Assessment of digestible lysine requirements in lipopolysaccharide-challenged pigs.

To evaluate the effect of an Escherichia coli lipopolysaccharide (LPS) challenge on the digestible lysine (Lys) requirement for growing pigs, a nitrogen (N) balance assay was performed. Seventy-two castrated male pigs (19 ± 1.49 kg body weight [BW]) were allocated in a 2 × 6 factorial design composed of two immune activation states (control and LPS-challenged) and six dietary treatments with N levels of 0.94, 1.69, 2.09, 3.04, 3.23, and 3.97% N, as fed, where Lys was limiting, with six replicates and one pig per unit. The challenge consisted of an initial LPS dose of 30 µg/kg BW via intramuscular (IM) injection and a subsequent dose of 33.6 µg/kg BW after 48 h. The experimental period lasted 11 d and was composed of a 7-d adaptation and a subsequent 4-d sampling period in which N intake (NI), N excretion (NEX), and N deposition (ND) were evaluated. Inflammatory mediators and rectal temperature were assessed during the 4-d collection period. A three-way interaction (N levels × LPS challenge × time, P < 0.05) for IgG was observed. Additionally, two-way interactions (challenge × time, P < 0.05) were verified for IgA, ceruloplasmin, transferrin, haptoglobin, α-1-acid glycoprotein, total protein, and rectal temperature; and (N levels × time, P < 0.05) for transferrin, albumin, haptoglobin, total protein, and rectal temperature. LPS-challenged pigs showed lower (P < 0.05) feed intake. A two-way interaction (N levels × LPS challenge, P < 0.05) was observed for NI, NEX, and ND, with a clear dose-response (P < 0.05). LPS-challenged pigs showed lower NI and ND at 2.09% N and 1.69 to 3.97% N (P < 0.05), respectively, and higher NEX at 3.23% N (P < 0.05). The parameters obtained by a nonlinear model (N maintenance requirement, NMR and theoretical maximum N deposition, NDmaxT) were 152.9 and 197.1 mg/BWkg0.75/d for NMR, and 3,524.7 and 2,077.8 mg/BWkg0.75/d for NDmaxT, for control and LPS-challenged pigs, respectively. The estimated digestible Lys requirements were 1,994.83 and 949.16 mg/BWkg0.75/d for control and LPS-challenged pigs, respectively. The daily digestible Lys intakes required to achieve 0.68 and 0.54 times the NRmaxT value were 18.12 and 8.62 g/d, respectively, and the optimal dietary digestible Lys concentration may change depending on the feed intake levels. Based on the derived model parameters obtained in the N balance trial with lower cost and time, it was possible to differentiate the digestible Lys requirement for swine under challenging conditions.

Preoperative Mental Health Component Scoring Is Related to Patient Reported Outcomes Following Lumbar Fusion.

STUDY DESIGN: Retrospective cohort review. OBJECTIVE: The objective of this study was to identify depression using the Mental Component Score (MCS-12) of the Short Form-12 (SF-12) survey and to correlate with patient outcomes. SUMMARY OF BACKGROUND DATA: The impact of preexisting depressive symptoms on health-care related quality of life (HRQOL) outcomes following lumbar spine fusion is not well understood. METHODS: Patients undergoing lumbar fusion between one to three levels at a single center, academic hospital were retrospectively identified. Patients under the age of 18 years and those undergoing surgery for infection, trauma, tumor, or revision, and less than 1-year follow-up were excluded. Patients with depressive symptoms were identified using an existing clinical diagnosis or a score of MCS-12 less than or equal to 45.6 on the preoperative SF-12 survey. Absolute HRQOL scores, the recovery ratio (RR) and the percent of patients achieving minimum clinically important difference (MCID) between groups were compared, and a multiple linear regression analysis was performed. RESULTS: A total of 391 patients were included in the total cohort, with 123 (31.5%) patients reporting symptoms of depression based on MCS-12 and 268 (68.5%) without these symptoms. The low MCS-12 group was found to have significantly worse preoperative Oswestry disability index (ODI), visual analogue scale back pain (VAS Back) and visual analogue scale leg pain (VAS Leg) scores, and postoperative SF-12 physical component score (PCS-12), ODI, VAS Back, and VAS Leg pain scores (P < 0.05) than the non-depressed group. Finally, multiple linear regression analysis revealed preoperative depression to be a significant predictor of worse outcomes after lumbar fusion. CONCLUSION: Patients with depressive symptoms, identified with an MCS-12 cutoff below 45.6, were found to have significantly greater disability in a variety of HRQOL domains at baseline and postoperative measurement, and demonstrated less improvement in all outcome domains included in the analysis compared with patients without depression. However, while the improvement was less, even the low MCS-12 cohort demonstrated statistically significant improvement in all HRQOL outcome measures after surgery. LEVEL OF EVIDENCE: 3.

Stimulatory tests of growth hormone secretion in prepubertal major depression: depressed versus normal children.

