[Cardiac neuroses]. / Herzneurose.

Cardiac neurosis is defined as heart complaints for which no organic cause can be found. Other common terms are "cardiac anxiety neurosis", "cardiac anxiety disorder", "cardiac phobia", "functional heart complaints" and "somatoform autonomous functional disorders of the cardiovascular system" (ICD-10). Although cardiac neurosis is rarely diagnosed, it is estimated that approximately 30 bis 40% of patients with cardiovascular disorders are actually suffering from functional complaints. Predisposing to the development of cardiac neurosis are insufficient internalization processes during childhood, leading to an insoluble autonomy dependency conflict. Cardiac neurosis is treated with drugs and psychotherapy.

No evidence for long-term facilitation after episodic hypoxia in spontaneously breathing, anesthetized rats.

Repeated electrical or hypoxic stimulation of peripheral chemoreceptors has been shown to cause a persistent poststimulus increase in respiratory motoneuron activity, termed long-term facilitation (LTF). LTF after episodic hypoxia has been demonstrated most consistently in anesthetized, vagotomized, paralyzed, artificially ventilated rats. Evidence for LTF in spontaneously breathing animals and humans after episodic hypoxia is equivocal and may have been influenced by the awake state of the subjects in these studies. The present study was designed to test the hypothesis that LTF is evoked in respiratory-related tongue muscle and inspiratory pump muscle activities after episodic hypoxia in 10 spontaneously breathing, anesthetized, vagotomized rats. The animals were exposed to three (5-min) episodes of isocapnic hypoxia, separated by 5 min of hyperoxia (50% inspired oxygen). Genioglossus, hyoglossus, and inspiratory intercostal EMG activities, along with respiratory-related tongue movements and esophageal pressure, were recorded before, during, and for 60 min after the end of episodic isocapnic hypoxia. We found no evidence for LTF in tongue muscle (genioglossus, hyoglossus) or inspiratory pump muscle (inspiratory intercostal) activities after episodic hypoxia. Rather, the primary poststimulus effect of episodic hypoxia was diminished respiratory frequency, which contributed to a reduction in ventilatory drive.

Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise.

Our purpose was to determine the influence of posture and breathing route on electromyographic (EMG) activities of nasal dilator (NDM) and genioglossus (GG) muscles during exercise. Nasal and oral airflow rates and EMG activities of the NDM and GG were recorded in 10 subjects at rest and during upright and supine incremental cycling exercise to exhaustion. EMG activities immediately before and after the switch from nasal to oronasal breathing were also determined for those subjects who demonstrated a clear switch point (n = 7). NDM and GG EMG activities were significantly correlated with increases in nasal, oral, and total ventilatory rates during exercise, and these relationships were not altered by posture. In both upright and supine exercise, NDM activity rose more sharply as a function of nasal inspired ventilation compared with total or oral inspired ventilation (P < 0.01), but GG activity showed no significant breathing-route dependence. Peak NDM integrated EMG activity decreased (P = 0.008), and peak GG integrated EMG activity increased (P = 0.032) coincident with the switch from nasal to oronasal breathing. In conclusion, 1) neural drive to NDM and GG increases as a function of exercise intensity, but the increase is unaltered by posture; 2) NDM activity is breathing-route dependent in steady-state exercise, but GG activity is not; and 3) drive to both muscles changes significantly at the switch point, but the change in GG activity is more variable and is often transient. This suggests that factors other than the breathing route dominate drive to the GG soon after the initial changes in the configuration of the oronasal airway are made.

Consequences of periodic augmented breaths on tongue muscle activities in hypoxic rats.

