Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

The Sesto Fiorentino study: point and one-year prevalences of psychiatric disorders in an Italian community sample using clinical interviewers

BACKGROUND: It has been argued that lay interviewers' use of fully-structured interviews could lead to a diagnostic pattern different to that by treating physicians. Clinical interviewers in community samples should probably identify cases that are closer to those seen in clinical settings. The greatest advantage of using clinical interviewers consists of the immediate assessment of a possible psychopathology, i.e. the evaluation of current disorders. METHODS: Two thousand three hundred and sixty-three citizens from the community of Sesto Fiorentino, Italy, were interviewed by their own general practitioners using the Mini International Neuropsychiatric Interview (MINI). Positive cases for any lifetime psychiatric disorder as well as a random sample of the negative cases were re-interviewed by psychiatrists or trained residents in psychiatry using the Florence Psychiatric Interview (FPI). RESULTS: The point prevalence for any current disorder was 8.7%; the two disorders with the highest prevalence were generalised anxiety disorder (2.9%) and major depressive episode (2.7%). The figures increase about 50% when the sub-threshold sequelae of previous disorders are considered. Current comorbidity was generally high. The one-year prevalence of any disorder was 10.6%. Ninety-two percent of the cases sought help, 82% were being treated at the moment of interview. Social impairment was considerable. CONCLUSIONS: The period prevalence rates for most of the disorders considered were generally comparable with the range defined by previous studies conducted in other Western countries, despite using different methodologies. Conversely, the use of health facilities, the treatment received and the social impairment were much higher than those reported by the other studies, suggesting a greater similarity with the clinical samples.     

A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

P300 amplitude in nonalcoholic adolescent twin pairs who become discordant for alcoholism as adults

Past reports suggest that reduced P300 amplitude is associated with risk for alcoholism. We examined whether visual P300 amplitude could identify familial risk for alcohol disorders in individuals not known to be at risk at the time P300 was recorded. These individuals were twins from pairs where neither twin had an alcohol disorder at age 17 but familial risk was established at age 20 when one twin developed an alcohol disorder whereas the other did not. Of special interest was the P300 of the unaffected twin recorded at age 17 when both twins were alcoholism free. We found reduced P300 in the unaffected twin compared to pairs where both members were continuously disorder free. Hence, P300 was reduced in alcohol disorder-free individuals whose twin siblings subsequently developed alcoholism, further supporting reduced P300 amplitude as an endophenotype indexing familial risk for alcoholism.     

Searching for Interactive Effects in the Etiology of Early-Onset Substance Use

This study sought to expand the modest literature investigating gene × environment interactions in the prediction of substance use. Our sample consisted of 591 male twins from the Minnesota Twin Family Study. Their relative genetic risk was estimated from their parents' substance-related diagnoses and their environmental risk from their affiliations at age 11 with social groups likely to either encourage or discourage substance use. At age 14, the boys' own substance use was assessed. We hypothesized both main effects and an interaction between our genetic- and environmental-risk variables in the prediction of substance use by this young age. We further theorized that the boys' inherited risk might take the form of temperament, specifically externalizing tendencies. Using regression analyses and biometrical modeling, we corroborated earlier research by finding evidence for a significant interactive effect in the etiology of substance use. Our results suggest that low levels of environmental risk may buffer against the potentially unfavorable effects of high familial risk; however, when environmental risk is high, the degree of familial risk is consequential. We were not able to support our second hypothesis; rather, temperament predicted substance use only through shared environmental factors.     

Risk for recurrence in depression

Depression is a highly recurrent disorder with significant personal and public health consequences. Prevention of recurrence would be extremely desirable, and thus researchers have begun to identify risk factors that are specific to recurrence, which may be different from risk factors for first onset of depression. Methodological issues in this area of research are briefly reviewed (e.g., the various definitions of "recurrence" and "depression"), followed by a review of studies on specific risk factors, including demographic variables (gender, socio-economic status, and marital status), clinical variables (age at first onset, number of prior episodes, severity of first/index episode, and comorbid psychopathology), family history of psychopathology, and psychosocial and psychological variables (level of psychosocial functioning, cognitions, personality, social support, and stressful life events). In addition, scar theories are evaluated for their potential to explain how these variables and recurrent depression are linked. Our review suggests that recurrent depression reflects an underlying vulnerability that is largely genetic in nature and that may predispose those high in the vulnerability not only to recurrent depressive episodes, but also to the significant psychosocial risk factors that often accompany recurrent depression.     

