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Biomedical subjects

L B Dahlin

Publications and source records attributed to L B Dahlin.

At least 37 records · Page 2Linked to original sources

Sutures alone are sufficient to support regeneration across a gap in the continuity of the sciatic nerve in rats.

We have proposed that it is sufficient to provide a simple substratum on which regenerating axons may traverse a gap in a peripheral nerve. To test this hypothesis we set up a new experimental model in which sutures were used to bridge a 10 mm long defect in a peripheral nerve. A defect was created bilaterally in 25 rat sciatic nerves. The cut ends of the nerve were joined by three laps of a continuous suture, on one side with 8/0 polyamide (non-absorbable) and on the other with 8/0 polyglactin (absorbable), leaving a 7 mm gap. At two weeks a matrix that contained capillaries, fibroblast-like cells, and mononuclear cells had formed between the nerve endings, and the sutures were surrounded by foreign-body-like tissue reactions. At four weeks axons had grown into the distal nerve segment on both sides in 65%-90% of the cases as indicated by a response to the pinch reflex test and immunocytochemistry for presence of neurofilament protein. Axons were organised in minifascicles and these tended to grow larger as the demarcation of the entire regenerated segment by a perineurial-like structure improved with time. At 12 weeks axonal counts of cross-sections of the distal tibial trunk showed many myelinated nerve fibres but no significant difference in axonal counts or degree of myelination between the polyamide and polyglactin sides. The results show that conventional sutures alone are sufficient to support regeneration across a short gap in a peripheral nerve, a method that may be of potential clinical value.

Animals↗

Assessment of functional outcome after nerve repair in a longitudinal cohort.

To investigate the temporal changes in the results of clinical tests of the functional outcome after nerve repair, we followed up 19 patients periodically over a four year period after repair of the median or ulnar nerve at the forearm. Between the first and last follow-up four of the instruments used--Semmes-Weinstein monofilaments, manual muscle testing, Sollerman grip test, and Jamar dynamometer--indicated significant and moderate to large improvements. A moderate and significant improvement was also noted during the same period in patients' estimation of pain or discomfort. Results of the two-point discrimination test did not change significantly over time. Most changes occurred during the first postoperative year, and thereafter it was principally motor function that improved. We conclude that four of the six used tests showed useful temporal dynamics during the follow-up time. The lack of responsiveness in two-point discrimination test suggests that other or complementary test instruments should be used for assessment of tactile gnosis after nerve repair.

Adolescent↗

Spatiotemporal progress of nerve regeneration in a tendon autograft used for bridging a peripheral nerve defect.

We have previously shown that a tendon autograft from the rat tail can support regeneration across a gap in the continuity of the rat sciatic nerve. In this study, we characterized the spatiotemporal progress of regeneration in such a graft bridging a 10-mm defect in the sciatic nerve of the rat. Regeneration was assessed 7, 10, 14, or 18 days postoperatively, by immunocytochemistry for axons, Schwann cells, and macrophages and histochemistry for blood vessels. Axonal regrowth into the grafts showed an initial delay period of 6.8 days, whereafter axons grew at a rate of 1.0 mm/day. Schwann cells grew into the grafts from both the proximal and distal nerve segments, proximally just ahead of the axonal front. Macrophages were initially preferentially located at the periphery of the grafts, but gradually increased inside the grafts. Blood vessels entered the grafts from both the proximal and distal aspects of the severed nerve. The onset of vascularization appeared to coincide with axonal regeneration into the grafts.

Alkaline Phosphatase↗

Bridging defects in nerve continuity: influence of variations in synthetic fiber composition.

