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1.
Psychopharmacology (Berl) ; 239(7): 2277-2288, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35394159

ABSTRACT

RATIONALE: Pre-ejection period (PEP) and T-wave amplitude (TWA) have been used to assess sympathetic nervous system (SNS) activity. Here we report two single-blinded, placebo-controlled intravenous (IV) drug application studies in which we pharmacologically modified SNS activity with epinephrine (study 1) as well as dexmedetomidine (alpha2-agonist) and yohimbine (alpha2-antagonist) (study 2). Restricted heart rate (HR) intervals were analyzed to avoid confounding effects of HR changes. OBJECTIVE: Study 1 served to replicate previous findings and to validate our approach, whereas study 2 aimed to investigate how modulation of central SNS activity affects PEP and TWA. METHODS: Forty healthy volunteers (58% females) participated in study 1 (between-subject design). Twelve healthy men participated in study 2 (within-subject design). TWA and PEP were derived from ECG and impedance cardiography, respectively. RESULTS: Epinephrine shortened PEP and induced statistically significant biphasic TWA changes. However, although the two alpha2-drugs significantly affected PEP as expected, no effects on TWA could be detected. CONCLUSION: PEP is better suited to reflect SNS activity changes than TWA.


Subject(s)
Adrenergic Agents , Arrhythmias, Cardiac , Epinephrine/pharmacology , Female , Heart Rate , Humans , Male , Sympathetic Nervous System
2.
Diabet Med ; 30(5): 603-9, 2013 May.
Article in English | MEDLINE | ID: mdl-23324032

ABSTRACT

AIMS: The Hypoglycemia Fear Survey (HFS)-II Behaviour and Worry subscales were developed to measure behaviours and anxiety related to hypoglycaemia in diabetes. However, previous studies found lower reliability in the HFS Behaviour subscale and inconsistent relationships with glucose control. The purpose of this study was to conduct extensive analyses of the internal structure of the HFS Behaviour subscale's internal structure and its relationships with diabetes outcomes, including HbA1c and episodes of severe hypoglycaemia. METHODS: HFS-II survey data from 1460 adults with Type 1 diabetes were collected from five countries. This aggregated sample underwent exploratory factor analysis and item analysis to determine the internal structure of the survey and subscales. RESULTS: A three-factor solution showed the best fit for the HFS, with two subscales emerging from the HFS Behaviour representing tendencies towards (1) maintenance of high blood glucose and (2) avoidance of hypoglycaemic risks by other behaviours, and a third single HFS Worry subscale. Subscale item analysis showed excellent fit, separation and good point-measure correlations. All subscales demonstrated acceptable (0.75) to excellent (0.94) internal reliability. HbA(1c) correlated with Maintain High Blood Glucose subscale scores, r = 0.14, P < 0.001, and severe hypoglycaemia frequency correlated with all subscales. CONCLUSIONS: The HFS Worry subscale measures one construct of anxiety about various aspects of hypoglycaemia. In contrast, the HFS Behaviour subscale appears to measure two distinct aspects of behavioural avoidance to prevent hypoglycaemia, actions which maintain high blood glucose and other behaviours to avoid hypoglycaemic risk. These results demonstrate the clinical importance of the HFS Behaviour subscales and their differential relationships with measures of diabetes outcome such as HbA1c .


Subject(s)
Anxiety , Fear , Hypoglycemia/psychology , Hypoglycemic Agents/adverse effects , Adult , Anxiety/epidemiology , Anxiety/psychology , Blood Glucose Self-Monitoring , Fear/psychology , Female , Germany/epidemiology , Glycated Hemoglobin/metabolism , Humans , Hypoglycemia/epidemiology , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Male , Middle Aged , Netherlands/epidemiology , Patient Compliance , Psychometrics , Quality of Life , Reproducibility of Results , Self Care , Slovenia/epidemiology , Surveys and Questionnaires , Turkey/epidemiology , United States/epidemiology
3.
Cell Mol Neurobiol ; 32(5): 725-35, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22113371

ABSTRACT

There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders.


