Effects of access to feed, water, and a competitive exclusion product in the hatcher on some immune traits and gut development in broiler chickens.

1. This study evaluated the effect of access to feed, water, and the competitive exclusion (CE) product Broilact®, administered in the hatcher, on broiler performance, caecal microbiota development, organ development, intestinal morphology, serum levels of IgY and vaccine-induced antibody responses.2. In total, 250 chicks were hatched in a HatchCareTM hatcher and divided into four groups, given access to feed, water and the CE product sprayed on the chicks (CEs); access to feed, water, and the CE product in water (CEw); access to feed and water (Cpos); or no access to feed and water (Cneg) in the hatcher.3. At the research facility, 10 chicks per hatching treatment were euthanised for organ measurements. The remaining 200 chicks were randomly distributed to 20 pens. On d 11, all birds were vaccinated against avian pneumovirus (APV). Three focal birds per pen were blood-sampled weekly for quantification of IgY and serum antibodies to APV. On d 11 and 32, two birds per replicate pen were euthanised for organ measurements and sample collection. Feed intake and body weight were recorded weekly.4. Delayed access to feed and water reduced weight gain and feed intake early in life. At the end of the study, no differences in body weight remained.5. There were some early effects on organs, with depressed intestinal development and higher relative gizzard weight for the Cneg group at placement. No treatment effects on the immune traits measured were detected.6. The relative abundance of seven bacterial genera differed between treatment groups at d 11 of age. The results suggested that chickens are capable of compensating for 40 h feed and water deprival post-hatch. Provision of Broilact® did not have any persistent performance-enhancing properties, although different outcomes under rearing conditions closer to commercial production cannot be ruled out.

Effects of phytoestrogen supplementation in the feed on the shell gland of laying hens at the end of the laying period.

Shell quality decreases as laying hens age and the aim of present study was to investigate how a supplement of daidzein, a natural phytoestrogen in soya, affects key factors in the shell gland and eggshell quality in late-stage laying hens. Hybrids of Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB), received either a daidzein diet (50 mg/kg feed) or a control diet from 60 to 72 weeks of age. Both the total number of capillaries and capillaries with carbonic anhydrase (CA) activity were higher in the LSL hybrid than in the LB. After daidzein supplementation the number of CA positive capillaries was unaffected in the LSL but increased in the LB hybrid indicating a higher sensitivity to daidzein in this hybrid. Estrogen receptor alpha and beta (ERα, ERß) were localized and the complete picture of the two ERs can now be described in shell gland of domestic hens. Nuclear and cytoplasmic staining was generally stronger for ERß, while membrane associated staining was present only for ERα. Interestingly, capillary endothelium contained only ERß and since estrogen regulation of CA is well documented, the presence of an endothelial ER provides one possible route for the increase in CA positive capillaries found in LB hybrids. Eggshell quality or egg production was not affected by daidzein supplementation. The hybrids used in this study showed anatomical differences and reacted differently to daidzein supplementation, but if this can be explained by the divergences in ERß localization noted between the hybrids remains to be clarified.

A history of childhood attention-deficit hyperactivity disorder (ADHD) impacts clinical outcome in adult bipolar patients regardless of current ADHD.

OBJECTIVE: The occurrence of comorbid attention-deficit hyperactivity disorder (ADHD) might have an impact of the course of the bipolar disorder. METHOD: Patients with bipolar disorder (n = 159) underwent a comprehensive evaluation with respect to affective symptoms. Independent psychiatrists assessed childhood and current ADHD, and an interview with a parent was undertaken. RESULTS: The prevalence of adult ADHD was 16%. An additional 12% met the criteria for childhood ADHD without meeting criteria for adult ADHD. Both these groups had significantly earlier onset of their first affective episode, more frequent affective episodes (except manic episodes), and more interpersonal violence than the bipolar patients without a history of ADHD. CONCLUSION: The fact that bipolar patients with a history of childhood ADHD have a different clinical outcome than the pure bipolar group, regardless of whether the ADHD symptoms remained in adulthood or not, suggests that it represent a distinct early-onset phenotype of bipolar disorder.

A nosocomial outbreak of Candida parapsilosis in southern Sweden verified by genotyping.

In a haematology ward, Candida parapsilosis was found in blood cultures from 4 patients within a month. As C. parapsilosis is known to have a restricted genetic diversity, a combined methodological approach was adopted to establish a possible epidemiological relationship among the isolates (n = 9). Multilocus sequence typing and random amplified polymorphic DNA analysis suggested a clonal origin of the isolates. The clonal origin was confirmed by microsatellite analysis, a method that displayed the highest discriminatory level and readily differentiated cluster isolates from 2 epidemiologically unrelated strains of C. parapsilosis. The use of novel methods of genotyping such as microsatellite analysis will facilitate epidemiological investigations of potential clonal outbreaks of fungaemia.

