Impact of feeding and housing systems on disease incidence in dairy calves.

Contentious issues in calf rearing include milk feeding level and single versus group housing. The current study was performed on a high-producing 170 Holstein cow dairy farm to investigate the impact of nutrition and housing on disease incidence. Calves (n=100) were allocated in birth order to one of two commonly used feeding strategies. Group A calves were group housed from birth and fed ad libitum milk replacer (MR) via a computerised machine using a single teat, with weaning commencing at 63 days. Group R calves were initially housed in individual pens receiving 2.5 litres of MR twice daily via a bucket until three weeks of age when they were group housed and fed 3 litres of MR twice daily via a group trough with weaning commencing at 56 days. In total, 80 (80 per cent) calves suffered from at least one incident of disease during the period from birth to 12 weeks. Group A calves had a greater risk of disease than group R calves (diarrhoea: OR 3.86 (95 per cent CI 1.67 to 8.9); pneumonia: OR 5.80 (95 per cent CI 2.33 to 14.44)). There was a 5.1 per cent incidence of failure of passive transfer of Ig assessed via measurement of plasma total protein concentrations at 48 hours of age. It is hypothesised that the increased diarrhoea risk in group A calves was most likely associated with group housing, while the increased pneumonia risk was associated with the use of a single teat allowing increased transmission of pathogens from calf to calf.

Assessment of body fat in the pony: part II. Validation of the deuterium oxide dilution technique for the measurement of body fat.

REASONS FOR PERFORMING THE STUDY: Excessive accumulations or depletions of body fat have been associated with increased morbidity and mortality in horses and ponies. An objective, minimally-invasive method to accurately quantify body fat in living animals is required to aid nutritional management and define welfare/performance limits. OBJECTIVES: To compare deuterium oxide (D(2) O) dilution-derived estimates of total body water (TBW) and body fat with values obtained by 'gold standard' proximate analysis and cadaver dissection. HYPOTHESIS: D(2) O dilution offers a valid method for the determination of TBW and body fat in equids. METHODS: Seven mature (mean ± s.e. 13 ± 3 years, 212 ± 14 kg, body condition scores 1.25-7/9), healthy, Welsh Mountain pony mares, destined for euthanasia (for nonresearch purposes) were used. Blood samples were collected before and 4 h after D(2) O (0.11-0.13 g/kg bwt, 99.8 atom percent excess) administration. Plasma was analysed by gas isotope ratio mass spectrometry following filtration and zinc reduction. After euthanasia, white adipose tissue (WAT) mass was recorded before all body tissues were analysed by proximate chemical analyses. RESULTS: D(2) O-derived estimates of TBW and body fat were strongly associated with proximate analysis- and dissection-derived values (all r(2) >0.97, P≤0.0001). Bland-Altman analyses demonstrated good agreements between methods. D(2) O dilution slightly overestimated TBW (0.79%, limits of agreement (LoA) -3.75-2.17%) and underestimated total body lipid (1.78%, LoA -0.59-4.15%) and dissected WAT (0.72%, LoA -2.77-4.21%). CONCLUSIONS AND POTENTIAL RELEVANCE: This study provides the first validation of the D(2) O dilution method for the minimally-invasive, accurate, repeatable and objective measurement of body water and fat in living equids.

Assessment of body fat in the pony: part I. Relationships between the anatomical distribution of adipose tissue, body composition and body condition.

