Substance use and misuse among children and youth with mental illness : A pilot study.

OBJECTIVE: The aim of this study was to examine prevalence, patterns and predictors of substance use among a sample of adolescent psychiatric inpatients. METHODS: Participants included 25 minors aged 12-17 years admitted to an Austrian department of child and adolescent psychiatry. Lifetime use, initiation, frequency and quantity of substance use, sociodemographic, family and school-related data were collected by self-report measures. Substance use disorders were detected using CAGE (a screening instrument for problem drinking) and FTND (Fagerström Test For Nicotine Dependence). Clinical characteristics were extracted from medical records. RESULTS: Lifetime prevalence of any substance use (76%) and regular use (32%) were common. Prevalence was high for alcohol (76%), nicotine (44%) and illicit drug use (36%). Older age was associated with tobacco (p = 0.023), drug (p = 0.021) and cannabis use (p = 0.015) and regular use of psychotropic substances (p = 0.027). Family dysfunction predicted regular (p = 0.035) and cannabis use (p = 0.02). History of trauma prognosticated regular (p = 0.047) and tobacco use (p = 0.011). Use of any substance (p < 0.001) as well as regular use (p = 0.026) were significantly associated with peer substance use. Consuming adolescents were more likely to show academic failure, school absenteeism and behavioral problems. Alcohol (p = 0.02), drug (p = 0.017) and regular substance use (p = 0.007) were linked to suicidal ideation. A remarkable relationship between affective as well as externalizing disorders and alcohol, nicotine and drug use was found. CONCLUSIONS: Substance use is highly prevalent among youth with mental illnesses and associated with psychosocial consequences. These data highlight the need to carefully explore this population at high risk.

The connection of temperament with ADHD occurrence and persistence into adulthood - An investigation in 18 year old males.

BACKGROUND: This study intended to determine whether certain traits of temperament are associated with former and current ADHD symptomatology in a non-clinical sample of 18 year old males. METHODS: We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a socio-demographic questionnaire, screening for substance abuse, temperament (TEMPS-M), past (WURS) and current (ADHD symptom checklist) ADHD symptomatology. RESULTS: We found a correlation of cyclothymic (p<.001), irritable (p<.001) and anxious (p<.05) temperament with occurrence and severity of past and present ADHD symptomatology. No significant correlation has been detected for hyperthymic and depressive temperament. Judged retrospectively, ADHD symptoms were strongly consistent over time. LIMITATIONS: The sample consists of men only. These had to be fit enough to be enlisted for military service; men with severe mental or physical disorders were thus excluded. Furthermore, the cross-sectional study design does not allow making conclusions about the temporal relationships between ADHD symptoms and substance misuse. CONCLUSIONS: These results indicate that a temperament based approach towards those affected by ADHD might be useful. Subtyping ADHD by integrating temperament profiles in diagnosis and treatment of the disorder could help explain some of the heterogeneity of the disease.

Suicidal ideation and temperament: an investigation among college students.

BACKGROUND: Suicide is a major health problem accounting for up to 1.5 percent of all deaths worldwide and represents one of the most common causes of death in adolescents and young adults. A number of studies has been performed to establish risk factors for suicide in patients with psychiatric disorders including temperamental features. This study set out to assess the relationship between suicidal ideation and temperament in young adults. METHODS: A cross-sectional sample of healthy college students (n=1381) was examined using a self-rating questionnaire. Suicidal ideation, social background, educational status, substance abuse, and affective temperament according to TEMPS-M were assessed. Predictors of lifetime suicidal ideation were examined in multivariate logistic regression analyses. RESULTS: Suicidal ideation was reported by 12.5% of all subjects at some point in their life and was higher in nicotine dependents, youth with alcohol related problems and users of illicit substances as well as in youth with lower educational status. Lifetime suicidal ideation was associated with the anxious, depressive and cyclothymic temperament in both sexes and the irritable temperament in males. These results remained significant after adjustment for smoking status, frequency of alcohol consumption, drug experience and educational status in a multivariate logistic regression analysis. LIMITATIONS: The use of self-rating instruments always reduces objectivity and introduces the possibility of misreporting. CONCLUSIONS: Considering the fact that many subjects completing suicide have never been diagnosed with mental disorders it might be reasonable to include an investigation of temperament in screenings for risk of suicide. This might be especially useful for health care professionals without mental health care background.