OBJECTIVE: Blunted stimulation of growth hormone (GH) secretion after pharmacological stimuli has been linked to depressive and anxiety disorders throughout the life span. This study sought to better characterize this dysregulation in prepubertal depression. METHOD: GH regulation was compared in 38 medically healthy prepubertal children with current major depressive disorder and 19 control children who were medically and psychiatrically healthy. The study evaluated GH stimulatory responses to three pharmacological challenge agents: (1) insulin-induced hypoglycemia, using 0.1 IU/kg intravenous regular insulin; (2) 1.3 micrograms/kg intravenous clonidine; and (3) 1.0 microgram/kg intravenous human growth hormone-releasing hormone (GHRH). RESULTS: The results provide replication and extension of earlier findings. GH responses to insulin-induced hypoglycemia and to GHRH stimulation were blunted in depressed children compared to the normal controls. Clonidine stimulation results yielded a similar picture but did not reach statistical significance. CONCLUSIONS: Overall these results further strengthen the evidence showing GH dysregulation in childhood depression. However, the blunted GH response seen with GHRH (which reflects pituitary hyporesponsivity) was in contrast to our original hypothesis and has implications regarding the site (or sites) of dysregulation.

Cholinergic REM induction test with arecoline in depressed children.

Children with major depressive disorder often fail to exhibit electroencephalographic (EEG) sleep abnormalities similar to those reported in depressed adults. It was hypothesized that a cholinergic rapid eye movement (REM) induction test would contribute to the identification of EEG sleep abnormalities in depressed children. To test this hypothesis, prepubertal children meeting research diagnostic criteria for major depressive disorder (n = 33) and carefully screened healthy control children (n = 15) were enrolled in a 4-day psychobiologic protocol that included 1 night with infusion of arecoline (0.5 mg) during the first non-REM sleep period. Although there had been no significant group differences in baseline sleep measures, results on the arecoline night revealed significantly shorter REM latency in the group of depressed children compared with the control children (mean +/- SD = 105 +/- 51 minutes vs. 140 +/- 46 minutes). The design of the protocol (with an interval break immediately preceding the arecoline night) prevented a direct estimation of arecoline effects within subjects; however, these data provide promising preliminary results regarding cholinergic REM induction tests in childhood depression.

Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children.

The neuroendocrine response to L-5-hydroxytryptophan was compared in 37 prepubertal children who met the Research Diagnostic Criteria for major depressive disorder with that in 23 normal children with no lifetime history of any psychiatric disorder and very low rates of depression in both first- and second-degree relatives. Intravenous L-5-hydroxytryptophan (0.8 mg/kg) was given over a 1-hour interval after preloading with oral carbidopa, an inhibitor of peripheral but not central L-5-hydroxytryptophan metabolism. L-5-Hydroxytryptophan, a precursor of serotonin, increases serotonin turnover in the central nervous system when given after carbidopa. Seven (19%) of the 37 children with major depressive disorder and two (9%) of the 23 normal children had nausea or vomiting and therefore did not complete the full infusion. They were subsequently excluded from data analysis. After this stimulation, prolactin, cortisol, and growth hormone secretion were compared between diagnostic groups. The depressed children secreted significantly less cortisol (effect size, 0.70) and significantly more prolactin (effect size, 0.83). There was a sex-by-diagnosis interaction in prolactin response to L-5-hydroxytryptophan and, on examination, the prolactin hypersecretion was seen in depressed girls but not in depressed boys compared with same-sex controls. There was no significant stimulation of growth hormone in either group. These findings are consistent with dysregulation of central serotonergic systems in childhood major depression.

Dexamethasone suppression test in children with major depressive disorder.

The authors report a study of 24-hour serial cortisol determinations, measured during baseline and after the administration of 0.25 and 0.5 mg of dexamethasone in a sample of predominantly outpatient children with major depressive disorder, nonaffective psychiatric controls, and normal controls. In this sample, 24-hour baseline cortisol and the dexamethasone suppression test (DST) do not discriminate between the three groups. In addition, the authors measured 24-hour serum dexamethasone levels. There were no significant between group differences in serum dexamethasone. These results raise questions as to the utility of this test in the diagnosis of affective disorders in children. Possible reasons for the discrepancies in the dexamethasone suppression test results between in- and outpatient studies are discussed.

Electroencephalographic sleep measures in prepubertal depression.

Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) (n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children (n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects (n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects.

EEG sleep in adolescents with major depression: the role of suicidality and inpatient status.

All night sleep EEG recordings were performed for three consecutive nights in 27 adolescents with a diagnosis of major depressive disorder (MDD) and 30 normal adolescent controls. Group comparisons between the entire MDD group and the normal controls revealed no significant diagnostic group differences for any of the major sleep variables. Analyses within subgroups of MDD adolescents, however, revealed heterogeneity of EEG sleep findings in association with suicidality and inpatient status. The findings of this study suggest that the discrepancies among the EEG sleep studies in adolescent MDD may be accounted for by the relative proportions of inpatients, suicidality, or bipolarity within the MDD sample being studied.

Pharmacotherapy of adolescent major depression: beyond TCAs.

To date, controlled studies of tricyclic antidepressant (TCA) treatment of adolescent major depression have failed to demonstrate efficacy of these compounds despite multiple lines of evidence suggesting that adolescent major depression is related to the adult form of the disorder. One possible means of increasing the power of such studies is explored: examination of the pattern of response to medication and separation of placebo responders from medication responders using the technique proposed by Quitkin and colleagues (1984). Open label studies of nontricyclic antidepressant agents in adolescents are reviewed, and suggestions are made for future pharmacological trials in this population.