Biomedical subjects
J Hildebrandt
Publications and source records attributed to J Hildebrandt.
[Therapeutic approaches in chronic back pain].
Back pain is a common disease causing tremendous costs for treatment, work loss and pension payments. The reasons of back pain vary considerably and often remain doubtful. The effectiveness of common treatment concepts has not yet been proved significantly. Active treatment procedures should be preferred. In chronic pain patients only multimodal concepts of treatment seem to be successful as far as they take care of somatic, psychosocial, ergonomic and sport physiological aspects.
Modeling diffusion limitation of gas exchange in lungs containing perfluorocarbon.
We reported changes in alveolar-arterial PO2 gradient, ventilation-perfusion heterogeneity, and arterial-alveolar PCO2 gradient during partial liquid ventilation (PLV) in healthy piglets (E. A. Mates, P. Tarczy-Hornoch, J. Hildebrandt, J. C. Jackson, and M. P. Hlastala. In: Oxygen Transport to Tissue XVII, edited by C. Ince. New York: Plenum, 1996, vol. 388, p. 585-597). Here we develop two mathematical models to predict transient and steady-state (SS) gas exchange conditions during PLV and to estimate the contribution of diffusion limitation to SS arterial-alveolar differences. In the simplest model, perfluorocarbon is represented as a uniform flat stirred layer and, in a more complex model, as an unstirred spherical layer in a ventilated terminal alveolar sac. Time-dependent solutions of both models show that SS is established for various inert and respiratory gases within 5-150 s. In fluid-filled unventilated terminal units, all times to SS increased sometimes by hours, e.g., SF6 exceeded 4 h. SS solutions for the ventilated spherical model predicted minor end-capillary disequilibrium of inert gases and significant disequilibrium of respiratory gases, which could explain a large portion of the arterial-alveolar PCO2 gradient measured during PLV (14). We conclude that, during PLV, diffusion gradients for gases are generally small, except for CO2.
The role of the inhibitory nonadrenergic noncholinergic system in antigen-induced pulmonary hypersensitivity.
To study the role of the inhibitory nonadrenergic noncholinergic (i-NANC) system in regulating bronchial reactivity during antigen challenge, we first tested a blocker of the i-NANC system (oxyhemoglobin, HbO2, 2.5 microm) on the relaxation response of guinea pig tracheal strips (n=6) in vitro to electrical field stimulation (ES) in the presence of atropine (1 microg/ml) and propranolol (2 microg/ml). Fresh HbO2 significantly inhibited 35.3+/-4.5% (P<0.001) of the NANC relaxation response. Secondary, 26 anesthetized, ovalbumin-sensitized animals were divided into three groups: antigen challenged (n=10), pretreated with HbO2 (13 mg/kg) and challenged (n=9), and treated with HbO2 only (n=7). Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured 15-20 min prior to (baseline) and up to 30 min after antigen or HbO2 injection. Antigen challenge alone induced early maximal respiratory changes: RL increased 1646+/-115% above baseline (2 min) whereas Cdyn decreased 42+/-10% below baseline (4 min). These changes returned to baseline within 15 min. Pretreatment with HbO2 increased peak respiratory responses induced by antigen [RL, 3728+/-1680% above baseline; Cdyn, 69+/-7% below baseline (P<0.05)]. HbO2 delayed significantly (P<0.05) the time for recovery of RL and Cdyn. HbO2 alone had little effect on respiratory parameters. We conclude that HbO2 may antagonize the i-NANC system in the airway and this antagonism may accentuate pulmonary hypersensitivity during acute antigen challenge.
Demonstration of facilitatory I wave interaction in the human motor cortex by paired transcranial magnetic stimulation.
