Complex regional pain syndrome: a narrative review for the practising clinician.

Complex regional pain syndrome (CRPS) is a life-altering condition that usually affects the extremities after a trauma or nerve injury. The physiologic changes that occur as a result of the inciting injury are complex, as the name of the syndrome implies. The pain and disability associated with CRPS often lead to psychological co-morbidities that create a vicious cycle of pain, isolation, and depression. We review recent developments in the understanding of CRPS and advancements in management of this syndrome. Further research in targeting specific mechanisms involved in the pathophysiology of CRPS should lead to prevention of this condition.

The Influence of Provider Communication Behaviors on Parental Vaccine Acceptance and Visit Experience.

OBJECTIVES: We investigated how provider vaccine communication behaviors influence parental vaccination acceptance and visit experience. METHODS: In a cross-sectional observational study, we videotaped provider-parent vaccine discussions (n = 111). We coded visits for the format providers used for initiating the vaccine discussion (participatory vs presumptive), parental verbal resistance to vaccines after provider initiation (yes vs no), and provider pursuit of recommendations in the face of parental resistance (pursuit vs mitigated or no pursuit). Main outcomes were parental verbal acceptance of recommended vaccines at visit's end (all vs ≥ 1 refusal) and parental visit experience (highly vs lower rated). RESULTS: In multivariable models, participatory (vs presumptive) initiation formats were associated with decreased odds of accepting all vaccines at visit's end (adjusted odds ratio [AOR] = 0.04; 95% confidence interval [CI] = 0.01, 0.15) and increased odds of a highly rated visit experience (AOR = 17.3; 95% CI = 1.5, 200.3). CONCLUSIONS: In the context of 2 general communication formats used by providers to initiate vaccine discussions, there appears to be an inverse relationship between parental acceptance of vaccines and visit experience. Further exploration of this inverse relationship in longitudinal studies is needed.

Diel pattern of locomotor activity in populations of root voles, Microtus oeconomus.

Surface locomotor activity of root voles (Microtus oeconomus) during summer and autumn was recorded with passage-counters in four experimental populations in 0.5 ha outdoor enclosures. Populations differed considerably with respect to density, geographical origin and social behavior of animals, and year of observation. The general characteristics of diel activity patterns, however, were very similar among populations. Root voles were generally more active during daytime than during the night, and high activity always occurred around sunrise and sunset. The most prominent feature of the activity patterns was a clear-cut ultradian rhythm at both day and night, resulting in seven activity bouts per 24 h. Pattern adjustment to changing daylength was achieved by an interaction between endogenous ultradian rhythmicity and resetting of the ultradian rhythm at both sunrise and sunset. The daytime rhythm had a period length of 3.0 to 3.5 h, while the nighttime rhythm had a significantly longer period length of 3.5 to 4.0 h. Data in the literature suggest that this mechanism of triggering activity may also occur in other microtine species.

Mck2-dependent infection of alveolar macrophages promotes replication of MCMV in nodular inflammatory foci of the neonatal lung.

Infection with cytomegalovirus (CMV) shows a worldwide high prevalence with only immunocompromised individuals or newborns to become symptomatic. The host's constitution and the pathogen's virulence determine whether disease occurs after infection. Mouse CMV (MCMV) is an appreciated pathogen for in vivo investigation of host-pathogen interactions. It has recently been reported that a single base pair deletion can spontaneously occur in the open reading frame of MCMV-encoded chemokine 2 (MCK2), preventing the expression of the full-length gene product. To study the consequences of this mutation, we compared the Mck2-defective reporter virus MCMV-3D with the newly generated repaired Mck2(+) mutant MCMV-3DR. Compared with MCMV-3D, neonatal mice infected with MCMV-3DR showed severe viral disease after lung infection. Viral disease coincided with high viral activity in multiple organs and increased virus replication in previously described nodular inflammatory foci (NIF) in the lung. Notably, MCMV-3DR showed tropism for alveolar macrophages in vitro and in vivo, whereas MCMV-3D did not infect this cell type. Moreover, in vivo depletion of alveolar macrophages reduced MCMV-3DR replication in the lung. We proposed an Mck2-mediated mechanism by which MCMV exploits alveolar macrophages to increase replication upon first encounter with the host's lung mucosa.

In vitro and in vivo effects of kinin B(1) and B(2) receptor agonists and antagonists in inbred control and cardiomyopathic hamsters.

