The impact of direct-fed microbials and enzymes on the health and performance of dairy cows with emphasis on colostrum quality and serum immunoglobulin concentrations in calves.

Thirty-six cows were blocked by calving date and randomly assigned to one of three treatments. Cows were on treatments 3 weeks prepartum through 8 weeks post-partum. Treatments were as follows: (i) no direct-fed microbial (DFM) or cellulase and amylase enzymes (C), (ii) 45.4 g/day of DFM (D) or (iii) 45.4 g/day of DFM and 18.2 g/day of enzyme (DE). Total mixed ration fed and refused were measured daily to determine dry matter intake (DMI). Blood samples were taken three times weekly and analysed for ß-hydroxybutyrate, glucose and non-esterified fatty acids. Body weight (BW) was measured weekly. Colostrum was weighed and analysed for IgA and IgG concentration. Calves were fed 4 L of colostrum within 2 hr of birth. Calf blood samples were taken at 0 and 24 hr for analysis of IgA and IgG concentrations and apparent efficiency of absorption. Milk yield was measured daily and samples collected weekly. Initial BW was different among treatments with D being lesser than C or DE treatments. Body weight, weight gain, efficiency of gain, DMI and blood parameters were unaffected. Treatment did not affect colostrum yield. Ash percentage of colostrum tended to increase with D and DE, while IgA and total solids yield decreased with D. Colostrum fat yield was decreased in D and DE. Treatments did not impact BW, serum IgA and IgG concentrations or apparent efficiency of absorption of calves. Post-partum BW, DMI, blood parameters, milk production and composition were unaffected by treatment. However, cows on D gained more BW and tended to have greater efficiency of gain compared to those on DE, but were similar to C. Somatic cell scores were greatest for D. Results indicate that DFM and enzyme supplementation did not improve health and performance of dairy cattle during the pre- and post-partum periods under conditions of this study.

Caffeine consumption and fibrocystic breast disease: a case-control epidemiologic study.

In a hospital-based case-control study that included 634 women with fibrocystic breast disease and 1,066 comparison women in Connecticut, the occurrence of fibrocystic breast disease was positively associated with average daily consumption of caffeine. Women who consumed 31-250 mg of caffeine/day had a 1.5-fold increase in the odds of disease, whereas women who drank over 500 mg/day had a 2.3-fold increase in the odds. The association with caffeine consumption was especially high among women with atypical lobular hyperplasia and with sclerosing adenosis with concomitant papillomatosis or papillary hyperplasia, both of which have been associated with an increased breast cancer risk. The association was specific to fibrocystic breast disease in that there was no association of caffeine consumption with fibroadenoma or other forms of benign breast disease.

Risk factors for fibrocystic breast disease and its histopathologic components.

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.

Rebound phenomena in Tourette's syndrome after abrupt withdrawal of clonidine. Behavioral, cardiovascular, and neurochemical effects.

Following an open trial of clonidine hydrochloride (3 to 8 micrograms/kg/day for 12 weeks), we studied the behavioral, cardiovascular, and neurochemical effects of abrupt clonidine withdrawal in seven patients with Tourette's syndrome aged 9 to 13 years. Five patients showed marked worsening of tics. After reinitiation of clonidine therapy, the time required for patients to return to prewithdrawal levels of tic symptoms ranged from two weeks to four months. Increases in motor restlessness, blood pressure, and pulse rate were also observed over the 72-hour period following abrupt withdrawal of clonidine. Plasma levels of free 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and urinary excretion of norepinephrine and epinephrine increased during the withdrawal period. Clonidine's effectiveness in Tourette's syndrome may be dependent on changes in dopaminergic as well as adrenergic mechanisms.

Clonidine treatment of Gilles de la Tourette's syndrome.

The safety and effectiveness of clonidine hydrochloride (3 to 5 micrograms/kg per day) were evaluated in 47 subjects with Gilles de la Tourette's syndrome, aged 7 to 48 years. Twenty-four subjects were randomly assigned to clonidine treatment and 23 to placebo. Forty subjects (21 given clonidine and 19 placebo) successfully completed the 12-week, double-blind clinical trial. Clinical ratings of tic severity improved for both groups. The magnitude of response was greater in the group receiving clonidine. Clinician-rated measures of motor tic severity, the degree to which the tics are "noticeable to others," motor tic counts from videotaped interviews, and parent-rated measures of impulsivity and hyperactivity were the most responsive to clonidine treatment. These results indicate that clonidine is more effective than placebo in reducing some of the tic and other behavioral symptoms associated with Gilles de la Tourette's syndrome.

