The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Scrotal ultrasound reference ranges and associations with clinical, seminal, and biochemical characteristics.

BACKGROUND: Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. OBJECTIVES: To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. METHODS: A cohort of 248 HFM (35.3 ± 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. RESULTS: The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was ~ 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. CONCLUSIONS: The present findings will help in better understanding male infertility pathophysiology, improving its management.

Epididymal leiomyoma: a benign intrascrotal tumour.

Physicians will be rarely confronted with epididymal tumours. These represent only 5% of intrascrotal tumours and are mostly (75%) benign. We report the case of a 50-year-old white male who was presented with a 5-year history of a slow-growing, left scrotal mass, noted through self-examination. Ultrasound study of the scrotum identified a well-circumscribed paratesticular mass. On inguinal surgical exploration, a solid, encapsulated, grey-white mass at the tail of the left epididymis was identified and excised, with intra-operative pathological consultation showing no signs of malignancy. The diagnosis of an epididymal leiomyoma was determined through subsequent immune-histopathological analysis. Diagnostic steps preceding operative exploration of a paratesticular, epididymal tumour are briefly analysed and physicians are encouraged to avoid a radical approach, without prior pathological consultation. Epididymal leiomyomas are benign tumours that can be cured through simple, organ-preserving surgical excision.

Antenatal steroids and fluid balance in very low birthweight infants.

OBJECTIVES: To determine if insensible water loss (IWL) differed between infants exposed or not exposed antenatally to corticosteroids and to explore possible mechanisms for the early postnatal diuresis associated with antenatal steroid exposure. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Level three neonatal intensive care unit. PATIENTS: Ninety six infants, median gestational age 27.5 weeks (range 23-33). MAIN OUTCOME MEASURES: Comparison of the IWL, urine output and osmolality, fluid input, electrolyte imbalance, respiratory illness severity (as assessed by surfactant requirement, maximum peak inspiratory pressure, and inspired oxygen concentration), and cardiovascular status (as assessed by inotrope requirement) between infants with antenatal corticosteroid exposure and gestational age matched controls. RESULTS: The infants exposed to antenatal steroids differed significantly from the controls in having both a lower IWL (p = 0.0135) and a higher urine output (p = 0.0036) on day 1, and fewer developed hyponatraemia (p = 0.027) on day 2. Fewer of those exposed to antenatal steroids required inotropes (p = 0.06), but their respiratory status was similar to that of the controls. CONCLUSIONS: Infants exposed to antenatal corticosteroids have a lower IWL. The results suggest that greater skin maturation, but also better perfusion rather than less severe respiratory status, explains the early diuresis in infants exposed to antenatal steroids.

Single administration of 5-HT1A agonists decreases 5-HT1A presynaptic, but not postsynaptic receptor-mediated responses: relationship to antidepressant-like action.

The 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), buspirone or TVXQ 7821 (ipsapirone) but not the 5-HT1B agonist RU 24969, attenuated the hyperphagic response to 8-OH-DPAT administered on the next day. Attenuation was still apparent on the fifth day after either 8-OH-DPAT or buspirone but not on the tenth day after 8-OH-DPAT administration. The ability of 8-OH-DPAT to reduce raphe 5-HIAA levels was also impaired by previous 8-OH-DPAT treatment. However, the 8-OH-DPAT or 5-methoxy-N,N-dimethyltryptamine-induced 5-HT syndromes were unaltered. The results indicate that a single pretreatment with 5-HT1A agonists rapidly desensitises 5-HT1A presynaptic receptor-mediated responses. This effect may mediate the antidepressant-like action of the drugs in an animal model of depression.

Enhancement of brain dopamine metabolism by tyrosine during immobilisation: an in vivo study using repeated cerebrospinal fluid sampling in conscious rats.

