Time-dependent in-vivo effects of interleukin-2 on neurotransmitters in various cortices: relationships with depressive-related and anxiety-like behaviour.

We investigated the impact of systemically injected IL-2 (2.5 µg/kg, i.p.) on serotonergic and dopaminergic neurotransmission in various cortical areas by in-vivo microdialysis. IL-2 lastingly reduced extracellular 5-HT levels in the medial prefrontal (-75%), occipital (-70%), and temporal cortices (-45%), whereas dopamine was only moderately reduced in the medial prefrontal cortex. Based on the serotonergic time profile, we conducted further experiments to test for acute and delayed (2 h post injection) depressive-related effects of systemic IL-2 (0-5.0 µg/kg) in a forced swim test and delayed effects on anxiety-like behaviour in the elevated plus-maze. IL-2 had dose-dependent effects on depressive-related behaviour after delayed but not acute testing, but no effects on anxiety-like behaviour.

Individual behavioral differences in recovery from abdominal sepsis in rats.

OBJECTIVE AND DESIGN: In the present study we determined whether individual behavioral differences (high and low locomotor activity) differentially affected recovery from sepsis with high or low mortality. METHODS: Two trials were performed. Trial 1 with high mortality: Rats were randomly assigned to (1) control-A: anesthesia, (2) control-B: sham surgery, (3) sepsis: laparotomy and peritoneal contamination and infection (PCI) with human stool bacteria, (4) sepsis with antibiotic prophylaxis (cefuroxime/ metronidazole), and (5) sepsis with antibiotic plus G-CSF prophylaxis. Trial 2 with low mortality: Comparison of groups 3 and 5. Endpoints were mortality, behavior (open field and social interaction tests), and proinflammatory cytokines (interleukin-6 = IL-6 and macrophage inflammatory protein-2 = MIP-2). RESULTS: The combination of antibiotics plus G-CSF was most effective in reducing mortality in both trials and modified sickness behavior. Behavioral deficits were not statistically significantly improved by G-CSF. However, high versus low responders were differentially affected in both behavioral tests. Furthermore, IL-6 and MIP-2 were increased 24 hours after inoculum only in high responders with untreated sepsis and high mortality. CONCLUSION: Improvement of sickness behavior in sepsis with G-CSF/antibiotic prophylaxis is a promising approach. The course of recovery from sepsis may depend on premorbid individual differences.

Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials.

BACKGROUND AND AIM: In clinical sepsis research nearly all immune-modulators have demonstrated no benefit in regard to the 28-day mortality rate. Other endpoints such as quality of life have become more attractive, but clinically relevant animal models analyzing an equivalent to quality of life by measurement of sickness behavior are extremely rare. The concept of clinic modeling randomized trials was used in an animal trial to model clinical complexity and conditions of a randomized clinical trial. METHODS: 80 adult male Wistar rats were randomly assigned to (1) control: anesthesia and sham operation, (2) sepsis: laparotomy and peritoneal infection with human stool bacteria, (3) sepsis with antibiotic prophylaxis: cefuroxime/metronidazole and (4) sepsis with antibiotic plus a cytokine prophylaxis with granulocyte-colony stimulating factor (GCSF). Endpoints were physiological and behavioral parameters. RESULTS: The combination of antibiotics plus G-CSF was most effective in reducing mortality. All infected animals showed reduced open field activity acutely after infection, and recovery was improved during the 9 day follow-up in rats with prophylactic treatments. In the social interaction test, but not in the elevated plus-maze anxiety test, prophylaxis was also efficient, especially with antibiotics and G-CSF. CONCLUSIONS: The results show that improving sickness behavior in septic rats with G-CSF plus antibiotics may be a promising approach.