Intensive group cognitive treatment and individual cognitive therapy vs. treatment as usual in social phobia: a randomized controlled trial.

UNLABELLED: To compare the effects of an intensive group cognitive treatment (IGCT) to individual cognitive therapy (ICT) and treatment as usual (TAU) in social phobia (DSM-IV). METHOD: Hundred patients were randomized to: IGCT involving 16 group sessions spread over three weeks; ICT involving 16 shorter weekly sessions in 4 months and; TAU involving an indicated selective serotonin reuptake inhibitor (SSRI) with therapy sessions as required for 1 year. The main outcome measure was a Social Phobia Composite that combined several standardized self-report measures. Diagnostic assessment was repeated at 1-year follow-up. RESULTS: Significant improvements were observed with all treatments. ICT was superior to IGCT and TAU, which did not differ in overall effectiveness. CONCLUSION: The study confirms and extends previously reported findings that ICT is more effective than group cognitive treatment and treatment with SSRIs. IGCT lasts only 3 weeks, and is as effective as more protracted TAU.

Effects of long-term lithium treatment on monoaminergic functions in major depression.

Platelet [14C]serotonin uptake, the density of serotonin transporters and 5HT(2) receptors, and 5HT(2) and alpha(2) receptor function in platelets were investigated in 29 outpatients (15 women and 14 men) diagnosed as having a major affective disorder (21 bipolar and 8 unipolar). The data were compared with data for 26 healthy volunteers matched for age, sex and season. No differences were found in the mean values for the uptake velocity (V(max)) and the affinity (K(m)) of the transport carrier for serotonin between patients and controls. However, female patients had lower V(max) compared to male patients and female control subjects. A positive correlation between plasma lithium and V(max) and a tendency toward a negative correlation between plasma lithium and K(m) was observed. Furthermore, there were no differences in platelet B(max) and K(d) for [3H]paroxetine binding and K(d) for [3H]LSD binding between patients and controls. However, there was an increased number of platelet 5-HT(2) receptors and a difference in serotonin-mediated potentiation of platelet ATP secretion between patients compared to controls, especially in women. The findings in the present study suggest that lithium has a net ameliorating impact on serotonin uptake which may render it resistant to change. They also postulate that the effect of lithium may be attained by a dual influence on postsynaptic serotonergic structures, as it increases both the density and the sensitivity of 5-HT(2) receptors.

Serotonergic function in major depression and effect of sertraline and paroxetine treatment.

We investigated platelet [14C]serotonin (5-HT) uptake and lysergic acid diethylamide [N-methyl-3H] ([3H]LSD)- and phenyl-6'-paroxetine ([3H]paroxetine) binding in 30 patients with major depression at baseline and after 6 months of treatment with either paroxetine or sertraline. The study was of a double-blind design. Baseline data was compared with an age- and gender-matched group of healthy volunteers. Baseline Vmax was significantly lower in patients than in controls. Bmax for [3H]paroxetine binding were similar in patients and controls, but patients who suffered their first depression had significantly lower Bmax for [3H]paroxetine binding than patients who had suffered multiple depressions. Twenty-three patients (76%) (13 in the paroxetine group and 10 in the sertraline group) responded to treatment as judged by a 50% or more reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores after 6 months of treatment. There were no significant differences between the paroxetine and sertraline treated groups. Both paroxetine and sertraline caused a significant reduction in Vmax and a significant increase in Km. There was a strong correlation between Km and plasma drug concentration in patients who experienced their first depression but not in patients who had suffered multiple episodes. Bmax for [3H]paroxetine binding increased after paroxetine treatment while the opposite occurred after sertraline treatment. There was a significant interaction between the impact of drug and earlier depressions. All patients included in the study had been drug free for at least 2 months. Earlier antidepressant treatment may have long withstanding effects on the serotonin uptake machinery but it cannot be excluded that the sensitivity of the uptake mechanism may become more resistant to change in patients with recurrent depressive episodes.

[Patient based care registries as a tool to follow up services]. / Individbaserade vårdregister en hjälp vid verksamhetsuppföljning.

