Stabilization treatment of remitted psychotic depression: the STOP-PD study.

OBJECTIVE: We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD). METHODS: Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination. RESULTS: The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change. CONCLUSION: Continuation of acute treatment was associated with stability of remission.

Massive transfusions for critical bleeding: is everything old new again?

Massive transfusion or major haemorrhage protocols have been widely adopted in the treatment of critically bleeding patients. Following evidence that higher ratios of transfused plasma and platelets to red blood cells may offer survival benefits in military trauma patients, these ratios are now commonly incorporated into massive transfusion protocols. They more closely resemble the effects of whole blood transfusion, which in the second half of last century was largely replaced by individual blood component transfusion based on laboratory-guided indicators. However, high-quality evidence to guide transfusion support for critically bleeding patients across the range of bleeding contexts is lacking, including for both trauma and non-trauma patients. More data on major haemorrhage support and clinical outcomes are needed to inform guidelines and practice.

Abdominal obesity and hip fracture: results from the Nurses' Health Study and the Health Professionals Follow-up Study.

UNLABELLED: Abdominal obesity might increase fracture risk. We studied the prospective associations between waist circumference, waist-to-hip ratio, and hip fracture. The indicators of abdominal obesity were associated with increased hip fracture risk in women, but not in men. The increased risk was restricted to women with low physical activity. INTRODUCTION: Low weight is an established risk factor for osteoporosis and hip fracture. However, the association between fat tissue, muscle, and bone is complex, and abdominal obesity might increase fracture risk. We studied the prospective associations between indicators of abdominal obesity and hip fracture in two large US cohorts. METHODS: At baseline in 1986 and through biennial follow-up, information on hip fracture and potential risk factors was collected in 61,677 postmenopausal women and 35,488 men above age 50. Waist and hip circumferences were reported at baseline and updated twice. RESULTS: During follow-up, 1168 women and 483 men sustained a hip fracture. After controlling for known risk factors, there was a significant association in women between increasing waist circumference and hip fracture (RR per 10-cm increase 1.13 (95 % CI 1.04-1.23) and between increasing waist-to-hip ratio and hip fracture (RR per 0.1 unit increase 1.14 (95 % CI 1.04-1.23), but these associations were not seen in men. In women, both measures interacted with physical activity. Those in the highest (≥0.90) versus lowest (<0.75) category of waist-to-hip ratio had increased risk of hip fracture if their activity was less than the population median (RR = 1.61, 95 % CI 1.18-2.19) but not if their activity was higher (RR = 1.00, 95 % CI 0.72-1.40). A similar pattern was found for waist circumference. CONCLUSION: Indicators of abdominal obesity were associated with increased hip fracture risk after controlling for BMI in women. The increased risk was restricted to women with low physical activity. In men, no significant associations were found.

Rating scales measuring the severity of psychotic depression.

OBJECTIVE: Unipolar psychotic depression (PD) is a severe and debilitating syndrome, which requires intensive monitoring. The objective of this study was to provide an overview of the rating scales used to assess illness severity in PD. METHOD: Selective review of publications reporting results on non-self-rated, symptom-based rating scales utilized to measure symptom severity in PD. The clinical and psychometric validity of the identified rating scales was reviewed. RESULTS: A total of 14 rating scales meeting the predefined criteria were included in the review. These scales grouped into the following categories: (i) rating scales predominantly covering depressive symptoms, (ii) rating scales predominantly covering psychotic symptoms, (iii) rating scales covering delusions, and (iv) rating scales covering PD. For the vast majority of the scales, the clinical and psychometric validity had not been tested empirically. The only exception from this general tendency was the 11-item Psychotic Depression Assessment Scale (PDAS), which was developed specifically to assess the severity of PD. CONCLUSION: In PD, the PDAS represents the only empirically derived rating scale for the measurement of overall severity of illness. The PDAS should be considered in future studies of PD and in clinical practice.

Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults.