This study was designed to investigate the influence of hypoxia-evoked augmented breaths (ABs) on respiratory-related tongue protrudor and retractor muscle activities and inspiratory pump muscle output. Genioglossus (GG) and hyoglossus (HG) electromyogram (EMG) activities and respiratory-related tongue movements were compared with peak esophageal pressure (Pes; negative change in pressure during inspiration) and minute Pes (Pes x respiratory frequency = Pes/min) before and after ABs evoked by sustained poikilocapnic, isocapnic, and hypercapnic hypoxia in spontaneously breathing, anesthetized rats. ABs evoked by poikilocapnic and isocapnic hypoxia triggered long-lasting (duration at least 10 respiratory cycles) reductions in GG and HG EMG activities and tongue movements relative to pre-AB levels, but Pes was reduced transiently (duration of <10 respiratory cycles) after ABs. Adding 7% CO(2) to the hypoxic inspirate had no effect on the frequency of evoked ABs, but this prevented long-term declines in tongue muscle activities. Bilateral vagotomy abolished hypoxia-induced ABs and stabilized drive to the tongue muscles during each hypoxic condition. We conclude that, in the rat, hypoxia-evoked ABs 1) elicit long-lasting reductions in protrudor and retractor tongue muscle activities, 2) produce short-term declines in inspiratory pump muscle output, and 3) are mediated by vagal afferents. The more prolonged reductions in pharyngeal airway vs. pump muscle activities may lead to upper airway narrowing or collapse after spontaneous ABs.

Effect of co-activation of tongue protrudor and retractor muscles on tongue movements and pharyngeal airflow mechanics in the rat.

1. The purpose of these experiments was to examine the mechanisms by which either co-activation or independent activation of tongue protrudor and retractor muscles influence upper airway flow mechanics. We studied the influence of selective hypoglossal (XIIth) nerve stimulation on tongue movements and flow mechanics in anaesthetized rats that were prepared with an isolated upper airway. In this preparation, both nasal and oral flow pathways are available. 2. Inspiratory flow limitation was achieved by rapidly lowering hypopharyngeal pressure (Php) with a vacuum pump, and the maximal rate of flow (VI,max) and the nasopharyngeal pressure associated with flow limitation (Pcrit) were measured. These experimental trials were repeated while nerve branches innervating tongue protrudor (genioglossus; medial XIIth nerve branch) and retractor (hyoglossus and styloglossus; lateral XIIth nerve branch) muscles were stimulated either simultaneously or independently at frequencies ranging from 20-100 Hz. Co-activating the protrudor and retractor muscles produced tongue retraction, whereas independently activating the genioglossus resulted in tongue protrusion. 3. Co-activation of tongue protrudor and retractor muscles increased VI, max (peak increase 44 %, P < 0.05), made Pcrit more negative (peak decrease of 44 %, P < 0.05), and did not change upstream nasopharyngeal resistance (Rn). Independent protrudor muscle stimulation increased VI,max (peak increase 61 %, P < 0.05), did not change Pcrit, and decreased Rn (peak decrease of 41 %, P < 0.05). Independent retractor muscle stimulation did not significantly alter flow mechanics. Changes in Pcrit and VI,max at all stimulation frequencies were significantly correlated during co-activation of protrudor and retractor muscles (r2 = 0.63, P < 0.05), but not during independent protrudor muscle stimulation (r2 = 0.09). 4. These findings indicate that either co-activation of protrudor and retractor muscles or independent activation of protrudor muscles can improve upper airway flow mechanics, although the underlying mechanisms are different. We suggest that co-activation decreases pharyngeal collapsibility but does not dilate the pharyngeal airway. In contrast, unopposed tongue protrusion dilates the oropharynx, but has a minimal effect on pharyngeal airway collapsibility.

[Influence of psychotherapy motivation on the course of psychotherapy]. / Zum Einfluss der Psychotherapiemotivation auf den Psychotherapieverlauf.

The motivational characteristics of psychotherapy inpatients should be of crucial importance for treatment effectiveness. In the present study on 219 patients from two psychosomatic-psychotherapeutic treatment centers, four dimensions of motivation for psychotherapy (illness experience; lay etiology; treatment expectations; openness to psychotherapy) were assessed using the Questionnaire for the Measurement of Psychotherapy Motivation (Fragebogen zur Messung der Psychotherapiemotivation; FMP) and related to pre-post changes in symptomatology. In these analyses, psychological symptoms (SCL-90-R) as well as interpersonal problems (IIP) were considered as indicators of treatment effects. The results support the expectation that (a) a psychosocial causal attribution of illness symptoms and (b) a marked general openness to psychotherapy at the pretreatment interview predict more positive treatment outcomes. Implications of the results for the indication of pretreatment interventions are discussed.

