Relation of anxiety and other psychometric measures, balance deficits, impaired quality of life, and perceived state of health to dizziness handicap inventory scores for patients with dizziness.

BACKGROUND: An important question influencing therapy for dizziness is whether the strengths of the relationships of emotional and functional aspects of dizziness to 1) anxiety and other mental states, 2) perceived state of health (SoH) and quality of life (QoL) are different in patients with and without normal balance control. We attempted to answer this question by examining these dimensions' regression strengths with Dizziness Handicap Inventory (DHI) scores. METHODS: We divided 40 patients receiving group cognitive behavioural therapy (CBT) and vestibular rehabilitation for dizziness, into 2 groups: dizziness only (DO) and normal balance control; dizziness and a quantified balance deficit (QBD). Group-wise, we first performed stepwise multivariate regression analysis relating total DHI scores with Brief Symptom Inventory (BSI) sub-scores obtained pre- and post-therapy. Then, regression analysis was expanded to include SoH, QoL, and balance scores. Finally, we performed regressions with DHI sub-scores. RESULTS: In both groups, the BSI phobic anxiety state score was selected first in the multivariate regression analysis. In the DO group, obsessiveness/compulsiveness was also selected. The correlation coefficient, R, was 0.74 and 0.55 for the DO and QBD groups, respectively. When QoL and SoH scores were included, R values increased to 0.86 and 0.74, explaining in total 74, and 55% of the DHI variance for DO and QBD groups, respectively. Correlations with balance scores were not significant (R ≤ 0.21). The psychometric scores selected showed the strongest correlations with emotional DHI sub-scores, and perceived QoL and SoH scores with functional DHI sub-scores. CONCLUSIONS: Our findings suggest that reducing phobic anxiety and obsessiveness/compulsiveness during CBT may improve emotional aspects of dizziness and targeting perceived SoH and QoL may improve functional aspects of dizziness for those with and without normal balance control.

Effects of a program of cognitive-behavioural group therapy, vestibular rehabilitation, and psychoeducational explanations on patients with dizziness and no quantified balance deficit, compared to patients with dizziness and a quantified balance deficit.

BACKGROUND: We examined whether a program combining cognitive-behavioural therapy (CBT), vestibular rehabilitation (VR) and psychoeducation is equally effective in improving psychometric measures in patients with dizziness independent of a balance deficit. Measures of patients with dizziness only (DO) were compared to those of patients also having a quantified balance deficit (QBD). METHODS: 32 patients (23 female, 9 male) with persistent dizziness were analysed as 2 groups based on stance and gait balance control: those with QBD (pathological balance) or DO (normal balance). Dizziness Handicap Inventory (DHI) and Brief Symptom Inventory (BSI) questionnaires were used pre- and post-therapy to assess psychometric measures. Patients then received the same combination therapy in a group setting. RESULTS: The QBD group mean age was 60.6, SD 8.3, and DO group mean age 44.8, SD 12.1, years. Pre-therapy, questionnaire scores were pathological but not different between groups. Balance improved significantly for the QBD group (p=0.003) but not for the DO group. DHI and BSI scores improved significantly in the DO group (0.001

Mental body transformation deficits in patients with chronic balance disorders.

BACKGROUND: Movements may be generated consistent with imagining one's own body transformed or "disembodied" to a new position. Based on this concept we hypothesized that patients with objective balance deficits (obj-BD) would have altered neural transformation processes executing own body transformation (OBT) with functional consequences on balance control. Also we examined whether feeling unstable due to dizziness only (DO), without an obj-BD, also lead to an impaired OBT. METHODS: 32 patients with chronic dizziness were tested: 16 patients with obj-BD as determined by balance control during a sequence of stance and gait tasks, 16 patients with dizziness only (DO). Patients and 9 healthy controls (HCs) were asked to replicate roll trunk movements of an instructor in a life size video: first, with spontaneously copied (SPO) or "embodied" egocentric movements (lean when the instructor leans); second, with "disembodied" or "transformed" movements (OBT) with exact replication - lean left when the instructor leans left. Onset latency of trunk roll, rise time to peak roll angle (interval), roll velocity, and amplitude were measured. RESULTS: SPO movements were always mirror-imaged. OBT task latencies were significantly longer and intervals shorter than for SPO tasks (p < 0.03) for all groups. Obj-BD but not DO patients had more errors for the OBT task and, compared to HCs, had longer onset latencies (p < 0.05) and smaller velocities (p < 0.003) and amplitudes (p < 0.001) in both the SPO and OBT tasks. Measures of DO patients were not significantly different from those of HCs. CONCLUSIONS: Mental transformation (OBT) and SPO copying abilities are impaired in subjects with obj-BD and dizziness, but not with dizziness only. We conclude that processing the neuropsychological representation of the human body (body schema) slows when balance control is deficient.