REASONS FOR PERFORMING STUDY: Evaluation of equine body fat content is important for nutritional and clinical purposes. However, our understanding of total body fat and its regional distribution in the body is sparse. Currently, body fat evaluation relies on the subjective assessment of body condition score (BCS), which has never been validated against 'gold standard' chemical analysis or dissection measurements in ponies. OBJECTIVES: To define the relationships between subjective (BCS), objective (morphometric) indices of body fat and 'gold standard' measurements of actual body composition. HYPOTHESES: BCS and morphometry offer valid, noninvasive methods for determination of body fat in equids. METHODS: Seven mature (mean ± s.e. 13 ± 3 years, 212 ± 14 kg, BCS 1.25-7/9), Welsh Mountain pony mares, destined for euthanasia (for nonresearch purposes), were used. For all ponies, body mass (BM), BCS and various morphometric measurements were recorded. Following euthanasia, all ponies were systematically dissected. Discrete white adipose tissue (WAT) depots were independently described. Gross, body chemical composition was determined by proximate analyses. RESULTS: Total somatic soft tissues increased linearly (r(2) = 1.00), whereas body WAT content (1-26% live BM) increased exponentially (r(2) = 0.96), with BCS. WAT was equally distributed between internal and external sites in all animals irrespective of BCS. Nuchal fat was a poor predictor of total WAT (r(2) = 0.66). Periorbital WAT did not alter with BCS (r(2) = 0.01). Heart girth:withers height and ultrasonic retroperitoneal fat depth were closely associated with total, chemically-extracted lipid which comprised 1-29% live BM (r(2) = 0.91 and 0.88, respectively). CONCLUSIONS AND POTENTIAL RELEVANCE: The exponential relationship between BCS and total body WAT/lipid suggests that BCS is unlikely to be a sensitive index of body fat for animals in moderate-obese states. Morphometric measurements (body girths and retroperitonel fat depth) may be useful to augment subjective BCS systems.

Effect of dietary restriction on body condition, composition and welfare of overweight and obese pony mares.

REASONS FOR PERFORMING STUDY: Increased prevalence of obesity among UK horses and ponies demands evidence-based advice to promote weight loss. HYPOTHESIS: Restriction of dry matter intake (DMI) to 1% of body mass (BM, 67% [corrected] of predicted maintenance digestible energy [DE] requirements) would promote weight loss without compromise to health. METHODS: Five mature (mean ± s.e. 10 ± 2 years), overweight/obese pony mares (BM, 257 ± 20 kg: body condition score [BCS] 6.8/9 ± 0.5) were studied over 12 weeks. Animals were individually housed. Daily provision of a chaff-based, complete diet (measured DE, 8.5 MJ/kg DM) was restricted to 1% of actual BM as DMI daily. BCS, girth measurements and ultrasound-derived measures of subcutaneous fat depth overlying the gluteal region and 12th intercostal space (rib-eye) were recorded weekly. Body fat content was estimated at the beginning and end of the study by deuterium oxide dilution methods. Clinical biochemistry was monitored weekly. Behaviour was observed (24 h, 3/5 ponies) on 3 occasions. RESULTS: BM decreased by 4.3 ± 1.1% during the first week and thereafter by 0.7 ± 0.1% of BM at end of Week 1 each week. BCS remained constant. Heart and belly girths, rump width and subcutaneous fat depth at rib-eye decreased significantly with time and BM. Fat comprised 45 ± 19% of BM loss. Fatter animals lost relatively more fat. With decreased feeding activity, time spent in 'play' and rest increased by 36 ± 11% and 438 ± 95%, respectively. CONCLUSIONS: This plane of nutrition resulted in an overall rate of weight loss of 1% of outset BM weekly. BCS was not a useful index of early weight loss but heart and belly girths and subcutaneous rib-eye fat were identified as alternative markers. POTENTIAL RELEVANCE: This study provides an evidence-base for the management of weight loss in obese animals, especially those for which exercise may be contra-indicated.

Height measurement in horses and ponies: optimising standard protocols.

Standard and modified measuring sticks were used to record height at the withers and a 'non-contact' laser was used to measure withers and loin heights. Sixty horses and ponies, ranging in height (115 to 155 cm) and body condition score (BCS) (moderate to obese) were measured by each method at 10-minute intervals for 40 minutes. Measurement series were repeated over three successive days. Unique regression models were constructed for method-specific data. Coefficients of variation were similar for stick and laser methods (0.002 to 0.004 per cent). Models were not influenced by day of measurement or BCS. Withers height decreased significantly (0.48 cm, 95 per cent confidence intervals -0.61 to -0.36 cm, P<0.001) over the first 20 minutes. In living animals, laser-derived measurements of withers height at T(20) exceeded stick measurements by approximately 1 cm (P<0.001). Loin height remained similar across time. Some alteration in relaxed withers height is an inevitable consequence of changes in muscle tone at the scapulothoracic synsarcosis.

