Cerebral processing of painful oesophageal stimulation: a study based on independent component analysis of the EEG.

BACKGROUND AND AIMS: Independent component analysis (ICA) of the electroencephalogram (EEG) overcomes many of the classical problems in EEG analysis. We used ICA to determine the brain responses to painful stimulation of the oesophagus. METHODS: Twelve subjects with a median age of 41 years were included. With a nasal endoscope, two series of 35 electrical stimuli at the pain threshold were given to the distal oesophagus and the EEG was subjected to ICA. The sessions were separated by 30 minutes. For each component head models, event related images, spectral perturbation, coherence analysis, and dipoles were extracted. The most valid components were found according to time/frequency information and reliability in both experiments. RESULTS: Reliable components with the most valid dipoles were found in the thalamus, insula, cingulate gyrus, and sensory cortex. Time locked activities were consistent with upstream activation of these areas, and cross coherence analysis of the sources demonstrated dynamic links in the beta(14-25 Hz) and gamma(25-50 Hz) bands between the suggested networks of neurones. The thalamic components were time and phase locked intermittently, starting around 50 ms. In the cingulate gyrus, the posterior areas were always firstly activated, followed by the middle and anterior regions. Components with dipoles in the sensory cortex were localised in several regions of the somatosensory area. CONCLUSIONS: The method gives new information relating to the localisation and dynamics between neuronal networks in the brain to pain evoked from the human oesophagus, and should be used to increase our understanding of clinical pain.

The relationship between selective sleep deprivation, nocturnal jaw-muscle activity and pain in healthy men.

The relationship between nocturnal jaw-muscle activity and temporomandibular disorders (TMD) is still controversial. The aim of this study was to investigate the effect of selective slow wave sleep (SWS = non-rapid-eye-movement (NREM) stage 3 + 4) deprivation on jaw-muscle activity using a new automatic system. Ten healthy men without signs of symptoms of TMD participated. The subjects slept in the laboratory for six continuous nights including one adjustment night, one baseline night, three nights with experimental sleep deprivation and one recovery night. Polysomnographic recordings of electroencephalography (EEG) and electromyography (EMG) were obtained for recognition of sleep stages and masseter muscle activity. During the three experimental nights, computer-controlled sound stimulation (60--90 dB(A), 1000 Hz) were given as long as the subjects were in SWS. Maximum voluntary occlusal force (MVOF), pain pressure threshold (PPT) and visual analogue scales (VAS) were used to assess the state of the masseter muscles every morning and evening during the study period. The results showed that the time spent in SWS was significantly decreased during the first sleep deprivation night, but there were no significant effects on nocturnal EMG activity (i.e. the numbers of bruxism episodes per hour of sleep, bruxism bursts per episodes bruxism bursts per hour of sleep), MVOF, VAS or PPT. Furthermore, the automatic system only deprived the SWS in five subjects for the following two nights although the sound stimulation was given at the maximum intensity. These results suggest that deprivation of SWS may not interact immediately with nocturnal jaw-muscle activity and jaw-muscle pain.

Ulnar neuropathy at the elbow: clinical and electrophysiological outcome of surgical and conservative treatment.

The objective was to evaluate and compare the clinical and electrophysiological outcome of treatment in patients with ulnar neuropathy at the elbow in 32 consecutive patients who were studied prospectively. Based on the electrophysiological findings 15 patients were treated by surgical decompression and 17 were treated conservatively. Sensory and motor nerve conduction studies across and below the elbow were done in all patients before treatment and again after one year. Postoperatively 10/15 patients (67%) improved clinically and 12 patients (80%) had improved nerve conduction results. There was clinical and electrophysiological agreement in eight patients in the surgically-treated group, all of whom improved both clinically and electrophysiologically. In the conservatively-treated group six patients (35%) showed clinical improvement, 10 patients had no improvement, and one patient was worse. The nerve conduction studies improved in six patients (35%), were unchanged in eight patients, and worse in three. There was clinical and electrophysiological agreement in 11 patients. We conclude that the electrophysiological examination was valuable in deciding which patients to operate on, and that most of the patients improved clinically or electrophysiologically postoperatively.

Amiodarone for rapid cardioversion of chronic atrial tachyarrhythmia?