Development and introduction of a ready-to-use pediatric pentavalent vaccine to meet and sustain the needs of developing countries--Quinvaxem®: the first 5 years.

Quinvaxem(®) injection (DTwP-HepB-Hib fully-liquid combined vaccine) is a ready-to-use, preservative-free, fully-liquid combined vaccine containing diphtheria and tetanus toxoids, Bordetella pertussis inactivated cellular suspension, hepatitis B surface antigen (HBsAg), and Haemophilus influenzae type b conjugated oligosaccharide. The vaccine was the first ready-to-use, fully-liquid pentavalent vaccine to gain WHO pre-qualification status in 2006. The immunogenicity and safety of Quinvaxem(®) was assessed in four clinical trials and a large post-marketing surveillance study. Quinvaxem(®) was found to be highly immunogenic in each of the primary vaccination studies and was also shown to be suitable as a booster with the advantage that it could be given concomitantly with measles vaccine. Quinvaxem(®) has become a cornerstone in EPI vaccination programs. To further support the needs of EPI vaccination processes and developing countries, a simple, all-in-one, compact, prefilled, auto-disabled Uniject(®) injection system has been chosen and optimized as a potential new presentation for Quinvaxem(®). Hopefully, Quinvaxem(®) in the Uniject(®) presentation will help vaccination programs in developing countries to achieve more.

Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans.

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. It is hypothesised to play a key role in energy balance stimulating food intake and body weight. Besides GH-releasing hormone (GHRH) and somatostatin, it is thought to be a regulating factor of GH release. Ghrelin also appears to be involved in sleep regulation. We showed recently that ghrelin promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin in humans. Similarly, promotion of non-rapid-eye-movement (NREM) sleep was reported in mice after systemic ghrelin. If ghrelin is a factor that induces and/or maintains sleep, it should be enhanced after a period of sleep deprivation (SD). To clarify this issue, nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined and simultaneously sleep electroencephalogram (EEG) was recorded (2300-0700 h) during sleep before and after 1 night of total SD in 8 healthy subjects. Compared to baseline, ghrelin levels increased earlier by a non-significant trend, already before the beginning of recovery sleep. Further a non-significant trend occurred, suggesting higher ghrelin secretion in the first half of the night. The ghrelin maximum was found significantly earlier after SD than at baseline. GH secretion during the first half of the night and total night after SD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night. No effects of SD on the time of the maximum were found for GH, ACTH and cortisol. The increase in ACTH after SD is a novel finding. Whereas the effects of SD on ghrelin levels were relatively weak, our findings are in line with the hypothesis that ghrelin is a sleep-promoting factor in humans. Ghrelin may be involved in sleep promotion after SD.

T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity.

BACKGROUND: Quinolones are widely used, broad spectrum antibiotics that can induce immediate- and delayed-type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2-3% of treated patients. OBJECTIVE: To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX). METHODS: We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone-specific T cell clones (TCC). RESULTS: The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX- and MXFX-specific CD4(+)/CD8(+) T cell receptor (TCR) alphabeta(+) TCC were generated to investigate the nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross-reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross-reactivity and clones showing a broad cross-reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)-peptide complex, as glutaraldehyde-fixed Ag-presenting cells (APC) could present the drug and washing quinolone-pulsed APC removed the drug, abrogating the reactivity of quinolone-specific TCC. CONCLUSION: Our data show that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among the different quinolones is frequent.

Treatment with the CRH1-receptor-antagonist R121919 improves sleep-EEG in patients with depression.

Well documented changes of sleep electroencephalogram (EEG) in patients with depression include rapid eye movement (REM) sleep disinhibition, decreases of slow-wave-sleep (SWS) and increase in wakefulness. Twenty-seven inpatients with major depression were admitted subsequently to a clinical trial with the CRH(1)-receptor-antagonist R121919 administered in two different dose escalation panels. A random subgroup of 10 patients underwent three sleep-EEG recordings (baseline before treatment, at the end of the first week and at the end of the fourth week of active treatment). SWS time increased significantly compared with baseline after 1 week and after 4 weeks. The number of awakenings and REM density showed a trend toward a decrease during the same time period. Separate evaluation of these changes for both panels showed no significant effect at lower doses, whereas in the higher doses after R121919 REM density decreased and SWS increased significantly between baseline and week 4. Furthermore positive associations between HAMD scores and SWS at the end of active treatment were found. Although these data might indicate that R121919 has a normalizing influence on the sleep EEG, the design of the study does not allow to differentiate genuine drug effects from those of clinical improvement and habituation to the clinical setting.

Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients, measured by the Dex-CRH test.

The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPA-axis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed in-patients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.

Ghrelin promotes slow-wave sleep in humans.

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 x 50 microg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans (n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated delta-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200-0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.