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Biomedical subjects

S Klosterhalfen

Publications and source records attributed to S Klosterhalfen.

14 recordsLinked to original sources
PubMed2006

[Placebo response in functional bowel disorders].

The placebo response in functional bowel disorders is incompletely understood, and is usually either mystified or down-played; a rational approach to the understanding of the placebo response, however, can be deduced from the scientific literature. We present 3 theories that may explain most of the placebo response in medical and psychological interventions. a) Regression to the Mean (RTM): This refers to "errors" in measuring the outcome of therapies that are due to small samples sizes, global assessment variables, spontaneous variability of symptoms, and other methodological reasons. b) Pavlovian Conditioning (PC): Here the placebo response occurs as the consequence of successful association of diagnostic and therapeutic procedures in the past (illness history) of the individual that resulted in symptom improvement. Stimuli in the context of a treatment can thus gain therapeutic potency (become conditioned stimuli), e. g., the procedure of an injection or the colour of a drug. c) Signal Detection theory (SDT): Manipulation of expectations and cognitions of the patient by suggestions and verbal instructions of the health-care system will change the willingness of the patient to perceive symptoms as improved/worsened, specifically if this happens under "noisy" circumstances, e. g., with high spontaneous variability of symptoms. All three models are illustrated with examples from the medical and psychological treatments or experiments, including recent findings of cortical correlates of the placebo response in functional brain imaging investigations. Potential biological mechanisms for the placebo response are discussed, including he possibility of the genetic predisposition to be a placebo responder.

Clinical Trials as Topic↗
PubMed2005

[Determination of placebo effect in irritable bowel syndrome].

BACKGROUND AND OBJECTIVE: The determinants of the placebo effect are not well established. Goal of this study was to explore likely predictive factors in an already published data set. METHODS: We re-analysed data from a study in 120 patients with the irritable bowel syndrome (IBS) that were randomly assigned to three arms of the study to receive (double-blind) either a drug (mebeverin) (n = 40) or placebo (n = 40), or (in an open trial) dietary treatment (fibre) (n = 40) for up to 16 week. Treatment was conducted by 3 different doctors (A, B, C) with 44, 27, and 18 patients, resp. A fourth group (n = 31) was treated by different varying physicians. Symptoms were assessed every 4 weeks, and the degree of patient compliance and the number of drop-outs, the number of patients improved/not improved (in %), symptom severity (Kruis Score) at enrolment, and age and gender as covariates were included into the analysis. RESULTS: Drop-out rate was 30 % for placebo, 30 % for mebeverin, and 15 % for the diet. For the patients remaining in the study, average compliance was 75 % with placebo, but 89 % for the drug and 82 % for the diet. Response rates were 39 % for placebo, but 20 % for the drug; response rate for the diet (open trial) was 43 % under all doctors. Response rates for drug and placebo combined were 32 % for doctor A (female,43 years), but 19 % for doctors B and C together (both males, 32 and 40 years)); this effect was not significant. Placebo responders were more often women (47 %) than men (28 %), while age effects were only found with dietary treatment: responders were younger. Placebo responders had an overall lower Kruis Score than non-responders (45 vs 52 points), but this was also true for drug (52 vs. 62 points) and diet responders (56 vs 68 points). CONCLUSION: The major factors contributing to the placebo response are the treating physician (gender, training), and the patients gender (female). Patients with lower Kruis score (more likely non-functionally disordered) may be prone to higher (placebo) response rates.

Adult↗
PubMed2005

The placebo response in functional bowel disorders: perspectives and putative mechanisms.

The nature and determinants of the placebo response are widely unknown, as are the underlying psychological and biological mechanisms. High placebo response rates in functional bowel disorders (functional dyspepsia, irritable bowel syndrome) are similar to those in non-intestinal diseases (depression, pain, Parkinson's disease) and not too dissimilar to other organic gastrointestinal diseases (duodenal ulcer, inflammatory bowel diseases). Methodological reasons (regression to the mean, shift in signal detection through manipulation of expectations) and psycho-biological mechanisms (Pavlovian conditioning of biological processes) are proposed to explain a large component of the response variance in clinical trials. Psychobiological mechanisms of the placebo response in functional and organic diseases can also be identified in brain function studies (such as imaging).

Gastrointestinal Diseases↗
PubMed2000

Anticipatory symptoms and anticipatory immune responses in pediatric cancer patients receiving chemotherapy: features of a classically conditioned response?