1. Transcranial magnetic stimulation (TMS) of the human motor cortex results in multiple discharges (D and I waves) in the corticospinal tract. We tested whether these volleys can be explored non-invasively with paired TMS. The intensity of the first stimulus (S1) was set to produce a motor-evoked potential (MEP) of 1 mV in the resting contralateral abductor digiti minimi (ADM) muscle; the second stimulus (S2) was set to 90 % of the resting motor threshold. At interstimulus intervals of 1.1-1.5, 2.3-2.9 and 4.1-4.4 ms the MEP elicited by S1 plus S2 was larger than that produced by S1 alone. 2. Varying the S1 intensity between 70 and 130 % resting motor threshold with S2 held constant at 90 % resting motor threshold showed that the threshold for the first MEP peak was <= 70 % resting motor threshold. The second and third MEP peaks appeared only at higher S1 intensities. The latency of all peaks decreased with increasing S1 intensity. 3. Varying the S2 intensity with S1 held constant to produce a MEP of 1 mV on its own showed that the amplitude of all MEP peaks increased with S2 intensity, but that their timing remained unchanged. 4. Paired TMS in the active ADM (S1 clearly suprathreshold, S2 just above threshold; interstimulus interval, 1 ms) produced strong MEP facilitation. The onset of this facilitation occurred later by about 1.5 ms than the onset of the MEP evoked by S2 alone. No MEP facilitation was seen if the magnetic S2 was replaced by anodal or cathodal transcranial electrical stimulation. 5. It is concluded that the MEP facilitation after paired TMS, at least for the first MEP peak, is due to facilitatory interaction between I waves, and takes place in the motor cortex at or upstream from the corticospinal neurone.
Pharmacological control of facilitatory I-wave interaction in the human motor cortex. A paired transcranial magnetic stimulation study.
A novel paired transcranial magnetic stimulation (TMS) paradigm with a suprathreshold first and a subthreshold second stimulus was used in healthy volunteers to investigate the acute effects of a single oral dose of various CNS-active drugs on short-interval motor evoked potential (MEP) facilitation. MEPs were recorded from the relaxed abductor digiti muscle. Three peaks of MEP facilitation were consistently observed at interstimulus intervals of 1.1-1.5 ms, 2.3-2.7 ms, and 3.9-4.5 ms. The size of these MEP peaks was transiently suppressed by drugs which enhance gamma-aminobutyric acid (GABA) function in the neocortex (lorazepam, vigabatrin, phenobarbital, ethanol), while the GABA-B receptor agonist baclofen, anti-glutamate drugs (gabapentin, memantine), and sodium channel blockers (carbamazepine, lamotrigine) had no effect. The interstimulus intervals effective for the production of the MEP peaks remained unaffected by all drugs. The MEP peaks are thought to be due to a facilitatory interaction of I-(indirect) waves in the motor cortex. Therefore, the present results indicate that the production of I-waves is primarily controlled by GABA related neuronal circuits. The potential relevance of this non-invasive paired TMS protocol for the investigation of I-waves in patients with neurological disease will be discussed.
Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ.
Treatments available to improve compliance in surfactant-deficient states include exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air-PFC interfaces introduced during PLV compared with TLV, we hypothesized that compliance would be worse during PLV than during TLV. Because surfactant is able to reduce interfacial tension between air and lung as well as between PFC and lung, we further hypothesized that compliance would improve with surfactant treatment before PLV. In excised preterm lamb lungs, we used Survanta for surfactant replacement and perflubron as the PFC. Compliance during PLV was intermediate between TLV and gas inflation, both with and without surfactant. Surfactant improved compliance during PLV, compared with PLV alone. Because of the force-balance equation governing the behavior of immiscible droplets on liquid surfaces, we predict that PFC droplets spread during PLV to cover the alveolar surface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets in surfactant-sufficient lungs, except at end inspiration.
Lung volume reduction surgery has variable effects on blood gases in patients with emphysema.
