Administration of recombinant bovine somatotropin prior to fixed-time artificial insemination and the effects on fertility, embryo, and fetal size in beef heifers.

Our objectives were to determine the effects of the administration of recombinant bovine somatotropin (bST) at the initiation of a fixed-time AI (TAI) protocol on concentrations of plasma IGF-1, follicle diameter, embryo/fetal size, and pregnancy rates in replacement beef heifers. Four hundred and fourteen Angus-based beef heifers were enrolled in a completely randomized design at 4 locations from January to July of 2016. All heifers were exposed to the 7-d CO-Synch + controlled internal drug release (CIDR) protocol where they received a 100-µg injection of GnRH and a CIDR insert on day -9, 25 mg of PGF2α at CIDR removal on day -2, followed by a 100-µg injection of GnRH and TAI 54 ± 2 h later on day 0. Within location, all heifers were randomly assigned to 1 of 2 treatments: 1) heifers that received 650 mg of bST on day -9 (BST; n = 191); or 2) heifers that did not receive bST on day -9 (CONTROL; n = 223). Blood samples were collected on day -9, 0, 28, and 60 to determine the plasma concentrations of IGF-1. Follicle diameter was determined on day -2 and 0 by transrectal ultrasonography. Pregnancy was diagnosed via transrectal ultrasonography on day 28 or 35, and again at least 30 d after the end of the breeding season. Embryo morphometry was assessed by measuring crown-to-rump length (CRL) on day 28, and fetal size was assessed by measuring crown-to-nose-length (CNL) on day 60. Concentrations of plasma IGF-1 did not differ between treatments on day -9 (P = 0.924), 28 (P = 0.075), and 60 (P = 0.792); however, concentrations of plasma IGF-1 were greater (P < 0.001) in BST-treated heifers at TAI (372.4 ± 16.6 vs. 193.7 ± 16.6 ng/ml). No differences (P = 0.191) were detected for follicle diameter between CONTROL and BST treatments on day -2 or 0. Pregnancy rates to TAI (PR/AI) were greater (P = 0.028) for CONTROL compared to BST heifers (42.5 ± 4.0 vs. 29.9 ± 4.1%). No differences (P = 0.536) in CRL were observed on day 28 between CONTROL and BST heifers. In addition, no difference (P = 0.890) was observed for CNL between CONTROL and BST treatments. Final pregnancy rates did not differ (P = 0.699) between treatments. The administration of bST to beef heifers at the initiation of a TAI protocol increased plasma concentrations of IGF-1 at TAI; however, failed to enhance follicle diameter, embryo/fetal size, and reduced PR/AI.

Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study.

OBJECTIVE: The incidence and course of neuropsychiatric symptoms were determined in pediatric patients with rheumatic fever. METHOD: The Leyton Obsessional Inventory and National Institute of Mental Health Global Obsessive-Compulsive Scale were used to evaluate children and adolescents who had rheumatic fever with Sydenham's chorea (N=30) or without chorea (N=20). They were assessed three times over 6 months from the onset of rheumatic fever. Psychiatric diagnoses were also determined. RESULTS: Obsessive-compulsive symptoms abruptly appeared and peaked during the 2 months after the onset of rheumatic fever in 21 patients with chorea (70.0%) and were absent in all patients without chorea. Obsessive-compulsive disorder (OCD) was diagnosed in five patients with chorea (16.7%). CONCLUSIONS: The association between Sydenham's chorea and OCD supports suggestions that similar mechanisms involving the basal ganglia underlie both disorders. Obsessive-compulsive symptoms occurred at the beginning of rheumatic fever, so early psychopathological assessments are essential.

Psychiatric manifestations of systemic lupus erythematosus: clinical features, symptoms, and signs of central nervous system activity in 43 patients.