The Federation of Swedish County Councils and six medical specialties are working together in a project aiming to support and stimulate the development of patient based case registers as a tool to follow up, evaluate, develop and manage medical units. The project is based on participation on the part of the medical professions in a process-oriented way. Each case register shall be based on the individual patient, and will integrate inpatient and outpatient care, all medical professions and important procedures. In hematology the project also seeks to merge case costing data with the patient based case registers in order to facilitate more comprehensive cost analysis and comparison. This episodic perspective is useful for providers per se as well as in discussions between purchasers and providers as a method for understanding and analyzing medical services. The six specialties are hematology, obstetrics and gynecology, ophthalmology, otorhinolaryngology, dermatology and sexually transmitted diseases, and lastly psychiatry.

Tryptophan depletion in lithium-stabilized patients with affective disorder.

Central serotonergic function abnormalities are thought to be associated with the pathogenesis of affective disorder. Reduced serotonergic function, induced by tryptophan depletion, has in several studies transiently reversed the antidepressant effect of SSRIs in depressed patients in remission. Serotonergic pathways are suggested to be of importance in the mechanisms of the action of lithium. The purpose of this study was to investigate whether the stabilizing effect of lithium is dependent on short-term availability of serotonin. Tryptophan depletion was induced in thirty patients with affective disorder (20 bipolar and 10 unipolar), all stabilized on lithium treatment for at least one year. The study was performed using a randomized, double-blind, controlled design. Plasma tryptophan was reduced by 80% in the experimental group and 16% in the control group. However, no clinically relevant mood changes were observed. Transient reduction in serotonergic function does not seem to affect mood in affective-disorder patients stabilized on lithium treatment.

Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy.

reuptake inhibitors (SSRIs) during continuation therapy. This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression, quality of life, and personality outcomes. Outpatients with unipolar major depression (DSM-III-R) were randomly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine (20-40 mg) or sertraline (50-150 mg). Assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale, the Battelle Quality of Life Questionnaire, and the Structured Clinical Interview for DSM-III-R Personality Disorders screen questionnaire. One hundred seventy-six patients (mean age, 43 years; 64% female; baseline MADRS, 30.3) were treated with sertraline and 177 patients (mean age, 42 years; 71% female; MADRS, 30.7) with paroxetine. Antidepressant efficacy during continuation therapy was sustained, with only 2% of patients receiving sertraline and 9% of patients receiving paroxetine suffering a relapse. Continuation therapy resulted in a substantial conversion of responders during short-term treatment to full remission: remitter rates increased from 52% to 80% for sertraline and from 57% to 74% for paroxetine. The improvements in quality of life were related to a reduced depression score. SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality. A logistic regression analysis identified early response (25% reduction in MADRS scores at week 2) as the most important predictor of treatment response, whereas high severity, chronicity, and poor baseline quality of life had no effect. Both treatments were well-tolerated, with sertraline having a somewhat lower side effect profile. Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy. Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology.

[Medical revision a way to treat blindness when it comes to home defects. Report from the first scrutiny of psychiatric care]. / Medicinsk revision ett sätt att bota hemmablindhet. Rapport från de första granskningarna av psykiatrisk vård.

Results from medical revision of eight psychiatric clinics show that the points of view of "outsiders" can be of help to improve routines and procedures.

Age of onset in affective disorder: its correlation with hereditary and psychosocial factors.

BACKGROUND: Affective disorders probably have a multifactorial aetiology, both biological and psychosocial factors may be of importance at onset as well as at relapses. The aim of the study was to investigate how the age of onset of bipolar and unipolar disorder relates to family history of affective disorder, early parental separation and life events. A second purpose of this study was to analyze the importance of life events preceding the first and subsequent episodes of affective disorder. METHODS: The case records of 282 patients (161 females/121 males; mean age 56) were investigated. They all had a DSM-IV based diagnosis of either bipolar I/II (67%) or unipolar (33%) disorder. Variables, such as family history, early parental loss and life events according to Paykel life events scale, were examined. RESULTS: We found a significantly lower age of onset in bipolar patients with a family history of affective disorder (28.9 vs. 33.9 years). Bipolar patients with preceding life events had a higher age of onset (33.1 vs. 28.3 years). Moreover, bipolar patients with heredity, had less life events at onset. For the bipolar, as well as the unipolar group, life stressors more frequently preceded the first episode of affective disorder than the subsequent episodes. LIMITATIONS: The major limitation of this study is the retrospective approach, with e.g. difficulties to decide whether a life event plays a role in aetiology of affective disorder or is its consequence. CONCLUSIONS: Bipolar patients with high constitutional vulnerability have an earlier age of onset and need less stress factors to become ill. Better knowledge about the stress- and the vulnerability-factors in affective disorder might contribute to development of individually tailored therapeutic strategies in future.

