Minimizing Carry-Over Effects After Treatment Failure and Maximizing Therapeutic Outcome

2014 ◽  
Vol 222 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Mareile Hofmann ◽  
Nathalie Wrobel ◽  
Simon Kessner ◽  
Ulrike Bingel

According to experimental and clinical evidence, the experiences of previous treatments are carried over to different therapeutic approaches and impair the outcome of subsequent treatments. In this behavioral pilot study we used a change in administration route to investigate whether the effect of prior treatment experience on a subsequent treatment depends on the similarity of both treatments. We experimentally induced positive or negative experiences with a topical analgesic treatment in two groups of healthy human subjects. Subsequently, we compared responses to a second, unrelated and systemic analgesic treatment between both the positive and negative group. We found that there was no difference in the analgesic response to the second treatment between the two groups. Our data indicate that a change in administration route might reduce the influence of treatment history and therefore be a way to reduce negative carry-over effects after treatment failure. Future studies will have to validate these findings in a fully balanced design including larger, clinical samples.

2012 ◽  
Vol 26 (4) ◽  
pp. 471-478 ◽  
Author(s):  
Floris Klumpers ◽  
Damiaan Denys ◽  
J Leon Kenemans ◽  
Christian Grillon ◽  
Jasper van der Aart ◽  
...  

Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB1 receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB1 or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-)clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB1 agonist.


1968 ◽  
Vol 20 (01/02) ◽  
pp. 044-049 ◽  
Author(s):  
B Lipiński ◽  
K Worowski

SummaryIn the present paper described is a simple test for detecting soluble fibrin monomer complexes (SFMC) in blood. The test consists in mixing 1% protamine sulphate with diluted oxalated plasma or serum and reading the optical density at 6190 Å. In experiments with dog plasma, enriched with soluble fibrin complexes, it was shown that OD read in PS test is proportional to the amount of fibrin recovered from the precipitate. It was found that SFMC level in plasma increases in rabbits infused intravenously with thrombin and decreases after injection of plasmin with streptokinase. In both cases PS precipitable protein in serum is elevated indicating enhanced fibrinolysis. In healthy human subjects the mean value of OD readings in plasma and sera were found to be 0.30 and 0.11, while in patients with coronary thrombosis they are 0.64 and 0.05 respectively. The origin of SFMC in circulation under physiological and pathological conditions is discussed.


Author(s):  
Buqing Yi ◽  
Igor Nichiporuk ◽  
Matthias Feuerecker ◽  
Gustav Schelling ◽  
Alexander Chouker

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 618
Author(s):  
Riley Larson ◽  
Courtney Nelson ◽  
Renee Korczak ◽  
Holly Willis ◽  
Jennifer Erickson ◽  
...  

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.


2003 ◽  
Vol 104 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Mario VAZ ◽  
A.V. BHARATHI ◽  
S. SUCHARITA ◽  
D. NAZARETH

Alterations in autonomic nerve activity in subjects in a chronically undernourished state have been proposed, but have been inadequately documented. The present study evaluated heart rate and systolic blood pressure variability in the frequency domain in two underweight groups, one of which was undernourished and recruited from the lower socio-economic strata [underweight, undernourished (UW/UN); n = 15], while the other was from a high class of socio-economic background [underweight, well nourished (UW/WN); n = 17], as well as in normal-weight controls [normal weight, well nourished (NW/WN); n = 27]. Baroreflex sensitivity, which is a determinant of heart rate variability, was also assessed. The data indicate that total power (0–0.4Hz), low-frequency power (0.04–0.15Hz) and high-frequency power (0.15–0.4Hz) of RR interval variability were significantly lower in the UW/UN subjects (P<0.05) than in the NW/WN controls when expressed in absolute units, but not when the low- and high-frequency components were normalized for total power. Baroreflex sensitivity was similarly lower in the UW/UN group (P<0.05). Heart rate variability parameters in the UW/WN group were generally between those of the UW/UN and NW/WN groups, but were not statistically different from either. The mechanisms that contribute to the observed differences between undernourished and normal-weight groups, and the implications of these differences, remain to be elucidated.


1993 ◽  
Vol 148 (6_pt_1) ◽  
pp. 1571-1575 ◽  
Author(s):  
M. Jeffery Mador ◽  
Ulysses J. Magalang ◽  
Angel Rodis ◽  
Thomas J. Kufel

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