What does local tenderness say about the origin of pain? An investigation of cervical zygapophysial joint pain

BACKGROUND: Mechanical pain sensitivity is assessed in every patient with pain, either by palpation or by quantitative pressure algometry. Despite widespread use, no studies have formally addressed the usefulness of this practice for the identification of the source of pain. We tested the hypothesis that assessing mechanical pain sensitivity distinguishes damaged from healthy cervical zygapophysial (facet) joints. METHODS: Thirty-three patients with chronic unilateral neck pain were studied. Pressure pain thresholds (PPTs) were assessed bilaterally at all cervical zygapophysial joints. The diagnosis of zygapophysial joint pain was made by selective nerve blocks. Primary analysis was the comparison of the PPT between symptomatic and contralateral asymptomatic joints. The secondary end points were as follows: differences in PPT between affected and asymptomatic joints of the same side of patients with zygapophysial joint pain; differences in PPT at the painful side between patients with and without zygapophysial joint pain; and sensitivity and specificity of PPT for 2 different cutoffs (difference in PPT between affected and contralateral side by 1 and 30 kPa, meaning that the test was considered positive if the difference in PPT between painful and contralateral side was negative by at least 1 and 30 kPa, respectively). The PPT of patients was also compared with the PPT of 12 pain-free subjects. RESULTS: Zygapophysial joint pain was present in 14 patients. In these cases, the difference in mean PPT between affected and contralateral side (primary analysis) was −6.2 kPa (95% confidence interval: −19.5 to 7.2, P = 0.34). In addition, the secondary analyses yielded no statistically significant differences. For the cutoff of 1 kPa, sensitivity and specificity of PPT were 67% and 16%, respectively, resulting in a positive likelihood ratio of 0.79 and a diagnostic confidence of 38%. When the cutoff of 30 kPa was considered, the sensitivity decreased to only 13%, whereas the specificity increased to 95%, resulting in a positive likelihood ratio of 2.53 and a diagnostic confidence of 67%. The PPT was significantly lower in patients than in pain-free subjects (P < 0.001). CONCLUSIONS: Assessing mechanical pain sensitivity is not diagnostic for cervical zygapophysial joint pain. The finding should stimulate further research into a diagnostic tool that is widely used in the clinical examination of patients with pain.

Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells

Activation of hepatic stellate cells (HSC) and transdifferentiation to myofibroblasts following liver injury is the main culprit for hepatic fibrosis. Myofibroblasts show increased proliferation, migration, contraction, and production of extracellular matrix (ECM). In vitro, HMG-CoA reductase inhibitors (statins) inhibit proliferation and induce apoptosis of myofibroblastic HSC. To investigate the antifibrotic effects of atorvastatin in vivo we used bile duct ligated rats (BDL).

Synthesis, structures, redox and photophysical properties of benzodifuran-functionalised pyrene and anthracene fluorophores

Benzodifuran-functionalised pyrene and anthracene fluorophores 1 and 2 were obtained in reasonable yields. Their single crystal structures, electrochemical, optical absorption, and fluorescence characteristics have been described. They show strong luminescence with high quantum yields of 0.53 for 1 and 0.48 for 2.

Break detection of annual Swiss temperature series

[1] Instrumental temperature series are often affected by artificial breaks (“break points”) due to (e.g.,) changes in station location, land-use, or instrumentation. The Swiss climate observation network offers a high number and density of stations, many long and relatively complete daily to sub-daily temperature series, and well-documented station histories (i.e., metadata). However, for many climate observation networks outside of Switzerland, detailed station histories are missing, incomplete, or inaccessible. To correct these records, the use of reliable statistical break detection methods is necessary. Here, we apply three statistical break detection methods to high-quality Swiss temperature series and use the available metadata to assess the methods. Due to the complex terrain in Switzerland, we are able to assess these methods under specific local conditions such as the Foehn or crest situations. We find that the temperature series of all stations are affected by artificial breaks (average = 1 break point / 48 years) with discrepancies in the abilities of the methods to detect breaks. However, by combining the three statistical methods, almost all of the detected break points are confirmed by metadata. In most cases, these break points are ascribed to a combination of factors in the station history.

Sensitivity of Nd isotopic composition in seawater to changes in Nd sources and paleoceanographic implications

It has been argued that past changes in the sources of Nd could hamper the use of the Nd isotopic composition (ϵNd) as a proxy for past changes in the overturning of deep water masses. Here we reconsider uncertainties associated with ϵNd in seawater due to potential regional to global scale changes in the sources of Nd by applying a modeling approach. For illustrative purposes we describe rather extreme changes in the magnitude of source fluxes, their isotopic composition or both. We find that the largest effects on ϵNd result from changes in the boundary source. Considerable changes also result from variations in the magnitude or ϵNd of dust and rivers but are largely constrained to depths shallower than 1 km, except if they occur in or upstream of regions where deep water masses are formed. From these results we conclude that changes in Nd sources have the potential to affect ϵNd. However, substantial changes are required to generate large-scale changes inϵNd in deep water that are similar in magnitude to those that have been reconstructed from sediment cores or result from changes in meridional overturning circulation in model experiments. Hence, it appears that a shift in ϵNdcomparable to glacial-interglacial variations is difficult to obtain by changes in Nd sources alone, but that more subtle variations can be caused by such changes and must be interpreted with caution.

Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis

BACKGROUND AND PURPOSE: Basilar artery occlusion (BAO) is an infrequent form of acute stroke, which invariably leads to death or long-term disability if not recanalized. A traditional recanalization approach based on historical controls and pathophysiological consideration is local intra-arterial thrombolysis (IAT) in eligible patients. This necessitates diagnostic evaluation and treatment in stroke centers equipped with an interventional neuroradiological service on a 24-hour basis, but its superiority to the technically simple intravenous thrombolysis (IVT) remains unproven. METHODS: We analyzed systematically published case series of substantial size reporting the outcome of BAO after IAT or IVT. RESULTS: In 420 BAO patients treated with IVT (76) and IAT (344), death or dependency were equally common: 78% (59 of 76) and 76% (260 of 344), respectively (P=0.82). Recanalization was achieved more frequently with IAT (225 of 344; 65%) than with IVT (40 of 76; 53%; P=0.05), but survival rates after IVT (38 of 76; 50%) and IAT (154 of 344; 45%) were equal (P=0.48). A total of 24% of patients treated with IAT and 22% treated with IVT reached good outcomes (P=0.82). Without recanalization, the likelihood of good outcome was close to nil (2%). CONCLUSIONS: Recanalization occurs in more than half of BAO patients treated with IAT or IVT, and 45% to 55% of survivors regain functional independence. Although improved therapy forms for BAO are necessary, hospitals not equipped for IAT may set up IVT protocols. The effect of IVT is probably not much different from the effect of IAT. IVT represents probably the best treatment that can be offered to victims of acute BAO in such hospitals.

Fast DNA serotyping of Escherichia coli by use of an oligonucleotide microarray

Classical antibody-based serotyping of Escherichia coli is an important method in diagnostic microbiology for epidemiological purposes, as well as for a rough virulence assessment. However, serotyping is so tedious that its use is restricted to a few reference laboratories. To improve this situation we developed and validated a genetic approach for serotyping based on the microarray technology. The genes encoding the O-antigen flippase (wzx) and the O-antigen polymerase (wzy) were selected as target sequences for the O antigen, whereas fliC and related genes, which code for the flagellar monomer, were chosen as representatives for the H phenotype. Starting with a detailed bioinformatic analysis and oligonucleotide design, an ArrayTube-based assay was established: a fast and robust DNA extraction method was coupled with a site-specific, linear multiplex labeling procedure and hybridization analysis of the biotinylated amplicons. The microarray contained oligonucleotide DNA probes, each in duplicate, representing 24 of the epidemiologically most relevant of the over 180 known O antigens (O antigens 4, 6 to 9, 15, 26, 52, 53, 55, 79, 86, 91, 101, 103, 104, 111, 113, 114, 121, 128, 145, 157, and 172) as well as 47 of the 53 different H antigens (H antigens 1 to 12, 14 to 16, 18 to 21, 23 to 34, 37 to 43, 45, 46, 48, 49, 51 to 54, and 56). Evaluation of the microarray with a set of defined strains representing all O and H serotypes covered revealed that it has a high sensitivity and a high specificity. All of the conventionally typed 24 O groups and all of the 47 H serotypes were correctly identified. Moreover, strains which were nonmotile or nontypeable by previous serotyping assays yielded unequivocal results with the novel ArrayTube assay, which proved to be a valuable alternative to classical serotyping, allowing processing of single colonies within a single working day.

Efficacy of gatifloxacin alone and in combination with cefepime against penicillin-resistant Streptococcus pneumoniae in a rabbit meningitis model and in vitro

Gatifloxacin penetrated well into cerebrospinal fluid (CSF) (49 +/- 11%), measured by comparison of AUC(CSF)/AUC(serum), and showed good bactericidal activity (leading to a decrease of 0.75 +/- 0.17 log10 cfu/mL/h) in the treatment of experimental meningitis in rabbits caused by a penicillin-resistant pneumococcal strain (MIC 4 mg/L). It was significantly more effective than the standard regimen, ceftriaxone with vancomycin, which led to a decrease of 0.53 +/- 0.17 log10 cfu/mL/h. The addition of cefepime to gatifloxacin slightly improved the killing rates (giving a decrease of 0.84 +/- 0.14 log10 cfu/mL/h). In vitro, synergy was demonstrated between cefepime and gatifloxacin by the chequerboard method (fractional inhibitory concentration index = 0.5) and by viable counts over 8 h.

Incidence and correlates of drug-eluting stent thrombosis in routine clinical practice. 4-year results from a large 2-institutional cohort study

OBJECTIVES: We sought to determine the risk of late stent thrombosis (ST) during long-term follow-up beyond 3 years, searched for predictors, and assessed the impact of ST on overall mortality. BACKGROUND: Late ST was reported to occur at an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation. METHODS: A total of 8,146 patients underwent percutaneous coronary intervention with a sirolimus-eluting stent (SES) (n=3,823) or paclitaxel-eluting stent (PES) (n=4,323) and were followed up to 4 years after stent implantation. Dual antiplatelet treatment was prescribed for 6 to 12 months. RESULTS: Definite ST occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient-years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30 days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI: 1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR: 1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively. CONCLUSIONS: Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to 4 years. Diabetes is an independent predictor of early ST, whereas acute coronary syndrome, younger age, and PES implantation are associated with late ST.