UNLABELLED: There is considerable evidence from studies in adult patients that classical conditioning contributes to anticipatory nausea and/or vomiting (ANV) in cancer chemotherapy: The stimuli predicting the infusion serve as conditioned stimuli (CS). When reexposed to the CS, some patients experience ANV prior to infusion onset. In adult patients, anticipatory immunomodulation (AIM) has also been observed. The present study examines whether ANV and AIM occur in pediatric cancer patients and whether they show features of a conditioned response. METHODS: Nineteen pediatric cancer patients (M = 10.1 years, > 2 previous chemotherapies) were studied over two consecutive cycles (A, B). In both cycles, self-reported symptoms, for example nausea and vomiting, were recorded from two days prior to the onset (Day -2), during infusion, and two days after the end of the infusion (Day +2). In Cycle B, blood was drawn at home at Day -2, and at Day 0 in the hospital prior to infusion onset, thus using a quasi-experimental variation of the CS content of the environment. Immune parameters valid for tumor defense and cytotoxic competence (natural killer cell activity [NKCA], plasma interleukin [IL]-1beta, IL-2, IL-10, interferon [IFN]-gamma, tumor necrosis factor [TNF]-alpha) and cortisol were measured. RESULTS: ANV was reported by 7 patients in at least one cycle. In Cycle A, ANV was positively associated with emetogenity of chemotherapy. Features of ANV-duration and occurrence-tended to be positively associated with those of posttreatment nausea and vomiting. AN increased as infusion onset time approached. NKCA and IFN-gamma increased from home to hospital, independent from cortisol level. The NKCA increase was predominantly observed in patients with ANV. CONCLUSIONS: ANV in pediatric patients showed features of a CR. Immune parameters were sensitive to the CS content of the environment, predominantly in patients with ANV. This is consistent with the manifestation of multiple CRs.

Adolescent↗
PubMed1998

Effects of overshadowing on conditioned nausea in cancer patients: an experimental study.

The infusion of cytotoxic drugs in cancer patients is often accompanied by posttreatment nausea (PN). In addition, patients complain about nausea prior to an infusion [i.e., anticipatory nausea (AN)]. AN is mainly explained by classical conditioning, with the infusion as the unconditioned stimulus (US) and with the stimuli signaling the infusion as conditioned stimuli (CS). Despite this conditioning etiology, a specifically derived therapy to attenuate the CS-US contingency is missing. The purpose of this study is to develop and to test an overshadowing procedure for prevention of AN, and also for the modification of PN intensity. Sixteen cancer patients were assigned to one of two groups: Overshadowing+ (OV+) and Overshadowing- (OV-). At the start of all infusions of two consecutive chemotherapy cycles A and B (acquisition), OV+ subjects drank a saliently tasting beverage (the overshadowing CS), whereas group OV- drank water. All patients received water in cycle C (test). Self-reported symptoms and heart rates were recorded. As expected, in cycle C (test), no patient of group OV+ showed AN, whereas two patients of group OV- developed AN. There was a tendency for a reduction of the intensity of PN, in terms of duration and latency after overshadowing, in cycle C: OV+ patients tended to show a shorter duration and a longer latency between end of infusion and PN onset. In OV-, there was a significantly larger heart rate deceleration in both measurement periods, in the anticipatory and the posttreatment measurement period. Data suggest to apply overshadowing for prevention of AN and modification of PN. Physiological markers of conditioned nausea are revealed. After its procedural implementation, the technique can be used in larger samples now.

Antineoplastic Agents↗
PubMed1990

Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats.

In 2 experiments, the development of adjuvant arthritis (an experimental autoimmune disease) was inhibited by exposing rats to a flavored solution that had previously been paired with injections of cyclosporine (an immunodepressive drug) compared with rats with the same history but exposed to a flavored solution that had previously not been paired with drug injections. In contrast to earlier experiments on conditioned cyclophosphamide effects, rats did not avoid the taste that had previously been paired with drug administration. Thus, conditioned immunopharmacologic effects were not confounded with taste aversion. These observations are interpreted as reflecting an associative learning process that affected the development of an autoimmune disease.

Animals↗
PubMed1985

Habituation of heart rate in functionally decorticate rats.

Habituation of acoustically evoked heart rate responses and retention of this habituation was studied in functionally decorticate rats. An improved technique to induce cortical spreading depression (CSD) resulted in a pronounced and continuous depression of electroencephalographic activity. In Experiment 1, short-term habituation (STH) was demonstrated in decorticate rats and surgical controls; long-term habituation (LTH, 24 hr) occurred only in intact animals. In Experiment 2, only CSD groups were used. As in the first experiment, STH but not LTH was obtained under CSD. However, there was clear evidence that habituation could be retained subcortically for 30 min. It is concluded that the rat's cortex is not necessary for habituation of acoustically evoked heart rate responses and retention of this habituation over a moderately long interval. However, the results suggest that the cortex is involved in LTH and that the neuronal substrates of STH and LTH are, in significant part, different.

