosterone with both salivary and seminal plasma levels of testosterone was statistically non-significant. Our observations on salivary testosterone are in accordance with the diffusion of non-protein-bound steroids into peripheral tissues, and consequently into their secretions. This model, however, does not appear to be applicable to the sex accessory glands.     

Hydroxymatairesinol and its mammalian metabolite enterolactone reduce the growth and metastasis of subcutaneous AH109A hepatomas in rats

Both epidemiological and experimental evidence is accumulating to show that a lignan-rich diet may reduce the risk of human breast cancer. Possible anti-cancer effects of dietary lignans on hepatomas or hepatoma cells have not been the topic of earlier studies. In the present study, we examined the effect of 7-hydroxymatairesinol (HMR) and its mammalian metabolite, enterolactone (ENL), on AH109A hepatoma cell proliferation and invasion in vitro. HMR and ENL inhibited the proliferation and invasion of AH109A hepatoma cells in vitro. The 50% inhibitory concentration (IC50) of hepatoma cell proliferation was lower for ENL (10 microM) than HMR (> 200 microM). Likewise, IC50 of hepatoma cell invasion was lower for ENL (9 microM) than HMR (144 microM). ENL suppressed hepatoma cell proliferation by accumulating cells in G1 phase and elongating doubling time of these cells, and by increasing the rate of apoptosis. Subsequently, we investigated in vivo the effect of dietary HMR and ENL on growth and metastasis of AH109A hepatomas in rats. Both of these compounds reduced the growth and metastasis of solid AH109A hepatomas in rats. These in vitro and in vivo findings suggest that HMR has inhibitory activities on tumor growth and metastasis in the hepatoma-bearing rats, and that this anti-tumor effect is mediated at least partially by ENL, a metabolite of HMR.     

HIV outbreak among injecting drug users in the Helsinki region: social and geographical pockets

BACKGROUND: Incidence of newly diagnosed HIV infections among injecting drug users (IDUs) in Helsinki rose from 0 per 100,000 inhabitants in 1997 to 2.9 in 1998 and to 11.1 in 1999. Thereafter incidence declined to 2.1 in 2003. METHODS: Data were collected from interviews with HIV-positive IDUs who attended the University Hospital in Helsinki from 1998 until 2003. We studied the sociodemographic profile and spatial distribution of IDUs who were diagnosed in the beginning of the outbreak and those diagnosed later. The indicator for the spatial differentiation within the metropolitan area is % employed males aged 25-64. RESULTS: The outbreak occurred among a marginalized population of IDUs characterized by a long history of injecting drug use (10.7 years), mean age 32 years, homelessness (66.3%), history of imprisonment (74.7%) and psychiatric hospital care (40.6%). Compared with 98 early cases diagnosed during the first 2 years until 2000, 47 recent cases diagnosed after 2001 were 4 years older, and as marginalized. Except for the city centre, both early and recent cases had been living or using drugs in the same deprived neighbourhoods with the highest unemployment rates. Up to 40% of cases in the two big geographical clusters did not have contact with the city centre, where the needle exchange services were available. CONCLUSIONS: The Finnish HIV outbreak is restricted socially to a very marginalized IDU population, and spatially to local pockets of poverty. In low prevalence countries, prevention programs should be targeted early at high-risk areas and populations.     

Rectal <Emphasis Type="Italic">E. coli</Emphasis> above ciprofloxacin ECOFF associate with infectious complications following prostate biopsy