Adrenaline-induced immunological changes are altered in patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether in rheumatoid arthritis (RA) patients the immunological changes induced by adrenaline are different from healthy controls (HC). METHODS: Fifteen female RA patients and 14 HC were infused with 1 micro g/kg adrenaline over 20 min. Blood was drawn before, immediately after, and 1 h after the end of infusion. Lymphocyte subpopulations, cytokine production and natural killer cell cytotoxicity were determined. RESULTS: Subjects exhibited mild cardiovascular changes with no differences between patients and controls. CD16(+)CD56(+)CD3(-) NK cells increased by a factor of 5.7, CD3(+) T cells by 1.5, monocytes by 1.6 and PMN by 1.2 in both groups. The numbers of IL-8- and IL-10-producing monocytes were higher in patients and presented a larger increase after infusion. NK cytotoxic activity was higher in RA patients and increased after infusion in both groups. Activated monocytes and T cells were preferentially recruited in patients and controls. Values returned to baseline 1 h later. CONCLUSION: We describe an altered response to adrenaline in patients with RA with both pro- and anti-inflammatory effects. Additionally, activated T cells and monocytes recruited to the peripheral blood may influence disease activity.

Systemic lupus erythematosus and rheumatoid arthritis patients differ from healthy controls in their cytokine pattern after stress exposure.

OBJECTIVE: To study whether patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) differ from healthy individuals in their immune responses to acute psychological stress. METHODS: The phenotype and function of peripheral blood lymphocytes were analysed before and after stress exposure in patients and healthy subjects. RESULTS: Natural killer (NK) cell numbers increased transiently in all groups under stress. NK activity, however, increased in healthy controls only. We observed a stress-induced increase in interleukin (IL)-4-producing (IL-4(+)) cells in SLE patients only, whereas interferon (IFN) gamma(+) cell numbers increased due to stress in all three groups. An analysis of supernatants from phytohaemagglutinin (PHA) cultures revealed increased IFN gamma and IL-10 levels in healthy subjects but not in SLE or RA patients after stress exposure. CONCLUSIONS: These data demonstrate that RA and SLE patients differ in their immune response to stress from healthy controls. Changes in cytokine patterns might be responsible for stress-induced exacerbation of disease activity in RA and SLE patients.

[Prevention of risky behaviors in adolescence]. / Prévention des conduites à risque à l'adolescence.

A workshop of the French speaking meeting of practical paediatrics was dedicated to the prevention of risk behaviour among adolescents. Concrete and every day issues were discussed through risk taking during the transitional stages of adolescence. Parents and adolescence demand and health needs were debated, such as the absence of demand and expressed needs from the adolescent him/herself. Evaluation of the at risk situation was clarified.

Casino gambling increases heart rate and salivary cortisol in regular gamblers.

BACKGROUND: Although the effects of gambling on cardiovascular parameters have been documented, no data exists describing the effect of gambling on stress hormone secretion. Our study investigated the effect of gambling on heart rate and salivary cortisol in a casino environment. METHODS: Ten male gamblers participated in both an experimental and control session. In the experimental session, gamblers played a game of blackjack using their own money. Gamblers played cards in the same setting during the control condition; however, the game was played for accumulation of points rather than money. Heart rate and endocrine parameters were recorded at baseline, 30 min, and 60 min following commencement of each session, and again at completion of the game. RESULTS: Heart rate increased significantly from baseline to 30 min in the experimental session and remained elevated for the remainder of the recording period. Salivary cortisol was raised at 30 min and further elevated at 60 min during gambling, then returned to control levels following completion of the game. CONCLUSIONS: These data indicate that gambling in a "real life" situation produces increases in salivary cortisol levels that accompany increased cardiovascular activity. Such effects may contribute to the development of gambling addiction.

High rate of GB virus type C/HGV transmission from mother to infant: possible implications for the prevalence of infection in blood donors.