Subject(s)
Cognition/physiology , Emotions/physiology , Gonadal Steroid Hormones/metabolism , Stress, Psychological/metabolism , Animals , Female , Humans , Male , Neuronal Plasticity , Receptors, Steroid/metabolism
4.
Physiol Behav ; 98(5): 587-93, 2009 Dec 07.
Article in English | MEDLINE | ID: mdl-19799919

ABSTRACT

Baroafferent signals originating from the 'high pressure' arterial vascular system are known to impact reflexive startle eye blink responding. However, it is not known whether baroafferent feedback of the 'low pressure' cardiopulmonary system loading status exerts a similar effect. Lower Body Negative Pressure (LBNP) at gradients of 0, -10, -20, and -30mm Hg was applied to unload cardiopulmonary baroreceptors. Acoustic startle noise bursts were delivered 230 and 530ms after spontaneous R-waves, when arterial baroreceptors are either loaded or unloaded. Eye blink responses were measured by EMG, and psychomotor reaction time by button pushes to startle stimuli. The new finding of this study was that unloading of cardiopulmonary baroreceptors increases startle eye blink responsiveness. Furthermore, we replicated the effect of relative loading/unloading of arterial baroreceptors on startle eye blink responsiveness. Effects of either arterial or cardiopulmonary baroreceptor manipulations were not present for psychomotor reaction times. These results demonstrate that the loading status of cardiopulmonary baroreceptors has an impact on brainstem-based CNS processes.


Subject(s)
Blinking/physiology , Carotid Arteries/physiology , Lower Body Negative Pressure/methods , Pressoreceptors/physiology , Pulmonary Artery/physiology , Reflex, Startle/physiology , Acoustic Stimulation/adverse effects , Adult , Analysis of Variance , Blood Pressure/physiology , Electrocardiography/methods , Electromyography/methods , Humans , Male , Psychomotor Performance/physiology , Psychophysics , Reaction Time/physiology , Young Adult
6.
Praxis (Bern 1994) ; 92(38): 1584-6, 2003 Sep 17.
Article in German | MEDLINE | ID: mdl-14535038

ABSTRACT

The human startle response is modulated by affective states. The startle response is facilitated in unpleasant, aversive context, such as fear, and reduced during pleasure. This association can be explored by simple technical methods. The modulation of startle is found also in animal. It offers the opportunity to investigate human emotional processes by a biologically based, language free paradigm.


Subject(s)
Emotions , Reflex, Startle , Acoustic Stimulation , Affective Symptoms/physiopathology , Affective Symptoms/psychology , Animals , Blinking/physiology , Dogs , Electromyography , Emotions/physiology , Fear/physiology , Humans , Phobic Disorders/physiopathology , Phobic Disorders/psychology , Photic Stimulation , Reaction Time , Reflex, Startle/physiology , Research , Spiders , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/physiopathology , Stress, Psychological/psychology
7.
Praxis (Bern 1994) ; 91(3): 53-60, 2002 Jan 16.
Article in German | MEDLINE | ID: mdl-11845613

ABSTRACT

Life style has to be adapted to insulin regimens in conventionally intensified insulin therapy. Functional insulin therapy (FIT) allows for flexible adjustments to changing insulin requirements. FIT is based on separating the substitution of basal, meal dependent and correction insulin by the patient. The patient has to acquire special knowledge. We here report longitudinal data of 183 patients out of 221 patients who have been educated by FIT outpatient programs in the years 1990 to 1996. The 3 month FIT education program consisted of sixteen hours in total. Five and a half hours were held in a whole day preparation seminar and the other seven hours in evening sessions each of 90 minutes duration. Prior to FIT education patients were treated by intensified conventional insulin therapy. Mean glycosylated hemoglobin prior to FIT education was 7.0% (normal range 3.7-5.6%). After FIT education glycosylated hemoglobin remained unchanged. However, the percentage of patients experiencing severe hypoglycemic episodes (stupor and coma) in a one year course was significantly reduced from 26% prior to FIT education to 14% after FIT education--hypoglycemic coma was reduced from 13% to 7% respectively. Thus, we can report that FIT reduces the risk of severe hypoglycemia. We believe that our data should stimulate the broad supply of FIT education programs available to diabetes patients in Switzerland.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemia/prevention & control , Insulin/therapeutic use , Patient Education as Topic , Adult , Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Diet, Diabetic , Female , Humans , Hypoglycemia/blood , Insulin/administration & dosage , Male , Middle Aged , Odds Ratio
8.
Hypertension ; 38(6): 1325-9, 2001 Dec 01.
Article in English | MEDLINE | ID: mdl-11751712