Forty-three female inpatients with active systemic lupus erythematosus (SLE) were studied by a multidisciplinary team to answer the following research questions: 1) What are the features of the psychopathology in patients with active SLE? and 2) In these patients, what is the relationship between psychiatric disorders and symptoms and signs suggesting activity of SLE in the CNS? Our a priori hypothesis was that, in patients with active SLE, those with psychiatric manifestations would have more symptoms and signs of CNS activity than those without psychiatric manifestations. Psychiatric evaluation consisted of standardized psychiatric instruments and diagnostic criteria. The assessment of SLE systemic and central nervous system (CNS) activity consisted of rheumatologic, neurologic, and ophthalmologic evaluations; serum and cerebral spinal fluid (CSF) analysis; brain computerized tomography (CT); and electroencephalogram (EEG). Twenty-seven patients (63%) presented psychiatric symptoms (Psychiatric Group), and 16 (37%) patients presented no current psychiatric diagnosis (Nonpsychiatric Group). These groups were compared in terms of the above variables. Depressive syndrome was the most frequent diagnosis (44%) followed by delirium (7%) and dementia (5%). Psychiatric symptoms were associated with subjective cognitive impairment (85%) and neurologic abnormality (85%). Widened cortical sulci was the most frequent CT alteration and was equally common in both groups. No statistical difference was found between the 2 groups regarding their general clinical evaluation, serum and CSF exams, or EEG alterations. To determine whether the severity of psychiatric symptoms was related to CNS activity, we divided the 27 patients with psychiatric manifestations into 2 groups: the Major Group--18 patients with major psychopathology, and the Minor Group--9 patients with mild depressive syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Why is the reproductive performance lower in Becker (BMD) as compared to limb girdle (LGMD) muscular dystrophy male patients?

We had previously reported that patients affected with BMD have a significantly reduced reproductive performance (f = 0.12) as compared to male LGMD patients of similar age and physical impairment (f = 0.98). In the present study parameters such as the socio-economic level, as well as psychosocial, intellectual, and psychiatric functionings could not explain the low fitness of BMD patients. The effect of genetic counseling, a greater difficulty in coping with the disease, and relating to women and/or a potential malfunction of reproductive physiology are discussed as possible causes.

Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia.

It has been suggested that the serotonin transporter (5-hydroxytryptamine-transporter or 5-HTT) may be involved in the pathogenesis of affective disorders. Recently, Collier et al. (1996) found that the frequency of the low-activity short variant (s) of the 5-HTT-linked polymorphic region (5-HTTLPR) was higher among patients with affective disorders than in normal controls. However, since the observed level of significance was not high, they suggest that these findings should be replicated in independent samples. We have analyzed 86 unrelated patients (47 with bipolar disorder and 39 with schizophrenia) and 98 normal controls from the Brazilian population for the 5-HTTLPR. Statistical analysis revealed that the genotypes (LL, Ls, ss) as well as the estimated allele frequencies (L,s) did not differ significantly among the three studied groups or between bipolar and normal controls. In addition, although not statistically significant, the genotype ss in our sample was less frequent among our bipolar patients than in our normal controls (12.8% versus 16.3%) which is the opposite of what was found by Collier et al. (24% versus 18%) in the European study. Although it will be important to extend the present analysis in a larger sample, our preliminary results suggest that the 5-HTTLPR does not seem to play a major role in the genetics of bipolar and schizophrenic disorders at least in this group of Brazilian psychiatric patients.

Becker and limb-girdle muscular dystrophies: a psychiatric and intellectual level comparative study.

There are some indications that Becker muscular dystrophy (BMD) might be related to mental disorders and mental retardation (MR). To investigate this question, we made a standardized psychiatric and intellectual level assessment of 22 BMD patients in comparison with 22 limb-girdle muscular dystrophy (LGMD) patients. There were not significant differences between the two groups. Twelve patients (54.5%) in each group received at least one lifetime psychiatric diagnosis, the most frequent being depressive disorders. The intelligence quotient means for BMD was 85.9 and 87.8 for LGMD. There was one case of mild MR among BMD patients and two cases among LGMD patients.

Residual and acute effects of flurazepam and triazolam in normal subjects.

Residual and acute effects of flurazepam and triazolam were studied in two double-blind, crossover, placebo controlled, single-dose experiments. Psychological and physiological effects were determined 10 h after night administration (flurazepam 30 mg and triazolam 0.5 mg), and for 6 h after morning ingestion (flurazepam 15 mg and triazolam 0.25 mg). Both drugs produced similar "hangover" effects, impairing motor performance and increasing sleepiness on the following morning. After morning administration pronounced sedative effects were found with triazolam, while flurazepam effects were mild and hard to distinguish from placebo. The clinical relevance of these findings is discussed, suggesting that these drugs may be conceived as belonging to two different types of hypnotic agents.

Tranylcypromine isomers: single-dose effects in normal human subjects.

Moderately high single doses of (+)- and (-)tranylcypromine were given to normal subjects, in the morning and evening, in two double-blind placebo-controlled experiments. Effects were determined up to 24h later by psychological and physiological measures. No significant differences were found on most measures, but the subjects consistently reported stronger effects after the (+)isomer. Both active drugs induced sedative effects when given in the morning. Following the evening administration, delayed sleep onset was reported after the (-)isomer, while the (+)isomer was associated with more awakenings during the night. The mechanisms responsible for these effects are discussed.