The aims of this study were to examine the possible alterations occurring in the effects of kinins on isolated aortae of inbred control (CHF 148) and cardiomyopathic (CHF 146) hamsters of 150 - 175 and 350 - 375 days of age. Bradykinin (BK) and desArg(9)BK contracted isolated aortae (with or without endothelium) of hamsters of both strains and ages. After tissue equilibration (90 min), responses elicited by both kinin agonists were stable over the time of experiments. The patterns of isometric contractions of BK and desArg(9)BK were however found to be different; desArg(9)BK had a slower onset and a longer duration of action than BK. Potencies (pEC(50) values) of BK in all groups of hamsters were significantly increased by preincubating the tissues with captopril (10(-5) M). No differences in the pEC(50) values and the E(max) values for BK or desArg(9)BK were seen between isolated vessels from inbred control and cardiomyopathic hamsters. The myotropic effect of BK was inhibited by the selective non peptide antagonist, FR 173657 (pIC(50) 7.25+/-0.12 at the bradykinin B(2) receptor subtype (B(2) receptor)). Those of desArg(9)BK, at the bradykinin B(1) receptor subtype (B(1) receptor) were abolished by either R 715 (pIC(50) of 7. 55+/-0.05; alpha(E) = 0), Lys[Leu(8)]desArg(9)BK (pIC(50) of 7.21+/-0. 01; alpha(E) = 0.22) or [Leu(8)]desArg(9)BK (pIC(50) of 7.25+/-0.02; alpha(E) = 0.18). FR 173657 had no agonistic activity, exerted a non competitive type of antagonism and was poorly reversible (lasting more than 5 h) from B(2) receptor. In vivo, FR 173657 (given per os at 1 and 5 mg kg(-1), 1 h before the experiment) antagonized the acute hypotensive effect of BK in anaesthetized hamsters. It is concluded that aging and/or the presence of a congenital cardiovascular disorder in hamsters are not associated with changes in the in vitro aortic responses to either BK or desArg(9)BK.

Avian predation upon a mixed community of common voles (Microtus arvalis) and wood mice (Apodemus sylvaticus).

Pellets of diurnal avian predators (mainly kestrels and buzzards) were analysed to prove the hypothesis of selective predation for a mixed population of small rodents. It was found that voles heavily predominated as prey over mice (up to a factor of 19 during winter). Within both prey species, predation focussed on distinct parts of the populations: during winter the heaviest specimens were preferentially captured, during summer the subadults were in an exposed position. In the voles, an additional predominance of males occurred (up to a factor of 5.2 during summer). These findings verify the assumption of Errington (1956) that speciments of a low social rank are susceptible to the highest risk of predation.

Wood mice (Apodemus sylvaticus L.) as pioneers of recolonization in a reclaimed area.

A population of wood mice, Apodemus sylvaticus, was studied by live-trapping for 15 months in an area recently reclaimed from lignite open-mining, where the species is a pioneer of recolonization. Population dynamics, spacing behaviour and feeding habits were compared with data in the literature in order to investigate how these characteristics were affected by the peculiar habitat conditions and the special situation of early colonization. Population density was remarkably high with a peak of 86 individuals/ha in autumn and a low of 20 individuals/ha in late spring. The sex-ratio was always biased towards males except during periods of low density, when the ratio was close to unity. Individual body weights and the annual course of weight class distribution showed no distinct peculiarities, although body weight increased relatively slowly in late winter. Low juvenile survival, relatively low litter sizes and early termination of breeding were special features of the population. Furthermore, very few juveniles matured in the year of birth, and the best winter survival was found in mice born in the middle of the breeding season. Activity ranges were small compared with those given in the literature, and space use was similar in both sexes. As a direct effect of the habitat conditions, the diet was largely dominated by weed seeds. The possible reasons for and causal relations of these features are discussed.

Circadian activity patterns, photoperiodic responses and population cycles in voles : I. Long-term variations in circadian activity patterns.

Patterns of above-ground activity were recorded in two free-ranging populations of Microtus agrestis (L.) and one population of M. arvalis (Pall.) over several years by means of passage counters. Long-term variations of the circadian patterns were observed, but did not repeat themselves in a 12-month cycle. Variations in all three populations could be described by a sinusoidal function of an 18-month period. Maxima and minima of the sine-function were connected to distinct photoperiods (equinoxes and solstices). In a cyclic North Swedish population, the sine-function was superimposed by a second function which shows saturation behaviour. The relevance of these findings is discussed with respect to vole population cycles.

Effects of inhaled nano-TiO2 aerosols showing two distinct agglomeration states on rat lungs.

