Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression.

The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV1) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74-0.90) per 10% increase of the predicted FEV1 and 1.06 (1.02-1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16-2.68)) and in subjects with low health status (total SGRQ score >60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03-1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.

Novel information on peripheral tactile mechanisms in man acquired with concentric needle electrode microneurography.

Microneurography with tungsten electrodes has provided a wealth of new data on peripheral nerve fibre function in man. Yet, some lingering controversies pertaining to the technique and its results have not been resolved. In particular, the working principles of microneurography allowing single unit sampling in man are not fully understood. Additionally debated, especially during recent years, was the validity of some neurographic data which supported the long standing conventional concept that myelinated fibres are randomly distributed intraneurally. A novel approach to address these issues was provided by microneurography with concentric needle electrodes. Data obtained with the latter technique suggested that these electrodes record activity extraaxonally from single myelinated fibres in man, possibly at or close to a node of Ranvier. The mechanisms described, which allow single unit resolution in humans, might well also be valid when performing microneurography with tungsten electrodes. Other sets of data indicated that Ranvier nodes tend to occur in clusters within certain regions of a nerve fascicle. Interestingly, the nerve fibres belonging to these clustering nodes were of the same modality and tended to innervate the same skin area in the hand. The discovered nerve fibre segregation involved all the four main classes of myelinated low threshold skin afferents in the hand (RA, PC, SAI and SAII units). The fact that sensory nerve fibres with clustering nodes and of the same modality tend to run together suggests at least a partially ordered intrafascicular nerve fibre organisation. The demonstrated intraneural fibre systematisation could be of profound functional significance both under normal conditions and in disease

Population behaviour of human cutaneous mechanoreceptive units.

Groups of fibres rather than single afferents may be responsible for encoding various intensity aspects of tactile skin stimulation. Reconstruction of population responses of primary afferent fibres to skin displacement provided data in support of this idea, but evidence from direct recordings that demonstrated multifibre activity deriving from groups of single units firing in response to defined skin stimuli were not reported. Procedures are summarised which allow identification and sampling of such recordings in man. For SAII units it was demonstrated how different directions of skin stretch engaging a particular cutaneous area produced different responses of a unit population innervating that site. In response to localised vibratory stimuli synchronous discharges of several co-activated PC afferents were recorded at each vibratory cycle, which is a previously not described pattern of peripheral PC encoding. Population projection of activity within modality segregated clusters of afferents supplying the same skin area might serve as basic projection units and constitute the peripheral counterparts to sensory columns, believed to be the central cognitive correlates, in the cortex. Thus, it is tempting to postulate fibre population projection as a peripheral basis for somatosensory processing in man.

Fitting pieces in the peripheral nerve puzzle.

Findings from comparative microneurography are reviewed, i.e., data obtained by exploring human nerves with tungsten electrodes or concentric needle electrodes under similar conditions. It has emerged that activity in single myelinated fibers originates near nodes of Ranvier. Other data have shown that Ranvier nodes tend to cluster in certain regions of a fascicle and belong to fibers of the same modality which innervate the same skin area. This segregation involves all four main classes of myelinated low-threshold skin afferents. Fiber populations of the same modality may act as peripheral projection modules involved in somatosensory processing of tactile stimuli to cognitive levels. The fiber bundle arrangement of the nerves may be important for conserving functional gnosis in conditions where peripheral nerve fibers are lost. This organization may also be critical as a substrate to promote reinnervation after nerve cut followed by peripheral nerve suture. It is therefore less critical for an outgrowing fiber to find its exact distal counterpart. Even if misguided outgrowth occurs into the endoneurial tube of a neighboring distal fiber of the same modality with an adjacent receptive field, function can be reestablished. A precise nerve topography might also be of significance for obtaining a functionally satisfactory recovery after avulsion injuries treated by nerve root implantation into the spinal cord. Thus, there is in man an ordered nerve fiber organization, both in the periphery and in the CNS, which may have profound functional significance both under normal conditions and in disease.

Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X.