Persistent respiratory irregularity in patients with panic disorder.

BACKGROUND: Dysregulated respiratory control may play a role in the pathophysiology of panic disorder. This could be due to abnormalities in brain stem respiratory nuclei or to dysregulation at higher brain levels. Results from previous studies using the doxapram model of panic have yielded an unclear picture. A brief cognitive manipulation reduced doxapram-induced hyperventilation in patients, suggesting that higher level inputs can substantially alter their respiratory patterns. However, respiratory abnormalities persisted, including a striking irregularity in breathing patterns. METHODS: To directly study respiratory irregularity, breath-by-breath records of tidal volume (V(t)) and frequency (f) from previously studied subjects were obtained. Irregularity was quantified using von Neumann's statistic and calculation of "sigh" frequency in 16 patients and 16 matched control subjects. Half of each group received a standard introduction to the study and half received a cognitive intervention designed to reduce anxiety/distress responses to the doxapram injection. RESULTS: Patients had significantly greater V(t) irregularity relative to control subjects. Neither the cognitive intervention nor doxapram-induced hyperventilation produced significant changes in V(t) irregularity. The V(t) irregularity was attributable to a sighing pattern of breathing that was characteristic of panic patients but not control subjects. Patients also had somewhat elevated f irregularity relative to control subjects. CONCLUSIONS: The irregular breathing patterns in panic patients appear to be intrinsic and stable, uninfluenced by induced hyperventilation or cognitive manipulation. Further study of V(t) irregularity and sighs are warranted in efforts to localize dysregulated neural circuits in panic to brain stem or midbrain levels.

Effect of alcohol on social phobic anxiety.

OBJECTIVE: Previous research has demonstrated a greater-than-expected association between social phobia and alcohol use disorders. The purpose of this study was to test the hypothesis that drinking alcohol reduces social phobic anxiety. METHOD: Treatment-seeking individuals with social phobia (N = 40) were asked to give two impromptu speeches. Twenty subjects received a placebo alcoholic drink before both speeches, and 20 subjects received a placebo before the first speech, followed by a moderate dose of alcohol before the second speech. Subjective anxiety ratings, heart rate, and cognitions related to social anxiety were used as measures of anxiety. RESULTS: Repeated measures analyses of variance yielded no significant differences in anxiety (subjective, physiological, cognitive) between the alcohol and placebo groups. Current and past drinking habits did not significantly alter the effect of alcohol on anxiety. The belief that one received alcohol was significantly related to levels of subjective anxiety and negative cognitions. CONCLUSIONS: Alcohol does not directly reduce social phobic anxiety. The belief that one received alcohol may reduce social anxiety.

Serotonin transporter and seasonal variation in blood serotonin in families with obsessive-compulsive disorder.

The serotonin transporter (HTT) is a candidate gene for obsessive-compulsive disorder (OCD) that has been associated with anxiety-related traits. The long (l) and short (s) variants of the HTT promoter have different transcriptional efficiencies. HTT promoter genotype and blood 5-HT concentration were examined in 70 subjects from 20 families ascertained through children and adolescents with a DSM-III-R diagnosis of OCD. The HTT promoter variant had a significant effect on blood 5-HT content. Subjects with the l/l and l/s genotypes had significantly higher blood 5-HT levels than did those with the s/s genotype. There was a significant interaction between HTT promoter genotype and seasonal variation in blood 5-HT content, with significant seasonal differences in 5-HT occurring only in the subjects with the l/l genotype. Further studies of the regulation of HTT gene expression are indicated.

Specific fears and phobias. Epidemiology and classification.

BACKGROUND: Data on eight specific fears representing DSM-III-R simple phobia were analysed to evaluate: (a) their prevalence and (b) the validity of subtypes of specific phobia defined by DSM-IV. METHOD: A modified version of the Composite International Diagnostic Interview was administered to a probability sample of 8098 community respondents. Correlates of responses to questions concerning these fears were analysed. RESULTS: The most prevalent specific fears were of animals among women, and of heights among men. Slight evidence was found for specific phobia subtypes. Number of fears, independent of type, powerfully predicted impairment, comorbidity, illness course, demographic features, and family psychopathology. CONCLUSION: Number of specific fears may mark a general predisposition to psychopathology. More detailed information is needed to resolve the question of specific phobia subtypes.