Synthetic filaments introduced into a silicone tube may help to enhance axonal growth over extended defects in nerve continuity [1]. Here we test the influence of number (0, 3, 7 or 15), size (diameter 150 or 250 microm) and material of filaments (polyamide or catgut) enclosed in such tubes (inner diameter 1.98 mm) on axonal growth across a 10 mm defect in rat sciatic nerve. The morphology of the tube content was analyzed four weeks post-surgery. The area of the formed tissue matrix inside the tube showed no difference between the groups. Myelinated axons were observed in the formed tissue matrix inbetween and peripheral to the filaments, however, separated from the filaments by concentric cell layers. The number of myelinated axons was less in the tubes with 15 filaments, most pronounced when catgut filaments were used. In most cases, except in tubes with 15 catgut filaments, fibers had grown into the distal nerve segment (pinch reflex test/light microscopy). We conclude that an intrinsic framework consisting of a limited number of synthetic filaments inside an extrinsic framework (silicone tube) does not disturb nerve regeneration. The formed tissue matrix was neither influenced by the presence or the numbers (if less than or equal to seven filaments), type of filaments nor the size of the filaments indicating the importance of the inserted nerve segments.

Journal Article↗

Neurophysiological findings in vibration-exposed male workers.

Fractionated nerve conduction, vibrotactile sense, and temperature thresholds were studied in 73 symptomatic vibration-exposed male workers. Three symptomatic groups were distinguished: patients with isolated sensorineural symptoms; with isolated vasospastic problems; and with both. Clinical carpal tunnel syndrome occurred in 14 patients and abnormal cold intolerance (without blanching of the fingers) in 23. In the group as a whole, nerve conduction studies were abnormal in the median nerve but not in the ulnar nerve and vibration perception and temperature thresholds were impaired. Of the three symptomatic groups, patients with isolated sensorineural symptoms differed from controls. No differences were seen between patients with and without clinical carpal tunnel syndrome. With severe sensorineural symptoms the vibration perception thresholds, but not the values of the nerve conduction studies, were further impaired. The results indicated two injuries that are easily confused: one at receptor level in the fingertips and one in the carpal tunnel. Careful clinical assessment, neurophysiological testing, and examination of vibrotactile sense are required before carpal tunnel release should be considered in these patients.

Adult↗

Autologous tendons used as grafts for bridging peripheral nerve defects.

This study was performed to investigate whether autologous collagen and other extracellular matrix components could be used in nerve repair by bridging a 10 mm defect in the rat sciatic nerve. Three models of repair were examined. In the first model, a rat tail tendon was teased and subsequently rolled to form a loose collagen roll which was sutured over the defect. In the second model, an intact tendon was used. In the third model, a teased tendon was pretreated with attachment of nerve segments to each end for 4 weeks before grafting. Both teased and intact tendons supported regeneration, to some extent. Pretreatment resulted in migration of Schwann cells into the graft, and enhanced regeneration.

Animals↗

Surgery of the spastic hand in cerebral palsy. Improvement in stereognosis and hand function after surgery.

Thirty-six patients with hemiplegic cerebral palsy had surgical treatment for the upper limb and were followed up for 18 months postoperatively. Various operations were done. A striking finding was a significant improvement of stereognosis (ability to describe and recognize objects without vision). Most patients had improvement in different functional grasps following surgical reconstruction. Range of movement in the forearm and wrist also increased in most patients. The thumb-in-palm deformity was completely corrected in 31 of the patients and improved in the other five. Most patients had some or all of their expectations of the procedure fulfilled.

Activities of Daily Living↗

Vibrotactile sense in the hand-arm vibration syndrome.