BACKGROUND: Because GB virus type C(GBV-C)/HGV (GBV-C/HGV) is blood-borne and sexually transmitted, persons at risk of infection with such viruses have a high prevalence of GBV-C/HGV markers. However, adults with no apparent risk factors, such as blood donors, frequently are positive for GBV-C/HGV markers. Mother-to-infant transmission could explain this high prevalence, but it has been studied only through small series of GBV-C/HGV-infected mothers co-infected with HCV or HIV. STUDY DESIGN AND METHODS: To determine the rate of mother-to-infant transmission of GBV-C/HGV RNA in women who are HCV- or HIV-negative, a prospective study was performed in a cohort of 288 mothers screened for viral RNA and in the infants born to GBV-C/HGV-infected mothers. RESULTS: Thirteen mothers (4.5%) were found positive for GBV-C/HGV RNA. Of the infants in whom at least one blood sample was collected between the third and the ninth months of life, 89 percent were positive for viral RNA. The majority of these newborns were negative for GBV-C/HGV RNA at birth and positive after the third month. The viral RNA titers of infants born to GBV-C/HGV-infected mothers appeared as elevated as those of their mothers. All the GBV-C/HGV-infected infants remained positive for viral RNA during the entire study period. No clinical events possibly linked to a primary GBV-C/HGV infection were reported in infants. Serum ALT level and blood count remained within normal values throughout the follow-up of all GBV-C/HGV-infected infants. CONCLUSION: The frequency of mother-to-infant GBV-C/HGV transmission is elevated and could explain the high prevalence of GBV-C/HGV markers (viral RNA and E2 antibody) in adults at low risk for blood-borne or sexually transmitted viruses, such as blood donors.

Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress.

Clinical observations suggest that psychological stress induces exacerbation of disease activity in patients with systemic lupus erythematosus (SLE). In order to determine whether SLE patients differ from healthy controls in their stress response, we analyzed heart rate, blood pressure, catecholamine concentration, lymphocyte subpopulations, natural killer (NK) cell activity, and expression of beta-adrenoceptors on PBMC before, immediately after, and 1 h after a public speaking task in 15 SLE patients and 15 healthy subjects. Both groups demonstrated similar psychological, cardiovascular, and neuroendocrine responses to acute stress. However, natural killer (CD16(+)/CD56(+)) cell numbers transiently increased after stress exposure, with significantly less pronounced changes in SLE patients. In addition, NK activity increased in healthy controls (n = 8) but not in SLE patients (n = 4) after acute stress. Furthermore, the number of beta(2)-adrenoceptors on PBMC significantly increased only in healthy subjects (n = 8) after stress but not in SLE patients (n = 7). These data indicate that SLE patients differ from healthy controls in stress-induced immune responses.

Anxiety disorders, comorbidity, and suicide attempts in adolescence: a preliminary investigation.

The prevalence of anxiety disorders and associated DSM-III-R diagnoses were measured in a sample of 80 female adolescents aged between 15 to 20 years consulting an outpatient psychiatric service for adolescents. The suicide attempt group (SA) included 40 patients evaluated within 24 h after attempted suicide. This is compared to 40 consecutive patients consulting the same center but without any history of suicide attempt (the no attempt group, NA). The global prevalence of anxiety disorders was similar in both groups (SA: 65% vs. NA: 60%, NS) as was the relative importance of the different disorders in each group, generalized anxiety being the most frequent specific anxiety disorder. The most striking difference between the two groups was in the prevalence of affective disorders in 90% (SA) vs. 32.5% (NA) (P < 0.001), leading to high rates of comorbidity on axis I in the SA group. Of the 24 patients with anxiety disorders who attempted suicide, 21 (95%) fulfilled criteria for associated major depression, compared to five out of 21 (24%) patients with anxiety disorders who had not attempted suicide. Adolescents with anxiety disorders developing major depression are at a high risk for suicide. The depression may be of short duration (less than two weeks) when compared to that of the anxiety disorder (greater than six months). To improve suicide prevention, our findings if confirmed should encourage clinicians to perform a close follow-up of adolescents with anxiety disorders for an early detection of sudden depressive breakdowns.

Typology and correlates of sexual abuse in children and youth: multivariate analyses in a prevalence study in Geneva.

