Evaluation of cloxacillin concentrations in plasma and muscle tissue during cardiopulmonary bypass.

Concentrations of cloxacillin in plasma and deep thoracic muscle tissue were measured in 10 patients who underwent elective coronary bypass surgery or valve replacement. One g of cloxacillin was administered after the induction of anaesthesia and 1 g cloxacillin was added to the oxygenator pump priming fluid before the start of the procedure. Blood and tissue samples were obtained before, during and after cardiopulmonary bypass. The relation between unbound plasma concentrations and total tissue contents of the drug was calculated. It was shown that measurement of the free plasma concentration may provide fairly reliable information on the free concentrations of cloxacillin in the tissues, and that determination of tissue contents may therefore not be necessary. Due to the administration of the second dose of cloxacillin at the start of cardiopulmonary bypass free tissue contents were just adequate in most patients. However, to obtain adequate tissue concentrations after bypass it is recommended that a third dose of the antibiotic be administered before the end of the operation.     

Long-term results of two schedules of radioiodine treatment for toxic multinodular goitre

The long-term effects of two schedules of radioiodine therapy in patients with toxic multinodular goitre were evaluated. Forty-five patients (group A) were treated with low doses and 58 patients (group B) with calculated doses adjusted for thyroid weight (1.85–3.70 MBq/g) and radioactive iodine uptake. Follow-up (mean ± SEM) was 4.3 ± 0.2 years and 5.2 ± 0.3 years, respectively (P>0.1). At the end of follow-up, hyperthyroidism was successfully reversed in 73% (group A) and 88% (group B). In each group, hypothyroidism was present in 7%. The total dose per gram of thyroid tissue was not significantly different in groups A and B (2.1 ± 0.2 vs 2.7 ± 0.2 MBq/g). However, for patients treated with calculated doses the number of ¹³¹I administrations was significantly lower (1.3 ± 0.1) than for patients treated with low doses (2.2 ± 0.2), and the percentage of patients who were adequately treated with a single dose was more than twice as high (66% in group B versus 27% in group A). Euthyroidism was reached within a significantly shorter time after treatment with calculated doses (median time 0.6 years in group B vs 1.5 years in group A; life table analysis). It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a low risk of post-treatment hypothyroidism and that calculated (higher) doses appear to be preferable to low doses.     

Mediastinal rupture of a thoracoabdominal mycotic aneurysm caused by Salmonella typhimurium in an immunocompromised patient

A case is presented of rupture of a mycotic thoracoabdominal aneurysm caused by Salmonella typhimurium in a patient on immunosuppressive therapy following kidney transplantation. After initial medical treatment, surgery consisted of local debridement and implantation of an aortic prosthesis. Lifelong antibiotic treatment was prescribed because of the combination of immunosuppressive therapy, the history of recurrent S. typhimurium bacteremia and the presence of an aortic prosthesis.     

Quantification of tremor sensitivity and inhibition of exploratory behaviour during alcohol withdrawal in rats

Rats given a 10% (v/v) alcohol liquid diet over two weeks reached high blood alcohol levels of around 200mg/dl. Discontinuation of the alcohol intake resulted within 6h in several withdrawal reactions including a tremorogenic activity and a reduction in exploratory behaviour in novel environments. The tremorogenic activity of the alcohol withdrawal could be quantified, using a piezo-film technique, in terms of a supersensitivity to both an inactive and a moderately active dose of the tremorogenic compound harmine. As compared to controls, the rats in alcohol withdrawal revealed more frequent tremor after both 5 and 10mg/kg harmine. The supersensitivity to harmine-induced tremor started within 6h after alcohol withdrawal and remained present with 10mg/kg harmine for up to 48h. The supersensitivity was independent of the length of the tremor bursts used to quantify harmine-induced tremor. Alcohol withdrawal also resulted in an inhibition of exploratory behaviour in a neutral two-chamber box. Both in terms of the number of transits into the open field as well as the time spent in the open area, rats in alcohol withdrawal were significantly less active than control animals. The reduced exploration started within 6h after withdrawal and remained present for up to 24h after the last alcohol intake. These results indicate that both alcohol withdrawal-induced sensitivity to tremorogenic agents and inhibition of exploratory behaviour can be quantified over time, allowing the pharmacological mechanisms involved to be studied.     

Health-related quality of life deviations from population norms in patients with lumbar radiculopathy: associations with pain,pain cognitions,and endogenous nociceptive modulation

Quality of Life Research - The primary goal of this study was to compare the health-related quality of life (HRQoL) of people with lumbar radiculopathy to age- and sex-adjusted population norms....     

Prediction of outcome using pretreatment <Superscript>18</Superscript>F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy

Purpose

The aim of this study is to determine if radiomics features from ¹⁸fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer.

Methods

One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. ¹⁸F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer? in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control.

Results

In the training cohort, median follow-up was 3.0 years (range, 0.43–6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I–II vs. III–IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non Uniformity_GLRLM in PET and Entropy_GLCM in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50–60% for clinical parameters).

Conclusions

In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.

     

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

Introduction: The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization.

Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development.

Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.