Manual Cervical Traction and Trunk Stabilization Cause Significant Changes in Upper and Lower Esophageal Sphincter: A Randomized Trial.

OBJECTIVES: Dysfunctions in the lower esophageal sphincter (LES) and the upper esophageal sphincter (UES) levels can occur owing to poor muscle coordination, contraction, or relaxation. Such condition can possibly be addressed by functional rehabilitation. The aim of this study was to measure pressure changes in the UES and LES at rest and during routine rehabilitation techniques, that is, cervical manual traction and trunk stabilization maneuver. METHODS: This study was conducted in a University Hospital Gastrointestinal Endoscopy Center. Cervical manual traction and a trunk stabilization maneuver were performed in a convenient group of 54 adult patients with gastroesophageal reflux disease. High-resolution manometry was used to measure pressure changes in the LES and UES at rest and during manual cervical traction and trunk stabilization maneuver. RESULTS: Average initial resting UES pressure was 90.91 mmHg. A significant decrease was identified during both cervical traction (average UES pressure = 42.13 mmHg, P < .001) and trunk stabilization maneuver (average UES pressure = 62.74 mmHg, P = .002). The average initial resting LES pressure was 14.31 mmHg. A significant increase in LES pressure was identified both during cervical traction (average LES pressure = 21.39 mmHg, P < .001) and during the trunk stabilization maneuver, (average pressure = 24.09 mmHg, P < .001). CONCLUSION: Cervical traction and trunk stabilization maneuvers can be used to decrease pressure in the UES and increase LES pressure in patients with gastroesophageal reflux disease.

Effects of a metabotropic glutamate(2/3) receptor agonist (LY544344/LY354740) on panic anxiety induced by cholecystokinin tetrapeptide in healthy humans: preliminary results.

RATIONALE: Preclinical findings have repeatedly shown an anxiolytic-like action of agonists at metabotropic glutamate receptors type II, such as LY354740. OBJECTIVE: We aimed to investigate the effect of LY544344, the prodrug of LY354740, upon experimental panic anxiety in humans. METHODS: Twelve healthy human volunteers were treated orally with 80 mg bid LY544344 for 1 week in a randomized placebo-controlled cross-over study before 50 mug cholecystokinin tetrapeptide (CCK-4) was injected intravenously. We assessed CCK-induced panic and anxiety symptoms and measured stress hormone release. RESULTS: While no significant treatment effect emerged in the entire sample, a significant reduction of the number of CCK-4-induced panic symptoms and of CCK-4-induced subjective anxiety ratings was detected after removing two subjects who did not show decreased CCK-4-elicited adrenocorticotropin (ACTH) release after LY544344 compared to placebo treatment. CONCLUSIONS: Further studies are needed to clarify the potential of LY544344 as a new anxiolytic or antipanic drug.

Adjunctive use of reboxetine in schizophrenia.

BACKGROUND: Schizophrenia is frequently complicated by depressive or negative symptoms that respond only moderately to treatment with antipsychotic drugs. Reboxetine is a novel antidepressant, which inhibits the reuptake of norepinephrine. We sought to study the efficacy and tolerability of the adjunctive use of reboxetine in a cohort of schizophrenic patients with prominent depressive or negative symptoms. METHODS: Sixteen schizophrenic inpatients were recruited for this study. All subjects received 4-8 mg of reboxetine/day while the antipsychotic medication (typical antipsychotics = 4; atypical antipsychotics = 12) was continued. All subjects underwent a standardized assessment including PANSS, CGI, HAMD, and CDSS before and after treatment with reboxetine (mean 26 +/- 17 d). RESULTS: All subjects tolerated treatment with reboxetine. Adverse effects were mild and did not require discontinuation of reboxetine. All clinical scores (PANSS 93.1 vs. 63.1; CGI 5.4 vs. 4.1; HAMD 20.4 vs. 8.1; CDSS 12.5 vs. 4.6) improved significantly under adjunctive treatment with reboxetine (all P < 0.01). CONCLUSION: The adjunctive use of reboxetine in schizophrenic patients was safe and well-tolerated. Our results suggest that the adjunctive use of reboxetine may be an effective treatment for depressive and negative symptoms in schizophrenia.

Modulation of sympathetic activity by corticotropin-releasing hormone and atrial natriuretic peptide.