The effect of citalopram treatment on platelet serotonin function in panic disorders.

We investigated the effect of the selective serotonin reuptake inhibitor (SSRI) citalopram after 6-8 weeks and 6 months of treatment on clinical and peripheral indexes for central serotonergic function: platelet [14C]serotonin uptake and [3H]paroxetine- and [3H]LSD-binding to platelets membranes in 33 patients with panic disorder. Basal data from patients were compared with data from a control material consisting of 33 healthy volunteers. Bmax for platelet [3H]paroxetine binding was significantly lower in patients than in controls. There were no differences in serotonin uptake or [3H]LSD-binding between patients and controls. The degree of anxiety and depression was assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory self-assessment scales, and the Clinical Anxiety Scale and the Montgomery Asberg Depression Rating Scale for clinical evaluation. Complete remission was found in one third of the patients after 6-8 weeks and in two-thirds after 6 months of treatment. The reduction in assessment scores was parallelled with similar reductions in platelet 5-HT2-receptor density, [3H]LSD affinity variable (Kd) and Vmax for platelet [14C]5-HT uptake. Citalopram treatment did not alter Bmax and Kd for platelet [3H]paroxetine-binding. A positive correlation was found between Vmax for the platelet [14C]5-HT uptake and BAI after 6 months citalopram treatment. The present study shows that citalopram has a therapeutic effect in panic disorders. A prerequisite of responding to treatment might be plasticity in the serotonergic system.

Patient satisfaction with the information provided at a psychiatric emergency unit.

OBJECTIVE: Evaluation of patient satisfaction with information at a psychiatric emergency unit. DESIGN: Patient survey. SETTING: Psychiatric patients assessed information provided by staff on illness, symptoms, treatment alternatives, treatment design, medication, time schedule for treatment and the expected therapeutic response. PARTICIPANTS: The sample included 100 subjects (63% response rate). OUTCOME MEASURE: Patient satisfaction. RESULTS: 59% were women. Mean age was 43 years. 87% were Swedish. 30% had psychotic, 35% bipolar and 35% anxiety disorders. 87% were admitted voluntarily. Almost 80% were satisfied with the patient-staff relationship. Questions on information, except medication, scored low. Patients with non-psychotic disorder were more satisfied with information on symptoms, treatment alternatives and treatment design, and voluntary patients with information about medication. Patients born in Sweden and voluntary patients awarded influence on treatment planning higher scores. CONCLUSIONS: Psychiatric patients requiring emergency care did understand information. The staff provided satisfactory information only when knowledgeable.

Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.

AIMS: To investigate the change in disposition of tolterodine during coadministration of the potent cytochrome P450 2D6 (CYP2D6) inhibitor fluoxetine. METHODS: Thirteen patients received tolterodine l-tartrate 2 mg twice daily for 2.5 days, followed by fluoxetine 20 mg once daily for 3 weeks and then concomitant administration for an additional 2.5 days. They were characterized as extensive metabolizers (EM1 with one functional CYP2D6 gene, EM2 with two functional genes) or poor metabolizers (PM). RESULTS: Nine patients, three EM2 and four EM1 and two PM, completed the trial. Following tolterodine administration, the area under the serum concentration-time curve (AUC) of tolterodine was 4.4-times and 30-times higher among EM1 and PM, respectively, compared with EM2. The AUC of the 5-hydroxymethyl metabolite (5-HM) was not quantifiable in PM. Fluoxetine significantly decreased (P<0.002) the oral clearance of tolterodine by 93% in EM2 and by 80% in EM1. The AUC of 5-HM increased in EM2 and decreased in EM1. However, the exposure to the active moiety (unbound tolterodine +5-HM) was not significantly increased in the two phenotypes. The subdivision of the EM group showed a 2.1-fold increase in active moiety in EM2 but the exposure was still similar to EM1 compared with before the interaction. CONCLUSIONS: The study suggests a difference in the pharmacokinetics of tolterodine and its 5-hydroxymethyl metabolite depending on the number of functional CYP2D6 genes. Fluoxetine significantly inhibited the hydroxylation of tolterodine. Despite the effect on the pharmacokinetics of tolterodine in extensive metabolizers, the clinical effect is expected to be within normal variation.

Platelet serotonin functions in untreated major depression.