OBJECTIVES: The aim of this study was to evaluate the effects of exercise training and body-awareness training in female patients with Syndrome X. BACKGROUND: Patients with Syndrome X, defined as effort-induced angina pectoris, a positive exercise test and a normal coronary angiogram, suffer from a chronic pain disorder. We hypothesized that this disorder results in physical deconditioning with decreased exertional pain threshold. METHODS: Twenty-six patients were randomly assigned to two training groups (A, B) and a control group (C). Group A (n = 8) started, after baseline measurements, with eight weeks of body-awareness training followed by eight weeks of exercise training on a bicycle ergometer three times a week for 30 min at an intensity of 50% of peak work rate. Group B (n = 8) performed only eight weeks of exercise training. Group C (n = 10) acted as controls without any intervention whatsoever. The effects on exercise performance, hormonal secretion, vascular function, adenosine sensitivity and quality of life were evaluated. RESULTS: Body-awareness training did not change the pain response. The two training groups did not differ in effects of exercise training. Exercise capacity before training was below the gender- and age-matched reference range and improved by 34% with training to a level not different from the reference range. Onset of pain was delayed by 100% from 3 +/- 2 to 6 +/- 3 min (p < 0.05) while maximum pain did not change. Thus the pain-response-to-exercise curve was shifted to the right. Syndrome X patients showed a hypersensitivity to low-dose adenosine infusion compared to healthy age- and gender-matched controls (p < 0.0001) that did not change with exercise training. Endothelium-dependent blood flow increase was at baseline within reference range and tended to increase (p < 0.06) following training. In Group A the concentration of cortisol in urine decreased by 53% after body-awareness training (p < 0.05), and this change from baseline remained after physical exercise training (p < 0.05). A similar decrease occurred with only exercise training (Group B). CONCLUSIONS: Physical deconditioning with lower exertional threshold for pain is a prominent feature in Syndrome X. Physical training in Syndrome X results in an increased exercise capacity with lesser anginal pain. We suggest physical training as an effective treatment in Syndrome X.

Spinal nerve root repair and reimplantation of avulsed ventral roots into the spinal cord after brachial plexus injury.

OBJECT: The authors review the first series of 10 cases in which injured intraspinal brachial plexus were surgically repaired. They describe the technique of spinal cord implantation or repair of ruptured nerve roots, as well as patient outcome. METHODS: Spinal root repair/implantation was performed from 10 days to 9 months postinjury. There were nine male patients and one female patient. Postoperatively in most cases, regeneration of motor neurons from the spinal cord to denervated muscles could be demonstrated. The first signs of regeneration were noted approximately 9 to 12 months postoperatively. Useful function with muscle power of at least Medical Research Council Grade 3 occurred in three of 10 cases. Magnetic brain stimulation studies revealed a normal amplitude and latency from the cortex to reinnervated muscles on surgically treated and control sides. A certain degree of cocontraction between antagonistic muscles (for example, biceps-triceps) compromised function. With time there was a reduction of cocontractions, probably due to spinal cord plasticity. In these cases there was also, surprisingly, a return of sensory function, although the mechanism by which this occurred is uncertain. Sensory stimulation (thermal and mechanical) within the avulsed dermatomes was perceived abnormally and/or experienced at remote sites. There was some return of patients' sense of joint position. CONCLUSIONS: A short time lag between the accident and the surgery was recognized as a significant factor for a successful outcome. Reimplantation of avulsed nerve roots may be combined with other procedures such as nerve transfers in severe cases of brachial plexus injury.

Clustering of Pacinian corpuscle afferent fibres in the human median nerve.

To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 microm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors.

Spinal cord implantation of avulsed ventral roots in primates; correlation between restored motor function and morphology.