Evidence of very delayed clinical reactions to cow's milk in cow's milk-intolerant patients

BACKGROUND: In patients with cow's milk protein intolerance (CMPI), delayed clinical reactions to cow's milk (CM) ingestion may be misdiagnosed if the clinical symptoms are not "classical" and there is a long time lapse between ingestion of CM and the clinical reaction. The aim was to evaluate the clinical outcome of CMPI in a cohort of CM-intolerant children, with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge. METHODS: Eighty-six consecutive patients (44 boys, 42 girls) with new CMPI diagnoses were enrolled; median age at diagnosis was 4 months. Patients were followed up for a mean period of 40 months. In all patients, CMPI diagnosis was made on the observation of symptoms, their disappearance after elimination diet, and their reappearance on double-blind CM challenge. At CMPI diagnosis, immunologic tests to demonstrate IgE-mediated hypersensitivity were performed. After 12 months of CM-free diet, CM tolerance was re-evaluated with a CM challenge continued at home for up to 30 days, according to a double-blind, placebo-controlled method. Patients who did not achieve CM tolerance continued a CM-free diet and subsequently underwent yearly CM challenge. RESULTS: The percentages of CMPI patients who became CM-tolerant after 1, 2, and 3 years of CM-free diet were 30%, 54.5%, and 70%, respectively. At the end of the follow-up period, 26/86 subjects showed persistent CMPI; these patients had a higher percentage of positivity of total serum IgE (P<0.05), RAST (P<0.01), and cutaneous prick tests for CM antigens (P<0.001) than all the others. At CMPI diagnosis, all patients had a clinical reaction within 72 h from the beginning of the CM challenge; at the subsequent "cure" challenges, we observed patients who first reacted to CM more than 72 h after ingestion. In total, 10 out of 86 patients showed "very delayed reactions"; in these patients, the mean time between the beginning of CM challenge and the onset of a clinical symptom was 13.3 days (range 4-26 days). The number of "very late reactors" increased from the first to the third of the "cure" CM challenges, performed at yearly intervals. The "very delayed" CMPI manifestations in these subjects were constipation (five cases), wheezing (two cases), dermatitis plus constipation (two cases), and dermatitis alone (one case); in 6/10 patients, the symptoms observed at the "cure challenge" were different from those at CMPI onset. CONCLUSIONS: Very delayed clinical reactions to reintroduction of CM in the diet can occur in CMPI patients; thus, accurate follow-up and frequent outpatient observation in patients with a long history of CMPI are probably more useful and safer than prolonged CM challenge.     

Physical Similarity and Twin Resemblance for Eating Attitudes and Behaviors: A Test of the Equal Environments Assumption

The Equal Environments Assumption (EEA) in twin studies of eating pathology was investigated by examining the hypothesis that twin resemblance for eating attitudes and behaviors is affected by their degree of physical similarity. Eating attitudes and behaviors were assessed in 338 female adolescent twin pairs with a revised version of the Eating Disorder Inventory (EDI). General physical similarity as well as body size/shape similarity were assessed using ratings of color photographs, ratings of body shape, and body mass index. All physical similarity assessments were conducted blind to twin zygosity. Significant associations between physical similarity and twin similarity for eating attitudes and behaviors were not found. Mean EDI within-twin pair absolute difference scores did not differ significantly among more versus less physically-similar groups. Additionally, correlation and regression analyses failed to find a significant association between EDI absolute difference scores and physical similarity indices. The current findings provide support for the EEA in twin studies of eating attitudes and behaviors.     

Genetic and environmental influences on adolescent substance use and abuse

The inheritance of substance use and abuse among adolescents was investigated in a sample of 626 male and female 17-year-old twin pairs. Both licit (tobacco) and illicit (e.g., marijuana, amphetamines) substance use and abuse was assessed and analyzed using standard biometric methods. The heritability of use and abuse of illicit substances was modest (25% or less), whereas the heritability of tobacco use and nicotine dependence was substantial (40% to 60%). There was no evidence that gender moderated the strength of genetic influences. Shared environmental influences were substantial for all substance use measures. The finding of greater genetic influence on the use and abuse of a licit substance than on the use and abuse of illicit substances suggests that inherited risk to drug abuse is considerably moderated by environmental control, at least in adolescence. The finding of significant environmental influences on all substance use measures underscores the importance of intervention on early adolescent substance use, a known predictor of adult substance abuse and dependence.     

Chronic pain in urological diseases: a clinical review

Chronic pain is the central problem in a variety of urological diseases. Pain is an unpleasant sensory and emotional experience associated with either actual or potential tissue damage, or described in terms of such damage. The aim of this research was to update knowledge about the ultrastructural, clinical, psychological and therapeutic aspects of chronic pain in urological diseases, in particular in chronic pelvic syndrome. In this paper we have revisited the most significant and discussed articles published in the last twenty five years, with particular references on the 2008 European Guidelines, searching key words (chronic pelvic pain syndrome, chronic pelvic pain, chronic prostatitis, interstitial cystitis, prostatodynia, urological disease) and data with a high level of evidence. The articles that we have analyzed show that pain is characterized by an initial tissue injury that can lead to sensitization, which is a decrease in the intensity of the stimulus needed to elicit a response by the nerve, involving the peripheral and central nervous systems. The chronic pain state is characterized by loss of inhibitory interneurons, establishment of aberrant excitatory synaptic connections and long-term potentiation of response due to changes in sensitivity of nerve synapses. Stress and hormones might also play a role in central sensitization. Pain also has a cognitive and emotional component. It is very difficult to treat, given the complex nature of the response and the interaction of physiological aspects