Electrical cardioversion of atrial tachyarrhythmia has disadvantages, such as the need for general anaesthesia, skin burns and thoracic pain. Pharmacodynamic cardioversion is without these side effects, but the reports of the efficacy of the treatment vary a lot. Amiodarone has been the only drug so far reported to give a combination of high efficacy and low frequency of serious side effects such as ventricular tachycardia and shock. The purpose of the present study was to assess the effect of amiodarone on chronic atrial tachycardia. Seventeen patients with chronic atrial fibrillation or flutter were given an oral dose of 30 mg/kg amiodarone. Serial blood tests after amiodarone ingestion were taken to document absorption. Patients, who did not convert to sinus rhythm within 24 hr were treated by electrical cardioversion. No patients converted pharmacodynamically to sinus rhythm. Twelve patients (71%) reached the recommended serum concentration of amiodarone (2-2.5 mg/l, median 2.4 mg/l, range 0.96-4.7). The concentration of desethylamiodarone remained low (<0.2 mg/l), and there were no objective or subjective side effects following the treatment. Sixteen patients (94%) were converted to sinus rhythm the day after by electrical cardioversion without complications. A single high dose of amiodarone is a safe but ineffective method of converting chronic atrial fibrillation and flutter, and may be used as adjuvant therapy in combination with electrical cardioversion.

The diagnostic headache diary--a headache expert system.

The purpose with the headache expert system was to develop a diagnostic and educational tool for the general practitioners (GP), in order to improve their management of headache disorders. This chapter describes the diagnostic headache diary, an expert system intended for education and diagnosing headache disorders. The diagnostic headache diary can be printed and used by headache patients at home to record their headache attacks and medicine consumption by a day to day basis. It can also be used by the GP at the clinic in order to provide the headache diagnoses. The diagnostic headache diary was written in the programming language Delphi and implemented as a stand-alone Windows 95 program. It was integrated as one of five modules in the headache tutorial described in another chapter of this book. The diagnostic headache diary consists of four modules: Patient data, diary, medication and diagnosis. Configured around a database, the diagnostic headache diary allows entries of several patients and search facilities. The diagnostic headache diary was tested and validated by entering expert-diagnosed data from different headache disorders which where compared to the computer generated diagnoses.

Headache tutorial.

The headache multimedia educational tool for the general practitioners, consists of five different modules, i.e. classification, clinical data, headache tutorial, diagnostic headache diary and nomenclature. It is possible to move between the modules both vertically and horizontally. This paper concerns the headache tutorial. It consist of case records that the user can test his diagnostic abilities on. Each case record is subdivided into an interview by the physician, physical and neurological examination, laboratory test, sum of positive diagnostic elements, suggestions of diagnoses and management. A total of 12 case records are provided. The system will be available on a CD-ROM.

Increased prognostic value of combined myocardial perfusion imaging and exercise electrocardiography in patients with coronary artery disease.

BACKGROUND: Myocardial perfusion imaging (MPI) with technetium-99m-labeled sestamibi and exercise electrocardiography (EECG) are widely used for risk stratification of patients with known or suspected coronary artery disease (CAD). However, no large-scale studies have addressed the prognostic power of the combined information from these diagnostic tools. METHODS AND RESULTS: We studied 697 consecutive patients who underwent a 2-day Tc-99m sestamibi cardiac perfusion imaging protocol. The EECG was performed on a bicycle ergometer by symptom-limited exercise. Causes of death were obtained from death certificates. Univariate survival analyses were performed with a Kaplan-Meier estimate and a corresponding log-rank test. A multivariate Cox proportional hazards model was applied to test for potential predictor covariates obtained from hospital records. The predominant risk factors of cardiac death were fixed perfusion defects (relative risk, 2.55; range, 1.43 to 4.55) and an impaired circulatory exercise response (relative risk, 3.26; range, 1.74 to 6.08). The major prognostic information of MPI was the ability to detect patients with a definitively low risk. Patients with impaired circulatory response to exercise test and fixed perfusion defects were at a very high risk. CONCLUSION: The combined results of MPI and EECG provide substantial information on the long-term risk of cardiac death in patients with suspected CAD.

Vibrotactilometry as a diagnostic tool in ulnar nerve entrapment at the elbow.