Nano-aerosols composed of large agglomerates (LA) (>100nm) are more likely to promote pulmonary clearance via macrophages phagocytosis. Small agglomerates (SA) (<100nm) seem to escape this first defense mechanism and are more likely to interact directly with biological material. These different mechanisms can influence pulmonary toxicity. This hypothesis was evaluated by comparing the relative pulmonary toxicity induced by aerosolized nano-TiO(2) showing two different agglomeration states: SA (<100nm) and LA (>100nm) at mass concentrations of 2 or 7mg/m(3). Groups of Fisher 344 male rats were nose-only exposed for 6h. The median number aerodynamic diameters were 30 and 185nm at 2mg/m(3), and 31 and 194nm at 7mg/m(3). We found in rat's bronchoalveolar lavage fluids (BALF) a significant 2.1-fold increase in the number of neutrophils (p<0.05) in the group exposed to the 7mg/m(3) LA nano-aerosol suggesting a mild inflammatory response. Rats exposed to the 7mg/m(3) SA nano-aerosol showed a 1.8-fold increase in LDH activity and 8-isoprostane concentration in BALF, providing evidence for cytotoxic and oxidative stress effects. Our results indicate that biological responses to nanoparticles (NP) might depend on the dimension and concentration of NP agglomerates.

Leading change, overcoming chaos--making change succeed in your organization.

The recent emphasis on reengineering has brought a lot of attention to the need to create a compelling vision. It has also forced management to face the realities of making a grand vision a concrete reality. This article focuses on the pragmatic elements--strategic tools and practical solutions--of implementing the change necessary to make your organization succeed.

A spontaneous temperature sensitive mutant of Japanese encephalitis virus: preliminary characterization.

A spontaneously arising temperature sensitive (ts) mutant of Japanese encephalitis virus (JEV), ts104, was isolated from chick fibroblast (CF) cell cultures of JEV strain M 1/311. Strain ts104 was plaque purified and characterized to ascertain its potential as a candidate for a live vaccine. Parameters of its growth, temperature lability, immunogenicity and virulence were examined. Ts104 has been shown to be stable ts JEV strain, multiplying as well as the parent strain in CF cultures at 35 degrees C, but not mutiplying at 39 degrees C. It was avirulent for embryonated chicken eggs incubated at 39 degrees C and of reduced virulence for intracerebrally (i.c.) inoculated mice as measured by LD50 in weanling mice and average day of death in weanling and suckling mice. Intraperitoneal injection of adult mice with either parent or ts strain resulted in similar levels of protection against challenge with either strain. The potential of ts104 as a candidate live JEV vaccine strain is discussed.

Use of a sensitive microplate enzyme-linked immunosorbent assay in a retrospective serological analysis of a laboratory population at risk to infection with typhus group rickettsiae.

A microplate enzyme-linked immunosorbent assay (ELISA), developed for the detection of antibodies to typhus group rickettsiae, was used to analyze human sera from individuals engaged directly or indirectly in rickettsial research. The earliest serum available from each of 112 individuals was tested for immunoglobulin M (IgM) and IgG antibodies against Rickettsia typhi and Rickettsia prowazekii by ELISA at a 1:500 dilution. In at least one assay, nine sera had ELISA optical densities of greater than 0.2, which were above the mean optical densities plus three standard deviations of the other 103 sera. Three of the positive sera were from individuals with known clinical cases of typhus infection. The other sera with predominantly IgG titers were from individuals with extended laboratory exposure to rickettsiae or histories of typhus vaccination, or both. During continued serological surveillance, eight additional people with repeated occupational exposure to typhus rickettsiae had seroconversions in the ELISA to optical densities of greater than 0.2. No apparent clinical illness occurred in two individuals, whereas six clinical cases of infection occurred in others subsequent to accidental laboratory autoinoculation (one) or aerosol exposures (five). In the clinical infections, antibodies were first detected at 7 days, but in subsequent sera, rises and declines in titers were quite variable and were influenced by vaccination, relapse, and time and extent of antibiotic therapy. In primary infections the sera of several individuals who received immediate antibiotic therapy had brief strong IgM responses without pronounced increases in IgG. In contrast, much higher IgG levels were attained in three cases in which relapse occurred, the individual had previously been immunized, or treatment had been delayed. The microplate ELISA proved to be a highly sensitive and reliable test for detection of the human serological response to typhus antigens.

Sensitive microplate enzyme-linked immunosorbent assay for detection of antibodies against the scrub typhus rickettsia, Rickettsia tsutsugamushi.