INTRODUCTION: Mechanisms for liraglutide-induced weight loss are poorly understood. OBJECTIVE: We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals. DESIGN: Participants (N=49, 18-75 years, body mass index: 30-40 kg m(-2)) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed. RESULTS: Five-hour gastric emptying (AUC(0-300 min)) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80-1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5-0.6 mmol l(-1) versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC(0-300 min) (by ∼26% versus placebo, P=0.02). Glucagon iAUC(0-300 min) decreased by ∼30%, and iAUC(0-60 min) for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. FUNDING: Novo Nordisk. CONCLUSION: Gastric emptying AUC(0-300 min) was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

Measuring psychotic depression.

OBJECTIVE: Psychotic depression (PD) is a highly debilitating condition, which needs intensive monitoring. However, there is no established rating scale for evaluating the severity of PD. The aim of this analysis was to assess the psychometric properties of established depression rating scales and a number of new composite rating scales, covering both depressive and psychotic symptoms, in relation to PD. METHOD: The psychometric properties of the rating scales were evaluated based on data from the Study of Pharmacotherapy of Psychotic Depression. RESULTS: A rating scale consisting of the 6-item Hamilton melancholia subscale (HAM-D6 ) plus five items from the Brief Psychiatric Rating Scale (BPRS), named the HAMD-BPRS11 , displayed clinical validity (Spearman's correlation coefficient between HAMD-BPRS11 and Clinical Global Impression - Severity (CGI-S) scores = 0.79-0.84), responsiveness (Spearman's correlation coefficient between change in HAMD-BPRS11 and Clinical Global Impression - Improvement (CGI-I) scores = -0.74--0.78) and unidimensionality (Loevinger's coefficient of homogeneity = 0.41) in the evaluation of PD. The HAM-D6 fulfilled the same criteria, whereas the full 17-item Hamilton Depression Scale failed to meet criteria for unidimensionality. CONCLUSION: Our results suggest that the HAMD-BPRS11 is a more valid measure than pure depression scales for evaluating the severity of PD.

The once-daily human GLP-1 analogue liraglutide impacts appetite and energy intake in patients with type 2 diabetes after short-term treatment.

The aim was to investigate effects of liraglutide on appetite and energy intake in a randomized, placebo-controlled, double-blind, crossover study. Eighteen subjects with type 2 diabetes were assigned to treatment with once-daily subcutaneous liraglutide (increasing by weekly 0.6 mg increments) or placebo for 3 weeks. Appetite ratings were assessed using visual analogue scales during a 5-h meal test. Energy and macronutrient intake during the subsequent ad libitum lunch were also measured. After 3 weeks, mean postprandial and minimum hunger ratings were significantly lower with liraglutide 1.8 mg than placebo (p < 0.01), and the mean overall appetite score was significantly higher (p = 0.05), indicating reduced appetite. Liraglutide was associated with higher maximum fullness ratings (p = 0.001) and lower minimum ratings of prospective food consumption (p = 0.01). Mean estimated energy intake was 18% lower for liraglutide than placebo [estimated ratio 0.82 (95% CI 0.73;0.94); p = 0.004], but no significant differences in macronutrient distribution were noted. Findings suggest that reduced appetite and energy intake may contribute to liraglutide-induced weight loss.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

AIMS: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. FUNDING: Novo Nordisk A/S. RESULTS: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. CONCLUSIONS: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia.

Point-of-Care Glucose and Lipid Profile Measures Using a Human Point-of-Care Device in Mouse Models of Type 2 Diabetes Mellitus, Aging, and Alzheimer Disease.

A point-of-care (POC) device to measure mouse glucose and lipid profiles is an important unmet need for cost-effective, immediate decision making in research. We compared metabolic analyte profiles obtained using a human clinical POC device with those from a veterinary laboratory chemical analyzer (LCA). Unfasted terminal blood samples were obtained by cardiac puncture from C57Bl/6J mice used in a diet-induced obesity model of type 2 diabetes mellitus; age-matched C57Bl/6J controls; a transgenic mouse model of Alzheimer's disease on a C57BL/6J background (16 wk old); and aged C57BL/6J mice (24 to 60 wk old). Aliquots of the blood were immediately assayed onsite using the POC device. Corresponding serum aliquots were sent analyzed by LCA. Measures from the POC and LCA devices were compared by using the Bland-Altman and Passing-Bablok methods. Of a total of 40 aliquots, LCA results were within reported reference ranges for each model. POC results that fell beyond the device range were excluded from the analyses. The coefficient of determination and Passing-Bablok analysis demonstrated that POC glucose and HDL had the best agreement with LCA. The Bland-Altman analysis found no value-dependent bias in glucose and no significant bias in HDL. The remaining lipid analytes (cholesterol and triglyceride) showed significant bias. Until an improved, validated mouse POC device with lipid profile capability is available, the POC device that we tested appears adequate for screening glucose and HDL in mouse blood. Disadvantages of this clinical POC device are the narrow human ranges relative to ranges found in mice and its limited precision as compared with the LCA. This study demonstrates that when the samples are within the device range limits, this human POC device can accurately track metabolic syndrome and be used to compare patterns in glucose and HDL.