Vibrotactilometry with testing of the thresholds of the vibration sense at seven frequencies between 8-500 Hz in different intensities has been correlated with nerve conduction studies of the ulnar nerve to evaluate its diagnostic power in neuropathies at the elbow. Thirty-nine patients with entrapment symptoms were studied. Vibrotactilometry was abnormal in 33 patients (85%) and nerve conduction studies were abnormal in 19 (49%). The sensitivity of vibrotactilometry in relation to nerve conduction studies was 89%, and in relation to the patients' symptoms was 85%. We conclude that vibrotactilometry is a sensitive test that correlates well with the patients' symptoms, while nerve conduction studies are less sensitive (49%) in relation to the patients' symptoms. Vibrotactilometry in the frequency area of 8-500 Hz is recommended in the screening of ulnar nerve entrapment. Nerve conduction studies are recommended in clinically doubtful cases to localise the entrapment to the elbow region.

Zopiclone as night medication in rheumatoid arthritis.

Sleep disturbances and related daytime complaints are frequent in rheumatoid arthritis (RA). The aim of the current study was therefore to evaluate the effect of a newer hypnotic on sleep structure and clinical parameters in RA. Forty outpatients were randomized to a two week treatment regimen with either 7.5 mg zopiclone or placebo at bedtime. Clinical examinations were performed before and after treatment and the degree of pain, fatigue, sleepiness, morning stiffness, and activities of daily living were assessed. Two sleep questionnaires were also completed weekly. Polysomnography was performed before the study and after 14 days of treatment. Recordings were evaluated using conventional sleep scoring as well as frequency analysis of the electroencephalography (EEG). Patients in the zopiclone group had subjective improvement of sleep, but otherwise no differences in pain score or the other clinical parameters were found. Conventional sleep assessments showed only minor changes during treatment, but frequency analysis demonstrated a shift from the lower towards the higher EEG frequencies in the active treatment group. Although the modulation of the EEG can represent a non-specific pharmacologic epiphenomenon, it might also reflect a disturbance of sleep microstructure. In conclusion, treatment with zopiclone may be of value for subjective sleep complaints in selected patients with RA, but it is doubtful whether hypnotics improve daytime symptoms in this patient group.

Sleep in rheumatoid arthritis: a comparison with healthy subjects and studies of sleep/wake interactions.

Sleep complaints are frequent in patients with rheumatoid arthritis (RA) and sleep disturbances may contribute to pain and other daytime complaints. The aims of the current study were to compare ambulatory sleep recordings from consecutively selected patients with RA to those obtained in healthy controls, and to study the relationships between sleep structure and clinical symptoms. Sleep recordings were obtained from 41 out-patients with RA and 19 matched controls. All had clinical examinations and completed different questionnaires. Recordings were scored traditionally and, moreover, the electroencephalography (EEG) was subjected to frequency analysis. For the study of sleep-wake interactions in the patients, a graphical chain model was used. The patients had many sleep-related complaints. An increase in the number of periodic movements of the legs (PML) during sleep was seen in comparison with controls, but otherwise only minor differences were observed in classical sleep stages. Data from frequency analysis showed an increase in alpha (8-12 Hz)-EEG activity in sleep stages non-rapid eye movement (NREM) 2-4 in most sleep cycles. The statistical model demonstrated a complex but independent correlation between morning stiffness, pain and joint tenderness on the one hand, and awakenings, stage NREM2, slow-wave sleep and stage REM on the other, probably reflecting a relationship between sleep patterns and pain in RA. In conclusion, only the increase in PML and alpha-EEG activity distinguished the sleep in RA patients from that of healthy controls. However, the demonstrated interaction between daytime complaints and sleep patterns may increase the understanding and treatment of the disease. In future research, graphical chain models may improve our understanding of complex relationships between multiple variables.

[Training on a wobble board following lateral ankle joint sprains]. / Traening med vippebraet efter laterale ankelledsdistorsioner.

The aim of this study was to investigate whether the number of patients with residual symptoms following ankle sprains could be reduced by training on a wobble board during a 12-week training recovery period. The effect of a 12-week training program was compared to no training. Forty-eight patients completed the study. In the follow-up period (mean 230 days) we found significantly fewer recurrent distorsions and fewer patients had functional instability in the study group compared to controls. There were no differences between the two groups concerning subjective complaints during the recovery period. Volumetric measurements revealed no difference in the speed of reduction of haematoma and oedema in the two groups. We conclude that training on a wobble board is effective in reducing residual symptoms following ankle sprains.

The effect of cutaneous and deep pain on the electroencephalogram during sleep--an experimental study.

