A method of electrical cervical motor root stimulation: effect of stimulation parameters and normal values

Following percutaneous stimulation over the cervical column, a compound action potential (CMAP) can be recorded from the muscles of the arm. The actual site of excitation is located on the spinal motor roots, probably near to their exit from the spinal column. This method allows the electroneurographical assessment of the proximal brachial plexus and is used to calculate a central motor conduction time following motor cortex stimulation. So far, the optimal placement of the stimulating electrodes is unknown, and normal values must be established. We measured onset latencies of CMAPs of Mm biceps brachii and abductor digiti minimi (ADM) after supramaximal cervical motor root stimulation in 31 healthy subjects. Distances between the stimulating electrodes varying from 3 to 12 cm were studied. With 6 cm interelectrode distance, the electrodes were then placed either in a longitudinal or in a transversal direction, with the cathode over the interspace C7/T1 or C6/7. In addition, for the longitudinal stimulation, the effect of cathodal versus anodal stimulation over the C7/T1 interspace was studied. The results of various stimulating electrode positions and directions over the lower cervical column were then compared statistically. With the longitudinal electrode position, the cathode over C7/T1 and the anode placed 6 cm cranially, it was always possible to excite muscles from both sides simultaneously. When a very proximal stimulation site at the nerve roots was required in both muscles after one single stimulus, this method was superior to the transversal electrode position with the cathode C6/7 or C7/T1, or to the longitudinal electrode position with the anode over C7/T1 and the cathode placed cranially. For the ADM (29 subjects, 58 sides), the mean onset latency was 13.795 +/- 1.307 ms (mean +/- 1 SD), the mean side-to-side difference (SSD) was 0.452 +/- 0.388 ms. The mean amplitude was 7.71 +/- 2.64 mV, the mean side-to-side quotient (SDQ) was 41.88 +/- 97.59%. For M. biceps (29 subjects, 58 sides), the mean onset latency was 5.138 +/- 0.582 ms, the mean SSD 0.166 +/- 0.193 ms. The mean amplitude was 7.91 +/- 3.45 mV, the mean SSQ was 55.42 +/- 67.94%.     

Effect of motilin on gastric emptying in patients with diabetic gastroparesis

OBJECTIVES: Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND METHODS: The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects. RESULTS: During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values. CONCLUSIONS: These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects.     

Mutational analysis of pulmonary tumours with neuroendocrine features using targeted massive parallel sequencing: a comparison of a neglected tumour group

Background:

Lung cancer is the leading cause of cancer-related deaths worldwide. The typical and atypical carcinoid (TC and AC), the large-cell neuroendocrine carcinoma (LCNEC) and the small-cell lung cancers (SCLC) are subgroups of pulmonary tumours that show neuroendocrine differentiations. With the rising impact of molecular pathology in routine diagnostics the interest for reliable biomarkers, which can help to differentiate these subgroups and may enable a more personalised treatment of patients, grows.

Methods:

A collective of 70 formalin-fixed, paraffin-embedded (FFPE) pulmonary neuroendocrine tumours (17 TCs, 17 ACs, 19 LCNECs and 17 SCLCs) was used to identify biomarkers by high-throughput sequencing. Using the Illumina TruSeq Amplicon-Cancer Panel on the MiSeq instrument, the samples were screened for alterations in 221 mutation hot spots of 48 tumour-relevant genes.

Results:

After filtering >26 000 detected variants by applying strict algorithms, a total of 130 mutations were found in 29 genes and 49 patients. Mutations in JAK3, NRAS, RB1 and VHL1 were exclusively found in SCLCs, whereas the FGFR2 mutation was detected in LCNEC only. KIT, PTEN, HNF1A and SMO were altered in ACs. The SMAD4 mutation corresponded to the TC subtype. We prove that the frequency of mutations increased with the malignancy of tumour type. Interestingly, four out of five ATM-mutated patients showed an additional alteration in TP53, which was by far the most frequently altered gene (28 out of 130; 22%). We found correlations between tumour type and IASLC grade for ATM- (P=0.022; P=0.008) and TP53-mutated patients (P<0.001). Both mutated genes were also associated with lymph node invasion and distant metastasis (P⩽0.005). Furthermore, PIK3CA-mutated patients with high-grade tumours showed a reduced overall survival (P=0.040) and the mutation frequency of APC and ATM in high-grade neuroendocrine lung cancer patients was associated with progression-free survival (PFS) (P=0.020).

Conclusions:

The implementation of high-throughput sequencing for the analysis of the neuroendocrine lung tumours has revealed that, even if these tumours encompass several subtypes with varying clinical aggressiveness, they share a number of molecular features. An improved understanding of the biology of neuroendocrine tumours will offer the opportunity for novel approaches in clinical management, resulting in a better prognosis and prediction of therapeutic response.     

