A randomized targeted amino acid therapy with behaviourally at-risk adopted children.

BACKGROUND: Increasing numbers of children are at-risk for behavioural and emotional disorders, a phenomenon contributing to increased use of pharmacological interventions for paediatric clients. Adverse side effects and other risks associated with pharmacological approaches have helped fuel interest in nutritional interventions for behaviourally at-risk children. METHODS: The current randomized clinical trial evaluates the efficacy of a neurochemical intervention involving the glutamine and glutamate analogue L-theanine and 5-hydroxytryptophan, the precursor for serotonin, with children adopted from traumatic backgrounds. RESULTS: Results include significant increases in urinary levels of the biomarkers for serotonin and gamma-aminobutyric acid, coupled with significant decreases in parent reports of the children's behaviour problems. CONCLUSIONS: While further research is needed, these initial findings are encouraging and are consistent with a growing number of studies indicating the efficacy of nutritional approaches to help behaviourally at-risk children.

Decreased Leydig cell responsiveness in the testicular feminized male rat.

The Stanley-Gumbreck pseudohermaphrodite or testicular feminized male (tfm) rat exhibits a decreased Leydig cell sensitivity to human CG (hCG) measured by androgen and cyclic-3',5',-adenosine monophosphate production in vitro. These changes were associated with an 80% reduction in the number of LH receptors in the tfm testis, when compared on the basis of equivalent amounts of testis particle protein or per 10(6) isolated Leydig cells. Androstenedione and not testosterone is the major androgen secreted by the tfm Leydig cell and androstenedione secretion is, therefore, a more appropriate end point than testosterone secretion for Leydig cell function in tfm animals. A dose of hCG (3 ng/2 ml) which elicited a near maximal response in androgen production from the decapsulated testes and Leydig cell suspensions of normals rats, did not significantly stimulate androgen production from Leydig cells of the tfm animals. A much higher dose of hCG (200 ng/2 ml) gave a response from the tfm Leydig cells which was comparable to that obtained with 3 ng from Leydig cells of normal littermates. This indicates that the small number of LH receptors on the tfm Leydig cell membrane are functional and that the reduction in receptor number results in a decrease in the sensitivity of response to LH rather than a reduction in the maximum steroid response.

Cofactor dependency of soluble 3 alpha-hydroxysteroid oxidoreductases in rat testis, prostate, and epididymis.

The present paper demonstrates the presence of at least two 3-hydroxysteroid oxidoreductases (3-HSO) in rat testis, prostate, and epididymis cytosol preparations. The enzymes were either NADH or NDAPH dependent. Further investigation by Sephadex G-200 chromatogrphy revealed the presence of enzyme activities in the void volume (peak 1) and also eluting close to the methyl-carbonic anhydrase standard (mol wt, 34,000; peak 2). Enzyme activity in peak 1 was predominantly stimulated by NADH and that in peak 2 was stimulated mainly by NADPH. Both 3 alpha- and 3 beta-HSO activities were observed in testicular eluates from 1; 3 beta-Adiol accounted for up to 50% of the 5 alpha-androstanediols formed. In peak 2,3 alpha-HSO constituted more than 90% of the enzyme activity. In contrast, the prostatic and epididymal eluates revealed only 3 alpha-HSO activity; 3 beta-Adiol constituted less than 5% of the 5 alpha-androstanediols formed in either peak 1 or 2. The apparent Km values for enzyme activation reveal differences in sensitivity to cofactors for enzymes in peaks 1 and 2 and also among testis, epididymis, and prostate. NADH caused a very similar activation of enzyme activity in peak 1 or the prostate and epididymis (Km 50-100 micro M), whereas the enzyme in the testis was activated by much lower cofactor concentration (Km approximately 5 microM). It is possible that this enzyme activity may represent microsomal contamination. The enzyme activity in peak 2 revealed very similar sensitivity to NADPH in all three organs (Km, 0.6-1.7 microM), confirming previous studies from our laboratory that the soluble. NADPH-dependent enzymes in all three tissues are very similar, if not identical.

Standardized instructions: do they improve communication of discharge information from the emergency department?

To determine whether standardized instructions enhance communication of discharge information, we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department: (1) instruction by individual housestaff and medical students after consultation with an attending physician (control group); (2) standardized verbal instructions given by housestaff and students trained in their use (verbal group); or (3) the same instructions given to the verbal group, together with a type-written copy of the information to take home (verbal + written group). Prior to leaving the emergency department and, again, by phone, 1 and 3 days later, parents were questioned concerning the prescribed medication's name, dose, frequency, and duration of administration (medication data), three signs of improvement, and eight signs indicating the need for medical advice (worrisome signs). The mean percentage of correct responses per parent in each group was computed for each information category. Both at exit interview and at follow-up, parents receiving either form of standardized instructions showed significantly greater knowledge of information related to their child's illness than did controls. Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs. The addition of written instructions to standardized verbal instructions did not improve parental recall of discharge information.