Most studies of bilateral lung volume reduction surgery (LVRS) report increases in arterial oxygenation (PaO2). Some suggest this results from an increased alveolar ventilation, but others imply that ventilation-perfusion heterogeneity is reduced. We measured arterial blood gases (ABGs) on air before and 3 mo following LVRS in 46 patients (61% of eligible patients), estimate the difference between alveolar and arterial O2 (AaPO2), and correlated the changes observed with preoperative ABGs, and with pre-and postoperative pulmonary function. The mean +/- SD change in PaO2 and AaPO2 was +3 +/- 10 mm Hg (p = 0.058) and +1 +/- 11 mm Hg (p = NS), respectively, and the range of change was large (-17 to +29 mm Hg and -24 to +23 mm Hg, respectively). The mean change in PaCO2 was -3 +/- 5 mm Hg (p < 0.05) and ranged from -11 to +5 mm Hg. Changes in PaO2 and AaPO2 were poorly correlated with changes in PaCO2 or with pre- or postoperative pulmonary function. Although some patients had a marked improvement in ABGs following LVRS, almost as many deteriorated. On average, only minimal effects were seen. Although mean alveolar ventilation improved somewhat, the effect of LVRS on PaO2 primarily resulted from alterations in ventilation-perfusion heterogeneity.
[Backache--diagnosis, therapy and prognosis].
Back pain is a common disease causing tremendous costs for treatment, rehabilitation, pension payments and work-loss. The reasons of back pain vary considerably and often remain doubtful. The effectiveness of current treatment concepts has not yet been proven significantly. In accordance with the literature, in chronic pain only multimodal concepts of treatment seem to be successful as far as they take care about somatic, psycho-social, and sport physiological aspects.
[Fear-avoidance-beliefs in patients with backpain].
INTRODUCTION: In recent years most industrialized nations have been confronted with a dramatic increase in cases dealing with back pain which, because of the associated costs, has put a strain on health care systems. Because of the tremendous costs caused by patients with chronic illnesses, there is a common interest in identifying determinants responsible for the pain becoming chronic. According to the fear-avoidance model, chronic back pain is the cause of specific patient beliefs according to their perception and appraisal of back pain and their assumptions about the connection between pain and work activities. These fear-avoidance beliefs are assumed as the main cognitive factors of adapting to chronic invalidism. In this study a German version of a self-reporting instrument that assesses fear-avoidance beliefs (FABQ, Waddell et al. 1993) is presented. METHODS: A translated version of the "Fear-Avoidance Beliefs Questionnaire" was given to 87 patients with back pain, who took part in a multimodal treatment program in an outpatient pain unit. The questionnaire was administered at different times in the therapeutic process. We examined the factor structure of the questionnaire and conducted the first examinations concerning its psychometric properties. RESULTS: The results of our data set concerning different aspects of reliability and validity conform the good psychometric properties of the questionnaire. The factor analysis revealed a three-factor solution, which accounted for nearly 60% of the variance. The first factor made up 34% of the variance. The six corresponding items dealt with "back pain caused by work". The second factor made up 13% of the variance. The content of the 5 items is focused on the patients' view about his/her probable return to work. Beliefs about physical activity in back pain (factor 3, 5 items) accounted for 12% of the variance. Correlation analysis demonstrated that all three factors are of independent value, which showed satisfactory reliability. Furthermore, we analyzed the prognostic value of the three factor dimensions. Patients completed multidisciplinary treatment according to the concept of "functional restoration". At the end of treatment, factor 1 (causation by work) was not diminished, but both other factors showed significant reductions. In a discriminant factor analysis, back-to-work could be significantly predicted by factor 3 (beliefs about physical activity) and factor 2 (patients' prognosis about their probable return to work at the beginning of treatment). Furthermore, length of time off work and age accounted for an additive classification rate of 77%. The FABfactor 1 (causation by work) was of no predictive value. CONCLUSIONS: The results suggest that primary target points for further investigation include an analysis of the patients' beliefs about their pain, with special emphasis on fear-avoidance beliefs. It is also necessary to analyze the behavioral assumptions of the fear-avoidance model in an experimental design. Furthermore, our results concerning the psychometric properties of the questionnaire should be proved in a far larger sample of back pain patients.
[The importance of bodily complaints in patients with chronic back pain].