Functional restitution following spinal cord implantation of avulsed ventral roots was assessed electromyographically and correlated with the morphology of the regenerated neural structures in primates. The C5-C8 ventral roots were avulsed from the spinal cord in seven Macaca fascicularis monkeys. In three animals the roots were immediately reimplanted into the ventrolateral part of the spinal cord. In two monkeys the avulsed roots were reimplanted with a delay of 2 months and in two control animals the roots were not reimplanted. There was substantial recovery of function after both immediate and delayed spinal cord implantation of the avulsed ventral roots. The population of neurons that had regenerated was larger than on the control side, indicating a rescue of cells after an immediate root implantation. Different functional types of neurons had been attracted to regrow axons to the implanted root as judged by their position in the ventral horn. Thus, neurons normally supplying antagonistic muscles, such as the triceps muscle, participated in the innervation of the biceps muscle. Functionally this deficient directional specificity was correlated to both spasticity and co-contractions among agonistic and antagonistic muscles. Occasional electromyographic signs of function occurred also in control animals where the avulsed roots had not been implanted. This recovery was found to depend on regrowth from the site of avulsion, within the pia mater among the leptomeningeal cells and to the avulsed roots. The acceptable functional dexterity regained due to corrective surgery is discussed in terms of neurotrophism and plasticity.

Distribution of human Pacinian corpuscles in the hand. A cadaver study.

The subcutaneous distribution and number of Pacinian corpuscles were studied in ten fresh cadaver hands. They were found to cluster close to nerves and vessels at the metacarpophalangeal joints and the proximal phalanx. The total mean number in the hand was 300 (192-424). The percentage of the total was 44 to 60% in the fingers, 23 to 48% in the metacarpophalangeal area and 8 to 18% in the thenar and hypothenar regions. Corpuscles in palmar skin overlying the distal phalanx were smaller than receptors in the metacarpophalangeal area. The lowest density of corpuscles was along the nerves and vessels of the middle phalanx.

Consistency of unitary shapes in dual lead recordings from myelinated fibres in human peripheral nerves: evidence for extracellular single-unit recordings in microneurography.

Percutaneous microneurography is a powerful technique allowing studies of activity in single nerve fibres of conscious humans. However, the mechanisms by which single-unit recordings are achieved with this technique are not fully understood. To further elucidate these mechanisms, dual-lead recordings, using a modified concentric needle electrode with two separate recording surfaces at the tip, were performed in normal subjects. Sixty-two single units supplied by large myelinated afferents were studied. The majority (90%) of the units were recorded simultaneously on both surfaces but with different action potential amplitudes. Four types of unitary waveforms were encountered. The potentials recorded on the two channels were of the same type, although occasionally some details differed. Parallel waveform changes of the same units occurred simultaneously on the two surfaces. A displacement of a single fibre from one recording surface to the other with or without concomitant waveform-type transitions was observed when the electrode was slightly repositioned intraneurally. The results provided direct evidence to confirm that concentric needle electrodes record single-unit activity extracellularly from myelinated nerve fibres, probably at or close to a node of Ranvier. All the types of action potentials encountered with conventional tungsten electrodes were also identified in dual-channel recordings with concentric electrodes, which casts doubt on the previous explanation that single-unit activity recorded with tungsten electrodes is derived from intracellular sources. Some biological and technical aspects of the findings are discussed, especially concerning the applicability of in vivo measurements of the time course of the action potentials in humans and ways to improve microneurography towards multichannel recordings.

Clustering of slowly adapting type II mechanoreceptors in human peripheral nerve and skin.

The intrafascicular organization of human peripheral nerves was studied with percutaneous microneurography in the median, radial and peroneal nerves with one-surface or two-surface thin diameter concentric needle electrodes. Data from 33 recording sites containing 47 slowly adapting type II (SAII) units were analysed. At many sites two, sometimes even three, neighbouring SAII units were recorded from the explored nerve fascicle and they had adjacent or even overlapping cutaneous receptive fields. Among pairs of SAII units found at the same site, one unit often had ongoing discharge, whereas the other was silent under resting conditions. The neighbouring SAII units were optimally activated by stretching the skin in different directions. Stretching the same skin area in different directions produced different unit recruitment. Clustered SAII units were often found in sites where Pacinian afferents and skin sympathetic activity were also recorded. No significant difference was observed in the degree of grouping of SAII units either between recordings obtained with one-surface versus two-surface electrodes or between glabrous and hairy skin. The data do not support the notion that myelinated fibres are randomly organized in peripheral nerve fascicles. Instead, the findings suggest that SAII units tend to be clustered in human peripheral nerves. Furthermore, the response of groups of SAII units to skin stretch suggests that they play a role in proprioception. Dual channel recordings with two-surface concentric needle electrodes may provide a novel approach to study fibre organization in human peripheral nerves and the behaviour of groups of nerve fibres.