Thyrotrophin-releasing hormone in human ejaculate.

Immunoassayable TRH in human ejaculate was eluted from a gel column in a form with a molecular weight larger than that of the native peptide. With reverse-phase high-performance liquid chromatography (HPLC) the same activity co-eluted with standard TRH. Incubation of ejaculates at room temperature for 8 h was associated with a time-related increase in the total immunoassayable TRH. Analysis by HPLC of ejaculates after 12 h of incubation at room temperature indicated that, whereas the levels of the peptide co-eluting with native TRH declined with time, there was a concomitant increase in the concentration of a molecular species which also cross-reacted with the TRH antiserum, but which was more hydrophobic. The latter species is presumably identical to the tetrapeptide recently described by others and which may arise from the proteolytic degradation of secretory macromolecules. Although immunological activity was present in all six fractions of split ejaculates, the bulk of the peptide was associated with the later portions, implying a major vesicular contribution. However, secretions isolated from surgical preparations of the seminal vesicles contained undetectable levels of peptide, suggesting that the ejaculation process may represent a stimulus for its appearance in the semen. This study is further support for a local involvement of TRH in male reproductive function.

Endocrine effects of masturbation in men.

The levels of pregnenolone, dehydroepiandrosterone (DHA), androstenedione, testosterone, dihydrotestosterone (DHT), oestrone, oestradiol, cortisol and luteinizing hormone (LH) were measured in the peripheral plasma of a group of young, apparently healthy males before and after masturbation. The same steroids were also determined in a control study, in which the psychological antipation of masturbation was encouraged, but the physical act was not carried out. The plasma levels of all steroids were significantly increased after masturbation, whereas steroid levels remained unchanged in the control study. The most marked changes after masturbation were observed in pregnenolone and DHA levels. No alterations were observed in the plasma levels of LH. Both before and after masturbation plasma levels of testosterone were significantly correlated to those of DHT and oestradiol, but not to those of the other steroids studied. On the other hand, cortisol levels were significantly correlated to those of pregnenolone, DHA, androstenedione and oestrone. In the same subjects, the levels of pregnenolone, DHA, androstenedione, testosterone and DHT, androstenedione and oestrone. In the same subjects, the levels of pregnenolone, DHA, androstenedione, testosterone and DHT in seminal plasma were also estimated; they were all significantly correlated to the levels of the corresponding steroid in the systemic blood withdrawn both before and after masturbation. As a practical consequence, the results indicate that whenever both blood and semen are analysed, blood sampling must precede semen collection.

Independent control of citrate production and ornithine decarboxylase by prolactin in the lateral lobe of the rat prostate.

Prolactin stimulated the citric acid content of the lateral lobe of the prostate of androgenized-hypophysectomized rats in a time-dependent manner. This stimulation of citric acid levels was not blocked by pretreatment of the animals with the ornithine decarboxylase (ODC) inhibitor, alpha-difluoromethyl ornithine (DFMO), suggesting that the prolactin induction of citric acid in this organ is not mediated through activation of the ODC. The efficacy of the dose of inhibitor used was monitored by analysis of the diamine product of ODC, putrescine. Further evidence of an independent control of citric acid and polyamine synthesis in the lateral lobe was provided by their differing age distributions in intact animals. ODC activity decreased sharply with age, whereas the tissue concentrations of citric acid remained relatively constant. Both studies suggest that although citric acid and ODC are modulated by prolactin, their synthesis or activation are controlled independently of each other.

Prolactin selectively stimulates ornithine decarboxylase in the lateral lobe of the rat prostate.

In androgenized-hypophysectomized rats, ovine prolactin stimulated the activity of the ornithine decarboxylase (ODC) of the lateral lobes, but not the ventral and dorsal lobes of the prostate glands in a time- and dose-dependent fashion. High degrees of enzyme stimulation were associated with significant elevations in the endogenous levels of its product, putrescine. The relative response to prolactin over basal activities was relatively unaffected by indomethacin but decreased with cycloheximide, suggesting that prostaglandins do not mediate the effects of the hormone, but that a high rate of protein synthesis is a prerequisite for its expression. Indomethacin alone significantly increased the basal activity of the enzyme above control levels, suggesting that prostaglandins may normally exert a degree of inhibition on the ODC. The selective activation of the lateral lobe ODC supports previous reports of a differential response of the various prostatic lobes to prolactin, and also provides a convenient biochemical response for examining details of prolactin action on this organ.

hCG suppression of LH receptors and responsiveness of testicular tissue to hCG.