The interaction between sleep and pain has been insufficiently studied, and no experiments have investigated whether pathologic sleep patterns as seen in pain patients can be replicated experimentally by well-defined pain stimuli. An experimental model would therefore be valuable for further studies on the interaction between pain and sleep. In this study, three well-defined experimental stimuli (muscle, joint, and cutaneous pain) were applied during sleep, and the electroencephalogram (EEG) pattern was quantified. The pain stimuli were applied during slow-wave sleep in 10 healthy subjects. Using nine surface recordings, the EEG was sampled before and during pain stimuli. Frequency analysis was performed, resulting in 10 EEG features describing the responses to pain. During the muscle-pain stimulus an arousal effect was observed and a decrease in delta (0.5-3.5 Hz) and sigma (12-14 Hz) as well as increases in alpha 1 (8-10 Hz) and beta (14.5-25 Hz) activities were seen. During joint pain, however, more universal EEG changes were seen with a decrease in the lowest frequency bands [delta, theta (3.5-8 Hz) and alpha 1] and an increase in the higher frequencies [alpha 2 (10-12 Hz), sigma and beta bands]. No background EEG changes were observed during the cutaneous stimulus. There were several differences in the responses from the nine EEG channels, but no derivation seemed especially sensitive to detect the evoked changes. The study highlights the complexity of pain on the sleep EEG. The experimental model has shown that pain from different body structures, as well as signals from various EEG derivations, may give different responses in sleep microstructure.

[The health project Ebeltoft: health check ups and discussions in general practice. Basic data from a 5-year, prospective, randomized, controlled population study]. / Sundhedsprojekt Ebeltoft: Helbredsundersøgelser og helbredssamtaler i almen praksis. Basisdata fra en fem¿rig, prospektiv, randomiseret, kontrolleret befolkningsunders|gelse.

A study was carried out to investigate people's interest in participating in health check-up and in discussions about health with their own general practitioner, participants' health status, the proportion who received health advice following health check-up, and the lifestyle goals they set following discussion with their general practitioner. This study reports the baseline data from a five-year randomized, controlled, prospective, population-based study in general practices in Ebeltoft, Denmark. All general practitioners from the four practices in Ebeltoft and a random sample of 2,000 people aged between 30 and 50 years were invited to participate. Participants were randomly divided into three groups-one control group and two intervention groups. One intervention group was given a health check-up which included a range og tests (Table 2 and 3); this group received written feedback from the general practitioner. The other intervention group was also given a health check-up and written feedback, in addition, they were given the opportunity to attend their general practitioner to discuss health-promoting measures. A total of 1370 people participated in the study (69% response rate). Health advice was given to 76% of 905 participants following health check-up. Almost all of the 456 participants (96%) who were offered the opportunity of discussing their health with their general practitioner took up the offer: 64% of the 456 participants reported that they had decided to undertake lifestyle changes. Eleven of those who discussed their health with the doctor were referred to a specialist (2%). There was considerable interest in participating in health promotion. Three out of four of those who had a health check-up were given health advice. Two out of three of those who were offered a health talk with the general practitioner appeared willing to make relevant lifestyle changes. Longterm follow up is needed to determine effects and side effects of health check-up and health talks.

Causal probabilistic network and power spectral estimation used in sleep stage classification.

A new method for sleep-stage classification using a causal probabilistic network as automatic classifier has been implemented and validated. The system uses features from the primary sleep signals from the brain (EEG) and the eyes (AOG) as input. From the EEG, features are derived containing spectral information which is used to classify power in the classical spectral bands, sleep spindles and K-complexes. From AOG, information on rapid eye movements is derived. Features are extracted every 2 seconds. The CPN-based sleep classifier was implemented using the HUGIN system, an application tool to handle causal probabilistic networks. The results obtained using different training approaches show agreements ranging from 68.7 to 70.7% between the system and the two experts when a pooled agreement is computed over the six subjects. As a comparison, the interrater agreement between the two experts was found to be 71.4%, measured also over the six subjects.

Ambulatory polysomnography using a new programmable amplifier system with on-line digitization of data: technical and clinical findings.