ABSTRACT

Salt-sensitive normotensive men exhibit an enhanced pressor response to mental stress. Although an enhanced pressor response is associated with higher affective startle modulation in men, an association between salt sensitivity of blood pressure and affective startle modulation has not been studied so far. We studied reactivity to mental stress and startle modulation in 14 salt-sensitive healthy white male students and 14 salt-resistant control subjects, who were well matched for age, body mass index, physical fitness, and family history of hypertension. Subjects performed a computerized information-processing task under time pressure (manometer test), while heart rate and blood pressure were continuously registered. In a separate session, subjects viewed a series of 42 pictures of the International Affective Picture System (IAPS), varying in pleasure and arousal, while acoustic startle probes were administered randomly, and electromyogram activity of the orbicular eye muscle was continuously recorded. Startle modulation was calculated as the difference between startle responses under negative and positive affective stimuli. In contrast to salt-resistant subjects, salt-sensitive subjects showed significantly enhanced startle amplitudes under negative stimuli and diminished amplitudes under positive stimuli. Thus, salt-sensitive subjects displayed a significantly higher startle modulation than did salt-resistant subjects (P<0.05). Subjective ratings of the presented IAPS pictures did not differ between the groups. The increased startle modulation of salt-sensitive subjects suggests an enhanced activity of the central nucleus of the amygdala. This enhanced central nervous responsiveness may contribute to higher sympathetic pressor reactivity and, thus, to the later development of hypertension in salt-sensitive individuals.


Subject(s)
Blood Pressure/physiology , Reflex, Startle/physiology , Sodium, Dietary/pharmacology , Adult , Analysis of Variance , Electromyography , Genetic Predisposition to Disease , Humans , Hypertension/genetics , Male , Mental Processes/physiology , Reference Values , Sodium, Dietary/metabolism
9.
Psychosom Med ; 63(5): 788-96, 2001.
Article in English | MEDLINE | ID: mdl-11573027

ABSTRACT

OBJECTIVE: A number of sympathetic nervous system (SNS) parameters have been used in cardiovascular psychophysiology. This study aimed to describe the pattern and redundancy of a set of SNS parameters during peripherally induced changes of cardiac sympathetic activation and reflex modulation of central SNS control. Preejection period (PEP) was assessed as a marker of peripheral sympathetic activation. Low-frequency blood pressure variability (BPV) was assessed as an estimate of central SNS control. METHODS: Peripheral beta-sympathetic stimulation and blockade were achieved with epinephrine and esmolol hydrochloride (beta1-blockade), respectively. Changes in central SNS output were induced by loading and unloading arterial baroreceptors with norepinephrine and nitroprusside sodium, respectively. This single-blinded, crossover study in 24 healthy men also included two placebo control periods. PEP was derived from impedance cardiography and adjusted individually for heart rate. BPV was calculated by power spectral analyses of beat-to-beat heart rate and systolic blood pressure (Finapres system) data. RESULTS: PEP decreased during epinephrine infusion (-40.1 +/- 3.8 ms, p <.0001) and increased during esmolol infusion (+6.6 +/- 3.5 ms, p =.05). PEP was shortened after central SNS activation by nitroprusside (-16.8 +/- 2.9 ms, p < 0.0001). Systolic BPV in the low-frequency range (0.07-0.14 Hz, Mayer waves) increased during nitroprusside infusion (+0.44 +/- 0.19 ln mm Hg(2), p =.03) and decreased during norepinephrine infusion (-0.67 +/- 0.13 ln mm Hg(2), p < 0.0001). Low-frequency BPV did not change significantly during epinephrine or esmolol infusion. CONCLUSIONS: Our data provide empirical evidence of separable peripheral and central sympathetic response components. The combined report of low-frequency BPV and PEP gives distinct information on both central SNS control and the level of sympathetic cardiac activation achieved.


Subject(s)
Cardiovascular Physiological Phenomena/drug effects , Cardiovascular System/drug effects , Sympathetic Nervous System/drug effects , Adrenergic alpha-Agonists/administration & dosage , Adrenergic beta-Agonists/administration & dosage , Adrenergic beta-Antagonists/administration & dosage , Adult , Blood Pressure/drug effects , Cross-Over Studies , Epinephrine/administration & dosage , Heart Rate/drug effects , Humans , Male , Nitroprusside/administration & dosage , Norepinephrine/administration & dosage , Propanolamines/administration & dosage , Single-Blind Method , Sympathetic Nervous System/physiology , Vasodilator Agents/administration & dosage
10.
Clin Physiol ; 20(6): 483-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11100396