A single injection of 75 IU of human chorionic gonadotropin (hCG) into adult male rats caused a dramatic reduction in the concentration of membrane receptors for luteinizing hormone (LH) in the testis. The mean receptor level reached a nadir which was 5--10% of that in the control testes, 3 days after the injection, after which it gradually returned toward normal. This cannot be due to increased competition caused by the injected hCG since no decrease was observed at a time when the circulating levels of hCG were at a maximum (2--24 h after injection). Furthermore, at a time when receptor levels had been maximally reduced, circulating hCG was at or below the level of detection. Reduction in the number of LH binding sites in the testis was associated with a decreased responsiveness of the testicular tissue to hCG as measured by hCG-stimulated testosterone production in vitro. This inhibitory effect of large quantities of LH on its own receptor is suggested as a possible explantation for the previously observed low concentrations of LH receptor in the testis of the testicular feminized male (tfm) rat. This syndrome is characterized by high endogenous levels of plasma LH (Sherins et al., 1971).

Homologous up-regulation of the prolactin receptor in rat prostatic explants.

Exposure of explants of rat ventral prostates and a rat Leydig cell tumour to ovine prolactin for 20 h caused alterations of the subsequent membrane binding of 125I-human prolactin to an extent and in a direction dependent on the dose of hormone used. Low prolactin concentrations (1-10 micrograms/2 ml) were associated with an increase in binding (up-regulation) which was 75% in the case of the prostatic tissue and 500% in the case of the tumour tissue above control levels. Higher concentrations caused a dose-dependent decrease in binding to below control levels (down-regulation), alterations which could not be explained by receptor occupancy. Time studies with an up-regulatory dose of hormone (3 micrograms/2 ml) indicated that the effects of prolactin on its receptor did not begin to become manifest until after 6-12 h of culture. The results suggest that homologous up-regulation of prolactin binding may be a general feature of prolactin target organs and that explant cultures of prostatic tissue may provide a convenient model for exploring its mechanisms.

Prolactin desensitizes the prostaglandin E1-dependent adenylyl cyclase in the rat prostate gland.

Prior exposure of the rat ventral prostate to a high dose of ovine prolactin in vivo or in vitro caused the specific desensitization of the prostaglandin E1-dependent adenylyl cyclase. Maximal desensitization was achieved in vivo 6 h after exposure to 100 micrograms prolactin and complete resensitization occurred after 7 days. No heterologous desensitization of the response of the cyclase to other hormones tested was observed. Incubation of isolated secretory cells with prolactin and prostaglandin E1 desensitized the subsequent response to the same prostaglandin. Simultaneous exposure of the cells to indomethacin prevented the prolactin-induced effect. Prolactin could also induce similar changes in the prostaglandin E1-dependent cyclase of rat Leydig cell tumour cells in vivo, suggesting that this may represent a phenomenon shared by other prolactin target organs. This study supports the hypothesis that prostaglandins may constitute second messengers for prolactin effects on the prostate gland.

Distribution of Thyroliberin (TRH)- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-activated adenylyl cyclase in normal and neoplastic tissue with special reference to the prostate.

Tissue specificity of the Thyroliberin (TRH)- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-sensitive adenylyl cyclase has been studied using normal or neoplastic organ samples or cells from the pituitary gland, stomach, prostate, myocardium, liver and bone. It appeared that TRH stimulates the adenylyl cyclase in both normal (basal cells), hyperplastic and adenocarcinomatous prostate as well as in the pituitary and stomach. TPA also stimulated the enzyme from the prostate and other organs/cells, but to a greater extent in neoplastic tissue. Functional links from protein kinase C to adenylyl cyclase and from protein kinase C to tyrosine kinase/oncogene expression have been established. Hence it is believed that TRH, which stimulates the adenylyl cyclase and protein kinase C in the pituitary, may serve as a factor contributing to transformation of prostatic cells or enhanced cell proliferation in prostatic cancer.

Androgen stimulation of prolactin receptors in rat prostate.