The effects of adrenaline injections on human platelet monoamine oxidase and related measures.

A double-blind, placebo-controlled, cross-over study in ten normal volunteers assessed the effects of the subcutaneous administration of adrenaline on platelet MAO activity, in an attempt to replicate previous findings of increased MAO activity following adrenaline. Platelet counts, cortisol plasma concentrations, and uptake of metaraminol by the platelets were also determined to elucidate possible mechanisms of action. Blood pressure and heart rate were used as indices of the concentration of adrenaline effectively in circulation. MAO activity towards benzylamine was significantly increased by adrenaline. Non-significant increases were noted in the deamination of tyramine and tryptamine, in platelet counts, cortisol concentrations and metaraminol uptake. Increases in MAO activity were also noted early in the experimental sessions suggesting that other experimental variables such as venepuncture may affect platelet MAO activity. Possible mechanisms for this adrenaline effect are discussed and it is suggested that variables such as "arousal" and "stress" must be taken into account when interpreting clinical data on platelet MAO.

Acute reversal of flunitrazepam effects by Ro 15-1788 and Ro 15-3505: inverse agonism, tolerance, and rebound.

A phase 1 double blind crossover comparison of a new benzodiazepine antagonist (Ro 15-3505) with Ro 15-1788 and placebo, in the reversal of sedative and psychophysiological effects of single IV doses of flunitrazepam (2 mg), was carried out in 12 normal volunteers. The antagonists were equally effective, leading to full reversal of all effects with a potency ratio of approximately 2.5 mg Ro 15-1788 for 1 mg Ro 15-3505. Inverse agonism, in the form of unpleasant feelings and symptoms, was reported by all subjects following Ro 15-3505 but none after Ro 15-1788. Adaptational phenomena such as acute tolerance and rebound of sedative effects of flunitrazepam were also detected and their potential implications are discussed.

Linkage analysis between bipolar affective disorder and markers on chromosome X.

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.

Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea.

The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS.

Alcoholism and phobic anxiety--a clinical-demographic comparison.

The prevalence of anxious and phobic symptoms in 97 alcohol-dependent and alcohol abuse patients, and that of alcohol abuse and dependence in 90 patients with panic/agoraphobia (PAG), were respectively determined in out-patients attending alcoholism and anxiety clinics in a university psychiatric hospital. The clinical and socio-demographic data of both the phobics and non-phobics of the alcoholic sample, and the alcohol dependents and non-dependent of the PAG sample, were compared. Panic attacks and phobias were associated with increased severity and worse prognosis for alcoholism. The infrequent instances of alcohol use to cope with anxiety in the PAG sample were associated with symptoms of social phobia. Alcohol abuse and dependence were more frequent in PAG men who used alcohol to cope with anxiety. Finally, the frequency and intensity of the panic and phobic symptoms of the alcoholic and PAG samples were contrasted. The alcoholism clinic patients with anxiety had less frequent and milder panic attacks. The predominant diagnosis of this group was agoraphobia, which was infrequent in the anxiety disorders clinic.

Linkage studies in bipolar affective disorder with markers on chromosome 21.

Straub et al. (1994: Nature Genet. 8. 291-296) have suggested that a susceptibility gene for bipolar affective disorder is located at chromosome 21q22.3, on the basis of linkage analysis in one large family. This result has been supported by Gurling et al. (1995: Nature Genet. 10, 8-9) who also found some evidence for linkage to this region under locus heterogeneity. In order to investigate the validity of these results and to estimate how broadly applicable they are, we performed a linkage study between bipolar affective disorder and two DNA markers (D21S171 and PFKL) from 21q22.3 using 60 bipolar pedigrees from three European centres and Brazil. The most positive result obtained was a maximised admixture lod score of 1.2 for the marker PFKI, under the assumption of locus heterogeneity, dominant transmission and a diagnostic classification which included recurrent unipolar depression. However, since lod scores obtained for both markers were substantially negative overall, we conclude that there is no common major gene for bipolar affective disorder at 21q22.3. It remains possible that a gene of major effect in this region operates in a minority of families.

The association of panic/agoraphobia and asthma. Contributing factors and clinical implications.

The point prevalence of phobic anxiety disorders was determined in 107 asthmatic outpatients through a standardized psychiatric interview and DSM-III-R diagnostic criteria. Agoraphobia and panic disorder were more prevalent (13.1% and 6.5%, respectively) than in the general population. Contributing factors and the clinical implications of this association are discussed. The recognition of specific anxiety syndromes enhances the efficacy of the treatment of anxious asthmatic patients.