[How can psychodynamic diagnosis in childhood and adolescence be operationalized?]. / Wie ist psychodynamische Diagnostik im Kindes- und Jugendalter operationalisierbar?

Multiaxial diagnostics and classifications in child and adolescent psychiatry based on ICD-10 generally now have been operationalized. Initial procedures to operationalize psychodynamically oriented concepts are currently underway. One of them is the operationalized psychodynamic diagnostics (OPD), which consists of five axes: illness concepts and treatment predispositions, human relationships, intrapsychic conflict, psychic structure, and the ICD-10. A team is currently adapting the adult version of the OPD for use in children and adolescents. Such an OPD-CA would affiliate with the MAS, a well-established system of classification. Central methodological and conceptual topics of the OPD-CA are presented.

Dopaminergic modulation of respiratory motor output in peripherally chemodenervated goats.

We examined the ventilatory effects of exogenous dopamine (DA) and norepinephrine (NE) administration in chloralose-anesthetized, paralyzed, artificially ventilated adult goats before and after carotid body denervation (CBD). Intravenous (iv) DA bolus injections and slow iv infusions caused dose-dependent inhibition of phrenic nerve activity (PNA) in carotid body (CB)-intact animals during normoxia and hyperoxia but not during hypercapnia. NE administration in CB-intact goats caused dose-dependent inhibition of PNA of similar magnitude to DA trials. The DA D2-receptor agonists quinelorane and quinpirole inhibited PNA, whereas the DA D1-receptor agonist SKF-81297 had no effect. After CBD, the ventilatory depressant effects of DA persisted, but responses were significantly attenuated compared with CB-intact trials. CBD abolished the inhibitory effect of low-dose NE administration but did not alter ventilatory responses to high-dose NE injection. The peripheral DA D2-receptor antagonist domperidone substantially attenuated the inhibitory effects of DA bolus injections and infusions and reversed the inhibitory ventilatory effect of high-dose DA administration to excitation in some animals. The alpha-adrenoceptor antagonist phentolamine had no effect on DA-induced ventilatory depression. Beta-Adrenoceptor stimulation with isoproterenol produced similar hemodynamic effects to DA administration but had no effect on PNA. We conclude that DA and NE exert both CB-mediated and non-CB-mediated inhibitory effects on respiratory motor output in anesthetized goats. The ventilatory depressant effects that persist in peripherally chemodenervated animals are DA D2-receptor mediated, but their exact location remains speculative.

Differential respiratory muscle recruitment induced by clonidine in awake goats.

The purpose of this study was to test the hypothesis that dysrhythmic breathing induced by the alpha2-agonist clonidine is accompanied by differential recruitment of respiratory muscles. In adult goats (n = 14) electromyographic (EMG) measurements were made from inspiratory muscles (diaphragm and parasternal intercostal) and expiratory muscles [triangularis sterni (TS) and transversus abdominis (Abd)]. EMG of the thyroarytenoid (TA) muscle was used as an index of upper airway (glottal) patency. Peak EMG activities of all spinal inspiratory and expiratory muscles were augmented by central and peripheral chemoreceptor stimuli. Phasic TA was apparent in the postinspiratory phase of the breathing cycle under normoxic conditions. During dysrhythmic breathing episodes induced by clonidine, TS and Abd activities were attenuated or abolished, whereas diaphragm and parasternal intercostal activities were unchanged. There was no tonic activation of TS or Abd EMG during apneas; however, TA activity became tonic throughout the apnea. We conclude that 1) alpha2-adrenoceptor stimulation results in differential recruitment of respiratory muscles during respiratory dysrhythmias and 2) apneas are accompanied by active glottic closure in the awake goat.

Carotid body dopaminergic mechanisms are functional after acclimatization to hypoxia in goats.

Ventilatory acclimatization to sustained hypoxia (VASH) is the time-dependent increase in ventilation that occurs during prolonged exposure to hypoxia. We tested the hypothesis that carotid body (CB) dopaminergic mechanisms are down-regulated during VASH, which would allow CB afferent discharge and ventilation to increase beyond the initial response to hypoxia. Domperidone (DOM; 1.0 mg.kg-1) was administered intravenously to block CB dopamine (DA) receptors after VASH was complete in awake goats. DOM caused a significant augmentation of the ventilatory response to hypoxia in acclimatized goats, failing to support the hypothesis. We conclude that inhibitory CB dopaminergic function is not significantly reduced following prolonged hypoxia, and that down-regulation of CB dopaminergic mechanisms may not be involved in VASH in the goat.

