Propofol and Sevoflurane in Subanesthetic Concentrations Act Preferentially on the Spinal Cord: Evidence from Multimodal Electrophysiological Assessment

Background: Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment.

Methods: We studied nine healthy volunteers in two sessions during steady state sedation with 0.5, 1.0, and 1.5 [mu]g/l (targeted plasma concentration) propofol or 0.2 and 0.4 vol% (end-tidal) sevoflurane. Following a 15-min equilibration period, motor responses to transcranial magnetic stimulation and peripheral (H-reflex, F-wave) stimulation were recorded, while electroencephalography and auditory evoked responses were recorded in parallel.

Results: At concentrations corresponding to two thirds of C50 awake, motor responses to transcranial magnetic stimulation were reduced by approximately 50%, H-reflex amplitude was reduced by 22%, F-wave amplitude was reduced by 40%, and F-wave persistence was reduced by 25%. No significant differences between sevoflurane and propofol were found. At this concentration, the Bispectral Index was reduced by 7%, and the middle-latency auditory evoked responses were attenuated only mildly (Nb latency increased by 11%, amplitude PaNb did not change). In contrast, the postauricular reflex was suppressed by 77%.     

Antigenic change in a human IgG4-specific CH3 epitope upon binding of a monoclonal antibody against a neighboring IgG4-specific epitope.

Two sets of monoclonal antibodies (mAbs) probably reacting with two different epitopes in the CH3 domain of the human IgG4 molecule were studied. We observed that the commercially available mAb HP 6011 inhibited the antigen binding of the three mutually inhibitable mAbs, 40-A2, 41-E8 and 43-F11 (40-series), made by us. However, the 40-series mAbs, including those with similar affinity such as mAb HP6011, were not able to inhibit mAb HP 6011. When the 40-series mAbs were preincubated with IgG4, the mAb HP 6011 could partially displace these antibodies. This one-way inhibition indicates that upon binding mAb HP 6011 changes the antigenic structure of the IgG4 molecule by disrupting the epitope for the 40-series mAbs. A steric hindrance of this epitope by mAb HP 6011 is more unlikely, since the small Fab fragment of mAb HP 6011 also inhibited the reaction of the 40-series mAbs.     

The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

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Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment,acupuncture and stabilising exercises on the pregnancy,mother, delivery and the fetus/neonate

Background  

Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone.     

Comparison of pleural pressure and transcutaneous diaphragmatic electromyogram in obstructive sleep apnea syndrome

STUDY OBJECTIVES: Based on studies of the impact of esophageal pressure on cardiovascular variables during sleep, this signal can be used to refine the severity level in the clinical diagnosis of obstructive sleep apnea syndrome. We hypothesized that relative changes in diaphragmatic electromyogram (EMG) can reflect short-term changes in esophageal pressure durng obstructive apneas and hypopneas. DESIGN: Diaphragmatic EMG was sampled at 0.25 kHz; diaphragmatic EMG waveform was band-pass filtered and digitally converted; the electrocardiogram artifact was eliminated; using a gating procedure, the waveform was fast-Fourier transformed and digitally rectified; and a moving average of 200 milliseconds was calculated. For each inspiratory effort during apnea or hypopnea, we calculated maximum diaphragmatic EMG and esophageal pressure. Data were normalized calculating the percentage difference between the first obstructed and each subsequent inspiratory effort during the respiratory event. SETTING: Sleep disorders laboratory. PATIENTS: 9 patients with moderate obstructive sleep apnea syndrome presenting with apneas and hypopneas during sleep. INTERVENTION: None. MEASUREMENTS AND RESULTS: 861 respiratory events were scored, and the evolution between esophageal pressure and diaphragmatic EMG were compared. Normalized data showed a good correlation between the 2 measures during apneas and hypopneas. There was a significant difference between the percentage increase in esophageal pressure and diaphragmatic EMG for apneas and hypopneas (esophageal pressure, apnea: 118.1% +/- 118.5%, hypopnea: 76.1% +/- 74.3%, P = .000; diaphragmatic EMG, 123.5% +/- 131.7%, hypopnea: 73.3% +/- 74.2%, P = .000). No significant differences for apnea or hypopnea were noted between the 2 measures under investigation. CONCLUSION: Diaphragmatic EMG may be clinically useful to describe relative changes in respiratory effort under conditions of apnea and hypopnea during sleep and to reliably dissociate central from obstructive events where esophageal pressure monitoring is not readily available.     