Specific receptors for iodine-labelled human prolactin ([125I]hPrl) are present in membrane preparations of the rat ventral prostate. The binding is saturable with an apparent association constant (Ka) of 2.2 X 10(9) M-1 and a binding capacity of about 1 pmol/100mg prostatic tissue. The binding of [125I]hPrl is inhibited by hPrl, ovine Prl (otprl) and human growth hormone, but not by ovine FSH or LH. Serum from rats having Prl-producing pituitary tumors caused a displacement of the [125I]hPrl from the receptors, and the displacement curve was parallel with that of the hPrl standard. Treatment of immature rats with varying doses of dihydrotestosterone propionate (10-5000 microng) causes a dose-dependent stimulation of Prl receptors calculated both as binding sites per mg of membrane protein and as binding sites per prostate. Androgen stimulation of prostatic Prl receptors increases the tissue sensitivity for circulating Prl and may be one reason for the known increases in endogenous cAMP levels in prostatic tissue after androgen treatment in vivo.

Prolactin binding in rat testis: specific receptors in interstitial cells.

Specific receptors for [125I]hPrl (human prolactin) are present in membrane preparations of rat testis. The receptors are specific for lactogenic hormones (prolactin and human growth hormone) but do not bind gonadotropins. The prolactin receptors are localized exclusively in the interstitial cell tissue, and are not present in membrane preparations from isolated seminiferous tubules. The localization of prolactin receptors interstitial tissue suggests that the effect of prolactin on LH/hCG-stimulated testosterone production is due to a direct effect of prolactin of Leydig cells.

Biphasic effect of testosterone propionate on Sertoli cell secretory function.

When various doses of testosterone propionate (10 to 10,000 mug/day) were given to 21-day-old rats for 10 days a biphasic effect was seen both on testis weight and production of androgen-binding protein (ABP). At low doses (10 to 100 mug testosterone propionate/day) there was a reduction in testis weight as well as ABP content in the epididymis. At higher doses of testosterone propionate, there was a stimulation of both testicular weight and ABP production in spite of suppressed serum FSH and LH levels. These effects of testosterone propionate on Sertoli cell secretory function strongly suggest that the Sertoli cell is a target cell for androgen.

Phonological processing, not inhibitory control, differentiates ADHD and reading disability.

OBJECTIVE: To test for the distinctiveness of attention-deficit hyperactivity disorder (ADHD) and reading disability (RD) and the independence of the cognitive domains, inhibition and phonological processing, which are proposed as central to ADHD and RD, respectively, using a classic double dissociation design. METHOD: A 2 (ADHD versus no ADHD) x 2 (RD versus no RD) model was used to examine the cognitive profile of 4 groups of children, aged 7 to 11 years. Two measures of inhibitory control and 3 phonological processing measures were used. RESULTS: The 2 RD groups (RD, ADHD + RD) were significantly impaired relative to the 2 non-RD groups (controls, ADHD) on all phonological processing measures. The 2 ADHD groups were significantly impaired on simple go-task responding relative to the non-ADHD groups and in inhibition. Contrary to predictions, an RD effect on inhibitory control was found on one inhibition measure. The comorbid group (ADHD + RD) generally exhibited the deficits of both single groups in an additive fashion. CONCLUSIONS: These findings question the role of inhibitory control as a unique cognitive marker for ADHD and suggest true comorbidity for children with both ADHD and RD.

Sperm quality in men with chronic abacterial prostatovesiculitis verified by rectal ultrasonography.

Semen analyses were performed on 50 men with chronic abacterial prostatovesiculitis (CPV) and 25 asymptomatic control subjects. All subjects had had symptoms of at least three months' duration, and the diagnosis was verified by rectal ultrasonography and after microbiologic culture of seminal plasma. Fifty-eight percent had increased concentrations of leukocytes (greater than 1 x 10(6)/mL) in the ejaculate compared with 15 percent in the controls. Only 10 percent of the CPV subjects could be classified as normospermic compared with 60 percent in the controls. The incidence of severe disturbances in sperm quality and azoospermia was also four times greater in the CPV group. Neither the degree of leukospermia nor the ultrasonographic findings could predict the extent of the disturbance in sperm quality.

Determinants of satisfactory rigidity after intracavernosal injection with prostaglandin E1 in men with erectile failure.

