MHPG and heart rate as correlates of nonresponse to drug therapy in panic disorder patients

Little is known about biological predictors of treatment response in panic disorder (PD). In the present study heart rate, blood pressure, plasma cortisol and plasma MHPG were investigated at baseline in a sample of 44 PD patients as possible predictors for nonresponse to treatment. We used a strict definition of nonresponse to find patients who did not respond at all after 12 weeks of treatment with brofaromine or fluvoxamine. Patients were considered nonresponders when they fulfilled two criteria: they did not show a 50% reduction of agoraphobic avoidance and they still experienced panic attacks at endpoint. The variables that differed significantly between the groups were used to predict nonresponse to drug therapy. Using this strict definition of nonresponse, 15 patients (32.6%) were considered nonresponders. These patients were characterised by a higher plasma MHPG concentration and a higher heart rate at baseline. These variables were subsequently used to predict nonresponse.     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT_1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K⁺ and perfusion with Ca²⁺-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT_1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT_1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT_1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT_1A receptors. Received: 11 September 1996 / Accepted: 25 November 1996     

PCR assessment of Chlamydia trachomatis infection of semen specimens processed for artificial insemination

In order to ascertain the microbiological quality of stored semen specimens processed for artificial insemination by a donor (AID), we developed a PCR assay targeting the chlamydial plasmid to detect Chlamydia trachomatis in semen. The lower limit of detection of this assay corresponded to 2.5 to 5 elementary bodies per microl of semen. A total of 669 cryopreserved ejaculates from 97 asymptomatic donors were tested for C. trachomatis infection. Twelve ejaculates, originating from four donors, were found to be positive, indicating a 4% prevalence of C. trachomatis infection among the donor population studied. Cross-contamination between the cryopreserved specimens in the storage container was studied by typing using sequence analysis of PCR-amplified omp1 genes of the strains. Two donors were infected with serovar E, one was infected with serovar F, and one was infected with serovar K. For two donors, the duration of C. trachomatis positivity could be assessed. One donor donated C. trachomatis-positive semen for at least 4 successive months, and the other did so for at least 16 months. The occurrence of C. trachomatis infection in cryopreserved donor semen indicates that ejaculates from donors not tested for a C. trachomatis infection just prior to donation should be tested for infection by a direct test such as the PCR described here. Direct testing of semen specimens will detect not only donors with an active infection but also C. trachomatis-infected ejaculates already stored and will thus improve the microbiological quality of AID, since discrepancies in the presence of C. trachomatis in urine and semen specimens have been reported.     

Serotonergic function and late luteal phase dysphoric disorder

Thirty-eight subjects who met criteria for the DSM-III-R diagnosis late luteal phase dysphoric disorder (LLPDD) were compared with 18 controls in 5-HT uptake kinetics of the platelets in the premenstrual (day 26) as well as in the postmenstrual phase (day 4) of the cycle. Furthermore, 5-hydroxytryptophan (5-HTP) was administered to LLPDD patients and controls in both phases of the cycle, to investigate pituitary sensitivity for serotonin. Plasma samples for the measurement of cortisol and -endorphin were taken before and after oral administration of 200 mg 5-HTP, and considered as an index of pituitary-adrenal function. LLPDD was not associated with a lower platelet 5-HT uptake and content in the premenstrual phase of the cycle, compared with the postmenstrual phase. Patients appeared not to be different from controls in 5-HT uptake kinetics of platelets in the premenstrual phase of the cycle. No main differences were observed between LLPDD patients and controls in their ability to respond with secretion of cortisol and -endorphin to 5-HTP stimulation, either in the premenstrual, or in the postmenstrual phase. This observation could not be attributed to differences in 5-HTP metabolism. The findings of the present study do not support a specific role for 5-HT in the pathophysiology LLPDD.     

Evoked potential decrements in auditory cortex. II. Critical test for habituation.