ABSTRACT

Little is known about mental stress effects on the pulmonary circulation in health and disease. The current study was conducted to investigate whether pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) would further increase during standardized mental stress testing in patients with severe pulmonary hypertension. The study was a prospective analysis of seven patients (average age: 40 years, range from 21 to 56 years) with severe pulmonary hypertension (primary: n = 4, secondary forms: n = 3; resting mean pulmonary artery pressure ranged between 48 and 65 mmHg). Right heart catheterization for the determination of PAP, pulmonary capillary wedge pressure (PCW) and cardiac output (CO) was clinically indicated (diagnostic workup, acute drug testing). Patients accomplished a standardized 10 min mental stress test (computer based, adaptive complex reaction-time task). Pulmonary haemodynamics during stress were compared to resting baseline. During mental stress mean PAP (+/- SEM) increased by 9.4 +/- 2.1 mmHg (P < 0.005). Pulmonary vascular resistance increased by 149 +/- 25 dyne s cm-5 (P < 0.001). Stroke volume decreased by 6.6 +/- 2.2 ml (P < 0.03). The data show that moderate mental stress increases right heart afterload in patients with severe pulmonary hypertension owing to elevation of PVR.


Subject(s)
Hypertension, Pulmonary/physiopathology , Pulmonary Circulation/physiology , Stress, Psychological/physiopathology , Adult , Blood Pressure/physiology , Cardiac Catheterization , Female , Heart Rate/physiology , Humans , Hypertension, Pulmonary/psychology , Male , Middle Aged , Respiration , Stroke Volume/physiology , Vascular Resistance/physiology
11.
Eur J Clin Invest ; 30(9): 823-31, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10998084

ABSTRACT

BACKGROUND: Hypocalcemia and increased serum levels of calcitonin precursors are common in critically ill patients, especially in those with sepsis. We investigated calcium homeostasis in such patients. PATIENTS AND METHODS: Serum concentrations of total and ionized calcium and known factors influencing or reflecting calcium homeostasis were measured in 101 consecutive patients of a medical intensive care unit. Calcitonin precursor levels were determined using a highly sensitive radioimmunoassay. RESULTS: Critical illness per se was associated with decreased serum total and ionized calcium levels, which correlated with the severity of the underlying disease as measured by the APACHE II score. In addition, total and ionized hypocalcemia was more pronounced with increasing severity of infection (P < 0.02), and occurred in parallel with a marked increase of calcitonin precursors (P < 0.001). Mature calcitonin levels, however, remained normal. Changes of serum ionized calcium concentrations from admission to discharge correlated significantly with changes in the serum calcitonin precursor concentration (r2 = - 0.14, P < 0.001). Circulating vitamin D levels, parathyroid hormone levels and other markers reflecting calcium homeostasis did not correlate with the severity of infection. CONCLUSIONS: In critically ill patients with sepsis, markedly elevated circulating calcitonin precursors might play a role in the development of the pronounced hypocalcemia. The specific calcitonin precursor(s) responsible for this effect and the pathophysiological mechanism remain to be elucidated.


Subject(s)
Calcitonin/blood , Calcium/blood , Protein Precursors/blood , Sepsis/blood , Adult , Aged , Female , Homeostasis , Humans , Hypocalcemia/etiology , Male , Middle Aged , Sepsis/physiopathology , Vitamin D/blood
12.
Br J Clin Pharmacol ; 50(3): 237-46, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10971308