The study examines the erectile response of intracavernosal injection with increasing doses of prostaglandin E1 (PGE) and papaverine/phentolamine (PP) in 516 men with erectile failure. The response was correlated to age, the duration of erectile failure, the quality of spontaneous erections, tobacco consumption and medicine use. In addition, the erectile response was related to penile brachial index (PBI) the free testosterone index and various hormonal parameters. Over 60% of the subjects obtained satisfactory rigidity of at least 30 min duration with 7-15 micrograms PGE. A further 15% (PGE non-responders at the doses tested) obtained rigidity with PP. The average dose necessary to achieve rigidity was 8.8 micrograms for PGE and 0.94 ml (papaverine: 15 mg/ml; phentolamine 0.5 mg/ml) for PP. The average duration of rigidity was 2.2 h and 2.3 h for PGE and PP, respectively. Tobacco consumption, the duration of erectile failure and the age of the subject did not influence the response to intracavernosal injection. Moreover the PBI, the free testosterone index or libido of the subject, did not appear to be generally important for obtaining satisfactory rigidity. In contrast, chronic medication, especially antihypertensive drugs, was associated with significantly higher numbers of poor responders, a shorter duration of erection in the responders and higher doses of PGE necessary to achieve a satisfactory response. The combination of increasing age and antihypertensive medication was predictive for a poor intracavernosal response. In general, a reduced incidence of morning erections was predictive of a weaker response to PGE. The proportion of men with a PBI lower than 0.75 increased with age. These subjects more often took chronic medication, had a lower frequency of morning erections and exhibited a significantly weaker reaction to PGE than subjects with higher PBI. In summary, a large number of men with erectile failure can obtain satisfactory rigidity with intracavernosal injection. In men taking antihypertensive medication, especially in higher age groups, the dose of the intracavernosal medication had to be increased. A reduced sensitivity to intracavernosal medication could be predicted from a lower PBI and a reduced frequency of spontaneous erections.

Intracavernosal therapy for erectile failure--impact of treatment and reasons for drop-out and dissatisfaction.

OBJECTIVES: To examine the impact of intracavernosal therapy on libido, ejaculatory control, quality of life and treatment dependency in men with erectile failure. Furthermore to assess the drop-out rate and reasons for dissatisfaction with the technique. SUBJECTS AND METHODS: Questionnaires were sent to 1116 subjects with erectile failure who had previously elected to use intracavernosal therapy in the period 1995-1997. RESULTS: The response rate was 72.5%. The majority of erections lasted 30-60 min, 10-20% of the erections were considered unsatisfactory for intercourse and 15% of subjects reported erections lasting longer than 5 h on at least 10% of the occasions. Bleeding at the injection site occurred in 60% on at least 10% of the occasions and various degrees of deformation of the penis shaft were reported by 10%. The latter was related to the age of the subject and not the type of medication employed. Forty percent experienced at least partially improved control over ejaculation and almost 50% experienced some degree of increase in libido. One quarter retained penile rigidity after ejaculation but this was age-dependent. In those satisfied with intracavernosal treatment, 80% admitted that it had improved the quality of their lives. Sixty percent did not feel that their dependency on intracavernosal treatment had lessened during the treatment period. Approximately 40% of subjects admitted to dropping out of the programme, the majority within the first six months. The age of the subject did not influence the decision and the type of medication or the mode of injection had only a minor impact on drop-out rate. Of those currently using IC therapy, 87% were either fully or partly satisfied with this form of treatment. The corresponding figure for those discontinuing treatment was 58%. Dissatisfaction was higher in the younger age groups and could not be clearly related to the mode of injection. The major reasons for drop out or dissatisfaction were inadequate penile rigidity, the expense of the treatment, penile discomfort and the lack of spontaneity it necessitated. Penile discomfort was more associated with younger age groups, whilst an inadequate response to medication was more often experienced by men over 60 y. Deformation of the penile shaft was observed in 5% of those dissatisfied with IC therapy and was four times more often reported by those over 70 compared to subjects younger than 40 y. In 6% of cases, a return of spontaneous erections was given as reason for drop-out. This was more often associated with younger subjects. In 16% of the subjects, the partner had expressed dissatisfaction with the technique primarily because of inadequate rigidity, lack of spontaneity or the complicated nature of the treatment. CONCLUSIONS: Intracavernosal treatment for erection failure is associated with side-effects such as penile fibrosis and bleeding at the injection site but has advantages including increased libido, an increase in the quality of life and ejaculatory control. Only a small proportion of men reduce their dependency on the technique with time. The therapy has a relatively high attrition rate. In many cases, the reasons for subject and partner dissatisfaction are potentially correctable e.g. by altering the medication used, by the use of injector devices or by obtaining financial support for IC medication from medical welfare.

Use of particle filters for increased practicability in sperm processing: application to the indirect immunobead test.

The use of sterile particle filters is described for the washing and incubation of living sperm before the indirect IBT. The filters greatly simplify the technique, shorten its duration, and remove all centrifugation steps that have potentially detrimental effects on the sperm. The same filters have a variety of applications and can be used whenever sperm have to be washed or incubated before biochemical tests including acrosome binding studies and flow cytometry.