Placebo Analgesia: Clinical considerations

Pain is the predominant symptom that prompts patients to seek medical advice and treatment from physiotherapists. Various treatment modalities such as heat and cold, electrical stimulation (Cheing and Hui-Chan, 1999), ultrasound, manipulative techniques, massage and laser treatment have been demonstrated in varying degrees to be clinically effective for managing pain of different pathologies. However, all these treatments could be assumed to have some placebo elements (French, 1994).

From a research design perspective, the presence of placebo response is undesirable and must be controlled as it complicates the demonstration of ‘real' treatment effect. From a clinical perspective, it is intriguing to note that the condition of patients in the placebo control groups did improve considerably in many of these validation studies, although in the majority the improvement was not so marked as in the treatment groups. Conspicuously, some neuro-physiological and psychological aspects of the placebo effects may have clinical use in enhancing the effect of pain treatments and their outcomes.

Unfortunately, although placebo response has been a subject of continuing interest among some physiotherapy researchers and clinicians, information about placebo analgesia and its clinical utility is seldom discussed. The purpose of this paper is to provide clinicians with an overview of the construct and research related to placebo analgesia as well as a discussion of the potential clinical use of certain components of placebo analgesia to enhance pain rehabilitation outcomes in physiotherapy practice.     

Structuring a safer donor-replacement program

BACKGROUND: Replacement donors are more likely than volunteer donors to have positive or abnormal tests for transfusion-transmissible disease. In an effort to increase the donor pool, workers sought to identify a safer replacement-donor subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS: In a retrospective review and cohort study, the replacement-donor effect was separated from the new- donor effect. The relative effect the replacement donor has on the risk of transfusion-transmissible diseases, donor retention, and frequency of returning donations was then quantified by comparison against the effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times the risk and 0.72 times the donor retention rate and made 0.81 times as many returning donations as the repeat volunteer donor. The figures for the new-donor effect were similar. The two risks were additive, making a new replacement donor particularly hazardous. If replacement donations only from repeat replacement donors were considered, the donor risk and the number of donations per returning donor were made comparable to those for the general (combined) volunteer donor. CONCLUSION: The negative effect of the replacement donor is similar in magnitude to that of the new volunteer donor. A replacement-donation program targeting repeat replacement donors has an acceptable risk profile and may be a valuable adjunct to the collection of blood from general volunteer donors.     

Microcatheter Looping to Facilitate Aneurysm Selection in Coil Embolization of Paraclinoid Aneurysms

ObjectiveDescribed herein is a microcatheter looping technique to facilitate aneurysm selection in paraclinoid aneurysms, which remains to be technically challenging due to the inherent complexity of regional anatomy.ResultsThrough this looping technique, a total of 59 paraclinoid aneurysms were successfully treated. After aneurysm selection as described, single microcatheter technique (n = 25) was most commonly used to facilitate coiling, followed by balloon protection (n = 21), stent protection (n = 7), multiple microcatheters (n = 3), and stent/balloon combination (n = 3). Satisfactory aneurysmal occlusion was achieved through coil embolization in 44 lesions (74.6%). During follow-up of 53 patients (mean interval, 10.9 ± 5.9 months), only one instance (1.9%) of major recanalization was observed. There were no complications related to microcatheter looping.ConclusionThis microcatheter looping method facilitates safe and effective positioning of microcatheter into domes of paraclinoid aneurysms during coil embolization when other traditional microcatheter selection methods otherwise fail.     

Macrolides increase the expression of 11β‐hydroxysteroid dehydrogenase 1 in human sinonasal epithelium,contributing to glucocorticoid activation in sinonasal mucosa

Background and Purpose

The anti‐inflammatory and immunomodulatory effects of macrolides include the ability to decrease mucus secretion and inhibit inflammatory mediators in chronic rhinosinusitis. Nevertheless, their mechanisms of action remain to be determined. Here we have investigated the effects of macrolide antibiotics (clarithromycin, azithromycin and josamycin; representating the 14‐, 15‐ and 16‐membered macrolides) on endogenous steroids in human sinonasal epithelial cells and mouse nasal mucosa.