Adrenocorticotropic hormone and cortisol responses to corticotropin-releasing hormone: changes in panic disorder and effects of alprazolam treatment.

This study applied the corticotropin-releasing hormone (CRH) stimulation test to patients with panic disorder, before and during treatment with alprazolam, and to control subjects. In contrast to some, but not all prior studies, untreated, nondepressed panic disorder patients failed to show blunted adrenocorticotropic hormone or cortisol responses to CRH. In fact, the responses were subtly enhanced in that they were more rapid than those of controls. After 12 weeks of alprazolam treatment, repeat testing gave results that were indistinguishable from those of controls. Inconsistency among reports of CRH testing in panic disorder may be related to interactions among illness mechanisms, concurrent subthreshold depressive symptoms, the chronic stress of the illness, and hyperresponsiveness of panic patients to the acute stress of experimental manipulations. Pretreatment abnormalities in hypothalamic-pituitary-adrenal axis function appear to resolve with alprazolam treatment. Preliminary observations suggest that pretreatment dysregulation of the hypothalamic-pituitary-adrenal system may predict a more difficult or less satisfactory treatment.

Childhood adversity and vulnerability to mood and anxiety disorders.

Based upon epidemiological surveys, adverse childhood events are proposed to be risk factors for adult depressive and anxiety disorders. However, the extent to which these events are seen in clinical patient populations is less clear. We examined the prevalence of a number of proposed risk factors for depression in 650 patients with mood and anxiety disorders at the time of presentation for treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse, or sexual abuse (childhood adversity) was found in approximately 35% of patients with major depression and panic disorder, was more common in women than men, and was associated with an earlier onset of symptoms. Childhood adversity was also strongly associated with marital discord/divorce, and psychopathology in a parent, suggesting family discord predisposes to childhood abuse. Furthermore, the association of childhood abuse with parental mental illness suggests that genetic and environmental factors are difficult to separate as etiological factors in vulnerability.

Absorption, pharmacokinetics and metabolism of 14C-sumatriptan following intranasal administration to the rat.

1. Studies have been carried out to investigate the absorption of sumatriptan after intranasal administration to rats. The pharmacokinetics, metabolism and excretion of 14C-sumatriptan were compared following intranasal and intravenous dosing to male and female albino rats using an aqueous buffered formulation at pH 5.5. 2. Following intravenous administration sumatriptan was eliminated from plasma with a half-life of about 1.1 h. After intranasal administration there was rapid absorption of part of the dose and two peak plasma concentrations were observed, initially at 0.5 and then at 1.5-2 h. The elimination half-life after the second peak was estimated as being about 4 h. 3. Radioactivity was largely excreted in urine (up to 89% of dose in 168 h) after both intravenous and intranasal administration, with a faster rate of excretion after intravenous dosage (73% males, 64% females within 6 h) than after intranasal dosage (37% males, 40% females within 6 h). 4. 14C-sumatriptan was the major component in urine and in extracts of faeces after both intravenous and intranasal administration. The major metabolite excreted in urine and faeces was GR49336, the indole acetic acid analogue. 5. The results of this in vivo rat study suggest that absorption of the dose via the nasal mucosa is incomplete after intranasal administration and that there is a secondary absorption phase probably reflecting oral absorption of part of the dose. The bioavailability is estimated as about 30%, for the period 0-6 h.

Platelet alpha 2-adrenoreceptors, catecholamines, hemodynamic variables, and anxiety in panic patients and their asymptomatic relatives.