OBJECTIVES: The purpose of this study was to investigate disturbances of the vibrotactile sense and their relation to clinical symptoms and findings among male symptomatic workers suffering from the hand-arm vibration syndrome. METHODS: Ninety-six such patients were interviewed and given a clinical and tactilometric examination. The symptoms were classified according to the Stockholm Workshop Scale. A sensibility index was used to quantify vibrotactile sense in the tactilogram. RESULTS: An abnormal sensibility index (<0.8) was recorded for 57.3% of the patients (mean of 4 fingers), at least 1 finger being abnormal in 72.9% of the patients. The sensibility index did not statistically differ between the patients suffering from sensorineural symptoms and those with vibration white finger. The stages of sensorineural symptoms, according to the Stockholm Workshop Scale, corresponded with the sensibility index, whereas the stages of vibration white finger did not. There were significant differences in the sensibility index between the fingers, between the right and left hands, and between the fingers innervated by the ulnar and median nerves. Bilateral symptoms and cold intolerance were associated with considerable impairment of the vibrotactile sense. Clinical median nerve involvement in the carpal tunnel was not reflected by the sensibility index. CONCLUSIONS: There is a considerable degree of neural involvement in all symptomatic vibration-exposed patients irrespective of symptoms. As symptoms progress, the severity of sensorineural symptoms, but not of vibration white finger, is reflected by the sensibility index. Cold intolerance is strongly related to nervous involvement and should be noted in the patient history. Tactilometry should be performed on 1 median and 1 ulnar nerve-innervated finger of both hands, as an examination of 1 finger alone may be misleading.

Adult↗

Nerve regeneration in a 'pseudo-nerve' graft created in a silicone tube.

The pseudo-nerve, which contains longitudinal Schwann cell columns without axons and surrounded by perineurium-like tissue but no axons (Q. Zhao, L.B. Dahlin, M. Kanje, G. Lundborg, Brain Res. 592 (1992) 106-114), was applied as a graft to repair nerve defect in rats. Creation of the pseudo-nerve was accomplished by inserting the proximal and distal stumps of a cut sciatic nerve into a silicone tube. The proximal insert was cut far proximally to prevent axons from entering the tube. After 4 weeks, the pseudo-nerve was harvested, trimmed into a 10-mm long graft and transplanted into a corresponding defect of the contralateral sciatic nerve. Nerve regeneration through the pseudo-nerve was examined by pinch reflex test and neurofilament staining after 6 days or by morphology after 4, 6 or 8 weeks. The results showed that the pseudo-nerve could induce nerve regeneration to a similar extend as a real nerve graft. The neurobiological composition of the pseudo-nerve and the factors influencing its formation were also studied. By double staining of S-100 and laminin we found that the longitudinally organized Schwann cell columns in the pseudo-nerve were surrounded by basal laminae and ensheathed by a layer of vascularized perineurium-like tissue. Macrophages (ED1 and ED2) and their products interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) were constantly present in the pseudo-nerve. Besides, the size of tube was a crucial factor in influencing pseudo-nerve formation, e.g. a thicker pseudo-nerve was formed in tubes with larger diameters or shorter gap lengths. No pseudo-nerve was formed when the gap was 15 mm long. When both proximal and distal inserts were isolated nerve segments the pseudo-nerve was still formed but thin, probably because of compromised vascular supply. Taken together, the results suggested that the pseudo-nerve contains the essential neurobiological elements to induce successful axonal elongation.

Animals↗

Persistent postoperative complaints after whole sural nerve biopsies in diabetic and non-diabetic subjects.

The postoperative effects of a whole sural nerve biopsy in diabetic (11) and non-diabetic (10 healthy controls, 10 patients with impaired glucose tolerance and 2 patients with polyneuropathy) subjects were investigated by a mailed questionnaire 20-44 months after the surgical procedure (10/11 vs 21/22 answers received). Pain in the biopsy area at follow-up was reported in 4/10 of the diabetic patients (p = 0.01) but in none of the non-diabetic subjects (0/21). An increased number (p = 0.01) of diabetic patients (5/10 vs 1/21) had cold intolerance in their foot or leg whereas 11/31 of all patients had dysaesthesia in the affected skin. Overall 6/31 patients described serious problems at the time of the questionnaire, and 4 of this 6 having diabetes. Loss of sensation was reported in almost all subjects irrespective of diabetes or not; however, a decrease in the area of loss of sensation was reported most often in diabetic patients (8/10 vs 8/21, p = 0.02). It is concluded that whole surval nerve biopsies give rise to persistent problems both in diabetic and non-diabetic subjects. The reason for a sural nerve biopsy has always to be carefully considered before being conducted.