Midazolam-pain, but one cannot remember it: a survey among Southern German endoscopists

BACKGROUND: Benzodiazepines, especially midazolam, are the most frequently used agents for gastrointestinal endoscopy worldwide. Among other parameters the quality of sedation is determined by patients' satisfaction assessed after endoscopy. This approach is misleading as the potent amnestic effect of midazolam conceals pain actually suffered during the endoscopic procedure involving distraction of the endoscopists from their actual tasks by audible reactions and defense movements. In this study, we eliminated the influence of patients' amnesia on the assessment of the quality of sedation and rather interviewed endoscopists and their assistant personnel about their experience with midazolam sedation. We replaced the mostly vague term 'compliance' by terms which unequivocally describe the reactions of the patient during an unpleasant endoscopy. METHODS: A short survey consisting of 12 questions was developed. The questionnaires were distributed to the participants - 115 endoscopists and their assistants - of a tutorial about sedation for gastrointestinal endoscopy in three major Southern German cities. The questionnaire retrieved the endoscopists' experience regarding patients' discomfort or pain under sedation with midazolam, their wish for better sedative agents, their preferred sedative regimens, their medical specialty and their professional experience. RESULTS: Participants were highly experienced with the majority having more than 10,000 procedures and a median of 18 years of endoscopic experience; 77% of endoscopists utilized midazolam for sedation. Ninety-eight percent of the questioned physicians felt that patients have pain during endoscopy with midazolam+/-opioid, but do not remember later. Ninety-two percent reported that it happens that patients moan aloud because of pain and almost half of the endoscopists (48%) reported of screaming. The majority of the endoscopists (91%) reported fierce defense movements with midazolam or the need to hold the patient down on the examination couch because of fierce movements, respectively (75%). Seventy percent of the endoscopists wished to have the rooms for endoscopy preferably soundproof away from the waiting room and 93% wished for better sedative agents. CONCLUSIONS: Midazolam was rated as insufficient for sedation by both endoscopists and their assistant personnel. A wish for better sedative drugs exists.     

Multidisciplinary rehabilitation for chronic back pain in an outpatient setting: a controlled randomized trial

Based on existing models for pain chronicity and effective treatment strategies for patients with chronic low back pain, a multidisciplinary rehabilitation programme for an outpatient group setting was developed. The main treatment components address the patient's physical functional capacity (functional restoring), cognitive and affective processes (pain management strategies), and behavioural and ergonomical aspects (back school elements). Short-term (immediately after intervention) and long-term effects (at 6-months follow-up) of the intervention were assessed in a randomized controlled study. Dependent variables were pain measures, functional capacity, disability, muscular strength and endurance, pain and posture-related self-efficacy, attitudes, depression, well-being, behavioural habits and posture assessed by a standardized behavioural observation method. Immediately after the intervention, patients in the treatment group (n=36) showed significant improvement over patients in the control group (n=29) in all variables except depression and muscular strength and endurance. At 6-months follow-up, compared to pretreatment scores, patients continued to show beneficial effects in pain intensity and frequency, posture, posture-related self-efficacy and well-being. In contrast to post-treatment results, there were also significant improvements in strength and endurance. Overall results testify to the effectiveness of the intervention programme. Future studies (with larger sample sizes) should aim at a further improvement of functional capacity and disability perception, an analysis of differential treatment effects, and strategies for an improved long-term maintenance of the changes induced by the programme.     

Lack of association of the Glu298Asp polymorphism of endothelial nitric oxide synthase with manifest coronary artery disease,carotid atherosclerosis and forearm vascular reactivity in two Austrian populations

OBJECTIVE: Conflicting data exists about the possible contribution of the homozygous Asp/Asp genotype of the Glu298Asp polymorphism of endothelial nitric oxide synthase to human atherosclerotic vascular disease. We investigated the polymorphism in two independent study populations: a case-control study including patients with angiographically verified coronary artery disease (CAD) on the one hand and a cross-sectional epidemiological study on the other hand. METHODS: The Glu298Asp polymorphism was determined by PCR-RFLP as established. In the case-control study (240 patients and 248 controls) a possible association between the polymorphism and CAD, and age of onset of CAD and myocardial infarction was investigated. In the cross-sectional epidemiological study (932 subjects) intima-media thickness (IMT) of the carotid artery as well as morphological plaque burden and forearm vascular reactivity (peak postischemic reactive hyperaemia, determined by venous occlusion plethysmography) were measured. RESULTS: In the case-control study genotype distribution (Glu/Glu; Glu/Asp; Asp/Asp) was not different between the CAD patients (43/46/11%) and the controls (49/41/10%, P = NS). No association of the polymorphism with age of onset of CAD or myocardial infarction was found. In the epidemiological study no influence of the genetic variant on IMT was observed after correction for classical determinants of IMT (average IMT: Asp/ Asp: 0.077 +/- 0.011 mm; Glu/Glu and Glu/Asp: 0.080 +/- 0.012 mm, P = NS). Forearm vascular reactivity was also not different between homozygous Asp/Asp subjects and Glu/Glu and Glu/Asp subjects (peak-reactive hyperaemia 20.1 +/- 7.3 mL min-1 100 mL-1 vs. 20.0 +/- 6.5 mL min-1 100 mL-1, P = NS). CONCLUSIONS: Our results suggest that there is no association of the Glu298Asp polymorphism with coronary or carotid atherosclerosis or forearm vascular reactivity in these populations recruited in a country with a rather high risk for atherosclerosis. We suggest additional investigations to be performed in populations at different risk for coronary events to further elucidate the possible contribution of this polymorphism to vascular disease.