Sequence variants in the bovine gonadotrophin releasing hormone receptor gene and their associations with fertility.

Seven sequence variants (SVs) have been identified in exon 1 and in the promoter region upstream of the bovine gonadotrophin releasing hormone (GnRH) receptor gene, at nucleotides g.-331A>G, g.-108T>C, g.+206G>A, g.+260C>T, g.+341C>T, g.+383C>T and g.+410C>T relative to the translation start site. The SVs at nucleotides g.-108, g.260, g.341 and g.410 and those at g.206 and g.383 formed two groups with complete linkage disequilibrium within groups, but incomplete linkage disequilibrium between groups, and none of the SVs altered receptor amino acid sequence. The g.-108T>C allelic variants were associated with an approximately 0.4 day reduction in predicted transmitting ability for days to first service. None of the allelic variants affected the pattern of circulating LH following administration of GnRH. The g.260C>T alteration introduced a new transcription factor binding site in a region of DNA with relatively low nucleosome formation potential. The data suggest that selection for animals carrying the g.-108T>C group of alterations will improve fertility in the dairy cow.

Homophilic binding of PTP mu, a receptor-type protein tyrosine phosphatase, can mediate cell-cell aggregation.

The receptor-like protein tyrosine phosphatase, PTPmu, displays structural similarity to cell-cell adhesion molecules of the immunoglobulin superfamily. We have investigated the ability of human PTPmu to function in such a capacity. Expression of PTPmu, with or without the PTPase domains, by recombinant baculovirus infection of Sf9 cells induced their aggregation. However, neither a chimeric form of PTPmu, containing the extracellular and transmembrane segments of the EGF receptor and the intracellular segment of PTPmu, nor the intracellular segment of PTPmu expressed as a soluble protein induced aggregation. PTPmu mediates aggregation via a homophilic mechanism, as judged by lack of incorporation of uninfected Sf9 cells into aggregates of PTPmu-expressing cells. Homophilic binding has been demonstrated between PTPmu-coated fluorescent beads (Covaspheres) and endogenously expressed PTPmu on MvLu cells. Additionally the PTPmu-coated beads specifically bound to a bacterially expressed glutathione-S-transferase fusion protein containing the extracellular segment of PTPmu (GST/PTPmu) adsorbed to petri dishes. Covaspheres coated with the GST/PTPmu fusion protein aggregated in vitro and also bound to PTPmu expressed endogenously on MvLu cells. These results suggest that the ligand for this transmembrane PTPase is another PTPmu molecule on an adjacent cell. Thus homophilic binding interactions may be an important component of the function of PTPmu in vivo.

Compartmentalization of algal bioluminescence: autofluorescence of bioluminescent particles in the dinoflagellate Gonyaulax as studied with image-intensified video microscopy and flow cytometry.

Compartmentalization of specialized functions to discrete locales is a fundamental theme of eucaryotic organization in cells. We report here that bioluminescence of the dinoflagellate alga Gonyaulax originates in vivo from discrete subcellular loci that are intrinsically fluorescent. We demonstrate this localization by comparing the loci of fluorescence and bioluminescence as visualized by image-intensified video microscopy. These fluorescent particles appeared to be the same as the previously described in vitro "scintillons." We attribute the endogenous fluorescence to that of the bioluminescence substrate, luciferin, because (a) the fluorescence excitation and emission characteristics are comparable, (b) the autofluorescence is lost after exhaustive stimulation of bioluminescence, and (c) the fluorescence of discharged particles in vitro can be restored by adding luciferin. The fluorescence in vivo exhibits a standard property of circadian (daily) rhythmicity: under constant environmental conditions, the intensity of the particle fluorescence fluctuates cyclically (it is maximal during the night phase and is low during the day). Thus, luciferin is localized within the cell at discrete loci from which the bioluminescence emanates; the cellular quantity of luciferin is rhythmically modulated by the circadian clock.