UNLABELLED: Pain perception is a complex psychosomatic phenomenon and is influenced by different psychological variables. Apart from their pain perception, chronic pain patients also suffer from different bodily complaints. The clinical significance of this finding is not yet clear. Bodily complaints in chronic pain patients may represent (a) a bodily expression of depressive symptoms, (b) a sign of chronicity, and (c) the expression of a heightened bodily awareness in the sense of hypochondriasis. METHODS: A psychometric study was done with 83 patients with chronic low-back pain. The patients were interviewed and tested psychometrically. We administered a German scale to measure bodily complaints (BL), an inventory to measure the extent of depressive symptoms (DS) and two subscales of an personality inventory (bodily complaints and hypochondriasis). In addition, patients were evaluated according to three stages of chronification ("Mainz Pain Staging System"). Ten anamnestic variables from four dimensions (temporal aspects, spatial aspects, medication usage behavior and patient's health care history) are added to yield a total chronification stage with three stages ranging from acute to chronic pain. RESULTS: Results indicate that bodily complaints have to be interpreted as signs of depressive disorder and chronicity. Signs of bodily 'awareness' or 'somatic anxiety'- in the sense of hypochondriasis - could not be found. Hypochondriasis does not seem to play a significant role in chronification of low back pain. CONCLUSIONS: From a cognitive-behavioral perspective the results support the hypothesis that psychological disturbance in chronic pain is a cause of long-standing pain perception and the result of the chronification process.
Prediction of success from a multidisciplinary treatment program for chronic low back pain.
STUDY DESIGN: The study included 90 disabled patients with chronic low back pain recruited from a pain clinic who were admitted to an 8-week program of functional restoration and behavioral support. Initial evaluations included a medical examination, rating of the physical impairment, a personal interview, a visual analogue scale to record pain intensity, an assessment of limitations for daily activities, a pain disability index, a depression and psychovegetative scale, and a scale to evaluate general living standards. The physical assessment included different flexibility measurements, measurement of power and endurance through standardized exercises, and measurements of isokinetic trunk and lifting strength and general endurance. The measurements were repeated at the end of the 8-week program and thereafter an intervals of 6 and 12 months. Final analyses were carried out on 82 patients. OBJECTIVES: To determine whether objective or subjective signs most influence the outcome of rehabilitation. SUMMARY OF BACKGROUND DATA: In recent years, several studies have shown that active and intensive multimodal treatment of chronic low back pain is successful. Until now there has been lack of information about which patients will respond to the therapy and what is the most effective part of treatment. METHODS: Prognostic factors (return to work, pain intensity, self-assessment of treatment success by patients) were tested by studying variance and regression analyses for their ability to predict treatment outcome. RESULTS: Certain factors were identified that had a significant impact on determining the probability of a patient's return to work and the reduction of pain intensity. These factors included self-evaluation for predicting a return to work, the length of absence from work, application for pension, and a decrease is disability after treatment. Overall satisfaction with treatment was best determined by the number of medical consultations before treatment, the extent of disability, previous measures taken for coping with the disease, and reduction of disability during treatment. Medical background, medical diagnosis, and physical impairment had no predictive value. Physical variables (i.e., mobility, strength, endurance, and physical performance) also demonstrated only limited predictive value. CONCLUSION: This study has demonstrated that the most important variable in determining a successful treatment of chronic low back pain is the reduction of subjective feelings of disability in patients.
[Multidisciplinary treatment program on chronic low back pain, part 4. Prognosis of treatment outcome and final conclusions].