Experimental Approach

The effects of macrolides on the expression of steroid‐converting enzymes [11β‐hydroxysteroid dehydrogenase (11β‐HSD1 and 11β‐HSD2)], steroid‐synthesizing enzymes (3β‐HSD, CYP21, CYP11B1 and CYP11A1) and cortisol levels were assessed in cultured human epithelial cells. In control and adrenalectomized mice , these enzymes and corticosterone levels were evaluated in nasal mucosa and serum after administration of macrolides.

Key Results

The expression levels of 3β‐HSD, CYP21, 11β‐HSD1 and CYP11B1 increased in human epithelial cells treated with clarithromycin and azithromycin, whereas the expression levels of 11β‐HSD2 and CYP11A1 were not affected. Josamycin had no effects on the expression of these enzymes. Cortisol levels increased in epithelial cells treated with clarithromycin or azithromycin. The expression of 3β‐HSD, CYP11A1, CYP21, CYP11B1 and 11β‐HSD1 was upregulated in nasal mucosa of mice treated with clarithromycin or azithromycin, but not in adrenalectomized mice.

Conclusions and Implications

This study provides evidence that 14‐ and 15‐membered macrolide antibiotics may affect the expression of steroid‐synthesizing and steroid‐converting enzymes in human sinonasal epithelial cells and mouse nasal mucosa, increasing the endogenous cortisol levels in sinonasal mucosa.

Abbreviations

11β‐HSD1

11β‐hydroxysteroid dehydrogenase 1

11β‐HSD2

11β‐hydroxysteroid dehydrogenase 2

3β‐HSD

3β‐hydroxysteroid dehydrogenase

CYP21A1

cytochrome P450, family 21, subfamily A, polypeptide 1

CYP11B1

cytochrome P450, family 11, subfamily B, polypeptide 1

CYP11A1

cytochrome P450, family 11, subfamily A, polypeptide 1

CRS

chronic rhinosinusitis

PBS‐T

phosphate‐buffered saline‐Tween 20

PF

915275, N‐(6‐amino‐2‐pyridinyl)‐4''‐cyano‐[1,1''‐biphenyl]‐4‐sulfonamide

siRNA

small interfering RNA

     

Identification of Fusobacterium Species Using Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry by Updating ASTA CoreDB

PurposeFusobacterium species can cause infections, and associations with cancer are being increasingly reported. As their clinical significance differs, accurate identification of individual species is important. However, matrix-assisted laser desorption/ionization-time of flight mass spectrometry has not been found to be effective in identifying Fusobacterium species in previous studies. In this study, we aimed to improve the accuracy and efficacy of identifying Fusobacterium species in clinical laboratories.Materials and MethodsIn total, 229 Fusobacterium isolates were included in this study. All isolates were identified at the species level based on nucleotide sequences of the 16S ribosomal RNA gene and/or DNA-dependent RNA polymerase β-subunit gene (rpoB). Where necessary, isolates were identified based on whole genome sequences. Among them, 47 isolates were used for updating the ASTA database, and 182 isolates were used for the validation of Fusobacterium spp. identification.ResultsFusobacterium isolates used for validation (182/182) were correctly identified at the genus level, and most (180/182) were correctly identified at the species level using the ASTA MicroIDSys system. Most of the F. nucleatum isolates (74/75) were correctly identified at the subspecies level.ConclusionThe updated ASTA MicroIDSys system can identify nine species of Fusobacterium and four subspecies of F. nucleatum in good agreement. This tool can be routinely used in clinical microbiology laboratories to identify Fusobacterium species and serve as a springboard for future research.     

