Blockade of the complement C5a receptor reduces incisional allodynia, edema, and cytokine expression

BACKGROUND: Activation of the complement system is one component of the inflammatory response. Various components of the complement system participate in killing foreign organisms, recruiting immune cells, enhancing edema, and stimulating cytokine formation. Complement-mediated enhancement of the inflammation surrounding surgical incisions may increase pain. METHODS: In these studies, the authors used a murine hind paw incisional model to study the role of the complement C5a receptor in supporting incisional inflammation. At baseline and at various time points after incision, they measured the effects of a highly selective C5a receptor antagonist on nociceptive thresholds, edema formation, and cytokine production in the skin surrounding the incision. They also measured changes in C5a receptor expression near the incisions. RESULTS: The once-daily injection of the C5a receptor antagonist AcF-[OPdChaWR] reduced mechanical allodynia and edema in the incised hind paw. A multiplexed cytokine assay revealed that 8 of the 18 cytokines examined showed significant increases in skin tissue abundance after incision. Distinct time courses for the patterns of elevation were seen, though some degree of resolution occurred for all cytokines within 96 h. For 7 of these 8 cytokines, the C5a receptor antagonist reduced the enhancement of expression. In addition, the authors found that the C5a receptor messenger RNA level increased 15-fold in the skin surrounding the incisions within 24 h and then slowly declined. CONCLUSIONS: The tissue directly surrounding incisions in mouse hind paws undergoes large changes in the content of specific cytokines in addition to demonstrating edema and nociceptive sensitization. By blocking the receptor for one component of the complement system, C5a, all of these changes can be reduced. Complement receptor inhibitors may constitute a novel group of compounds useful in reducing the pain and swelling of surgical incisions.     

Principles and regulations for clinical pilot studies on psycholeptic drugs (author's transl)]

Some difficulties concerning the patient selection for psychopharmacological trials are described. Problems, decisive factors and methodological principles are discussed, especially the duration of clinical trials and the placebo problem.     

Asthma and body weight change: a 20-year prospective community study of young adults

OBJECTIVE: There is increasing evidence for an association between asthma and body weight change. The objectives of these analyses were to examine the temporal relationships of this association and to explore the role of childhood depression as an explanatory factor. METHODS: Data were derived from six subsequent semistructured interviews on health habits and health conditions from a single-age community study of 591 young adults followed up between ages 20 and 40 years. RESULTS: Cross-sectionally (over the whole study period), asthma was significantly associated with obesity (odds ratio=3.9 [95% confidence interval 1.2, 12.2]). Multivariate longitudinal analyses revealed that asthma was associated with increased later weight gain and later obesity among women after controlling for potentially confounding variables, whereas weight gain and obesity were not associated with later asthma. A secondary analysis showed that depressive symptoms during childhood were associated with adult obesity and asthma, partially explaining the asthma-obesity comorbidity. CONCLUSION: This study encourages further research on mechanisms underlying the asthma-obesity comorbidity, particularly on shared psychosocial factors operating during critical periods in childhood and adolescence that may influence the development and persistence of both obesity and asthma during adulthood.     

Family patterns of decision-making in pediatric clinical trials

The decision-making process related to a child's participation in clinical trials often involves multiple family members. The aim of this study was to compare family patterns of decision-making within and across family units in pediatric clinical trials. Participants for this secondary analysis included 14 families from a larger study of informed consent. Four distinct patterns of decision-making were identified: Exclusionary, informative, collaborative, and delegated. These patterns varied with regard to three dimensions of parents' decision-making goals, child level of involvement, and the parental role. These patterns of decision-making affect how parents and children communicate with health professionals and influence the effectiveness of health care providers interactions with the family related to the decision-making process.     

Validation of the Chinese version of the hypomania checklist (HCL-32) as an instrument for detecting hypo(mania) in patients with mood disorders

BACKGROUND: Bipolar disorder (BP) has been consistently under-recognized and erroneously diagnosed as major depression. The resulting inappropriate or delayed treatment is associated with elevated risk of (hypo)mania or cycling. The recognition of (hypo)manic episodes is essential for the correct diagnosis of BP. The Hypomania CheckList (HCL-32) is developed to increase the detection of suspected or manifest but mistreated BP cases. We aimed to determine the accuracy and validity of the Chinese version of the HCL-32 in an adult psychiatric setting. We also compared the results with prior studies carried out in a comparable sample. METHODS: Patients suffering from mood disorders completed the HCL-32 before being interviewed with the Schedule for Affective Disorder and Schizophrenia-Lifetime (SADS-L) to make DSM-IV diagnosis. The 4-day duration criterion for hypomania was replaced by a 2-day cut-off for BPII. The internal consistency and discriminatory capacity of the HCL-32 were analyzed. RESULTS: Results indicated high internal consistency of the Chinese version of the HCL-32. The dual factor structure was confirmed. A score of 14 or more on the HCL-32 total scale distinguished between BP and MDD yielding a sensitivity of 82% and a specificity of 67%. This scale also distinguished between BPI and BPII with a sensitivity of 64% and a specificity of 73% for the cut-off score of 21. LIMITATIONS: The sample size of MDD patients needs to be increased. CONCLUSIONS: The Chinese HCL-32 is a useful screening tool for BP in a psychiatric setting. Its performance is also comparable to that reported in previous studies.     

Modulation of remifentanil-induced postinfusion hyperalgesia by the β-blocker propranolol in humans

Acute and chronic exposure to opioids has been associated with hyperalgesia in both animals and humans. A genetic analysis of opioid-induced hyperalgesia in mice linked the β(2)-adrenergic receptor to mechanical sensitization after opioid exposure. In humans, expansion of the area of mechanical hyperalgesia surrounding an experimentally induced lesion after the cessation of remifentanil infusion is a commonly used model of opioid hyperalgesia (remifentanil-induced postinfusion hyperalgesia, RPH). The purpose of our translational study was to test the hypothesis that the β-adrenergic receptor antagonist propranolol modulates the expression of RPH in humans. This double-blinded, randomized, placebo-controlled, crossover study was performed in 10 healthy human volunteers. During test sessions, intracutaneous electrical stimulation was used to generate areas of secondary mechanical hyperalgesia. The area of this sensitization was measured before, during, and after remifentanil infusion. Heat pain sensitivity was also followed. During one test session, subjects received propranolol infusion. We observed an average increase in the areas of secondary mechanical hyperalgesia to 141% of the baseline in subjects infused with remifentanil and placebo (P=0.00040). However, when remifentanil infusion was combined with propranolol, the area of secondary hyperalgesia after terminating remifentanil was not significantly different than the area before beginning the opioid infusion (P=0.13). Thermal hyperalgesia was not observed after remifentanil infusion. Propranolol infusion at the selected dose had minor hemodynamic effects. Concomitant infusion of propranolol with remifentanil prevented the expression of RPH. β-adrenergic receptor blockade may be a useful pharmacological strategy for preventing hyperalgesia in patients exposed to opioids.