[The advantage of a specialized HPV clinic within the department of proctology]. / Intérêt d'une consultation HPV spécialisée dans le cadre d'une unité de proctologie.

The "Human Papilloma Virus" (HPV) is the cause of carcinoma of the cervix. With 275000 deaths per year worldwide, this virus is the direct cause of the most common carcinoma in women. If these figures demonstrate that it is a true scourge, then the fact is that routine screening for the precancerous lesion linked to HPV infection has managed to significantly lower the mortality rate in countries where this has been introduced. The frequency of the anal carcinoma has grown in recent years, particularly in HIV+ patients participating in anal sex. Systematic screening and early vaccination should be able to stem this worrying development in the same way that screening for carcinoma of the cervix has in women.

Accuracy of measurement of puborectal contraction by perineal ultrasound in patients with faecal incontinence.

AIM: The study aimed to determine the accuracy of measurement of puborectal contraction, measured by perineal ultrasound during anal voluntary contraction in patients with incontinence. METHOD: Puborectalis sling contraction in 32 consecutive patients investigated for faecal incontinence was determined by two examiners on two occasions (four measurements per patient). The examiners were blinded to each other's results. RESULTS: The mean anterior movement of the puborectalis sling was between 11 and 12 mm for both examiners on both occasions. The global intraclass correlation coefficient for examiners and occasions together was 0.92. The absolute agreement on the movement exceeding or not 8 mm was 87.5% (28 of 32), and the corresponding κ statistic was 0.84. The differences between the two experts were minimal. CONCLUSION: The study confirms the reliability of puborectalis sling contraction measurement and its value as a preoperative predictive tool to assess the prognosis of sphincter repair for postdelivery faecal incontinence.

Risk factors for mortality-morbidity after emergency-urgent colorectal surgery.

BACKGROUND: The aim of this study was to assess the risk factors associated with mortality and morbidity following emergency or urgent colorectal surgery. MATERIALS AND METHODS: All data regarding the 462 patients who underwent emergency colonic resection in our institution between November 2002 and December 2007 were prospectively entered into a computerized database. RESULTS: The median age of patients was 73 (range 17-98) years. The most common indications for surgery were: 171 adenocarcinomas (37%), 129 complicated diverticulitis (28%), and 35 colonic ischemia (7.5%). Overall mortality and morbidity rates were 14% and 36%, respectively. In multivariate analysis, the only parameter significantly associated with postoperative mortality was blood loss >500 cm(3) (odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.63-6.82, p = 0.001). There were three parameters which correlated with postoperative morbidity: ASA score > or =3 (OR = 2.9, 95% CI 1.9-4.5, p < 0.001), colonic ischemia (OR = 3.4, 95% CI 1.4-7.7, p = 0.006), and stoma creation (OR = 2.2, 95% CI 1.4-3.4, p = 0.0003). CONCLUSIONS: The main risk factors for postoperative morbidity and mortality following emergency colorectal surgery are related to: (1) patients' ASA score, (2) colonic ischemia, and (3) perioperative bleeding. These variables should be considered in the elaboration of future scoring systems to predict outcome of emergency colorectal surgery.

Comparison of the pituitary effects of the mammalian endothelins: vasoactive intestinal contractor (endothelin-beta, rat endothelin-2) is a potent inhibitor of prolactin secretion.

Direct pituitary effects of vasoactive intestinal contractor (VIC), which has been described recently to be the rat form of endothelin-2 (ET-2), were compared to those previously reported for rat ET-1, rat ET-3, and human ET-2. In static incubations of cultured dispersed anterior pituitary cells, the minimum effective dose of VIC necessary to inhibit PRL release after 1-h incubation was 1 pM, and the maximum effective dose was 1 nM. Similar inhibition was observed with human ET-2. The minimum effective inhibitory dose of ET-1 was also 1 pM; however, that of ET-3 was 0.1 nM. PRL release inhibition by VIC was not mediated via the D2-dopamine receptor and was not prevented by calcium channel blockade with 100 nM nifedipine. The inhibitory effect of VIC was not present in cells treated with 100 nM staurosporine, a dose that inhibits protein kinase-C activity. Time-course studies revealed a transient stimulation of PRL release with higher doses of VIC (10 and 100 nM), which occurred within the first 15 min of incubation and was unaffected by calcium channel blockade or inhibition of protein kinase-C activity. No stimulation of PRL release was observed with doses of VIC lower than 10 nM. Instead, we observed the maintenance of the inhibitory effect for 4 h of incubation. GH release was not significantly affected by doses of VIC ranging from 10(-13)-10(-7) M; however, the release of LH was slightly, yet significantly, stimulated by 10 and 100 nM VIC. This release was prevented by pretreatment with nifedipine, but unaffected by protein kinase-C inactivation. A physiological role for VIC (rat ET-2) in the control of lactotroph function is suggested by its effectiveness at picomolar doses and its long-lasting action.