BACKGROUND: Heart rate variability represents a reliable marker to delineate the status of autonomic nervous system (ANS) function and alterations due to stress in vivo. Interestingly, up to now the effects of corticotropin-releasing hormone (CRH), a key regulator of the stress hormone system, upon heart rate variability are not sufficiently described. Hence, we attempted to investigate the ANS-effects of a CRH bolus and the modulatory influences of atrial natriuretic peptide (ANP), one of the most important functional antagonist of CRH actions. METHODS: 12 healthy male volunteers were administered 100 microg CRH as bolus injection at 15:00. Six randomly chosen subjects received 150 microg ANP dissolved in normal saline and six subjects a normal saline infusion from 14:45 to 15:15. From 13:00 to 17:00 an ECG was recorded and mean heart rate (HR), total power (TP), very low frequency (VLF), low frequency (LF), LF in normalized units (LF [nu]), high frequency (HF) domains and the LF/HF-ratio in the interval from 14:00 to 16:00 were determined. RESULTS: After administration of CRH a significant increase in HR and a fast reduction of TP were observed, which lasted about 1 h. Based upon spectral domain analyses the sympathetic activity after CRH administration as indicated by LF [nu] increased by 31% (mean location) during saline. Applying ANP this increase was reduced to 19% (mean location). The VLF component, which is considered to be based in part also on sympathetic influences, indicates comparable effect. During saline the VLF after CRH bolus remained largely unchanged, but was reduced to 66% by ANP. Though the vagal activity indicated by the HF component was reduced after CRH, no significant differences emerged between both treatments. The changes of the LF/HF-ratio were pronounced in both groups. During saline this ratio increased by about 111%, during ANP only by 43% (mean location). CONCLUSIONS: Based upon HRV analysis the CRH administration induced sympathotonic effects which were antagonized by ANP. The observed vagal changes were less pronounced and need further investigation. Further studies of autonomic effects by alterations of CRH secretion in depression and anxiety disorder are strongly warranted.

The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone.

Whereas animal studies have shown a clear inhibitory effect of hippocampal mineralocorticoid receptors (MR) on hypothalamic-pituitary-adrenal (HPA) axis activity, investigations in humans revealed equivocal results. To further clarify the influence of MR in HPA activity we studied 10 healthy men during the circadian nadir of HPA activity (14:00 to 21:00) after pre-treatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion. On three separate occasions, in a placebo-controlled design, subjects received in a randomized order either 0.5 mg fludrocortisone p.o. or 0.2 mg aldosterone i.v. or placebo. Fludrocortisone exerted a significant inhibition of ACTH, cortisol and 11-desoxycortisol (p < 0.05), whereas no such effect was observed after aldosterone or placebo. These preliminary data suggest that MR are involved in the inhibition of the HPA axis during the circadian nadir of glucocorticoid concentrations in humans.

Longitudinal course of salivary cortisol in post-traumatic stress disorder.

OBJECTIVE: In chronic post-traumatic stress disorder (PTSD) lowered cortisol secretion and hypersuppression to dexamethasone has been described repeatedly. However, so far no longitudinal data on the natural course or on the effect of therapy are available. METHOD: We measured basal and post-dexamethasone morning salivary cortisol in a drug-free patient with chronic PTSD (DSM-IV) monthly for nearly 2 years and assessed PTSD and depressive symptoms. RESULTS: Salivary cortisol decreased dramatically 3 months after the traumatic event and in the further course showed an inverse relation to fluctuating but gradually improving PTSD symptoms. Post-dexa-methasone cortisol was suppressed below the detection limit early after trauma and rose again more than 1 year post-trauma. CONCLUSION: Both the potential renormalization of low cortisol levels in improving chronic PTSD and the putative vulnerability to develop PTSD in subjects with increased dexamethasone suppression need further research.

Prolactin but not ACTH increases during sodium lactate-induced panic attacks.

Paradoxically, the pituitary-adrenal axis is not activated during sodium lactate-induced panic. We measured the response of another stress-sensitive hormone, prolactin, to standard lactate and placebo infusion in a double-blind randomised design in eight patients with panic disorder and eight matched normal controls. Prolactin release was significantly elevated (P < 0.05) in panickers compared with non-panickers, whereas ACTH secretion was not activated at all. This differential stress response needs further investigation.