OBJECTIVE: Child sexual abuse (CSA) encompasses a variety of distinct situations, which should be differentiated. There is a need for a working classification, taking into account various parameters. METHODS: The Geneva CSA prevalence study was based on 1116 randomly selected adolescents aged 14 to 16. Secondary analyses of the 252 reported cases of abuse was carried out using a multivariate approach combining multiple correspondence analysis and automatic classification, leading to descriptive analyses and to a new classification of CSA. RESULTS: Global prevalence of CSA, using a broad definition, was 10.9% for boys, and 33.8% for girls. Classification of cases of abuse differentiated 5 classes: (A) exhibitionism or other abuse without contact, by an adult (proportion of cases in boys: 22%; girls: 32%); (B) abuse of an adolescent boy by a peer without contact (62%); (C) abuse of an adolescent girl by a peer with physical contact (38%); (D) abuse inside the family, repeated (boys: 10%, girls: 16%); (E) child abuse with genital penetration, lasting 2 years or more (boys: 7%; girls: 14%). CONCLUSIONS: CSA is a complex and heterogeneous problem. Reported abuse situations can be classified into five classes, with different degrees of severity, causes, and consequences. Classification is essential in clinical research as well as in the design and conception of prevention programs.

Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis.

Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated with increased sensitivity to beta2-adrenergic activation.

Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men.

Data regarding the neuroendocrine response pattern to sexual arousal and orgasm in man are inconsistent. In this study, ten healthy male volunteers were continuously monitored for their cardiovascular and neuroendocrine response to sexual arousal and orgasm. Blood was continuously drawn before, during and after masturbation-induced orgasm and analyzed for plasma concentrations of adrenaline, noradrenaline, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, growth hormone (GH), beta-endorphin and testosterone. Orgasm induced transient increases in heart rate, blood pressure and noradrenaline plasma levels. Prolactin plasma levels increased during orgasm and remained elevated 30 min after orgasm. In contrast, none of the other endocrine variables were significantly affected by sexual arousal and orgasm.

Prevalence of child sexual abuse among adolescents in Geneva: results of a cross sectional survey.

OBJECTIVE: To measure the cumulative prevalence of child sexual abuse in a representative sample of the adolescent population of Geneva. DESIGN: Cross sectional survey with an anonymous self administered questionnaire centred on a factual description of sexual activities. SETTING: 68 classes (17 schools) randomly selected from the 201 ninth grade classes of the public school system in Geneva. SUBJECTS: 1193 adolescents aged 13-17 years, of whom 1116 (93.5%; 568 girls, 548 boys) consented to the study and returned completed questionnaires. RESULTS: 192 (33.8%) girls and 60 (10.9%) boys reported having experienced at least one sexually abusive event. The prevalence of abuse involving physical contact was 20.4% (116 cases) among girls and 3.3% (18) among boys. The prevalence of abuse involving some form of penetration was 5.6% (32 cases) among girls and 1.1% (six) among boys. One third of the abused adolescents had experienced more than one abusive event and 46.5% (92/198) had experienced the first event before age 12. Abuse by a family member was reported by 20.5% (36/176) of abused girls and 6.3% (3/48) of abused boys. Abusers were known to victims in two thirds of cases. Ninety per cent of abusers were male and 35.3% (71/201) came from the victim's peer group. Over 80% of participants found the questionnaire interesting, clearly formulated, and useful. CONCLUSIONS: Child sexual abuse is a universal social phenomenon. Adolescents themselves can contribute to research and so help in the search for more efficient prevention and intervention strategies.

[Clinical evaluation of two immunoassay methods for the rapid detection of chlamydia trachomatis: antigen in endocervical specimens from high risk female patients.].

Two rapid immunoassay methods, QuickVue-Chlamydia (Quidel Corp., San Diego California) and Kodak Surecell (Kodak Corp. Rochester, N.Y.) were evaluated for the detection of Chlamydia trachomatis antigen in endocervical swabs from high risk females attending a sexually transmitted disease clinic. The results were compared to McCoy cell culture and a polymerase chain reaction assay (Amplicor(R)-PCR, Roche Molecular Systems). Of the 240 females enrolled in the study 45 were considered infected (18.8%). Sensitivity, specificity, predictive value of a positive (PVP) and predictive value of a negative (PVN) of the QuickVue-Chlamydia assay were 96%, 99%, 96% and 99% respectively. Sensitivity, specificity, PVP and PVN of the Surecell assay were 96%, 100%, 100% and 99% respectively. The performance of the two immunoassay methods was similar, the sensitivity was the same and the specificity of the Kodak Surecell was slightly better than that of the QuickVue. On the other hand, the QuickWVL-Chlamydia assay was considerably simpler to perform (fewer steps) than the Kodak Surecell assay and took significantly less of technologists time.