PROBLEM: Studies using a multimodal approach in order to prognose therapeutic success in patients suffering from back pain were seen to have highly diverse results. However, in spite of various independent health care systems, a common interest prevails in identifying determinants of therapeutic success in order to improve therapy. METHODS: Ninety disabled patients with chronic low back pain were admitted to an 8-week out-patient program of functional restoration and behavioral support. The program consisted of a pre-program (education, stretching and calisthenic exercises 4 h a day, three times a week for 3 weeks) and an intensive treatment period (physical exercises, back school education, cognitive behavioral group therapy, relaxation training, occupational therapy, socioeconomic and vocational counseling) which took place for 5 weeks, 7 h a day as an outpatient program. The program's philosophy encourages active effort on the patients' part in order to improve their functional status within a therapeutic environment. This reinforces behavior conducive to getting well, enhances the patients' sense of self-control over their pain and the resulting disability. The main therapeutic target was to facilitate the patients' return to work. Apart from medical examination and personal interview, the patients' physical impairment, pain descriptions, and psychological distress were also measured. This included variables such as depression, psychovegetative complaints, quality of life and workplace satisfaction, disability, and coping with disease. Measurements were repeated at the end of the 8-week program, and following 6 and 12 month intervals. The reliability of prognostic factors in predicting treatment outcome (return to work, reduction of pain intensity, self-assessment of success by the patients) was tested by analyses of variance and discriminant function analyses. RESULTS: Patients' return to the workplace could be predicted in 85% of cases based on whether an application for pension had been made, on the length of duration of work disability, and on "fixed" assumptions on the part of the patient concerning his work situation. Pre-treatment somatic findings (for example, diagnosis, degree of physical impairment, and functional debilities), together with depressive and psychovegetative reactions, were shown to have no connection with the patient's ability to return to the workplace. Similar findings were demonstrated for the prediction of pain reduction and patient satisfaction with treatment. CONCLUSIONS: Predicting successful treatment is hardly possible without analyzing individual circumstances, focusing on sociodemographic variables, workplace-related conditions, and aspects of individual motivation. With regard to objective therapeutic success, subjective perceptions proved highly influential. Treatment proved successful only when the patient's perception of functional disability was minimized. Hence, individual perceptions and experiences were more important than physical capabilities.
[Opioid intoxication. Inappropriate administration of transdermal fentanyl].
A 22-year-old male suffering from neuropathic pain in his right leg had sufficient analgesia with oral tilidin 300 mg per day. Nevertheless, the general practitioner decided to change the therapy to transdermal fentanyl. Having cut a fentanyl patch (50 micrograms/h) into pieces, he applied one-fourth of the patch; 60 min later the patient developed signs of opioid intoxication, including heavy sedation, nausea and respiratory depression. After the patch was removed another 60 min later, the patient made a complete recovery. The risks following inappropriate application of transdermal fentanyl are discussed.
[Treatment and rehabilitation of chronic pain patients].
There is still a significant lack of treatment and rehabilitation facilities for chronic pain patients in Germany today. Most of all the treatment of low back pain and widespread pain syndromes or panalgesia is time consuming and complicated. The main problem of anaesthesiological pain clinics is the increase of these complex pain syndromes in the last years. The definition of chronic pain is a continuous noxious input modulated and compounded by the prolonged or recurrent nature of chronic state and further complicated by a multitude of economic and psychosocial factors. It is now clear that no one discipline or mode will suffice. Only a multidisciplinary and intensive approach will prevail, as discussed in this article. Unfortunately these multidisciplinary pain units are nearly not existing in Germany just as little as control of the effectiveness of pain treatment.
Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid glycoprotein, and C-reactive protein.
Based on previous studies we hypothesized that interleukin-6 (IL-6) plasma levels would increase during the menstrual cycle, in analogy to the increase in IL-1 levels seen during the luteal phase. Thus we have investigated menstrual cycle-associated changes in IL-6, alpha1 acid glycoprotein (AGP), and C-reactive protein (CRP). The study design was cross-sectional and was conducted in 18 healthy premenopausal women with regular menstrual cycles and in 15 age-matched men. The women had blood drawings in the follicular phase, at midcycle, and in the luteal phase of the menstrual cycle. A single blood sample was obtained from men to compare IL-6 levels between sexes. The median IL-6 level was 0.68 pg/ml (95% confidence interval (CI): 0.60 to 1.05) in the follicular phase and did not change significantly during the menstrual cycle. IL-6 levels did not differ between women and men (0.79 pg/ml; CI: 0.66 to 1.05; p > 0.05). Median AGP levels decreased by 6% (CI: -14% to 1%) during the luteal phase (p = 0.005), and a significant correlation between mean AGP and IL-6 levels was found (r = 0.60; p = 0.01). Median CRP levels increased by 44% (CI: 27% to 59%; p < 0.001) at midcycle and by 31% (CI: 17% to 68%; p = 0.002) in the luteal phase, and there was a significant correlation between the relative increase in CRP at midcycle and the relative increase in progesterone levels during midcycle (r = 0.60; p = 0.01) and the luteal phase (r = 0.71; p = 0.001). In conclusion, we found no sustained menstrual cycle-dependent changes in systemic IL-6 plasma levels. AGP and CRP levels may be differentially regulated during the menstrual cycle of healthy women: AGP levels correlated with IL-6 levels, and AGP levels decreased during the menstrual cycle, whereas CRP levels increased during the menstrual cycle and correlated with the increase in progesterone levels. The reason for the observed changes in CRP levels remains to be elucidated.