Central dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolism was monitored in conscious, freely moving rats by determination of levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF samples withdrawn repeatedly from the cisterna magna and treated with acid to hydrolyse DOPAC and HVA conjugates. The effect of tyrosine on DA metabolism was investigated. Time courses of metabolite concentrations in individual rats in a quiet room showed that tyrosine (20, 50, or 200 mg/kg i.p.) was without significant effect; brain changes were essentially in agreement. However, the increases of CSF DOPAC and HVA levels that occurred on immobilisation for 2 h were further enhanced by tyrosine (200 mg/kg). The associated increases of 5-HIAA level were unaffected. The corresponding increases of DA metabolite concentrations in the brains of immobilised rats given tyrosine were less marked than the CSF changes and only reached significance for "rest of brain" DOPAC. The CSF studies revealed large interindividual variation in the magnitude and duration of the effects of immobilisation on transmitter amine metabolism. These results may help toward the elucidation of possible relationships between the neurochemical and behavioural effects of stress.

Female rats are more vulnerable than males in an animal model of depression: the possible role of serotonin.

A single 2-h restraint stress reduces locomotion and increases defaecation of male rats placed in an open field 24 h later. After daily 2-h restraints for 5 days these effects were no longer observed. This adaptation was associated with enhanced sensitivity to the serotonin agonist 5-methoxy-N,N-dimethyltryptamine. Female rats were less affected by a single restraint but failed to adapt to the repeated stress procedure and did not exhibit enhanced sensitivity to 5-methoxy-N,N-dimethyltryptamine. Furthermore, females but not males killed 24 h after the final restraint period had decreased brain regional 5-hydroxyindoleacetic acid concentrations particularly in the frontal cortex. No sex differences in hypothalamic and striatal dopamine metabolism were observed. The above differences between male and female rats were unaffected by adult gonadectomy. Similar differences could be involved in the higher incidence of depressive illness in women.

Characteristics of analgesias induced by brief or prolonged stress.

Some characteristics of the effects of brief and prolonged stress on tail-flick latency are described. The pharmacological profiles of the latency responses to 30 sec and 30 min footshock are strikingly different. Thus, the increase of tail-flick latency after 30 sec shock is unaffected by naloxone and enhanced by drugs which decrease 5HT or DA-dependent transmission, while the increase after 30 min shock is blocked by naloxone and also by the above drugs. The increased tail-flick latency after 30 sec shock only occurs if tail-flick latency is also determined before shock. This finding, together with the attenuation or enhancement of the post-shock response by drugs that similarly affect conditioned avoidance behavior, suggests that the increased latency after brief shock occurs through a mechanism that is related to passive avoidance learning. Finally, a new approach to the investigation of stress-induced analgesia is described in which neurochemical changes during prolonged immobilization stress are repeatedly monitored using cisternal CSF samples taken in parallel with tail-flick latency measurements.

Monitoring dopamine metabolism in the brain of the freely moving rat.

Determination of DOPAC and HVA in cisternal CSF taken repeatedly from freely moving rats provides a useful means of monitoring central DA metabolism. A large proportion of both metabolites occurs in cisternal CSF as conjugates from which they are liberated by acid hydrolysis. The method enables DA turnover values to be determined for individual rats. Drug experiments indicate that these values reflect brain DA metabolism and that most of this occurs in extrastriatal DA neurons. Concurrent determination of 5HT turnover on the same CSF samples revealed a significant positive correlation between the turnovers of the two transmitters together with considerable inter-individual differences. The turnover method was particularly convenient when investigating daily variations of turnover. Repeated CSF withdrawal also appears to be useful in the analysis of stress-provoked changes of the metabolism of DA and other transmitters. For example, it was used to show that central DA metabolism becomes highly responsive to tyrosine availability if rats are subjected to immobilization stress. The method can also be used to compare the time dependencies of both metabolic and behavioral responses to the stress in the same animal. Preliminary results suggest that the increase of 5HT metabolism during immobilization (rather than that of DA) may oppose the suppression of open field activity that occurs 24 hr later.

