Spontaneous electromyographic activity of the tongue in amyotrophic lateral sclerosis

Introduction: Detection of denervation in muscles in the craniobulbar area is important to assure widespread lower motor neuron involvement in the diagnosis of amyotrophic lateral sclerosis (ALS). The value of spontaneous activity analysis in needle electromyography (EMG) of the tongue has been questioned in the recent literature. Methods: Spontaneous activity in the tongue and sternocleidomastoid (SCM) muscles was reviewed retrospectively in 17 ALS patients. Results: Needle EMG showed spontaneous activity in the tongue in 14 of 17 patients (82%) and in 6 patients of 17 (35%) in SCM. Spontaneous EMG activity in the tongue was found in patients with and without bulbar symptoms. Conclusions: Needle EMG is a valuable method for assessing clinical and subclinical involvement of the tongue in patients with bulbar and limb onset ALS. Adequate relaxation of the tongue is a prerequisite for proper spontaneous activity recording. Muscle Nerve, 48: 296–298, 2013     

Dual diagnosis and psychosocial interventions—Introduction and commentary

Treatment of patients with concurrent mental illness and substance abuse represents a challenge to the traditional treatment systems. This article gives: 1) an introduction of the concept and frequency of dual diagnosis (DD), 2) a presentation and discussion of the latest guidelines on DD treatment, 3) status on the current situation in the DD field in Denmark, and 4) potentials for future research. The article is based on systematic examination of evidence-based research and popularized latest guidelines on DD treatment. Methodologically, both treatment and research is challenged by the diversity in DD combinations. Although integrated treatment with the inclusion of cognitive–behavioural therapy, motivational interviewing and family intervention in DD treatment show promising results, it remains to establish which treatment programme is the most qualified in improving mental health and reducing substance use. A future priority is the development of DD treatment that targets specific co-morbid combinations and treatment needs.     

Penicillin G Treatment in Infective Endocarditis Patients – Does Standard Dosing Result in Therapeutic Plasma Concentrations?

Penicillin G is frequently used to treat infective endocarditis (IE) caused by streptococci, penicillin‐susceptible staphylococci and enterococci. Appropriate antibiotic exposure is essential for survival and reduces the risk of complications and drug resistance development. We determined penicillin G plasma concentration [p‐penicillin] once weekly in 46 IE patients. The aim was to evaluate whether penicillin G 3 g every 6 hr (q6 h) resulted in therapeutic concentrations and to analyse potential factors that influence inter‐ and intra‐individual variability, using linear regression and a random coefficient model. [P‐penicillin] at 3 hr and at 6 hr was compared with the minimal inhibitory concentration (MIC) of the bacteria isolated from blood cultures to evaluate the following PK/PD targets: 50% fT > MIC and 100% fT > MIC. [P‐penicillin] varied notably between patients and was associated with age, weight, p‐creatinine and estimated creatinine clearance (eCLcr). Additionally, an increase in [p‐penicillin] during the treatment period showed strong correlation with age, a low eCLcr, a low weight and a low p‐albumin. Of the 46 patients, 96% had [p‐penicillin] that resulted in 50% fT > MIC, while 71% had [p‐penicillin] resulting in 100% fT > MIC. The majority of patients not achieving the 100% fT > MIC target were infected with enterococci. Streptococci and staphylococci isolated from blood cultures were highly susceptible to penicillin G. Our results suggest that penicillin G 3 g q6 h is suitable to treat IE caused by streptococci and penicillin‐susceptible staphylococci, but caution must be taken when the infection is caused by enterococci. When treating enterococci, therapeutic drug monitoring should be applied to optimize penicillin G dosing and exposure.     

Effect of Permeation Enhancers on the Buccal Permeability of Nicotine: <Emphasis Type="BoldItalic">Ex vivo</Emphasis> Transport Studies Complemented by MALDI MS Imaging

Purpose

The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers.

Methods

The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [³H]-nicotine and [¹⁴C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI).

Results

Despite STDC significantly increasing permeability of [¹⁴C]-mannitol, no enhancing effect was seen on [³H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI.

Conclusions

The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.

     

ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

Background

Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed.

Objective

To examine the association between ERG expression at diagnosis and the risk of progression during AS.

Design, setting, and participants

This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10–12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression.

Outcome measurements and statistical analysis

Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events.

Results and limitations

A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p < 0.0001) and of the subgroups PSA progression (p < 0.0001) and histopathologic progression (p < 0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7–68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62–3.72; p < 0.0001). The main limitation of this study is its observational nature.

Conclusions

In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes.

Patient summary

The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.     

Endoscopic treatment of primary aorto-enteric fistulas: A case report and review of literature

BACKGROUNDPrimary aorto-enteric fistula (PAEF) is a rare condition, traditionally treated in the acute, bleeding phase with open surgery or endovascular repair. However, these approaches have high morbidity and mortality, indicating a need for new methods. With advances in endoscopic techniques and equipment, haemoclipping of fistulas has now become feasible. Therefore, we present a systematic review of the English literature and a rare case of a PAEF successfully treated by endoscopic haemoclipping. CASE SUMMARYA 74-year-old man with an abdominal aortic aneurysm presented with symptoms of haemorrhagic shock and bloody stools. An oesophago-gastro-duodenoscopy was performed with haemoclipping of a suspected PAEF in the third part of the duodenum. Afterward, a computed tomography-angiography showed a contrast filled protrusion from the abdominal aortic aneurysm. Based on the clinical presentation and the combined endoscopic and radiographic findings, we argue that this is a case of a PAEF. CONCLUSIONEndoscopic therapy appears capable of achieving haemodynamic stabilisation in patients with bleeding PAEF, serving as a bridge to final therapy.