Adult↗

Structural nerve changes at wrist level in workers exposed to vibration.

OBJECTIVES: To analyse the character of morphological changes occurring in a well defined peripheral nerve in humans exposed to vibration from hand held tools. METHODS: Biopsies of the dorsal interosseus nerve just proximal to the wrist were taken from 10 men exposed to vibration and from 12 male age matched necropsy controls. The nerve was resected for pain relief either as the sole procedure or in conjunction with carpal tunnel release. All specimens were sectioned and examined by light microscopy in standard sections, thin epon sections, and teasing preparations. RESULTS: The combined results of the analyses showed pathological changes in all 10 patients dominated by breakdown of myelin and by interstitial and perineurial fibrosis. All but one of the 12 controls were normal. CONCLUSION: These findings often show severe nerve injury previously not described at this level. They indicate that demyelination may be the primary lesion in neuropathy induced by vibration followed by fibrosis associated with incomplete regeneration or with organisation of oedema. Vibration can induce structural changes in peripheral nerves just proximal to the wrist and such changes may constitute a structural component in carpal tunnel syndrome among people exposed to vibration. This may help to explain the poor results achieved by carpal tunnel release in these patients.

Adult↗

Nerve injury induced by vibration: prevention of the effect of a conditioning lesion by D600, a Ca2+ channel blocker.

OBJECTIVES: Exposing a hind leg of a rat to vibration induces an injury to the sciatic nerve--a so called conditioning lesion. After such injury induced by vibration the regenerative capacity of the nerve is improved and can be detected as an increased axonal outgrowth from a test crush lesion to the same nerve. The purpose was to study whether the effect of a conditioning lesion induced by vibration can be prevented by local treatment with a Ca2+ channel blocker D600. METHODS: D600 (methoxyverapamil) or Ringer's solution was locally applied to the sciatic nerve on one side through a silicone tube connected to a miniosmotic pump, which was implanted subcutaneously. During the same period the hind leg was exposed to vibration (80 Hz; 32 m/s2 root mean squared) for five hours daily for five consecutive days. The other hind leg was not vibrated. After the end of exposure to vibration the sciatic nerves were crushed bilaterally (test crush lesions) and three or six days later the regeneration distances of sensory axons were measured by the pinch reflex test. RESULTS: Nerves in the control animals (without implanted miniosmotic pumps and nerves on to which Ringer's solution was locally applied) that were exposed to vibration showed a significantly increased outgrowth length of sensory axons from the test crush lesion compared with the non-vibrated side. Such an effect of a conditioning lesion from the exposure to vibration was suppressed by local application of D600. CONCLUSIONS: Local administration of a Ca2+ channel blocker D600 can prevent the effect of a conditioning lesion-that is, the nerve injury induced by vibration can be inhibited by D600. This may have implications for the treatment of patients with neuropathy of the hand induced by vibration.

Animals↗

Role of macrophages in the stimulation and regeneration of sensory nerves by transposed granulation tissue and temporal aspects of the response.

Application of granulation tissue, which is rich in macrophages, to a peripheral nerve induces a conditioning effect, in that it enhances the regeneration capability of peripheral nerves after a test crush lesion. The temporal aspects of this response and the role of macrophages and interleukin-1 beta (IL-1 beta) were studied in the sciatic nerves of 71 rats. Granulation tissue was implanted close to the sciatic nerve and test crush lesions were applied after various periods of time (0-21 days). Regeneration was evaluated after an additional two, three, four, or six days. Regeneration distances were longer in granulation-treated nerves than in nerves treated with subcutaneous tissue. Furthermore, in animals in which the test crush lesion was made at the same time as the granulation tissue was implanted (n = 6), regeneration distances were longer, 8.1 (0.8) mm compared with 7.2 (0.6), than those in which the crush was made after conditioning intervals of 3 (n = 6, 7.6 (0.4) compared with 6.9 (0.4), p = 0.03); 7 (n = 6, 7.4 (0.4) compared with 6.6 (0.1), p = 0.03); and 21 days [(n = 8, 7.2 (0.6) compared with 6.4 (0.5)]. Inactivation of the granulation tissue by freezing suppressed the conditioning effect. There were numerous ED1 and ED2 positive macrophages as well as positive staining for IL-1 beta in the granulation tissue on day 0. Positive staining for IL-1 beta was also seen in nerve fibres as well as in non-neuronal cells after a conditioning interval. The results suggest that regeneration is stimulated by factors released from the cells of the granulation tissue, and that the amount of factors released or the responsiveness of the regenerating nerve change during the conditioning interval.