Plasma MHPG: within- and across-day stability in children and adults with Tourette's syndrome.

Within- and across-day stability of unconjugated plasma 3-methoxy-4-hydroxyphenethyleneglycol (pMHPG, the major metabolite of norepinephrine) levels were assessed in several subgroups of 47 primarily child and adolescent subjects with Tourette's syndrome (TS). Mean morning pMHPG levels remained stable over a 20-min period from 8:30 to 8:50 AM at 3.5 +/- 0.8 ng/ml. However, the mean intraindividual fluctuation in pMHPG levels over 20 min was +/- 12%. Mean pMHPG levels remained stable in the morning from 8:00-8:30 AM to noon. However, an 11% decrease (p less than 0.01) in mean pMHPG levels was observed in the afternoon between noon and 3:00-4:00 PM. Monitored on consecutive days, mean morning pMHPG levels fell 12% (p less than 0.002). The afternoon and across-day falls in pMHPG levels observed in this study of primarily children and adolescents with TS have not been observed in studies of adult control subjects. The results suggest that the design of research protocols involving children and adolescents that use pMHPG should take into consideration the effects of time, both within- and across-day, in pMHPG levels.

Computed tomographic brain scanning in four neuropsychiatric disorders of childhood.

CAT scans were performed in 66 patients with neuropsychiatric disorders of childhood (infantile autism, attention deficit disorder, Tourette's disorder, and language disorder) and a control group of 20 medical patients. Ventricular volume and brain density were determined by quantitative, computer-based methods by researchers blind to the patients' diagnoses. There were no significant differences among diagnostic groups or between neuropsychiatric patients and medical control patients in total ventricular volume, right-left ventricular volume ratio, ventricular asymmetries, ventricle-brain ratios, or brain density.

Short- and long-term treatment of Tourette's syndrome with clonidine: a clinical perspective.

Thirteen patients with Gilles de la Tourette's syndrome were treated with clonidine (0.125 to 0.3 mg/d) for at least 60 weeks. In a single-blind, placebo-controlled trial, 6 of the 13 patients were judged to be unequivocal responders to clonidine, and 6 other patients had an equivocal response. There was significant improvement in motor and phonic tics, as well as in associated behavior problems, and there were no serious side effects. Tolerance to clonidine did not develop. Further placebo-controlled, randomized, double-blind studies of clonidine in Tourette's syndrome are needed to establish the drug's efficacy.

Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls.

To examine the role of noradrenergic, dopaminergic, and serotonergic mechanisms in the pathobiology of obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), concentrations of tyrosine (TYR), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the lumbar cerebrospinal fluid (CSF) of 39 medication-free OCD patients, 33 medication-free TS patients, and 44 healthy volunteers. CSF TYR concentrations were reduced (p < .05) in the OCD patients compared to the healthy subjects. CSF NE in TS patients was 55% higher than in healthy controls (p < .001) and 35% higher than in OCD patients (p < .001). After covarying for height, CSF HVA levels were reduced (p < .05) in the OCD group compared to TS patients but not compared to the normal volunteers. No mean differences in CSF MHPG, TRP, and 5-HIAA were observed in this study across the three groups. The CSF NE data support the hypothesis that noradrenergic mechanisms are involved in the pathobiology of TS. Alterations in the balance of noradrenergic, dopaminergic, and serotonergic systems are likely involved in the pathobiology of OCD.

The trajectory of cognitive development in males with fragile X syndrome.

The trajectory of cognitive development in males with fragile X syndrome was identified in a cross-sectional study of 56 males and in a smaller, longitudinal study of 10 fragile X males. Results from both studies indicated steady cognitive growth until late childhood and early adolescence (10 to 15 years of age), at which point mental age plateaued and IQ declined. Males with higher initial IQ scores manifested more IQ decline than those with initial lower levels of intelligence. The trajectories of IQ differ from those in other etiological groups and mixed groups of retarded individuals. Results have direct implications for intervention strategies with fragile X males. Parents and teachers should be informed about the possibility of an early plateau in mental age, the impact this may have on the child's academic performance, and that the plateau and IQ decline may not be apparent in the child's adaptive behaviors.

Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity.