Central peptidergic mechanisms controlling reproductive hormone secretion: novel methodology reveals a role for the natriuretic peptides.

A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment.

A prolactin release inhibiting activity isolated from neurointermediate lobe extracts is an endothelin-like peptide.

A prolactin release-inhibiting factor has been reported in extracts of rat and bovine neurointermediate lobes of the pituitary gland. This material when isolated by Sephadex G-25 chromatography or by C-8 high pressure liquid chromatography coelutes with synthetic forms of all members of the mammalian endothelin family of peptides and with their immediate precursors, big-ET-1 and big-ET-3. The endogenous material crossreacts in an endothelin radioimmunoassay. Immunohistochemical analysis of endothelin-like immunoreactivity in the neurointermediate lobe revealed a predominantly intermediate lobe localization. Individual immunopositive cells were visualized in the intermediate lobe. Preabsorption of chromatographically isolated prolactin release-inhibiting activity with an endothelin antiserum which recognizes all members of the ET family of peptides abolishes its in vitro bioactivity. These results suggest that a prolactin release-inhibiting activity present in the neurointermediate lobe is endothelin or an endothelin-like peptide.

Hypothalamic effects of C-type natriuretic Peptide on luteinizing hormone secretion.

Previous studies have demonstrated hypothalamic sites of action of A-type natriuretic peptide (ANP) in the inhibition of luteinizing hormone (LH) secretion, acting at least in part, via an opiatergic mechanism. C-type natriuretic peptide (CNP) was identified recently and is thought to be the predominant brain form of the family of natriuretic peptides. Third cerebroventricular injection of CNP in doses of either 0.1, 1.0 or 2.0 nmole significantly inhibited, in a dose-related fashion, plasma LH levels when compared to levels present in saline-injected controls. When compared to the LH-inhibiting action of ANP, CNP appeared more potent (effective at lower doses) and efficacious (longer duration of action for the maximum effective doses). The LH-inhibiting effect of CNP was blocked by prior treatment with the δ-opioid receptor antagonist naltrindole (50 µg), suggesting an enkephalinergic mechanism of action. CNP in log doses ranging from 0.01 to 1,000 nM did not significantly alter LH release from dispersed pituitary cells harvested from random cycle female rats, either under static or dynamic (perifusion) incubation conditions. These results indicate that CNP, like ANP, acts at the hypothalamic level to alter LH secretion and suggest that CNP may be the preferential neuroactive members of this family of peptides.

C-type natriuretic Peptide stimulates prolactin secretion by a hypothalamic site of action.

The most recently discovered member of the family of natriuretic peptides, C-type natriuretic peptide (CNP), exerts many pharmacologic actions similar to its structural homolog A-type natriuretic peptide (ANP). Like ANP it failed to significantly alter prolactin release from dispersed, rat anterior pituitary cells incubated under static or dynamic conditions. Unlike ANP, however, which inhibits prolactin secretion in vivo by a hypothalamic action, CNP injection into the third cerebroventricle significantly stimulated prolactin secretion in ovariectomized, conscious rats. The effect was highly significant 15 min after injection and transient, lasting 30 min in animals injected with 2 nmole CNP. In a companion group of rats, significant inhibition of plasma prolactin levels was observed after central administration of similar doses of ANP. These results suggest differing hypothalamic actions of the CNP and ANP perhaps mediated by multiple natriuretic peptide receptors present in the tissue. Further, they provide additional support for unique roles exerted within the central nervous system by these structural homologs.

CNP-22 stimulates, rather than inhibits, water drinking in the rat: evidence for a unique biological action of the C-type natriuretic peptides.

C-type natriuretic peptide (CNP) shares structural homology with A-type natriuretic peptide (ANP). Unlike ANP, which inhibits experimentally induced water drinking, CNP stimulates intake under similar conditions. The action of CNP to stimulate water drinking is not due to competition with ANP for the clearance receptor which recognizes both peptides since the ligand specific for that binding site, C-ANF 4-23, like ANP, inhibits water drinking under the same conditions.