ABSTRACT

AIMS: To investigate the effect of acute P-glycoprotein inhibition by the multidrug-resistance (MDR) modulator valspodar (SDZ PSC 833; PSC) on the pharmacokinetics, and potentially adverse pharmacodynamic effects of morphine, and its principal pharmacologically active metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). METHODS: In a double-blind, three-way crossover study, the pharmacokinetic and potentially adverse pharmacodynamic effects (reaction time, transcutaneous PCO2, blood pressure) of morphine were compared with and without acute inhibition of P-glycoprotein by PSC. The effects of PSC alone were also evaluated. The study was performed in 18 healthy male volunteers and pharmacodynamic effects analysed by measuring the area under the effect (AUE) curve. 150 mg PSC (or its placebo) was given as an i.v. infusion over 2 h. With the expected inhibition of Pgp 1 h after starting PSC infusion, 7.5 morphine HCl (or its placebo) was infused over 2 h. RESULTS: The infusion of PSC resulted in blood concentrations expected to inhibit Pgp mediated transport. While the pharmacokinetics of plasma morphine and M6G. were unaffected there was a small but statistically significant increase in the AUC and Cmax of M3G (11.8 and 8.3%, respectively). The t(1/2) and tmax were unaffected. The pharmacokinetic parameters of PSC were not affected by coadministration with morphine. PSC did not significantly affect the adverse events of morphine, as assessed by spontaneous reporting. Compared with PSC alone, morphine elicited an increase in reaction time (Emax 48 ms, compared with the predose absolute reaction time of 644 ms), which was not detected by the alertness-drowsiness score, indicating only slight sedation. There was a significant decrease in systolic blood pressure (Emin -9 mm Hg), and a trend for a fall in diastolic blood pressure (Emin -14.5 mm Hg) and respiratory rate (Emin -1.8 breath x min(-1)). For all these parameters, the effects of PSC/morphine were similar to that of PSC alone, suggesting some attenuation of morphine's effect. In contrast, morphine caused a significant increase in PCO2 (Emax 0.69 kPa) compared to PSC alone, indicating slight respiratory depression. This increase was similar to that of the PSC/morphine combination. CONCLUSIONS: Acute inhibition of P-glycoprotein by PSC in this setting does not affect the pharmacokinetic or safety-related pharmacodynamic profile of morphine in a clinically significant manner.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors , Analgesics, Opioid/adverse effects , Analgesics, Opioid/pharmacokinetics , Cyclosporins/pharmacology , Morphine/adverse effects , Morphine/pharmacokinetics , Adult , Area Under Curve , Blood Gas Monitoring, Transcutaneous , Cross-Over Studies , Cyclosporins/pharmacokinetics , Double-Blind Method , Drug Interactions , Half-Life , Humans , Injections, Intravenous , Male , Morphine Derivatives/blood , Reaction Time/drug effects , Sleep Stages/drug effects
13.
Br J Anaesth ; 84(3): 316-22, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10793589

ABSTRACT

Arterial pressure (AP) and inter-beat interval (IBI) length are under autonomic nervous system control. The control mechanisms can be investigated by transfer function analysis. It is not known if this type of analysis may be helpful in monitoring depth of sedation. In an open-label, uncontrolled investigation, the effect of midazolam on the transfer function between AP and IBI, and on spectral indices of AP and heart rate (HR) variability (APV, HRV) were assessed in the absence and presence of the benzodiazepine antagonist flumazenil. We studied 11 healthy male volunteers. After an initial control period of 60 min, we studied three consecutive periods, each of 60 min duration, with progressively increasing concentrations of midazolam (0.02, 0.06, 0.14 mg kg-1 h-1). A final 60-min period during administration of flumazenil 0.004 mg kg-1 h-1 and while the agonist was still present was also studied. To confirm midazolam-induced central nervous system effects, electroencephalography was performed and Ramsay sedation scores were determined. With increasing dose of midazolam, the high frequency (0.15-0.4 Hz) component of the transfer function between AP and IBI decreased progressively (mean 26.5 (SEM 3.7), 19.2 (2.9), 12.8 (1.7), 8.4 (1.6) ms mm Hg-1). This effect was antagonized by flumazenil (21.5 (3.2) ms mm Hg-1). Other indices (e.g. HRV, APV) did not reveal such a clear response to midazolam dose and flumazenil application. Thus in healthy male volunteers, the transfer function between AP and IBI in the parasympathetically dominated high frequency range varies according to benzodiazepine agonism and antagonism. This finding has potential implications for monitoring the effects of benzodiazepines.


Subject(s)
Anti-Anxiety Agents/pharmacology , Blood Pressure/drug effects , Heart Rate/drug effects , Midazolam/pharmacology , Adult , Anti-Anxiety Agents/blood , Blood Pressure/physiology , Dose-Response Relationship, Drug , Electroencephalography/drug effects , Heart Rate/physiology , Humans , Male , Midazolam/blood , Monitoring, Physiologic
14.
Crit Care Med ; 28(4): 977-83, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10809269