Crystal structure of human protein tyrosine phosphatase 1B.

Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that catalyze the dephosphorylation of phosphotyrosine residues and are characterized by homologous catalytic domains. The crystal structure of a representative member of this family, the 37-kilodalton form (residues 1 to 321) of PTP1B, has been determined at 2.8 A resolution. The enzyme consists of a single domain with the catalytic site located at the base of a shallow cleft. The phosphate recognition site is created from a loop that is located at the amino-terminus of an alpha helix. This site is formed from an 11-residue sequence motif that is diagnostic of PTPs and the dual specificity phosphatases, and that contains the catalytically essential cysteine and arginine residues. The position of the invariant cysteine residue within the phosphate binding site is consistent with its role as a nucleophile in the catalytic reaction. The structure of PTP1B should serve as a model for other members of the PTP family and as a framework for understanding the mechanism of tyrosine dephosphorylation.

Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B.

The crystal structures of a cysteine-215-->serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosphatase was accompanied by a conformational change of a surface loop that created a phosphotyrosine recognition pocket and induced a catalytically competent form of the enzyme. The phosphotyrosine side chain is buried within the period and anchors the peptide substrate to its binding site. Hydrogen bonds between peptide main-chain atoms and the protein contribute to binding affinity, and specific interactions of acidic residues of the peptide with basic residues on the surface of the enzyme confer sequence specificity.

Autophosphorylation of protein kinase C at three separated regions of its primary sequence.

The major autophosphorylation sites of the rat beta II isozyme of protein kinase C were identified. The modified threonine and serine residues were found in the amino-terminal peptide, the carboxyl-terminal tail, and the hinge region between the regulatory lipid-binding domain and the catalytic kinase domain. Because this autophosphorylation follows an intrapeptide mechanism, extraordinary flexibility of the protein is necessary to phosphorylate the three regions. Comparison of the sequences surrounding the modified residues showed no obvious recognition motif nor any similarity to substrate phosphorylation sites, suggesting that proximity to the active site may be the primary criterion for their phosphorylation.

Genetic variation of metabolite and hormone concentration in UK Holstein-Friesian calves and the genetic relationship with economically important traits.

The decline of dairy cattle fertility worldwide remains a major concern, with conception rates to first service commonly below 40%. The length and severity of negative energy balance postpartum are unfavorably correlated with fertility, suggesting that the length and severity of negative energy balance and fertility are linked via several hormones or metabolites. These compounds therefore have the potential to predict fertility at a genetic level. The addition of a predictor trait for fertility into present fertility indices would accelerate genetic gain, particularly if it was expressed before adulthood. The objective of this work was to estimate the genetic variation in several metabolites and hormones in calves, and to determine their genetic relationships with fertility and production through sire predicted transmitting abilities (PTA; sires of calves sampled). Circulating concentrations of free fatty acids (FFA), glucose, growth hormone (GH), insulin, and insulin-like growth factor 1 (IGF-1) in male and female UK Holstein-Friesian dairy calves (average age +/- SD; 126 +/- 12.7 d) were analyzed during 2 studies: data set 1 (n = 496 females; 1996-2001; 7 commercial dairy herds) and data set 2 (n = 326 females, n = 256 males; 2002-2006; multiple ovulation and embryo transfer breeding scheme). Univariate mixed models were fitted to the data using ASREML. Basal concentrations of FFA, glucose, GH, insulin and total IGF-1 were all moderately heritable in both sexes (heritability range +/- SE; 0.09 +/- 0.05 to 0.66 +/- 0.14). The sire PTA for protein percentage had significant regression coefficients and approximate genetic correlations with FFA and insulin, and the sire PTA for calving interval had significant regression coefficients and approximate genetic correlations with GH. Additive genetic variance seems responsible for a moderate proportion of the phenotypic variation in important metabolites and regulatory hormones in male and female UK Holstein-Friesian dairy calves, therefore supporting further investigation into their use as juvenile predictors for fertility in the mature female.