Acoustic Stimulation↗
PubMed1983

Pavlovian conditioning of immunosuppression modifies adjuvant arthritis in rats.

Ten days prior to induction of adjuvant arthritis (by injection of complete Freund's adjuvant into a rat's hind paw), three groups of rats were dosed with cyclophosphamide (CY), an immunosuppressive drug. A saccharin/vanilla solution (SV) was presented either 2 days (Group NC) or immediately before CY treatment (Groups C and C2). Three further SV presentations started either 30 min (Groups C and NC) or 2 days after antigenic stimulation (Group C2). The groups did not differ with respect to the degree of swelling in the injected paws. In contrast, Group C differed significantly from Groups NC and C2 with respect to the uninjected hind paws: Group C showed no external signs of a proliferation of inflammation, whereas approximately half of the animals in the other two groups developed small lesions. A second experiment, similar to the first, yielded the same results. These results essentially confirm previous findings on conditioned immunosuppression and extend them to an inflammatory joint disease.

Animals↗
PubMed1978

Modification of attention in honey bees.

Honey bees were trained in two consecutive two-dimensional (color-position) problems with one dimension (color or position) relevant and the other irrelevant in each problem. As in analogous experiments on dimensional transfer in rats and monkeys, performance in the second problem was more accurate when the relevant and irrelevant dimensions were the same as in the first problem than when they were interchanged. The results of further experiments suggest that the transfer is mediated by different modes of responding that develop in color and position problems rather than by some special process of dimensional selection, such as has been assumed to operate in vertebrates.

Animals↗
PubMedDate not supplied

Anticipatory nausea in cancer patients receiving chemotherapy: classical conditioning etiology and therapeutical implications.

The delivery of cytotoxic drugs in cancer treatment is often accompanied by posttreatment side effects (e.g., nausea). Moreover, there is evidence that cancer patients are at risk to develop these side effects in anticipation of chemotherapy (i.e., anticipatory nausea [AN]). AN can be explained as the result of a classical conditioning process with the cytotoxic drug as the unconditioned stimulus (US). Stimuli paired with the US (e.g., smells, tastes) can become conditioned stimuli (CSs) eliciting AN as the conditioned response (CR). The present study was conducted to test whether AN shows characteristics of a CR. Fifty-five ambulatory cancer patients were asked to record nine kinds of physical symptoms (e.g., nausea, vomiting, sweating) on time-scheduled symptom lists: after an infusion (indicating posttreatment symptoms) and prior to their next infusion (indicating anticipatory symptoms). Each measurement period covered a maximum of 48 hours. AN was reported by ten patients (18.08%). Data revealed (a) a statistically significant association between posttreatment nausea and vomiting, respectively, and AN; (b) the occurrence of AN increased with drug emetogenity (i.e., US-intensity); and (c) the duration of AN increased with temporal proximity to the infusion. The results support the conditioning model. Thus, it is proposed to prevent AN by classical conditioning techniques (e.g., overshadowing).

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Pavlovian conditioning of taste aversion using a motion sickness paradigm.

OBJECTIVE: Pavlovian conditioning of taste aversion has rarely been investigated in healthy humans using motion sickness as the unconditioned stimulus (US). METHODS: Ninety subjects were pretested for susceptibility to illusory motion (vection) in a rotating drum. Thirty-two subjects susceptible to pseudomotion were assigned randomly to two groups and received either water 1 hour before rotation and a novel taste (elderberry juice, conditioned stimulus, [CS]) immediately before rotation in a rotating chair (conditioning group), or the sequence of water and juice was reversed (control group). During the test session 1 week later, all subjects were exposed to water 1 hour before and juice immediately before rotation. The amount of liquids ingested, nausea ratings, rotation tolerance, and blood levels of hormones (ACTH, ADH, PP) were evaluated. RESULTS: Subjects in the conditioning group developed taste aversion toward the novel taste, but not subjects in the control group. Postrotation nausea rating was affected marginally by conditioning, but rotation tolerance was not changed by conditioning. ACTH and ADH but not PP levels increased with rotation, but were unaffected by conditioning. CONCLUSIONS: Pavlovian conditioning of behavioral, but not of endocrine, indicators was effective in susceptible subjects using a rotating chair as US and a single CS-US pairing.

Adrenocorticotropic Hormone↗