The uptake of [14C]5-HT, [3H]paroxetine and [3H]LSD binding was determined in platelets from 30 untreated patients with major depression and compared with corresponding variables from 30 healthy age-, sex- and season-matched control subjects. The maximum velocity (Vmax) for the 5-HT uptake was significantly decreased in patients (P = 0.014) compared to control subjects. Depressed women had significantly lower Vmax than female control subjects. In men, Vmax did not differ between patients and control subjects. Vmax was significantly lower in male inpatients compared with male outpatients (P = 0.05). The density (Bmax) of 5-HT uptake sites was found to be significantly increased in patients (P < 0.05) compared to control subjects and male patients had significantly higher Bmax than male control subjects, but there was no difference between female control subjects and female patients. No significant difference was found in Bmax of 5-HT2-receptors between patients and control subjects. A positive correlation was found between Bmax of 5-HT2-uptake sites and the degree of anxiety and between Bmax of 5-HT2 receptors and MADRS scores. Bmax of 5-HT2-receptors was positively correlated with the degree of suicidality. The results in the present study indicate that there may be a gender difference in serotonergic dysfunction in depression.

Kringle 2 mediates high affinity binding of plasminogen to an internal sequence in streptococcal surface protein PAM.

Many cells express receptors for plasminogen (Pg), although the responsible molecules in most cases are poorly defined. In contrast, the group A streptococcal surface protein PAM contains a domain with two 13-amino acid residue long repeated sequences (a1 and a2) responsible for Pg binding. Here we identify the region in Pg that interacts with PAM. A radiolabeled proteolytic plasminogen fragment containing the first three kringles (K1-K3) interacted with streptococci expressing PAM or a chimeric surface protein harboring the a1a2 sequence. In contrast, plasminogen fragments containing kringle 4 or kringle 5 and the activable serine proteinase domain failed to bind to PAM-expressing group A streptococci. A synthetic and a recombinant polypeptide containing the a1a2 sequence both bound to immobilized recombinant K2 (rK2) but not to rK1 or rK3. The interaction between the a repeat region and rK2 was reversible, and rK2 completely blocked the binding of Pg to the a1a2 region. The binding of the a repeat containing polypeptide to K2 occurred with an equilibrium association constant of 4.5 x 10(7) M-1, as determined by surface plasmon resonance, a value close to that (1.6 x 10(7) M-1) calculated for the a1a2-Pg interaction. Inhibition experiments suggested involvement of the lysine-binding site of K2 in the interaction. These data demonstrate that K2 contains the major Pg-binding site for PAM, providing the first well defined example of an interaction between an internal Pg-binding region in a protein and a single kringle domain.

Increased platelet 5-HT2 receptor binding after electroconvulsive therapy in depression.

We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C-serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10 women and 2 men) unresponsive to pharmacological treatment. The mean numbers of ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2 receptors increased significantly and uniformly after ECT (p = 0.011). There was no correlation between the degree of increase in 5-HT2 receptor densities and the reduction in MADRS scores after ECT. There was no difference in mean Bmax for platelet 3H-paroxetine binding before and after ECT. Bmax increased in six patients and decreased in six patients. The study shows an increase in platelet 5-HT2-receptor densities in depression after repeated ECT. Recognizing the similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems reasonable to assume that a similar upregulation of cortical 5-HT2 receptors occurs after ECT.

Platelet serotonergic functions and light therapy in seasonal affective disorder.

We investigated platelet 14C-serotonin uptake and platelet [3H]LSD and [3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD). Patients were reinvestigated after light therapy, applied at 07.00-09.00 h for 10 consecutive days. The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline data in patients were compared with data from a control group consisting of 11 age- and sex-matched healthy volunteers. Seven patients responded to light therapy with a > 50% reduction in CPRS scores. In non-responders, the reduction in CPRS was 24.7 +/- 5.5%. There was a significant inverse correlation (P = 0.014) between Km for platelet 14C-serotonin uptake and CPRS scores. Patients had significantly higher Bmax for platelet [3H]LSD binding (P = 0.04) and significantly lower Bmax for platelet [3H]paroxetine binding (P = 0.016). There was a strong, multiple correlation between Bmax for [3H]LSD, as the dependent variable, and Km, Vmax and Bmax for [3H]paroxetine binding in patients (P < 0.0001) but not in controls. Responders to light therapy had significantly higher Km (P = 0.023) and significantly lower Bmax for [3H]paroxetine binding (P = 0.028) than non-responders. Bmax for [3H]paroxetine binding increased significantly to normal levels after light therapy. The results indicate that SAD is associated with aberrations in the serotonin uptake mechanism. The enhanced 5-HT2-receptor density may reflect a consequential up-regulation.