Intracarotid dopamine infusion does not prevent acclimatization to hypoxia.

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation that occurs during sustained exposure to hypoxia. The mechanism for VAH remains elusive. We sought to determine whether a deficiency in the availability of carotid body dopamine is the mechanism of increased ventilatory responsiveness to hypoxia during VAH in awake goats. This was based on the evidence that dopamine (DA) is primarily an inhibitory neuromodulator of carotid body (CB) function. The hypothesis was tested by intracarotid infusion of DA (5.0 micrograms kg-1 min-1) throughout VAH. VAH was not prevented by DA infusion, failing to support the hypothesis. We conclude that a deficiency in the availability of inhibitory DA release within the CB is probably not responsible for VAH. However, increased ventilatory responses to acute hypoxia after either prolonged DA infusion or hypoxia may have similar CB mechanisms.

Lack of long-term facilitation of ventilation after exposure to hypoxia in goats.

Episodic hypoxia has been shown to induce augmented normoxic ventilatory drive or long-term facilitation (LTF, continued hyperventilation after termination of hypoxic stimulation) in awake dogs and awake goats. The main objective of these experiments was to examine whether continuous isocapnic hypoxia in awake goats elicits LTF and additionally, to determine if goats exhibit hypoxic ventilatory decline (roll-off) during the hypoxic exposure. Goats were exposed to either 4 h of isocapnic hypoxia (n = 10) or 30 min of isocapnic hypoxia (n = 7). Ventilation (VE), tidal volume and frequency were measured before, during and following the end of the isocapnic hypoxia (PaO2 40 Torr) exposure. During the 4 h period of hypoxia, VE increased in a time-dependent manner in a typical pattern of acclimatization, reaching a mean of 40.8 +/- 3.6 L/min at the end of 4 h. Five minutes after return to normoxia, VE was 13.0 +/- 0.8 L/min, not different than control VE (13.1 +/- 0.9 L/min) measured prior to the hypoxic exposure and remained unchanged from this value for another 30 min. During the 30 min hypoxic exposure, VE increased upon exposure to hypoxia, remained significantly elevated throughout the hypoxic exposure, but promptly returned to control levels upon return to normoxia. These results indicate that continuous isocapnic hypoxia elicits neither long term facilitation of ventilation nor hypoxic ventilatory decline in awake goats.

Consumption of quercetin and kaempferol in free-living subjects eating a variety of diets.

Quercetin and related flavonoids are anticarcinogenic in rats, but little is known about human intakes. The intake of five major flavonols and flavones was calculated using 1-day dietary records of 17 volunteers from 14 countries, and using both 3-day records and a food frequency questionnaire of eight Dutch adults. Total consumption (+/- SD) was 27.6 +/- 19.5 mg/day in the international subjects, 34.1 +/- 31.2 mg/day in the Dutch adults according to 3-day records, and 41.9 +/- 23.7 mg/day according to questionnaires. Quercetin contributed 68-73%, and kaempferol 22-29%, the major sources being tea and onions. A brief food frequency questionnaire may be a suitable method for ranking individuals by flavonol intake.

Acetylsalicylate and salicylates in foods.

Acetylsalicylic acid is effective in the prevention of cardiovascular disease. It was suggested that fruits and vegetables provide unknown amounts of acetylsalicylic acid. We could not find any acetylsalicylic acid in 30 foods using HPLC with fluorescence detection (detection limits: 0.02 mg/kg for fresh, and 0.2 mg/kg for dried products). We showed that urinary excretion of salicylates is a valid indicator for intake, and found a median salicylate excretion of 10 micromol (1.4 mg) in 24 h urine of 17 volunteers eating a variety of diets. Our data suggest that the content of (acetyl)salicylic acid of diets may be too low to affect disease risk.

Effects of carotid body hypocapnia during ventilatory acclimatization to hypoxia.