Incidence and treatment of inadequate postovulatory progesterone concentrations in repeat breeder cows.

The incidence of low day 5 milk progesterone in dairy cows has been investigated and the efficacy of treating the problem assessed. The incidence of inadequate milk progesterone (empirically defined as <3ng/mL) in repeat breeder cows was 34% compared with 11.4% in first insemination cows. Treatment with an intravaginal progesterone device for 7 days starting from day 5 or 6 did not improve pregnancy rate. Treatment with 1500 iu human chorionic gonadotrophin (hCG) on day 5 gave an increase in pregnancy rate that was dependent on initial progesterone concentration and significant (P<0.05) in multiparous but not primiparous cows. While the incidence of inadequate day 5 progesterone was high in repeat breeder cows, it was responsive to hCG treatment, although only in multiparous and not primiparous animals.

Nonsynaptic glycine receptor activation during early neocortical development.

Glycine receptors (GlyRs) contribute to fast inhibitory synaptic transmission in the brain stem and spinal cord. GlyR subunits are expressed in the developing neocortex, but a neurotransmitter system involving cortical GlyRs has yet to be demonstrated. Here, we show that GlyRs in immature neocortex are excitatory and activated by a nonsynaptically released endogenous ligand. Of the potential ligands for cortical GlyRs, taurine is by far the most abundant in the developing neocortex. We found that taurine is stored in immature cortical neurons and that manipulations known to elevate extracellular taurine cause GlyR activation. These data indicate that nonsynaptically released taurine activates GlyRs during neocortical development. As fetal taurine deprivation can cause cortical dysgenesis, it is possible that taurine influences neocortical development by activating GlyRs.

A PPAR-independent pathway to PUFA-induced COX-2 expression.

Polyunsaturated fatty acids (PUFAs) induce COX-2 in bovine endometrial stromal cells through activation of peroxisome-proliferator-activated receptor alpha (PPARalpha). We have investigated alternative (PPAR-independent) pathways to COX-2 induction using a reporter construct driven by a COX-2 gene promoter sequence lacking a PPAR response element. This construct was induced by PUFAs, but not by PPAR agonists. PPAR-independent reporter gene expression occurred 6h after PPAR-dependent induction of the endogenous COX-2 gene. In contrast to PPAR-dependent COX-2 induction, which is not affected by NF-kappaB inhibitors, the PPAR-independent pathway was blocked by the NF-kappaB inhibitor MG132 or following deletion of NF-kappaB sites in the COX-2 promoter. The PPAR-independent effect of PUFA was mimicked by the PKC activators 4beta-PMA and prostaglandin F(2alpha), but was not blocked by the PKC inhibitor RO318425. The results demonstrate a pathway to the induction of COX-2 by PUFAs requiring NF-kappaB but not PPAR or PKC.

Effects of interaural time and level differences on the binaural interaction component of the 80 Hz auditory steady-state response.

The auditory steady-state evoked response (ASSR) is a scalp-recorded potential elicited by modulated sounds or repetitive transient sounds presented at a high rate. The binaural interaction component (BIC) of the ASSR equals the difference between the response to binaural stimuli and the sum of the responses to a monaural stimulus presented to the left ear and the right ear. This study examined the effect of the interaural time (ITD) and level (ILD) difference on the BIC of the 80 Hz ASSR. Sixteen human participants with normal hearing were tested. The ITD and ILD were varied from -1.6 to +1.6 msec and from 0 to +12 dB, respectively. The ITD function of the BIC showed a "V" shape, with a 0 value of BIC at ITD 0 msec and a positive BIC at ITD +0.8 to +1.6 msec. For ILD conditions, the BIC displayed negative values, and its amplitude became more negative as the ILD was increased. The results indicate that the ITD and ILD may be processed by different groups of binaural neurons in different pathways. It is suggested that the 80 Hz ASSR provides an objective means for evaluating binaural functions in patients such as those with central auditory processing disorders.