Protocol for microneurography with concentric needle electrodes.

In 1968, the method of human percutaneous microneurography with solid tungsten electrodes was introduced. Since then many investigators used this technique to study peripheral mechanisms in the somatosensory, motor and autonomic systems of conscious humans. Although some modifications of the method were described, the basic construction of the recording electrode has remained the same over the years. In the present protocol we describe in detail the procedures of microneurography using a thin diameter concentric needle electrode. There are some advantages with the concentric electrodes in comparison with the tungsten needles: (1) the electrical and mechanical properties of the electrode are stable which allows repeated use, (2) its restricted and one-dimensionally directed recording area provides the possibility to study topographical aspects within even a part of a peripheral nerve fascicle, and (3) multi-channel recordings can be achieved by adding more recording surfaces to the electrode. Based on recent investigations evaluating the recording properties of concentric electrodes we propose a novel procedure for signal analysis where template matching is incorporated. The analyses described in this protocol might also be applicable for extracellular recordings from muscle or elsewhere within the nervous system.

Endovascular stents covered with pre-expanded polytetrafluoroethylene for treatment of iliac artery aneurysms and fistulas.

PURPOSE: This report describes the early clinical experience with use of a transluminally placed endovascular graft (TPEG) covered with pre-expanded polytetrafluoroethylene (PTFE) to treat iliac artery aneurysms and fistulas. MATERIALS AND METHODS: Eight patients with iliac artery aneurysms (n = 7) and common iliac artery to common iliac vein fistula (n = 1) were treated with TPEGs. The iliac artery aneurysms were either common iliac (n = 6) or hypogastric (n = 1). All of the patients had significant comorbid diseases. The TPEG devices were made with pre-expanded PTFE sutured to Palmaz stents and delivered through 10- or 12-F sheaths. RESULTS: The aneurysms were successfully excluded in six of seven patients and the one iliac artery-to-vein fistula was successfully occluded. There were no immediate procedural complications related to the TPEG devices. Follow-up was limited (mean, 12 months), but no stenoses or occlusions of the TPEG devices were detected. The one failure was probably due to the marked tortuousity of the iliac artery, which prevented an adequate seal. CONCLUSION: In the authors' early clinical experience, the use of TPEG devices with pre-expanded PTFE successfully treated iliac artery aneurysms and an iliac artery-to-vein fistula. Although the results are encouraging, longer follow-up is necessary to better evaluate this type of treatment.

Waveform complexity of unit activity recorded with concentric needle electrodes from human peripheral nerves.

Using standardised concentric needle electrodes 170 single units were recorded from myelinated cutaneous afferents in the human median or ulnar nerves. The unitary waveforms were of four types: single-peaked monophasic potentials (type I), double-peaked monophasic potentials (type II), biphasic potentials (type III) and triphasic potentials (type IV). Type II and IV occurred more frequently than the other types. Units of different functional classes had similar waveforms and there was no specific type of waveform distribution in any particular unit category. In some recording situations there were changes in unitary waveforms from one type to another. There was a tendency for the complex type IV, type III and type II waveforms to change to the simple type I. Adjustment of the electrode often provoked such waveform changes. The waveform profiles and waveform changes observed during recordings with concentric needles were significantly different from those encountered with conventional tungsten electrodes, which might be due to differences in recording properties between the two electrodes. Possible neural mechanisms underlying the observed waveforms and waveform transitions are discussed. In particular, our data suggest that concentric needle electrodes record single-unit activity from myelinated fibres extracellularly.

Peripheral afferents with common function cluster in the median nerve and somatotopically innervate the human palm.

Concentric needle electrodes with a central core diameter of 20-30 microm were used to explore median nerve fascicles in man. Such electrodes can simultaneously monitor subtle electrophysiological and topographical features even within parts of a fascicle. Single-unit recordings from myelinated fibres were more easily obtained at some intrafascicular sites than others. Typically, groups of identified myelinated fibres in these regions, possibly corresponding to a cluster of Ranvier nodes, tended to be fibres responding to stimuli of the same modality. These afferents innervated the glabrous skin of the human hand and fingers in a somatotopic manner. In particular, the somatotopy even seemed to be present at the receptor level in the skin. This novel aspect of peripheral nerve organisation is probably of fundamental importance for the interplay between peripheral and central processes involved in somatosensation both under normal conditions and in disease. Some clinical implications of the findings are discussed.