Clomipramine, a better reference drug for panic/agoraphobia. II. Psychomotor and cognitive effects.

The present reference drugs for the treatment of panic disorder and agoraphobia are imipramine and alprazolam. The latter decreases performance and cognitive functioning. No study of such functions in panic/agoraphobia is available. Fifty four out-patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia (PAG), taking part in a parallel groups controlled trial of imipramine (mean dose ±SEM 114±9 mg), clomipramine (50±4 mg) and propanteline (active placebo) over 8 weeks, were studied. A test battery of psychomotor and memory tests was administered at baseline, and after 1, 4 and 8 weeks of treatment. Their results were compared (at baseline and at the end of the trial) with those of a control group of 57 normal untreated subjects. There was no difference between treatments, and no drug effect on any test at any time. No consistent difference between patients and controls was detected. Given its apparently higher potency, and the absence of deleterious effects on cognitive measures known to be affected by benzodiazepines, we conclude that clomipramine is better than imipramine or alprazolam as a reference drug for panic/agoraphobia.

Clomipramine and initial worsening in panic disorder: beyond the 'jitteriness syndrome'.

The time course and the phenomenology of the initial response to clomipramine (10-20 mg/day) was investigated in 70 patients with panic disorder with or without agoraphobia. Nineteen (27.1%) patients reported worsening of their clinical state which, on average, began 28 h after the first dose and lasted for 5 days. Increase in the frequency and severity of panic attacks was the most frequent finding (14 patients), followed by psycho- stimulant (jitteriness; n=9), depressive (n=8) and tonic anxiety symptoms (n=7). This pattern of initial worsening is different from the 'jitteriness syndrome' described for other antidepressants. Its implications for the understanding of the pathophysiology of panic disorder are discussed.

Flumazenil-precipitated withdrawal symptoms in chronic users of therapeutic doses of diazepam.

A prototype benzodiazepine (BDZ) antagonist, flumazenil (1 mg, i.v.) or placebo was administered to eight chronic users (5-15 years) of therapeutic doses of diazepam (10-25 mg/d), in a double-blind, placebo-controlled design in order to evaluate the presence of physiological dependence. The three patients receiving flumazenil developed anxiety reactions, with significant increases in bodily and psychological symptoms, as measured by rating scales. In two these amounted to a panic attack. Subjects on placebo tended to show decreases in measures of anxiety. The severity of precipitated reactions was not related to the total cumulative exposure to diazepam, but to a history of panic attacks. Previous panic may increase the vulnerability to severe reactions to flumazenil.

Mood improvement in 'normal' volunteers.

To test the hypothesis that clomipramine is effective in improving subthreshold non-specific symptoms in subjects without any established psychopathology, we conducted a double-blind, cross-over controlled trial of clomipramine (oral doses of 10-40 mg/day) and propanteline (active placebo) for 5 weeks in nine normal volunteers. Four other subjects completed the first part of the trial. These subjects were selected from 275 respondents to newspaper and radio requests for subjects who considered themselves as normal but were unhappy about their usual moods. They did not reach cut-off scores in the Self-Report Questionnaire and did not meet diagnostic criteria for any lifetime or current ICD-10 or DSM-III-R condition, as assessed by an open psychiatric interview and the Schedules for Clinical Assessment in Neuropsychiatry. Despite the small sample and the low level of initial symptomatology, both subjects and observers consistently detected significant improvements with clomipramine in a number of assessments of mood, notably decreased irritability and anxiety. This controlled trial suggests that it is possible to improve subclinical complaints through psychopharmacological agents, raises questions about the mechanisms of their action and discusses their implications.

Clomipramine, a better reference drug for panic/agoraphobia. I. Effectiveness comparison with imipramine.

An 8-week, double-blind, flexible-dose trial comparing low doses of clomipramine (mean=50 mg) with moderate doses of imipramine (mean=113.8 mg and propanteline (active placebo), was carried out in 60 out-patients with panic disorder with or without agoraphobia. Efficacy evaluation included global, anxiety and depression rating scales, and the determination of rates of relapse over up to 10 weeks of single-blind placebo follow-up. Both tricyclics were significantly more effective than propanteline, but clomipramine tended to act faster and more consistently than imipramine on most measures. Given the degree of blindness achieved and the significantly lower doses of clomipramine, this seems a better reference drug than imipramine for clinical trials in panic/agoraphobia.