Challenges and Opportunities for Real-World Evidence in Metastatic Luminal Breast Cancer

BackgroundThe therapeutic armamentarium for patients with metastatic breast cancer is becoming more and more specific. Recommendations from clinical trials are not available for all treatment situations and patient subgroups, and it is therefore important to collect real-world data.SummaryTo develop recommendations for up-to-date treatments and participation in clinical trials for patients with metastatic breast cancer, the Prospective Academic Translational Research PRAEGNANT Network was established to optimize the quality of oncological care in the advanced therapeutic setting. The main aim of PRAEGNANT is to systematically record medical care for patients with metastatic breast cancer in the real-life setting, including the outcome and side effects of different treatment strategies, to monitor quality-of-life changes during therapy, to identify patients eligible for participation in clinical studies, and to allow targeted therapies based on the molecular structures of breast carcinomas.Key MessagesThis article describes the PRAEGNANT network and sheds light on the question of whether the various end points from clinical trials can be transferred to the real-world treatment situation.     

Risk factors for anastomotic dehiscence in colon cancer surgery—a population-based registry study

Purpose

The aim of this was to assess potential risk factors for anastomotic dehiscence in colon cancer surgery in a national cohort.

Methods

All patients, who had undergone a resection of a large bowel segment with an anastomosis between 2008 and 2011, were identified in the Swedish Colon Cancer Registry. Patient factors, socioeconomic factors, surgical factors, and medication and hospital data were combined to evaluate risk factors for anastomotic dehiscence.

Results

The prevalence of anastomotic dehiscence was 4.3 % (497/11 565). Male sex, ASA classification III–IV, prescribed medications, bleeding more than 300 mL, and uncommon colorectal resections were associated with a higher risk of anastomotic dehiscence. Hospital stay was increased with 14.5 days, and 30-day mortality as well as long-term mortality was higher in the anastomotic dehiscence group.

Conclusions

There are several factors that are possible to know preoperatively or during surgery that can indicate whether an anastomosis is an appropriate option. Anastomotic dehiscence increases hospital stay and long-term mortality.

     

Ca2+-dependent large conductance K+ currents in thalamocortical relay neurons of different rat strains

Mutations in genes coding for Ca²⁺ channels were found in patients with childhood absence epilepsy (CAE) indicating a contribution of Ca²⁺-dependent mechanisms to the generation of spike-wave discharges (SWD) in humans. Since the involvement of Ca²⁺ signals remains unclear, the aim of the present study was to elucidate the function of a Ca²⁺-dependent K⁺ channel (BK_Ca) under physiological conditions and in the pathophysiological state of CAE. The activation of BK_Ca channels is dependent on both voltage and intracellular Ca²⁺ concentrations. Moreover, these channels exhibit an outstandingly high level of regulatory heterogeneity that builds the basis for the influence of BK_Ca channels on different aspects of neuronal activity. Here, we analyse the contribution of BK_Ca channels to firing of thalamocortical relay neurons, and we test the hypothesis that BK_Ca channel activity affects the phenotype of a genetic rat model of CAE. We found that the activation of the β₂-adrenergic receptor/protein kinase A pathway resulted in BK_Ca channel inhibition. Furthermore, BK_Ca channels affect the number of action potentials fired in a burst and produced spike frequency adaptation during tonic activity. The latter result was confirmed by a computer modelling approach. We demonstrate that the β₂-adrenergic inhibition of BK_Ca channels prevents spike frequency adaptation and, thus, might significantly support the tonic firing mode of thalamocortical relay neurons. In addition, we show that BK_Ca channel functioning differs in epileptic WAG/Rij and thereby likely contributes to highly synchronised, epileptic network activity.