Hypoxic ventilatory sensitivity is increased during ventilatory acclimatization to hypoxia (VAH) in awake goats, resulting in a time-dependent increase in expired ventilation (VE). The objectives of this study were to determine whether the increased carotid body (CB) hypoxic sensitivity is dependent on the level of CB CO2 and whether the CB CO2 gain is changed during VAH. Studies were carried out in adult goats with CB blood gases controlled by an extracorporeal circuit while systemic (central nervous system) blood gases were regulated independently by the level of inhaled gases. Acute VE responses to CB hypoxia (CB PO2 40 Torr) and CB hypercapnia (CB PCO2 50 and 60 Torr) were measured while systemic normoxia and isocapnia were maintained. CB PO2 was then lowered to 40 Torr for 4 h while the systemic blood gases were kept normoxic and normocapnic. During the 4-h CB hypoxia, VE increased in a time-dependent manner. Thirty minutes after return to normoxia, the ventilatory response to CB hypoxia was significantly increased compared with the initial response. The slope of the CB CO2 response was also elevated after VAH. An additional group of goats (n = 7) was studied with a similar protocol, except that CB PCO2 was lowered throughout the 4-h CB hypoxic exposure to prevent reflex hyperventilation. CB PCO2 was progressively lowered throughout the 4-h CB hypoxic period to maintain VE at the control level. After the 4-h CB hypoxic exposure, the ventilatory response to hypoxia was also significantly elevated. However, the slope of the CB CO2 response was not elevated after the 4-h hypoxic exposure. These results suggest that CB sensitivity to both O2 and CO2 is increased after 4 h of CB hypoxia with systemic isocapnia. The increase in CB hypoxic sensitivity is not dependent on the level of CB CO2 maintained during the 4-h hypoxic period.

Consumption of ginger (Zingiber officinale roscoe) does not affect ex vivo platelet thromboxane production in humans.

OBJECTIVES: Ginger (Zingiber Officinale Roscoe) has been claimed to exert an anti-thrombotic effect in humans as ginger extracts inhibit cyclo-oxygenase activity of platelets in vitro. Effects of ginger consumption on ex vivo platelet function, however, are contradictory. We therefore investigated whether daily consumption of raw or cooked ginger decreases platelet cyclo-oxygenase activity as assessed by ex vivo maximally stimulated platelet thromboxane B2 production. DESIGN: We carried out a randomized placebo-controlled cross-over study of 3 x 2 weeks. SUBJECTS: Eighteen healthy volunteers aged 22 +/- 3 y (mean +/- s.d.) participated in the study; there were no dropouts. INTERVENTIONS: Subjects consumed 15 g of raw ginger root, 40 g of cooked stem ginger, or placebo daily for two weeks. We took fasted venous blood samples and measured thromboxane B2 production in maximally stimulated platelet-rich plasma at days 12 and 14 of each treatment period. RESULTS: Mean decrease in thromboxane production relative to placebo was 1 +/- 9% for ginger root, and -1 +/- 8% for stem ginger, with no effect of treatment order (P = 0.984). CONCLUSIONS: We cannot confirm the putative anti-thrombotic activity of ginger in humans.

Urinary salicylate excretion in subjects eating a variety of diets shows that amounts of bioavailable salicylates in foods are low.

Intake of acetylsalicylic acid reduces the risk of cardiovascular disease and is associated with a decreased risk for colorectal cancer. Amounts of salicylates in foods are thus of interest, but data are scarce and controversial. We gave 58 mumol (10.5 mg) pure acetylsalicylic acid or 66 mumol (9.1 mg) salicylic acid to six volunteers and recovered 77-80% in 24-h urine samples. Thus, urinary excretion is a valid indicator for intake of free forms of (acetyl)salicylic acid. To estimate the bioavailable salicylate contents of diets, we subsequently studied salicylate excretion in 17 volunteers from 14 countries and four continents who ate a wide variety of self-selected diets. Median 24-h urinary salicylate excretion was 10 mumol (range: 6-12 mumol). Values increased with the fiber content of the diet (r = 0.73), suggesting that vegetable foods are the main sources of salicylates. However, amounts of salicylates in a variety of diets are evidently low and probably insufficient to affect disease risk.