ABSTRACT

OBJECTIVE: The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading. For example, serum concentrations of calcitonin precursors are increased in patients with infections. However, their predictive accuracy for the diagnosis of sepsis in unselected patients in a medical intensive care unit (ICU) is unknown. Therefore, we compared the usefulness of serum concentrations of calcitonin precursors, C-reactive protein, interleukin-6, and lactate for the diagnosis of sepsis in consecutive patients suffering from a broad range of diseases with an anticipated stay of > or =24 hrs in a medical ICU. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit in a university medical center. PATIENTS: 101 consecutive critically ill patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected at various time points during the course of the disease. Systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock were diagnosed according to standardized criteria, and patients were reclassified daily without prior knowledge of the serum concentrations of calcitonin precursors or interleukin-6. At admission, 99% of the patients had systemic inflammatory response syndrome, 53% had sepsis, and 5% developed sepsis during their stay in the ICU. Calcitonin precursors, C-reactive protein, interleukin-6, and lactate levels increased with the severity of infection (p < .01, one-way analysis of variance). In a receiver operating characteristic curve analysis, calcitonin precursors were found to be the most reliable laboratory variable for the diagnosis of sepsis as compared with C-reactive protein, interleukin-6, and lactate (p < .01, for each comparison). Calcitonin precursor concentrations of >1 ng/mL had sensitivity of 89% and specificity of 94% for the diagnosis of sepsis. High serum concentrations of calcitonin precursors were associated with poor prognosis (p = .01). CONCLUSIONS: In a medical ICU, serum calcitonin precursor concentrations are more sensitive and are specific markers of sepsis as compared with serum C-reactive protein, interleukin-6, and lactate levels.


Subject(s)
Calcitonin/blood , Critical Care , Glycoproteins/blood , Protein Precursors/blood , Sepsis/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , Critical Illness , Female , Humans , Interleukin-6/blood , Lactic Acid/blood , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Sepsis/diagnosis
15.
Drugs ; 58(3): 429-46, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10493271

ABSTRACT

This article reviews the pharmacological treatment of severely hypoxaemic critically ill patients, notably those with acute respiratory distress syndrome (ARDS), acute lung injury or the sepsis syndrome. Haemodynamic support in hypotensive patients often initially requires aggressive fluid resuscitation with crystalloids or colloids, combined with vasopressors to maintain adequate end-organ perfusion. The catecholamine of choice in severe hypotension with low systemic resistance is norepinephrine (noradrenaline); dopamine is often used in mild hypotension. Once haemodynamic stabilisation is achieved, loop diuretics such as furosemide (frusemide) are used to obtain the lowest volaemia that guarantees adequate perfusion. If the fraction of inspired oxygen necessary to achieve the satisfactory haemoglobin oxygen saturation of 90% approaches 1, a trial of nitric oxide with or without almitrine is justified. Oxygen consumption can be lowered by treating fever with paracetamol (acetaminophen) and physical cooling. Occasionally, deep sedation using a combination of an opioid (most often morphine or fentanyl) and a benzodiazepine (lorazepam or midazolam) is necessary; in the presence of renal or hepatic insufficiency, propofol is a valid, although expensive, alternative. Paralysis with pancuronium or vecuronium has been associated with critical illness polyneuropathy and is used only as a last resort. Corticosteroids may be indicated in the subacute (fibroproliferative) phase of ARDS. Other anti-inflammatory treatments (such as cytokine antagonists, cyclo-oxygenase inhibitors, antioxidants or monoclonal anti-endotoxin antibodies), as well as surfactant supplementation, have failed to improve prognosis in randomised trials.


Subject(s)
Adjuvants, Pharmaceutic/therapeutic use , Hypoxia/complications , Oxygen/therapeutic use , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/etiology , Anti-Inflammatory Agents/therapeutic use , Bronchodilator Agents/therapeutic use , Clinical Trials as Topic , Humans , Surface-Active Agents/therapeutic use
16.
Br J Clin Pharmacol ; 47(4): 421-6, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10233207