OBJECTIVE: To evaluate the reliability and validity of a semistructured measure of obsessive-compulsive symptom severity in children and adolescents with obsessive-compulsive disorder (OCD). METHOD: Sixty-five children with OCD (25 girls and 40 boys, aged 8 to 17 years) were assessed with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Interrater agreement was assessed by four raters in a subsample (n = 24). Discriminant and convergent validity were assessed by comparing CY-BOCS scores to self-ratings of depression, anxiety, and obsessive-compulsive symptoms. RESULTS: Internal consistency was high, measuring .87 for the 10 items. The intraclass correlations for the CY-BOCS Total, Obsession, and Compulsion scores were .84, .91, and .68, suggesting good to excellent interrater agreement for subscale and total scores. The CY-BOCS Total score showed a significantly higher correlation with a self-report of obsessive-compulsive symptoms (r = .62 for the Leyton survey) compared with the Children's Depression Inventory (r = .34) and the Children's Manifest Anxiety Scale (r = .37) (p = .02 and .05, respectively). CONCLUSIONS: The CY-BOCS yields reliable and valid subscale and total scores for obsessive-compulsive symptom severity in children and adolescents with OCD. Reliability and validity appear to be influenced by age of the child and the hazards associated with integrating data from parental and patient sources.

Obsessive compulsive disorder in children and adolescents: phenomenology and family history.

Phenomenology and family history in 21 clinically referred children and adolescents with obsessive compulsive disorder are described. Each child and family participated in a standard clinical psychiatric assessment. The most frequently reported symptoms were repeating rituals, washing, ordering and arranging, checking, and contamination concerns. Controlling behaviors involving other family members were seen in 57% of the patients. Associated psychopathology was common: 38% received an anxiety disorder diagnosis; 29% received a mood disorder diagnosis; tics were observed in 24%. Fifteen (71%) of the children had a parent with either obsessive compulsive disorder (N = 4) or obsessive-compulsive symptoms (N = 11). The clinical and research implications of these findings are discussed.

The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity.

Despite the overt nature of most motor and phonic tic phenomena, the development of valid and reliable scales to rate tic severity has been an elusive goal. The Yale Global Tic Severity Scale (YGTSS) is a new clinical rating instrument that was designed for use in studies of Tourette's syndrome and other tic disorders. The YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. Data from 105 subjects, aged 5 to 51 years, support the construct, convergent, and discriminant validity of the instrument. These results indicate that the YGTSS is a promising instrument for the assessment of tic severity in children, adolescents and adults.

Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder.

Rigorously designed clinical trials have demonstrated the efficacy and safety of fluoxetine in adults with major depressive disorder and obsessive-compulsive disorder (OCD) but not in patients below 18 years old. This report describes a randomized, double-blind, placebo-controlled, fixed-dose (20 mg qd) trial of fluoxetine in 14 children and adolescents with OCD, ages 8 to 15 years old; the study was 20 weeks long with crossover at 8 weeks. Obsessive-compulsive symptom severity was measured on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinician's Global Impression-Obsessive Compulsive Disorder scale (CGI-OCD). The CY-BOCS total score decreased 44% (N = 7, p = .003) after the initial 8 weeks of fluoxetine treatment, compared with a 27% decrease (N = 6, p = .13) after placebo. During the initial 8 weeks, the magnitude of improvement for the fluoxetine group significantly exceeded that for the placebo group as measured by the CGI-OCD (p = .01) but not by the CY-BOCS (p = .17). The most common drug side effects were generally well tolerated. The results suggest that fluoxetine is a generally safe and effective short-term treatment for children with OCD.

Plasma-free homovanillic acid: within- and across-day stability in children and adults with Tourette's syndrome.

Within- and across-day stability of plasma-free homovanillic acid (pHVA) was assessed in children and adults with Tourette's syndrome. A diurnal fall in pHVA was observed in 13 of 15 subjects. There was a small but significant (p less than .0001) decrease (8%) in mean morning pHVA levels obtained just 20 minutes apart (8:30 A.M. and 8:50 A.M.). A substantial and significant (p less than .001) mean decrease in pHVA (25%) was observed when samples obtained between 8:00 and 8:30 A.M. were compared with samples obtained at 12:00 noon. Changes in pHVA levels observed during the afternoon (between 12:00 noon and 4:00 P.M.) were small, nondirectional, and nonsignificant. Repeated measurement of morning pHVA in the same individual after 24 or more hours revealed marked increases or decreases in many individuals, suggesting that morning pHVA is not a stable measure. The results of this and previous studies suggest that pHVA obtained at 12:00 noon or later in the day may be a more reliable measure of centrally produced HVA. Further studies are needed regarding the stability of pHVA over time.

Whole blood serotonin and tryptophan levels in Tourette's disorder: effects of acute and chronic clonidine treatment.