Transrectal prostate biopsies carry the risk of infection. By using non-selective culture plates, instead of commonly used ciprofloxacin (CIP)-containing plates, we analyzed the association between Escherichia coli CIP minimal inhibitory concentration (MIC) and post-biopsy infectious complications. A pre-biopsy rectal swab was taken from 207 consecutive men, scheduled for transrectal 12-core prostate biopsy with CIP 750 mg as the mostly used prophylaxis. CIP MIC of rectal Gram-negative bacilli was determined from a chromogenic agar. Rectal E. coli were categorized to resistant (R) and intermediate (I) isolates together (R + I, MIC >?0.25 mg/l) and to sensitive (S, MIC ≤?0.25 mg/l) using EUCAST clinical breakpoints. In addition, epidemiological cutoff (ECOFF R, MIC >?0.064 mg/l) was used for categorization. Eighteen (8.7%) men showed CIP R + I E. coli by the EUCAST breakpoints and 41 (19.8%) using the ECOFF R criteria. During follow-up, 15 (7.2%) men had infectious symptoms, of which 9 (4.3%) were culture-confirmed infections. Only 4 (26.7%) of these 15 patients showed R + I E. coli in the rectal swab according to EUCAST, but 10 (66.7%) using the ECOFF cutoff. Rectal E. coli CIP R + I by the EUCAST clinical breakpoints associated with infectious complications with OR 5.7 (95% CI 1.5–21.8, P?=?0.005) and ECOFF R E. coli by OR 10.7 (95% CI 3.0–37.6, P?<?0.001). Men carrying rectal E. coli with moderately lowered CIP susceptibility (MIC > ECOFF 0.064 mg/l) were identified and, interestingly, they showed a high risk of developing infectious symptoms after the biopsy. This explains why some men develop infectious complications despite appropriate antibiotics before prostatic biopsies. Trial registration: NCT02140502     

Altered structure and function of reproductive organs in transgenic male mice overexpressing human aromatase

Aromatization of androgens is a key step in estrogen production, and it regulates the delicate balance between estrogens and androgens in the gonads and sex steroid target tissues. In the present study, we generated transgenic mice (AROM(+)) bearing the human ubiquitin C promoter/human P450 aromatase fusion gene. AROM(+) male mice are characterized by an imbalance in sex hormone metabolism, resulting in elevated serum E(2) concentrations, combined with significantly reduced testosterone and FSH levels, and elevated levels of PRL and corticosterone. AROM(+) males present a multitude of severe structural and functional alterations in the reproductive organs, such as cryptorchidism associated with Leydig cell hyperplasia, dysmorphic seminiferous tubules, and disrupted spermatogenesis. The males also have small or rudimentary accessory sex glands with abnormal morphology; a prominent prostatic utricle with squamous epithelial metaplasia, and edema in the ejaculatory ducts and vas deferens. In addition, the abdominal muscle wall is thin, and the adrenal glands are enlarged, with cortical hyperplasia. Some of the abnormalities, such as undescended testes and undeveloped prostate, resemble those observed in animals exposed perinatally to high levels of exogenous estrogen, indicating that the elevated aromatase activity results in excessive estrogen exposure during early phases of development. Some of the disorders in the reproductive organs, furthermore, can be explained by the fact that AROM(+) males are hypoandrogenic, and have elevated levels of serum PRL and corticosterone. Thus, the AROM(+) mouse model provides a novel tool to investigate the consequences of a prolonged increase in conversion of androgens to estrogens which results in complex hormonal disturbances altering the structure and function of various male reproductive organs.     

Hydroxymatairesinol and Its Mammalian Metabolite Enterolactone Reduce the Growth and Metastasis of Subcutaneous AH109A Hepatomas in Rats

Both epidemiological and experimental evidence is accumulating to show that a lignan-rich diet may reduce the risk of human breast cancer. Possible anti-cancer effects of dietary lignans on hepatomas or hepatoma cells have not been the topic of earlier studies. In the present study, we examined the effect of 7-hydroxymatairesinol (HMR) and its mammalian metabolite, enterolactone (ENL), on AH109A hepatoma cell proliferation and invasion in vitro. HMR and ENL inhibited the proliferation and invasion of AH109A hepatoma cells in vitro. The 50% inhibitory concentration (IC ₅₀ ) of hepatoma cell proliferation was lower for ENL (10 μ M) than HMR (> 200 μ M). Likewise, IC ₅₀ of hepatoma cell invasion was lower for ENL (9 μ M) than HMR (144 μ M). ENL suppressed hepatoma cell proliferation by accumulating cells in G ₁ phase and elongating doubling time of these cells, and by increasing the rate of apoptosis. Subsequently, we investigated in vivo the effect of dietary HMR and ENL on growth and metastasis of AH109A hepatomas in rats. Both of these compounds reduced the growth and metastasis of solid AH109A hepatomas in rats. These in vitro and in vivo findings suggest that HMR has inhibitory activities on tumor growth and metastasis in the hepatoma-bearing rats, and that this anti-tumor effect is mediated at least partially by ENL, a metabolite of HMR.