Animals↗

Hand problems in 100 vibration-exposed symptomatic male workers.

Long-term use of hand-held vibrating tools may induce various types of hand problems. One hundred symptomatic men exposed to vibration from such tools were interviewed and examined with special reference to neurosensory and vasospastic problems. Three distinct symptomatic groups were identified: isolated neurosensory symptoms (48%), isolated vasospastic problems (20%), and combined neurosensory and vasospastic problems (32%). Abnormal cold intolerance (pain and coldness without blanching of the fingers on exposure to cold) occurred in 27% of the patients. Neurosensory problems were more predominant than vasospastic ones, especially during the first 20 years of vibration exposure. Of 80 patients with neurosensory symptoms, only 22 had signs of a carpal tunnel syndrome (CTS). It is concluded that vibration-induced neurosensory and vasospastic symptoms can occur separately or together, and that the neurosensory symptoms are often not due to a CTS.

Adult↗

Impaired regeneration in rat sciatic nerves exposed to short-term vibration.

We have studied the effects of vibration on the regeneration capacity of the peripheral nerve. A rat model was used where one hind limb was subjected to vibration of defined magnitude and duration while the contralateral hind limb was not exposed to vibration. Seven days later, the sciatic nerves were transected bilaterally and cross-joined giving the following groups: group A, a proximal vibrated nerve end sutured to a non-vibrated distal nerve end; group B, a non-vibrated proximal nerve end sutured to a distal vibrated nerve end, and group C, non-vibrated proximal nerve end sutured to a non-vibrated distal nerve end. The regeneration distances were measured 3, 6 and 8 days after surgery. The control group showed a normal linear outgrowth. The outgrowth in the two experimental groups was initially not different to controls but later became significantly different, indicating a retardation of outgrowth in these groups. It is concluded that short-term exposure to vibration can impair nerve regeneration after transection and nerve repair.

Animals↗

Tissue displacement is a causative factor in vibration-induced muscle injury.

The early skeletal muscle response to vibration stimulus at two different displacement levels was examined. Twelve rats were anaesthetized and the hind limb was exposed to vibration, 80 Hz, 63 micronsrms (root mean square) (group 1) and 40 Hz; 130 micronsrms (group 2) for 5 hours/day for 2 days. Cross-sectional areas of vibrated muscle fibres were significantly larger in group 2. Sizes of different fibre types were differently affected: the slow-twitch type 1 fibres were significantly enlarged in both groups, while the fast-twitch type 2 fibres demonstrated a mixed response pattern. Centrally positioned muscle fibre nuclei increased significantly after vibration in group 2. It is concluded that the level of tissue displacement is a crucial factor for development of vibration-induced muscle injury.

Animals↗

Anatomy, function, and pathophysiology of peripheral nerves and nerve compression.

The basic pathophysiology of nerve compression injuries is complex and it is important to consider the microanatomy of the neuron and the peripheral nerve. The clinical stages of nerve compression lesions can be related to changes in intraneural microcirculation and nerve fiber structure; alterations in vascular permeability, with subsequent formation of edema; and deterioration of nerve function observed in experimental studies. The double-crush and reversed double-crush syndromes are related to disturbances in axonal transport induced by compression, followed by morphologic and functional changes in the nerve cell bodies. An underlying neuropathy in subjects can make the peripheral nerves more susceptible to compression injuries.

Animals↗