The objectives of this study were to a) replicate our prior finding of a decreased number (Bmax) of platelet alpha 2-adrenoreceptors in panic disorder, b) determine if binding is also decreased in asymptomatic first-degree relatives of panic patients (known to be at increased risk for developing panic), and c) evaluate the effect of treatment on the presumptive decrease in binding (i.e., is the decrease a state or a trait marker for panic?). Panic patients had clonidine and yohimbine platelet-binding assays, symptom ratings, and measurement of lying and standing plasma epinephrine, norepinephrine, systolic and diastolic blood pressure, and heart rate before treatment, after approximately 2 months of medication (fluoxetine, tricyclics, or alprazolam) and/or cognitive behavioral treatment, and after symptom remission while drug free; normal subjects had determinations of the same measures at approximately the same time intervals. Relatives of both groups had one determination only of all measures. Tritiated clonidine binding was decreased and lying heart rate was increased in patients before treatment. Magnitude of binding decrease was correlated with symptom severity and standing norepinephrine. No binding abnormality was seen in first-degree relatives of patients. Treatment increased clonidine binding in patients. Both patients and relatives of patients showed significantly increased standing plasma norepinephrine in comparison to controls. There is a state-related decrease in binding, associated with symptom severity and norepinephrine, in panic disorder. Abnormal reactivity of norepinephrine to standing might be a marker for increased likelihood of panic development in individuals at risk.

Respiratory psychophysiology and anxiety: cognitive intervention in the doxapram model of panic.

UNLABELLED: The goals of this study were to: a) confirm prior evidence that the respiratory stimulant doxapram induces panic attacks and produces excessive hyperventilation in patients with panic disorder and b) explore the impact of cognitive mediators on symptom and respiratory responses. METHOD: Thirty-two subjects (16 patients and 16 controls) received doxapram (0.5 mg/kg) and placebo infusions while symptom, respiratory, and heart rate responses were monitored. Subjects were randomly assigned to receive either a standard introduction or a cognitive intervention designed to reduce the panic responses of panic patients to laboratory challenges. RESULTS: Doxapram was a potent and specific panicogenic agent, inducing panic in 75% of patients and 12.5% of controls. Compared with controls, patients also showed a greater decrease in end tidal carbon dioxide (CO2) and greater increases in minute ventilation, respiratory frequency, and heart rate. The cognitive intervention substantially attenuated the excessive hyperventilatory response of patients but did not fully normalize their breathing patterns. Tidal volume was the only respiratory measure not significantly altered by the cognitive intervention. CONCLUSIONS: In patients with panic disorder, doxapram (0.5 mg/kg) triggers panic attacks about as potently as 7% CO2 and more potently than 5% CO2 or lactate. Psychological factors can modulate the appearance of ventilatory abnormalities in panic patients, but persistent respiratory disturbances were still seen. Psychological factors and respiratory physiology both appear to be important phenomena in laboratory panic.

Neuroendocrine responses to laboratory panic: cognitive intervention in the doxapram model.

Doxapram is a respiratory stimulant that appears to be a potent and specific panicogenic agent. It also elicits an abnormal ventilatory response in patients with panic. A replication study confirmed these findings and demonstrated that behavioral and ventilatory responses to doxapram were significantly modified by a psychological intervention designed to cognitively block panic. The replication study provided an opportunity to simultaneously investigate the neuroendocrine effects of the illness, the drug, the drug-induced panic attacks, and the cognitive intervention. Epinephrine (EPI), norepinephrine (NE), growth hormone (GH), adrenocorticotropin (ACTH), and cortisol were studied in patients with panic and control subjects given placebo and doxapram injections after receiving either standard instructions or a brief cognitive intervention. Patients with panic had elevated levels of EPI, ACTH, and cortisol throughout the study. Doxapram had little or no detectable effects on plasma NE, GH, ACTH, and cortisol. Doxapram-induced panic attacks were not associated with elevations in NE, GH, ACTH, or cortisol. Doxapram led to a rapid and very brief rise in plasma EPI, which was small in subjects who did not panic and pronounced in patients who did panic. The cognitive intervention attenuated the EPI response to doxapram, perhaps through its effect on panic, and modified the temporal pattern of ACTH and cortisol secretion. These results suggest that: (1) further study of catecholamine responses within the first few minutes after panic induction is needed; (2) intense panic can occur without significant activation of the hypothalamic-pituitary-adrenal axis; and (3) cognitive factors can modulate neuroendocrine activity in laboratory studies of patients with panic.