Whole blood serotonin (WB5HT) and tryptophan (WBTRP) levels were studied in 20 patients (aged 8 to 45 years) with Tourette's disorder under medication-free baseline conditions and following acute and chronic clonidine treatment. Compared to 87 normal controls, Tourette's disorder patients had lower mean baseline WBTRP levels (mean +/- SEM: Tourette's, 5993 +/- 304 ng/ml vs. 6822 +/- 169 ng/ml; p less than .03). No significant differences in mean baseline WB5HT levels were found. Three hours after an acute dose of clonidine (2.5 - 5.1 micrograms/kg, p.o. at 9:00 A.M.), no mean differences were observed (baseline vs. post 3 hours) in WB5HT or WBTRP levels. However, following chronic treatment (greater than 3 weeks) with clonidine (3-8 micrograms/kg/day, p.o.), WB5HT levels were increased in 9 of 14 Tourette's disorder patients. The mean increases in WB5HT levels following chronic clonidine treatment were significant when WB5HT levels were expressed per 10(9) platelets. (mean +/- SEM: baseline, 471 +/- 45 ng/10(9) platelets vs. chronic, 697 +/- 82 ng/10(9) platelets, p = .02). No mean differences in WBTRP levels were observed after chronic clonidine treatment. These findings are discussed in light of a proposed intermediary role of 5HT systems in the mode of action of clonidine in the treatment of Tourette's disorder.

Brief debrisoquin administration to assess central dopaminergic function in children.

Central dopaminergic (DA) function in children was assessed by monitoring plasma-free homovanillic acid (pHVA) levels after brief (18 hour) administration with debrisoquin sulfate, a peripherally active antihypertensive agent that blocks peripheral, but not central, HVA production. Brief debrisoquin administration resulted in marked reductions in pHVA in each of six patients studied. In five of the six patients, post-debrisoquin pHVA levels remained relatively stable over the six-hour period of observation. No significant cardiovascular or behavioral side effects of debrisoquin were observed. The brief debrisoquin administration method appears to be a safe, simple, and potentially valid peripheral technique for evaluating aspects of central dopaminergic function in children with neuropsychiatric disorders. Additional work is needed to further establish this method's validity and reliability.

Fragile X syndrome: genetic predisposition to psychopathology.

Fragile X syndrome is a newly recognized X-linked disorder which has been associated with a high prevalence of psychiatric disturbance, particularly attention deficit disorder and autism. The present study involved the neuropsychiatric evaluation of 14 males with the disorder who were between the ages of 3 to 27 years. Pervasive hyperactivity, impulsivity, and attentional deficits were found among all of the subjects, while a significant degree of anxiety was manifested by more than half. Although the majority of subjects exhibited poor eye contact, atypical speech and language functioning, and stereotyped behavior, only one met DSM-III diagnostic criteria for a persistent pervasive developmental disorder. Gaze aversion, noted among half of the subjects, was attributed to underlying anxiety rather than to autistic social dysfunction because of the otherwise socially engaged and affectionate behavior exhibited by the subjects. Failure to make this distinction in the context of cognitive and linguistic impairments associated with fragile X syndrome may account for the high rates of autism reported by other investigators.

Changing patterns of intellectual strengths and weaknesses in males with fragile X syndrome.

Examined the changing profiles of intelligence in males with fragile X syndrome as these individuals increased in chronological age. Using a psychometric instrument designed to measure styles of information processing, 21 males aged 4 to 27 years were examined cross-sectionally in sequential processing, simultaneous processing, and achievement. The age of the subject was associated with age-equivalent levels of both simultaneous processing and achievement, but fragile X males did not show higher levels of sequential processing with increasing chronological age. Compared to younger fragile X males, the older subjects were more delayed in sequential processing skills relative to their in other areas. A smaller longitudinal study confirmed the presence of a plateau in sequential processing among those subjects tested two times after the age of 10 years. Implications are discussed for diagnosis, intervention, and the matching of subject groups in mental retardation research.

Trajectory of adaptive behavior in males with fragile X syndrome.

Adaptive behavior in males with fragile X syndrome was longitudinally examined in 17 subjects, ages 1 to 17. Subjects received adaptive behavior evaluations on two occasions within one of three age periods. All domains of the Vineland Adaptive Behavior Scales increased from youngest to oldest age groups, yet older subjects (ages 10 to 17) showed significant declines in their adaptive behavior scores from first to second testing. A relative strength in Daily Living Skills and weakness in Socialization emerged only among older subjects. There was a significant relationship between adaptive behavior and mental age scores in all subjects. Discussion emphasized the parallels between declines in IQ and adaptive behavior as well as the need for further research on adaptive skills in young adults with fragile X syndrome.