Effectiveness of a multimodal treatment program for chronic low-back pain.
In recent years, multidisciplinary pain programs were seen to successfully treat patients by basing treatment on a combination of physical exercise and psychological interventions. However, in spite of their effectiveness, it still remains to be clarified exactly which features of these programs were responsible for patient improvement. Cognitive-behavioral models posit that improvement is due, in part, to changes in patient coping strategies. Nonetheless, as reflected by the conflicting opinions present in the literature, it is questionable whether a so-called 'cognitive shift' is an accurate indicator for return to work of disabled patients. Ninety patients with chronic low back pain took part in a multidisciplinary treatment program. Therapeutic environment reinforces wellness behavior and enhances the patients' sense of control over their pain and resulting disability. The main therapeutic target point was to facilitate return to work. Ways of coping were measured by a well studied coping inventory in the German language (FEKB). Factor analysis revealed three factors: 'catastrophizing', 'search for information' and 'cognitive control'. In addition, assessment included measurements of pain intensity, depression, disability, flexibility of the lumbar spine, and different performance parameters. All of them were measured prior to and at the end of treatment, and following intervals of 6 and 12 months after discharge from program. Measurements showed significant changes over time, but more importantly, nearly all results were seen to stabilize at the 6- and 12-month evaluation following treatment. The coping strategies demonstrated little or poor change. In addition, coping measures and change in coping behavior showed poor prognostic relevance. But other psycho-social parameters like self-evaluation of potential return-to-work, application for pension, the length of pre-absence from work, and a decrease in subjective disability following treatment were effective indicators for 'back-to-work'. Other objective parameters, such as medical history, physical impairment and general physical variables were seen to have little predictive value in determining a return to work. The results suggest that the primary target point for further investigation is the analysis of the patients' beliefs about their pain. Our results indicate that future research must be attentive to the complex interactions between environmental factors and the coping demands posed by the specific nature of pain problems.
Quantitative analysis of transpleural flux in the isolated lung.
In this study, the loss of inert gas through the pleura of an isolated ventilated and perfused rabbit lung was assessed theoretically and experimentally. A mathematical model was used to represent an ideal homogeneous lung placed within a box with gas flow (Vbox) surrounding the lung. The alveoli are assumed to be ventilated with room air (VA) and perfused at constant flow (Q) containing inert gases (chi) with various perfusate-air partition coefficients (lambda p,x). The ratio of transpleural flux of gas (Vplx) to its total delivery to the lung via pulmonary artery (Vv), representing fractional losses across the pleura, can be shown to depend on four dimensionless ratios: 1) lambda p,x, 2) the ratio of alveolar ventilation to perfusion (VA/Q), 3) the ratio of the pleural diffusing capacity (Dplx) to the conductance of the alveolar ventilation (Dplx/VA beta g, where beta g is the capacitance coefficient of gas), and 4) the ratio of extrapleural (box) ventilation to alveolar ventilation (Vbox/VA). Experiments were performed in isolated perfused and ventilated rabbit lungs. The perfusate was a buffer solution containing six dissolved inert gases covering the entire 10(5)-fold range of lambda p,x used in the multiple inert gas elimination technique. Steady-state inert gas concentrations were measured in the pulmonary arterial perfusate, pulmonary venous effluent, exhaled gas, and box effluent gas. The experimental data could be described satisfactorily by the single-compartment model. It is concluded that a simple theoretical model is a useful tool for predicting transpleural flux from isolated lung preparations, with known ventilation and perfusion, for inert gases within a wide range of lambda.