Multiple action potential waveforms of single units in man as signs of variability in conductivity of their myelinated fibres.

Percutaneous microneurography was performed with concentric needle electrodes to record neural activity from myelinated fibres in human peripheral nerves. Template matching techniques were used together with interspike interval analysis and studies on functional class, receptive field characteristics, conduction velocities and other single fibre properties to classify single units. Sometimes the same fibres exhibited different action potentials at the same time. The potentials had some common features, but differed either in their waveform types or only in duration. There was a correlation between the occurrence of the different potential shapes and firing frequency of the studied unit. The outcome of the studies suggested that there was a common denominator which could explain the observations. Most likely, momentary fluctuations in excitability of the myelinated fibres occurring during the relative refractory period or the supernormal period were responsible for the variations in complexity of the studied units due to a partial block of fibre propagation probably caused by the recording electrode. Thus, action potentials deriving from the same axon may not always have the same shapes. Methods for unit classification, such as template matching, are discussed in the light of our findings.

Demonstration of a fibre afferents with overlapping receptive fields in humans.

According to previous data peripheral nerves may lack a detailed microanatomical organization. Nevertheless, stimuli within restricted skin areas might excite more than one afferent of the same modality. Since, as recently demonstrated, peripheral myelinated afferents are at least partially organized by both modality and somatotopy it might be possible to demonstrate such a phenomenon electrophysiologically provided that adequate procedures are used. To address this issue we recorded activity in single myelinated afferents supplying the hand with concentric needle electrodes. A combination of electrical and/or natural stimuli applied to the area where rapidly adapting (RA) or slowly adapting type I (SAI) fibres ended demonstrated that fibres of the same functional class may exhibit overlapping receptive fields in the skin.

Single unit discrimination among discharges from neighboring myelinated fibers in human peripheral nerves: improved unit identification by interspike interval analysis of nerve responses evoked by tactile stimuli.

Clustered rapidly adapting (RA) or slowly adapting type I (SA I) units recorded with concentric needle electrodes from median nerves of healthy human volunteers may exhibit overlapping receptive fields in the skin as also Paccini afferents (PC units) and slowly adapting type II unitary elements (SA II units) with their much larger innervation areas. Fundamental for the discrimination of such pairs of neighboring units in the nerve with overlapping peripheral fields was the refractory period of the studied fibers, which was assumed to be normal, i.e., of the order of 1-2 ms. When a unit belonging to one of the categories mentioned was found, it was activated by different tactile stimuli in the palm or fingers. Simultaneously, interspike interval analysis of the evoked responses was performed. In situations when the minimal interspike intervals were longer than the absolute refractory period of a single fiber the response derived from one single unit. Responses from at least two units were considered to contribute to the recorded sequences when computer analysis showed that the durations of the minimal intervals were shorter. In this way, the reported procedure facilitated the discrimination of both pairs of RA and SAI units and, in particular, pairs of neighboring PC or SA II units with overlapping receptive fields in human palmar skin.

Analgesic effects of adenosine during exercise-provoked myocardial ischaemia.

The analgesic potential of adenosine during myocardial ischaemia was studied in patients with coronary artery disease and exercise-limiting angina pectoris. Patients were given a low dose of adenosine or placebo in a double-blind cross-over fashion by continuous i.v. infusion before and during two exercise tests. Adenosine decreased chest pain by 45 +/- 13% (p < 0.02) while heart rate-blood pressure product and electrocardiographic signs of myocardial ischaemia did not change. Ten healthy volunteers received increasing doses of adenosine by continuous i.v. infusion. The heat pain threshold increased in skin covering the chest (p < 0.03) and also tended to increase at the left thenar eminence (p < 0.07). In conclusion, the neuromodulator adenosine can therefore act as an analgesic in myocardial ischaemia.