A new system for polysomnographic recording at home is presented. It consists of a 12 to 24-channel amplifier system with direct digitization of the polygraph signals using a portable computer. Sampling frequency, amplification and filter settings can be defined by the user, and the signals are evaluated at bedside. Technical testing proved a high signal/noise ratio, linear amplification and a good signal quality. Clinical testing of the first 100 recordings showed that they were acceptable for conventional sleep scoring in 98 cases. A comparison of two consecutive recordings was done in 9 healthy subjects and 11 patients with rheumatic disorders. Using conventional sleep staging, only a slight "first night effect" (FNE) was demonstrated in the sleep architecture. Power spectral analysis using autoregressive modeling demonstrated only a difference of power between the 2 nights in the beta (14.5-25 Hz) band. In conclusion, the usability and technical advantages make the system very suitable for ambulatory recordings and only a minimal FNE should be considered when results are evaluated.

Wobble board training after partial sprains of the lateral ligaments of the ankle: a prospective randomized study.

Ankle sprains are often complicated by functional instability and repeated sprains. Rehabilitation with wobble boards in patients with functional instability has been tested, and significant improvement has been found compared to no training. The aim of this study was to investigate whether the number of patients with residual symptoms following ankle sprains could be reduced by training on a wobble board during 12-week recovery period. In addition, the influence of training in the time course reduction of edema was investigated. We performed a prospective study including 61 patients, all active in sports for more than 2 hours a week with primary ankle sprains. The effect of a 12-week training program with wobble board was compared with no training. Forty-eight patients completed the study. In the follow-up period (mean X = 230 days), we found significantly fewer recurrent sprains, and significantly fewer patients in the training group had functional instability of the ankle compared with the no training group. There were no differences in the two groups in the time which elapsed before patients were painless at walking, during running, or at sports. Volumetric measurements revealed no difference in the speed of reduction of hematoma and edema of the ankle and foot between the two groups. We conclude that training on a wobble board early after primary stage 2 ankle sprains is effective in reducing residual symptoms following this lesion and that training does not seem to affect the time course reduction in edema.

Clustering of sleep electroencephalographic patterns in patients with the fibromyalgia syndrome.

Several electroencephalographic (EEG) abnormalities have been observed during sleep in patients suffering from the fibromyalgia syndrome (FMS). In this study, 12 patients with fibromyalgia and 14 control subjects had two polysomnographic recordings obtained at home. Data from the second night were subjected to blinded manual scoring as well as signal processing using linked or 'step-wise clustering for pattern recognition. In this procedure, a common learning set was generated using the spectral information in three 2 min EEG samples from each of the sleep stages selected from five patients with FMS and five controls. In this way, 17 characteristic EEG classes were defined. All 2 s EEG segments from the whole night from all subjects were then assigned to one of these classes. Five of the classes (dominated by 0.5-4.5 Hz activity) were more frequent in the control group, whereas three other classes (dominated by 8-11 Hz activity) were prevalent in the patient group. This trend was consistent in all sleep stages, although most striking in non-rapid eye movement (NREM) sleep. The predominance of these classes in the patient group may correspond to the alpha-EEG sleep anomaly previously reported in subjects with FMS. More importantly, as the EEG power in the lowest frequency range (prevalent in controls) probably is a marker for restorative sleep, the findings may reflect important aspects of sleep disturbances n subjects suffering from FMS, thereby contributing to some of the daytime symptoms in these patients.

Oligonucleotide analogues containing 4'-C-(hydroxymethyl)uridine: synthesis, evaluation and mass spectrometric analysis.

2',3'-Di-O-tert-butyldimethylsilyl-4'-C-(hydroxymethyl)uridine was synthesized and converted into the phosphoramidite building blocks 9 and 13. Novel oligodeoxynucleotide analogues containing 4'-C-hydroxymethyl linked phosphodiester internucleoside linkages and 3'-hydroxyl linked phosphodiester internucleotide linkages were synthesized on an automated DNA-synthesizer. The latter modification introduced an additional 4'-C-hydroxymethyl functionality. Oligodeoxynucleotides with one or two modifications in the middle or in the ends of 17-mers, 15-mers and 14-mers have been evaluated with respect to hybridization properties and enzymatic stability. Compared to unmodified oligomers, 3'-end-modified oligodeoxynucleotides were stabilized towards 3'-exonucleolytic degradation, but showed moderately to strongly lowered hybridization properties towards complementary DNA. However, more promising results were obtained in melting experiments with complementary RNA where only small decreases in melting temperature were detected. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was used to identify products from syntheses of the modified oligodeoxynucleotide analogues.