Untersuchungen über die Wirkungsweise der Hypophysenhinterlappenhormone auf den Kohlenhydrat- und Fettstoffwechsel

Zusammenfassung Die Wirkungsweise von synthetischem Oxytocin und Vasopressin auf den Kohlenhydrat- und Fettstoffwechsel wurde in Versuchen am intakten Tier und an Organschnitten untersucht. Die Hinterlappenhormone steigerten den Blutzuckergehalt auch an adrenalektomierten Katzen und Ratten. Da die Unterschiede gegenüber normalen Tieren nicht signifikant waren, ließ sich ausschließen, daß eine Adrenalinsekretion an der Blutzuckererhöhung wesentlich beteiligt ist. An isolierten Rattenleberschnitten hatten Oxytocin und Vasopressin eine glykogenolytische Wirkung, die bereits bei Konzentrationen um 10^–8 einsetzte. An isolierten Rattenzwerchfellstreifen, die 20 min lang in glucosehaltiger Krebs-Henseleit-Lösung inkubiert wurden, hemmten Oxytocin und Vasopressin meßbar nur den Glykogenaufbau, während Adrenalin auch im Muskel deutlich glykogenolytisch wirkte. In Versuchen an Hunden, die 0,2–20 mE/kg/min Oxytocin bzw. 0,2–40 mE/kg/min Vasopressin 60–90 min lang i.v. infundiert erhielten, zeigten sich folgende Stoffwechseleffekte: Der Blutzuckeranstieg war stets nur vorübergehend, die Ausgangswerte wurden nach 30–60 min trotz fortgesetzter Infusion wieder erreicht. Der Leberglykogengehalt nahm deutlich ab, das Muskelglykogen zeigte dagegen keine wesentlichen Änderungen. Regelmäßig und während der ganzen Infusionsdauer wurde die Konzentration der freien Fettsäuren im Plasma bis um etwa 50% herabgesetzt. Die minimal wirksamen Dosen betrugen beim Oxytocin 0,2 mE/kg/min bzw. beim Vasopressin 1 mE/kg/min. Dagegen hatte Oxytocin in Infusionsversuchen an Menschen selbst in Dosen bis zu 3 mE/kg/min für 60 min keinen deutlichen Einfluß auf die Konzentrationen von Glucose, Milchsäure, Brenztraubensäure und freien Fettsäuren im Blut.

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Summary The mode of action of synthetic oxytocin and vasopressin on carbohydrate and fat metabolism was investigated in experiments on intact animals and on organ slices. The hormones of the posterior pituitary raised blood sugar concentration also in adrenalectomized cats and rats. Since differences to normal animals proved to be insignificant epinephrine secretion could be ruled out as essential for the increase of blood sugar. In isolated rat liver slices oxytocin and vasopressin had a glycogenolytic action, beginning already in concentrations of approx. 10^–8. In isolated rat diaphragm slices, incubated for 20 min in glucose containing Krebs-Henseleit-solution, oxytocin and vasopressin only inhibited glycogen formation while epinephrine had a provable glycogenolytic action in muscles. In experiments on dogs which received continuous infusions of 0.2 to 20 mU/kg/min oxytocin respectively 0,2–40 mU/kg/min vasopressin for 60 to 90 min, the following effects on metabolism were observed: the increase of blood sugar proved to be only transient. In spite of continuous infusions initial values were reached within 30 to 60 min. The glycogen content of the liver decreased markedly while muscle glycogen did not show essential changes. Regularly and during the whole infusion time the concentration of free fatty acids in plasma was lowered down to 50%. Minimal effective dosages amounted to 0.2 mU/kg/min for oxytocin and 1 mU/kg/min for vasopressin. In infusion experiments on man, however, oxytocin in doses up to 3 mU/kg/min for 1 hour, had no clear effect on blood concentrations of glucose, lactic acid, pyruvic acid and free fatty acids.

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Mit 5 Textabbildungen

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.