Hypothalamic-pituitary-adrenal axis activity in panic disorder. 24-hour secretion of corticotropin and cortisol.

BACKGROUND: Oversecretion of corticotropin-releasing hormone and/or dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to pathophysiologic processes in panic disorder, but documentation of HPA axis disturbance in panic has been inconsistent. In the current study we examined HPA axis activity in panic disorder over a full circadian cycle, using frequent blood sampling to provide detailed assessment of corticotropin and cortisol secretion. METHODS: Twenty patients with panic disorder and 12 normal control subjects were studied. Blood samples were drawn every 15 minutes for 24 hours and assayed for corticotropin and cortisol levels. RESULTS: Patients with panic disorder had elevated overnight cortisol secretion and greater amplitude of ultradian secretory episodes. Patients who entered the study through clinical referral channels had greater cortisol secretion than those recruited by advertisements. Patients with panic disorder who had a low frequency of panic attacks had elevated daytime corticotropin levels and elevated corticotropin ultradian amplitude. Patients with a high frequency of attacks had shifted corticotropin circadian cycles. CONCLUSIONS: Patients with panic disorder demonstrate subtle alterations in HPA axis activity, characterized by overnight hypercortisolemia and increased activity in ultradian secretory episodes, but HPA axis alterations in panic are modulated by illness severity and treatment seeking. It remains unclear whether HPA axis dysregulation in panic represents a pathogenic defect within the axis itself. Inconsistencies in prior work may reflect the subtlety of the abnormalities seen, differences in clinical characteristics of patients studied, and the use of different probes and measurement contexts.

Hypothalamic-pituitary-adrenal axis activity in panic disorder: effects of alprazolam on 24 h secretion of adrenocorticotropin and cortisol.

Pre-clinical and some clinical evidence suggests that central overdrive within the hypothalamic-pituitary-adrenal (HPA) axis may play a role in panic disorder, and that the anti-panic efficacy of alprazolam may involve its ability to inhibit this drive. Detailed examination of 24 h secretion of adrenocorticotropin (ACTH) and cortisol in 20 panic patients had revealed subtle HPA axis abnormalities prior to treatment. In order to determine whether these abnormalities resolve with alprazolam therapy, these patients were re-studied over a full circadian cycle after 12 weeks on alprazolam. Alprazolam produced substantial improvement in clinical status which was accompanied by nearly full resolution of pre-treatment hypercortisolemia. The impact of treatment on ACTH was more complex and influenced by symptom severity. The results are consistent with the hypotheses that HPA axis regulation is subtly disturbed in panic disorder and that impact on the HPA axis may play a role in alprazolam's mechanism of efficacy.

Hypothalamic-pituitary-adrenal axis activity in panic disorder: prediction of long-term outcome by pretreatment cortisol levels.

OBJECTIVE: The authors sought to determine whether hypothalamic-pituitary-adrenal (HPA) axis activity in patients before their treatment for panic disorder can predict follow-up functional status. Although baseline HPA axis disturbances in patients with panic disorder appear to attenuate with treatment, there is evidence that they may be linked to poorer long-term outcomes. METHOD: Follow-up clinical data were obtained for 18 of 20 patients with panic disorder who participated in a detailed study of HPA axis activity in panic, both before and during their treatment with alprazolam. HPA axis assessment included monitoring of adrenocorticotropin and cortisol over a full circadian cycle. The relationships between disability and clinical status at 2-year follow-up and HPA axis overactivity at entry were examined. RESULTS: Mean 24-hour cortisol levels before treatment provided a strong, positive predictor of disability scores at follow-up. Those patients who achieved the treatment goal of medication-free remissions had less evidence of HPA axis overactivity at entry than those who were not in remission. CONCLUSIONS: HPA axis activity before treatment did predict outcome 2 years later. This relationship appears robust and reproducible. Further work is needed to define the neuroendocrine mechanisms underlying the HPA axis markers that are linked to long-term functioning and to determine the biological, psychological, and social processes that link HPA axis disturbance to poorer outcomes.