Evidence for dopamine autoreceptors in mesocortical dopamine neurons.

The effect of different treatments which are thought to modify dopamine (DA) synthesis by an action on DA autoreceptors was compared in the caudate nucleus and two frontal cortical areas: the medial prefrontal cortex and dorsolateral frontal cortex, having the highest and lowest DA concentration, respectively, but having equal concentrations of norepinephrine (NE); the NE to DA ratio being 3:2 and 8:1, respectively. DA synthesis was measured by the rate of DOPA accumulation after inhibition of DOPA decarboxylase. Gamma-butyrolactone (GBL) (750 mg/kg) increased DOPA accumulation by 200% in the caudate nucleus but only by 40% in the medial prefrontal cortex and was ineffective in the dorsolateral frontal cortex. Apomorphine (25-100 micrograms/kg) decreased DOPA accumulation by 7-30% in the medial prefrontal cortex and by 20-40% in the caudate nucleus in a dose-dependent manner. N-n-propylnorapomorphine (NPA) produced a similar effect within the dose range of 2.5-10 micrograms/kg. Both DA agonists were completely ineffective in the dorsolateral frontal cortical area. Haloperidol (0.5 mg/kg) increased DOPA accumulation by 80 and 220% in the medial prefrontal cortex and the caudate nucleus, respectively. It is concluded that DA autoreceptors regulate DA synthesis in the medial prefrontal cortex as in the caudate nucleus. Moreover, it was found that DOPA accumulation was approximately equal in the medial prefrontal cortex, with dense dopaminergic innervation, as in the dorsolateral area, devoid of dopaminergic terminals, suggesting that only a small fraction of cortical DA synthesis takes place in dopaminergic neurons, while the major part occurs in noradrenergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed inhibition of dopamine synthesis by gamma-butyrolactone and baclofen: dopamine autoreceptor supersensitivity?

The administration of gamma-butyrolactone (GBL) (750 mg . kg-1 i.p.) and baclofen (20 mg . kg-1 i.p.) to rats caused a transient increase followed by a long-lasting decrease in striatal dopamine (DA) synthesis, as measured by DOPA accumulation after decarboxylase inhibition. DA synthesis was reduced to 40-50% of the control value for 2-12 h following either treatment. The GBL- and baclofen-induced inhibition of DN synthesis was reversed by haloperidol (2-5 mg . kg-1 i.p.) and by a second dose of baclofen or GBL. The subcutaneous dose of 15 mg . kg-1 of apomorphine, insufficient to decrease DA synthesis in control rats, produced a further decrease in DA synthesis in animals pretreated with baclofen. These results suggest that the delayed DA synthesis inhibition following GBL or baclofen treatment was due to stimulation of supersensitive DA autoreceptors.

A study of dopamine receptors in guinea-pig renal tissue.

Dopamine and isoprenaline have been examined for their effects on guinea-pig renal blood flow in vivo and on cAMP production in a mainly isolated glomeruli/blood vessel preparation in vitro. The renal vasodilatation caused by both of these drugs can be differentiated by the use of specific antagonists, sulpiride blocking the effects of dopamine, and propranolol the vasodilatation produced by isoprenaline. Similarly, both drugs stimulated cAMP production, isoprenaline being much more active than dopamine (1000X) in this respect. Again, the dopamine antagonist fluphenazine specifically inhibited the dopamine-induced cAMP increases whilst the beta blocker atenolol blocked the rise in cAMP due to isoprenaline but not that due to dopamine. Sulpiride although potently inhibiting dopamine-induced renal vasodilatation was without effect on dopamine-stimulated cAMP levels. This result is similar to that reported in the CNS where sulpiride blocks dopamine activity in a variety of tests but is without effect on the dopamine-stimulated adenylate cyclase. Two dopamine agonists, ADTN and SKF 38393 were tested, and in both preparations had potent dopaminergic activity although SKF 38393 exhibited characteristics of a partial agonist on the adenylate cyclase model.