The goal of the present experiment was to rule out the hypothesis that evoked potential (EP) decrements during repetitive stimulation are due to a change in the subject's state; i.e., that the decrements are part of general, nonselective, non-specific decrement in all EPs as a result of a change in state during the course of the experiment. To this end, we obtained average evoked potentials (AEPs) to tone pips of two different frequencies; pips of one frequency were the repetitive stimuli, one and pips of the other frequency served as "test" stimuli. Before and again after a 15 min series of repetitive pips, AEPs to the repetitive stimuli and to the test stimuli were obtained. We found that from the beginning to the end of the 15 min repetitive-pip series, certain components of the AEPs to the repetitive stimuli decreased significantly in amplitude. However, comparable components in the AEPs to the test stimuli did not demonstrate significant decrements. These results suggested that the decrements were not part of a non-selective, non-specific, state-related decrement in all AEPs. However, the selective decrements could have been attributable to either of two aspects of the repetitive tone pips; their repetitive aspect, or their frequency. Because there were two independent variables, a counterbalanced design was required. We found that regardless of which frequency was repetitive, there were significant decrements in the AEPs to the repetitive stimuli and smaller decrements (if any) in the AEPs to the test stimuli. This ruled out the frequencies of the tone pips as critical factors in the decrements; by the process of elimination the repetitive aspect of the stimuli remained as the critical variable. Only decrements that were specific to the repetitive stimulus were considered to be habituatory. All of the habituatory decrements were in components subsequent to the initial AEP components and had latencies in the range of 17--105 msec. In several cases, when subjects participated in a supplemental experiment, the same AEP components demonstrated habituatory decrements in both experiments.     

Reduced sensitivity in the recognition of anger and disgust in social anxiety disorder

Introduction. The aim of this study was to investigate the recognition of facial expressions in patients with a generalised social anxiety disorder. It is well documented that in different psychiatric disorders (e.g., depression, schizophrenia) patients may show an altered processing of emotions. However, in generalised social anxiety, emotion recognition has not been studied.

Methods. 24 Patients with generalised social anxiety disorder and 26 healthy controls, matched on age, education, and sex were included. The task entailed the emotional labelling of faces with different facial expressions (happiness, fear, disgust, sadness, surprise, anger) presented in different intensities. Subjects were asked to make a forced‐choice response.

Results. These revealed that patients with a generalised social anxiety disorder were less sensitive for the negative facial expressions of anger and disgust compared to the control group.

Conclusions. This deficit could play a role in the development and/or the maintaining of the social anxiety. Both explanations are discussed.     

Assessment of left ventricular dyssynchrony in patients with conduction delay and idiopathic dilated cardiomyopathy: head-to-head comparison between tissue doppler imaging and velocity-encoded magnetic resonance imaging.

OBJECTIVES: This study sought to compare tissue Doppler imaging (TDI) with velocity-encoded (VE) magnetic resonance imaging (MRI) for left ventricular (LV) dyssynchrony assessment. BACKGROUND: Cardiac resynchronization therapy (CRT) is proposed for patients with heart failure, depressed LV function, and a wide QRS complex. Selection is based mainly on electrocardiogram criteria, but recent data suggest that intraventricular dyssynchrony may be preferred for selection. An LV dyssynchrony can adequately be assessed with TDI, but this has not been compared directly with other imaging modalities. A VE MRI potentially allows direct myocardial wall motion measurements similar to TDI. METHODS: Twenty patients with heart failure, systolic LV dysfunction, and a wide QRS complex were included, as well as 10 normal individuals with normal QRS duration and LV function. The TDI and VE MRI data were acquired to study intraventricular dyssynchrony. RESULTS: Left ventricular dyssynchrony was not observed in normal individuals (mean dyssynchrony -2 +/- 15 ms on TDI; mean -5 +/- 17 ms on MRI, p = NS). In patients, mean LV dyssynchrony was 55 +/- 37 ms on TDI; 49 +/- 38 ms on MRI (p = NS). Good correlation between both modalities was observed (linear regression TDI = 0.99 x MRI - 5, n = 30, r = 0.98, p < 0.01). The MRI showed a small, nonsignificant underestimation of 5 +/- 8 ms compared with TDI. Agreement between MRI and TDI for classification according to severity of LV dyssynchrony (minimal, intermediate, and extensive) was excellent (kappa +/- SE = 0.96 +/- 0.07, p < 0.01) with 95% of patients classified identical. CONCLUSIONS: Both MRI and TDI yield comparable information on LV dyssynchrony; MRI is useful in the selection of patients for CRT.