A microtiter enzyme-linked immunosorbent assay (ELISA) has been developed for the titration of antibodies against scrub typhus in human and animal sera. Scrub typhus rickettsiae were grown in monolayers of irradiated mouse LM3 cells and separated from host cell materials by differential centrifugation, filtration through a glass filter (AP-20, Millipore Corp.), and isopycnic banding in Renografin density gradients. The scrub typhus ELISA antigens were obtained from the purified viable rickettsiae by French pressure cell disruption and addition of 0.2% Formalin to the soluble extract. Antisera prepared in rabbits against the prototype Karp, the Kato, and the Gilliam strains of scrub typhus were used to standardize the ELISA and to compare its sensitivity and specificity to that of the indirect fluorescent antibody test (IFA). ELISA titers were measured as the greatest serum dilution showing an optical density 0.25 above controls or by the optical density achieved at a fixed serum dilution. The IFA and ELISA end point titers were quite similar, and all three measures of titer had comparable specificity for the strains of scrub typhus. No cross-reactions between the typhus and scrub typhus wera were observed by ELISA. Both the immunoglobulin M (IgM) and IgG antibody titers of 12 sequential sera from four patients with scrub typhus were obtained by IFA and ELISA. The IFA and ELISA end point titers for IgM and IgG had correlation coefficients of 0.91 and 0.97, respectively, whereas the ELISA optical density values at a serum dilution of 1:100 had slightly lower correlations with IFA titers (0.80 and 0.94). Early rising IgM titers followed by rising IgG titers were demonstrated by ELISA in three patients with primary scrub typhus infections, whereas the IgG response predominated in a patient with a reinfection. It is concluded that the ELISA for scrub typhus is a very satisfactory alternative to the IFA test.

Sensitive enzyme-linked immunosorbent assay for detection of antibodies against typhus rickettsiae, Rickettsia prowazekii and Rickettsia typhi.

An enzyme-linked immunosorbent assay (ELISA) has been developed for the titration of rickettsial antibodies in human and animal sera. Two preparations of soluble typhus-group antigens were obtained from Rickettsia typhi and Rickettsia prowazekii by ether extraction: a standard antigen from infected yolk sacs (YS antigen) and one free of yolk sac contaminants from Renografin-purified rickettsiae (PR antigen). Rabbit, mouse, and guinea pig sera were obtained by immunization with viable purified R. typhi or R. prowazekii. Human sera were obtained from individuals who had recovered from laboratory infections with either typhus rickettsia months or years previously. Goat-derived anti-immunoglobulins were conjugated to alkaline phosphatase with glutaraldehyde. Although the PR and YS antigens gave equivalent antibody titers in the complement fixation test, the PR antigen was clearly superior in the ELISA. With this antigen, the titration curves of all antisera were linear over a wider range of serum concentrations and the titers were higher than with the YS antigen. With YS and PR antigens, ELISA titers were higher than those obtained by complement fixation by one and two orders of magnitude, respectively. In human sera, immunoglobulin G and immunoglobulin M antibodies were demonstrated by their respective anti-immunoglobulins and by differential susceptibility to ethanethiol. ELISA titers showed some type specificity, whereas none was observed in complement fixation tests. The ELISA is highly sensitive, reproducible, and easily adaptable to the various requirements of clinical and research laboratories.

Stimulation of epithelial healing in chronic postoperative otorrhea using lyophilized cultured keratinocyte lysates.

OBJECTIVE: After tympanoplasty, despite a closed tympanic graft, some patients continue to have persistent otorrhea due to insufficient epithelial healing and granulation tissue formation in the depths of the outer ear canal. When all medical therapies fail, many otologists undertake revision surgery, usually with free skin grafting. To avoid surgery, the authors sought to improve this condition with a lysate of lyophilized cultured allogeneic keratinocytes. STUDY DESIGN AND PATIENTS: In this prospective pilot study, lyophilized cultured allogeneic keratinocyte lysates have been administered in 27 patients. These patients had uncontrollable otorrhea that resisted medical (topical) therapy for at least 6 months. MAIN OUTCOME MEASURE: The criterion of success was a complete epithelialization and cessation of otorrhea. RESULTS: After an average of 2 applications, cessation of otorrhea was achieved in 20 cases (74%). Three patients (11%) relapsed after 3 months. The other ears (63%) still were dry at the 1-year final evaluation. CONCLUSIONS: These results are similar to those obtained after application of sheets of viable cultured keratinocytes of autologous as well as of allogeneic origin. Because the soluble lysate can be incorporated into ototopical drops, the lysate technique is more "user-friendly" and can be applicable in any outpatient clinic. Because keratinocytes contain many growth factors (e.g., epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor), the authors speculate that the release of those intracellular growth factors is responsible for the observed therapeutic effect. This form of therapy by its combination of several growth factors might be considered a more physiologic method than the, also still experimental, growth factor therapy in which high doses of only single growth factor are used.