Possible neuroendocrine actions of endothelin-3.

The presence of endothelin (ET) immunoreactivity and binding sites in hypothalamus and pituitary gland suggests potential neuroendocrine actions of this family of vasoactive peptides. ET-3, the predominant member of the ET family in brain, exerted significant dose-related (1, 10, and 100 nM) inhibitory effects on PRL release from dispersed anterior pituitary cells in static incubations. The effect was not dependent on voltage-sensitive calcium channels, since the dihydropyridine calcium channel antagonist nifedipine failed to block this action. Nifedipine did, however, significantly reduce the transient acute stimulatory effect of ET-3 on PRL release in cultured cells incubated in dynamic perifusion. The longer lasting inhibitory effect on PRL release that followed the brief stimulatory action was not affected by nifedipine. ET-3 also stimulated a transient but significant release of LH from cells harvested from random cycle female rats, an effect that was not antagonized by a LHRH antagonist, but was blocked by nifedipine, suggesting the mobilization of extracellular calcium as a mechanism of action of ET-3. Nifedipine also reversed the acute stimulatory effect of ET-3 on GH secretion from these cells. Cerebroventricular injections of ET-3 (6 or 60 ng) failed to significantly alter PRL or LH secretion in conscious rats, suggesting that brain-derived ET does not act within the hypothalamus to alter the release of these two hormones. Similarly, iv infusion of even pressor doses of ET-3 (10, 30, or 300 ng) failed to significantly alter PRL, LH, or GH release; thus, it is unlikely that ET of peripheral origin acts within the gland. Our results suggest that locally produced ET may act as a neuroendocrine or paracrine factor controlling pituitary function in the rat.

Central nervous system action of endothelin-3 to inhibit water drinking in the rat.

Endothelin-3, a vasoconstrictor peptide produced not only in endothelial cells but also within the brain interstitium in magnocellular neurons of the hypothalamo-neurohypophysial system, exerted significant, dose-related, inhibitory effects on water intake when administered into the third cerebroventricle of rats exposed to exogenous and endogenous stimuli for drinking. Passive immunoneutralization of endogenous endothelin-3 accentuated water drinking in response to angiotensin II administration suggesting a physiological role for the peptide in the central control of fluid and electrolyte homeostasis.

Hypothalamic endothelin: presence and effects related to fluid and electrolyte homeostasis.

Endothelin-3-like immunoreactivity (ET-3-ir) was detected in extracts of rat hypothalamic median eminence, and in the anterior and neurointermediate lobes of the pituitary at levels (ng ET-3/mg protein) exceeding those present in extracts of abdominal aorta. This ET-3-ir appeared authentic because radioimmunoassay (RIA) dose-response curves parallel to those of synthetic ET-3 could be constructed and this ET-3-ir comigrated on C-8 high-pressure liquid chromatography (HPLC) with synthetic ET-3. Endothelin-1-like immunoreactivity, on the other hand, was abundant in extracts of abdominal aorta and cerebral cortex and only minimally present in hypothalamus and anterior pituitary gland. Central administration of 11 and 23 pmol ET-3 resulted in significant (4.2- and 5.7-fold, respectively) elevations of plasma levels of vasopressin. Oxytocin levels were transiently, yet significantly, elevated (1.8-fold) by the higher dose of ET-3. These results, and our findings that central administration of ET-3 inhibits stimulated water drinking, suggest a physiologically important role for endogenously produced endothelin in the central mechanisms regulating fluid and electrolyte homeostasis.

Pituitary site of action of endothelin: selective inhibition of prolactin release in vitro.

Endothelin-3 (ET-3) inhibited in a dose-dependent, significant fashion prolactin release from cultured anterior pituitary cells (ovariectomized female and intact male rat donors, ED50 = 5 X 10(-9) M). ET-3 in log doses ranging from 10(-11) to 10(-6) M did not alter significantly the release of luteinizing hormone, growth hormone or thyroid stimulating hormone. The inhibitory effect of ET-3 (rat, human) was specific for that molecule since ET-1 (porcine, human) was ineffective and was not due to an action on the dopamine receptor since the inhibitory action was still expressed in the presence of 100 nM domperidone. These data further suggest a role for neuropeptides of the posterior lobe in the control of lactotroph function.