ABSTRACT

AIMS: The eye-blink response following sudden acoustic noise bursts is part of the startle reflex. The magnitude of the startle response can be attenuated by presentation of a weak stimulus before the 'startle-eliciting' stimulus (prepulse inhibition, PPI). PPI is a stable finding in awake humans but may be altered by anaesthetic drugs. We investigated whether the application of benzodiazepines altered the magnitude of PPI in healthy male volunteers. METHODS: In an open-label noncontrolled investigation, the effect of the benzodiazepine agonist midazolam on PPI was assessed in the absence and presence of the antagonist flumazenil. After an initial control period of 60 min three consecutive periods, each of 60 min, with progressively increasing concentrations of midazolam were studied (0. 02, 0.06, 0.14 mg kg-1 h-1 ). A final 60 min period during the administration of flumazenil (0.004 mg kg-1 h-1 ) and while the agonist was still present was also studied. Drug was administered intravenuously as a combination of bolus, 50% of total dose and continuous infusion over the 60 min period. Electromyographic (EMG) response of the right orbicularis oculi muscle was used to assess the startle response to noise bursts of 50 ms duration (95 dB(A)). Noise bursts were randomly preceded by nonstartling prepulses (800 Hz sinus, 50 ms duration, 65 dB(A), prepulse to noise interval 120 ms). The magnitude of PPI was calculated by dividing the EMG response to nonprepulsed stimuli by the response to prepulsed stimuli for each individual and period. Eleven subjects participated in the study, two of them were excluded from the statistical analysis because startle responses could not be reliably elicited (final sample size n=9). RESULTS: The magnitude of PPI was inversely related to the concentration of midazolam. This relationship was described by a sigmoidal Emax model, giving an Emax of 0.65+/-0.13, an ED50 of 33.9+/-10.9 ng ml-1 and gamma of 3.5+/-1.0. During infusion of flumazenil and in the presence of midazolam, the magnitude of PPI increased by 0.11 (95% CI, 0-0.22, P

Subject(s)
Anti-Anxiety Agents/pharmacology , Blinking/drug effects , Midazolam/pharmacology , Reflex, Startle/drug effects , Acoustic Stimulation , Adult , Dose-Response Relationship, Drug , Electromyography , Flumazenil/pharmacology , Humans , Male , Midazolam/blood
17.
Clin Physiol ; 19(2): 143-52, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10200896

ABSTRACT

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21-39 years, during controlled frequency breathing (0.30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0.15-0.40 Hz) band (PROP 7.4 +/- 1.0; PLA 6.9 +/- 1.4; PIN 6.8 +/- 1.0 ln MI2; P = 0.003), decreased BPV in the low-frequency band (at 0.1 Hz, Mayer waves) (PROP 0.6 +/- 0.7; PLA 1.3 +/- 1.1; PIN 1.2 +/- 1.2 ln mmHg2; P = 0.001) and enhanced BRS (PROP 14.6 +/- 9.5; PLA 8.0 +/- 6.8; PIN 8.7 +/- 6.8 ms mmHg-1; P = 0.001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6.1 +/- 0.9; PLA 6.5 +/- 1.1; PIN 6.9 +/- 0.7 ln MI2; P < 0.001) and decreased Mayer waves (PROP 1.8 +/- 0.8; PLA 2.4 +/- 1.0; PIN 2.7 +/- 0.8 ln mm Hg2; P < 0.001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0.9 +/- 1.0; PLA + 0.3 +/- 1.3, PROP + 0.3 +/- 1.0 ln MI2; P = 0.026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Baroreflex/physiology , Pindolol/pharmacology , Propranolol/pharmacology , Sympathetic Nervous System/physiology , Sympathomimetics/pharmacology , Vagus Nerve/drug effects , Adult , Baroreflex/drug effects , Blood Pressure/drug effects , Cross-Over Studies , Double-Blind Method , Electrocardiography/drug effects , Female , Heart Rate/drug effects , Humans , Male , Supine Position/physiology , Sympathetic Nervous System/drug effects
18.
Schweiz Med Wochenschr ; 128(7): 231-44, 1998 Feb 14.
Article in German | MEDLINE | ID: mdl-9540147

ABSTRACT

Patients with somatoform disorders probably constitute the largest diagnostic group in daily medical practice. A major communication problem forms the core of somatoform disorders: patients report about complaints which their physicians do not understand; there is no sufficient biological reason for the patient's symptoms. This article discusses the multifactorial origin of somatoform disorders, consisting of minimal physiological changes, the perception of bodily sensations, and their interpretation as symptoms (non-normal perceptions), as well as ensuing emotional and behavioral consequences. Concerning the communication problem, it is important to realize that patients normally present symptoms, whereas the underlying bodily perceptions and the explanatory models are rarely communicated to the physician. On the physician's side, symptoms presented by patients are subjected to his or her explanatory concepts translating symptoms into indicators of certain diseases. Thus, the information introduced into physician-patient communication by the patient has usually passed several cognitive circuits within the patient or between the patients and other significant conversation partners thus shaping its specific components. It is recommended that physicians try to trace back their patients' symptoms to bodily sensations and explanatory models in order to base their diagnostic and therapeutic reasoning on the same kind of information. Empirical evidence is presented to support the inter-dependence of the components of the model, on both the patient's and the physician's side. Therapeutic interventions based upon the model are presented.