Characterization and physiological variation in prostaglandin, prostacyclin and thromboxane synthesis by corpora lutea, non-luteal and uterine tissues during pseudopregnancy in the rabbit.

To determine if luteal as well as uterine prostaglandin production is associated with luteal regression, the conversion of (14C) arachidonic acid into prostaglandin (PG) F2 alpha, PGE2, PGD2, prostacyclin (measured as its stable metabolite 6-keto-PGF1 alpha) and thromboxane (measured as its stable metabolite TXB2) was characterized and measured in microsomes from the uterus, corpora lutea and nonluteal tissue of the rabbit on days 8, 12 and 15 of pseudopregnancy. PGF2 alpha production was increased on day 15 compared to days 8 or 12 of pseudopregnancy in corpora lutea and in the uterus. In uterine microsomes, 6-keto-PGF1 alpha production was also elevated on day 15. No significant changes in the production of PGF2 alpha, TXB2 or PGD2 were observed with uterine or luteal microsomes. Arachidonic acid metabolism by microsomes from nonluteal tissue was not significantly different on any day examined. These results suggest that intraluteal, as well as uterine PGF2 alpha production may contribute physiologically to the final phase of luteal regression.

Usefulness of digital subtraction angiography for diagnosis of renal tumours.

DSA (digital subtraction angiography) is a new, highly effective method for visualization of kidney vascular system. By means of a digital subtraction angiography unit the image of bones and soft tissues is blotted out, and a subtractive picture of contrasted vessels alone emerges. Intra-arterial DSA is a less invasive and more comfortable method when compared to conventional angiography. Only 2-4 ml of contrast medium is administered, thinner catheters being employed at the same time. The examination can also be performed through intravenous administration of contrast medium. The DSA unit Angiotron CMP was installed at the Department of Radiology, Military Medical Academy of Lódz, in 1984. In the present material a diagnostic DSA investigation was performed in 22 patients with renal tumours. In 21 of them the tumour was correctly diagnosed on grounds of pathological vascularization and the result was dubious in only 1 patient with benign tumour.

Comparison of midazolam and oxazepam as hypnotics in elderly hospitalized patients. A double-blind clinical trial.

The efficacy and safety of 15 mg midazolam versus 15 mg oxazepam were compared in a double-blind clinical trial in 61 aged hospitalized patients (mean age 82.5, range 69 to 96), suffering from moderate to severe insomnia. The study covered 8 nights, i.e., 1 placebo night followed by 5 treatment nights and 2 further placebo nights. Both drugs were equally effective with respect to total sleep time, number of nocturnal awakenings, quality of sleep, condition on awakening, patients' assessment and dreams. However, sleep latency was significantly shorter in the midazolam group, which was also rated significantly more favorably by the medical staff. Side effects were mild and similar in both groups. No rebound or carry-over effects were noted. Midazolam can be considered an effective and safe sleep inducer in aged patients.

[Sleep in Pick disease]. / Le sommeil dans la maladie de Pick.

19 polygraphic sleep recordings from 12 patients with Pick's Disease, including four histologically proved cases, were compared to those of an age-matched control group. Symptoms had been present for a mean 8 years, the patients being aged 59 to 78 (mean 70.5 years). All sleep stages could be identified. Total sleep time was reduced and the number of awakenings was sharply increased. High proportion of stage 1 contrasted with the reduction in the other sleep stages with disappearance of stage 4 in advanced cases. REM Sleep was identified in all recordings, although reduced as a function of the length of the illness; its production as a function of total sleep time was not different from that of the control. REM Sleep appeared often fragmented and with a remarkably short latency, reminiscent of that observed in severely depressed patients.