Subject(s)
Communication , Physician-Patient Relations , Sick Role , Somatoform Disorders/psychology , Awareness , Humans , Somatoform Disorders/diagnosis
19.
J Hypertens ; 15(8): 839-44, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9280205

ABSTRACT

OBJECTIVE: To evaluate the psychophysiological response to mental stress of young healthy salt-sensitive normotensive subjects. METHODS: Thirty-two healthy volunteers who had previously been phenotyped for salt sensitivity were selected for the study. The 16 salt-sensitive and 16 salt-resistant subjects, who were matched for age, body mass index and family history of hypertension, underwent a mental stress test consisting of an information-processing task performed under time pressure (the Manometer test). During the experimental session the blood pressure, heart rate and pulse-wave velocity were registered continuously. Before and after the mental task subjects were instructed to complete several standardized psychological state and trait questionnaires. RESULTS: Mental stress resulted in a greater rise in blood pressure (P < 0.05) and in pulse-wave velocity (P < 0.01) in salt-sensitive than in salt-resistant individuals. Salt-sensitive subjects also displayed significantly higher levels of anxiety (P < 0.01) and a lower level of control of anger (P < 0.01) than did salt-resistant subjects. Furthermore, the level of irritation of the salt-sensitive subjects was higher both before (P < 0.01) and after (P < 0.05) the stress test CONCLUSIONS: An increased responsiveness of the blood pressure to mental stress and an increased level of irritation are associated with salt sensitivity in normotensive subjects. These findings are in line with the hypothesis that psychophysiological traits play a role in the development of salt-sensitive hypertension.


Subject(s)
Blood Pressure/drug effects , Sodium Chloride/pharmacology , Stress, Physiological/physiopathology , Adult , Body Mass Index , Drug Resistance , Heart Rate , Humans , Male , Pulse
20.
Cardiology ; 88(3): 277-84, 1997.
Article in English | MEDLINE | ID: mdl-9129850

ABSTRACT

Antihypertensive therapy has been thought to be a life-long treatment. Nevertheless, antihypertensive medication may be discontinued in a substantial proportion of hypertensive patients at least for some time. The current study focused on predictors for the development of elevated blood pressure levels after discontinuation of antihypertensive drug therapy. In an open, prospective study, 88 white male patients with newly discovered essential hypertension (age 42 +/- 7 years) were tested at baseline. Blood pressure was measured in various situations (at work, at rest, before and during treatment, and at follow-up), and the hemodynamic profile at rest and cardiovascular response patterns during stress tests were evaluated. Left ventricular mass and other cardiovascular risk factors were also carefully determined. After 6 months of strict blood pressure control (< 140/90 mm Hg), they were treated by their primary care physician (mean duration of antihypertensive therapy 1.3 +/- 1.7 years). After 6 years, 37 patients were still on antihypertensive therapy, but 19 of the 37 had blood pressure values > or = 160/95 mm Hg. In 51 patients, therapy was discontinued: 29 were hypertensive, 15 were borderline hypertensive and 7 were normotensive. Relapse of hypertensive blood pressure in these 51 patients off therapy was predicted by resting blood pressure values before therapy (138 +/- 11/91 +/- 5 vs. 131 +/- 11/85 +/- 7 mm Hg, p < 0.05/0.01), cardiac output at rest (7.5 +/- 1.9 vs. 6.2 +/- 2.1 l/min, p < 0.05), total peripheral resistance (20 +/- 9 vs. 14 +/- 4 U, p < 0.05), increased heart rate during ergometry (50 +/- 8 vs. 44 +/- 6 b.p.m., p < 0.05) and left ventricular mass determined by echocardiography (212 +/- 60 vs. 189 +/- 44 g, p < 0.01). There was no difference in age, blood pressure levels before and during treatment, the number of consultations with the primary care physician or cardiovascular risk factor profiles. In conclusion, intermittent rather than life-long antihypertensive treatment may be possible in hypertensive patients with low resting blood pressure, high cardiac output, low total peripheral resistance and low left ventricular mass.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Adult , Blood Pressure/drug effects , Cardiac Output , Exercise Test , Follow-Up Studies , Humans , Hypertension/etiology , Hypertension/physiopathology , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Male , Prevalence , Prospective Studies , Recurrence , Ultrasonography
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